Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
2014 Cards in this Set
- Front
- Back
Often precedes squamous cell carcinoma
|
Actinic keratosis
Sun exposure causes pre-malignant lesions (SCC) *Dysplasia ~ malignancy risk Red or brown papules Cutaneous horns (macroscopic) |
|
1 adrenocortical deficiency
|
Addison's disease
|
|
Polyostotic fibrous dysplasia
Precocious puberty Cafe-au-lait spots Short stature Young girls |
Albright's syndrome
|
|
Disease in which albuminocytologic dissociation is observed
|
Guillian-Barre
|
|
Albuminocytologic dissociation
|
CSF protein increase, but only modest increase in cell count
|
|
Hereditary nephritis
Nerve deafness |
Alport's syndrome
|
|
Anti-basement membrane antibodies
|
Goodpasture's syndrome
|
|
Anti-centromere antibodies
|
CREST
C --> C: Centromere --> CREST |
|
Anti-ds DNA
|
SLE (type 3 hypersensitivity)
|
|
Anti-epithelial cell antibodies
|
Pemphigus vulgaris
|
|
Antigliadin antibodies
|
Celiac disease
|
|
Anti-histone antibodies
|
Drug-induced SLE
|
|
Anti-IgG antibodies
|
Rheumatoid factor
Rheumatoid arthritis |
|
Antimitochondrial antibodies
|
Primary biliary cirrhosis
|
|
Anti-neutrophil antibodies
|
Vasculitis
p-ANCA, c-ANCA |
|
Anti-platelet antibodies
|
Idiopathic thrombocytopenic purpura
|
|
Arachnodactyly
|
Marfan's syndrome
|
|
Argyll Robertson pupil
|
Neurosyphilus
|
|
Arnold-Chiari malformation
|
Cerebellar tonsillar herniation
|
|
Aschoff bodies
|
Rheumatic fever
Aschoff = Webby area that contains anitschow cells (nuclei look like a football stitch) |
|
Atrophy of the mammillary bodies
|
Wernicke's encephalopathy
|
|
Auer rods
|
Acute myelogenous leukemia (especially the promyelocytic type-M3)
|
|
Autosplenectomy
|
Sickle cell anemia
|
|
Babinski's sign
|
UMN lesion
|
|
Baker's cyst in popliteal fossa
|
Rheumatoid arthritis
|
|
Bamboo spine on X-ray
|
Ankylosing spondylitis
|
|
Bartter's syndrome
|
Hyperreninemia
|
|
Basophilic stippling of RBCs
|
Lead poisoning
|
|
Becker's muscular dystrophy
|
Defective dystrophin
Less severe than Duchenne's |
|
Bell's palsy
|
LMN CN VII palsy
|
|
Bence Jones proteins
|
Multiple myeloma (kappa or lambda Ig light chains in urine--+lytic bone lesions)
Waldenstrom's macroglobulinemia (IgM) |
|
Berger's disease
|
IgA nephropathy
|
|
Bernard Soulier disease
|
Defect in platelet adhesion (GP1a)
|
|
Bilateral hilar adenopathy, uveitis
|
Sarcoidosis
|
|
Birbeck granules on EM
|
Histiocytosis X (eosinophilic granuloma)
|
|
Bloody tap on LP
|
Subarachnoid hemorrhage
|
|
Blue bloater
|
Chronic bronchitis
|
|
Blue-domed cysts
|
Fibrocystic change of the breast
(Subtype) |
|
Blue sclera
|
Osteogenesis imperfecta
Also multiple fractures Hearing loss (middle ear bones break) Dental imperfections (lack of dentin) |
|
Boot shaped heart on Xray
|
Right ventricular hypertrophy
Often as part of Tetralogy of Fallot |
|
Bouchard's nodes
|
PIP swelling as part of osteoarthritis
Secondary to osteophyte formation |
|
Boutonniere deformity
|
Rheumatoid arthritis
Flexion of PIP Hyperextension of DIP |
|
Branching rods in oral infection
|
Actinomyces Israelii
|
|
Bruton's disease
|
X-linked agammaglobulinemia
|
|
Budd-Chiari syndrome
|
Post-hepatic venous thrombosis
|
|
Buerger's disease
|
Burger vs. "le Buerger" (petite?)
SMALL AND MEDIUM VESSELS a.k.a. Thromboangitis obliterans Causes vascular thromboses: *Claudication and severe pain *Superficial nodular phlebitis *Raynaud's *GANGRENE Seen in HEAVY SMOKERS *Tx = Stop smoking |
|
Burkitt's lymphoma
|
8-->14 translocation
Associated w/EBV Starry sky (macros in lymphocytes) appearance on histology |
|
Burton's lines
|
Lead poisoning
Lead sulfide deposition at the interface of teeth and gums |
|
Cafe au lait spots on skin
|
Neurofibromatosis
(also Albright's syndrome) |
|
Caisson disease
|
Caisson --> Poisson --> FISH
a.k.a. "The bends," Decompression dz Gas emboli |
|
Calf pseudohypertrophy
|
Duchenne's muscular dystrophy
|
|
Call-Exner bodies
|
Granulosa-theca cell tumor of the ovary
Granulosa and theca surround an "egg" that isn't there--eosinophils instead |
|
Cardiomegaly w/apical atrophy
|
Chagas disease
|
|
Cerebriform nuclei
|
Cutaneous T cell lymphoma
a.k.a. Mycosis fungiodes Itchy skin patch --> Raised plaque --> Mushroom tumor (The other form of cutaneous TCL is Sezary syndrome) |
|
Chagas disease
|
Trypanosome infection
Cardiomegaly Megacolon Megaesophagus |
|
Chancre
|
Primary syphilus
Not painful |
|
Chancroid
|
Haemophilus ducreyi
PAIN differentiates from syphilus chancre |
|
Charcot's triad
|
There are 2!
JR Fudge sundaes are a SIN Multiple sclerosis: SIN *Scanning speech *Intention tremor *Nystagmus Cholangitis: JR Fudge *Jaundice *RUQ pain *Fever |
|
Charcot-Leyden crystals
|
Product of eosinophil breakdown (membrane component)
Seen as part of Bronchial asthma along w/Curschmann's spirals (whorled mucus plugs) |
|
Curschmann's spirals
|
Whorled mucus plugs
Seen as part of Bronchial Asthma along w/Charcot-Leyden crystals |
|
Chediak-Higashi disease
|
Phagocyte deficiency
|
|
Cherry-red spot on macula
|
Lysosomal storage diseases:
*Tay Sachs (Hexosaminidase A) *Neimann-Pick disease (sphingomyelinase) Central retinal artery occlusion |
|
Cheyne-Stokes respirations
|
Central apnea (irregular breathing)
Causes: CHF, Increased ICP |
|
Chocolate cysts
|
Feature of endometriosis
Frequently involves both ovaries |
|
Chronic atrophic gastritis
|
Predisposition to gastric carcinoma
|
|
Chvostek's sign
|
Facial muscle spasm upon tapping
Sign of hypocalcemia (Low Ca2+ tetany) |
|
Clear cell adenocarcinoma of the vagina
|
DES exposure in utro
|
|
Clue cells
|
Gardnerella vaginitis
|
|
Codman's triangle on X-ray
|
Osteosarcoma
|
|
Cold agglutinins
|
IgM
Mycoplasma pneumoniae Mononucleosis |
|
Cold intolerance
|
Hypothyroidism
|
|
Condyloma lata
|
2 Syphilis
Whitish confluence of smaller (red) skin rashes Often on the palms and soles |
|
Continuous machinery murmur
|
Patent ductus arteriosus
|
|
Cori's disease
|
Debranching enzyme deficiency
|
|
Cotton-wool spots
|
Chronic hypertension
Puffy white patches on retina |
|
Cough, conjunctivitis, coryza
+ Fever |
Coryza = Head cold
Measles |
|
Councilman bodies
|
Hepatitis
Toxic OR viral |
|
Cowdry A bodies
|
Herpes virus
|
|
Crescents in Bowman's capsule
|
Rapidly progressive crescentic glomerulonephritis
|
|
Crigler-Najjar syndrome
|
Congenital unconjugated hyperbilirubinemia
Type 1: Greatly REDUCED UDP-glucuronyl transferase Greatly reduced UDP-glucuronyl transferase *Tx: PHENOBARBITOL (increases liver enzyme synthesis) Type 2: ABSENT UDP-glucuronyl transferase *Jaundice *Kernicterus (bilirubin in brain) *Tx: Phototherapy, plasmapheresis |
|
Curling's ulcer
|
Acute gastric ulcer associated w/severe burns
|
|
Currant-jelly sputum
|
Klebsiella
|
|
Cushing's ulcer
|
Acute gastric ulcer associated w/CNS injury
|
|
D-dimers
|
DIC
|
|
Depigmentation of neurons in substantia nigra
|
Parkinson's disease
Rigidity, resting tremor, bradykinesia |
|
Dermatitis, dementia, diarrhea
|
Pellagra
Vitamin B3 (niacin) deficiency |
|
Diabetes insipidus
+ Exopthalmos + Lesions of skull |
Hand-Schuller-Christian disease
"Chronic progressive histiocytosis" A multifocal, unisystem langerhans cell histiocytosis seen mostly in children *Bone invasion *50% involve pituitary --> DI |
|
Dog or cat bite
|
Pasteurella multocida
|
|
Donovan bodies
|
Granuloma inguinale (bacterial infection)
|
|
Dressler's syndrome
|
Post-MI fibrinous pericarditis
Weeks-months later |
|
Duchenne's muscular dystrophy
|
Deleted dystrophin gene
X-linked recessive |
|
Eburnation
|
Osteoarthritis
Polished, ivory-like appearance of bone |
|
Edward's syndrome
|
Trisomy 18
Low-set ears Heart problems Rocker bottom feet |
|
Eisenmenger's complex
|
Change in pathological shunt flow direction during late cyanosis
*When R heart P > L heart L--> R changes to R --> L |
|
Elastic skin
|
Ehlers-Danlos syndrome
|
|
Erb-Duchenne palsy
|
Superior trunk (C5-C6) injury
"Waiter's tip" |
|
Erythema chonicum migrans
|
Lyme disease
|
|
Fanconi's syndrome
|
Proximal tubular reabsorption defect
|
|
Fat
Female Forty Fertile |
Acute cholecystitis
|
|
Fatty liver
|
Alcoholism
(+ Obesity) |
|
Ferruginous bodies
|
Asbestosis
|
|
Gardner's syndrome
|
Form of FAP
Colon polyps + Osteomas (usually skull), soft tissue tumors |
|
Gaucher's disease
|
Glucocerebrosidase Deficiency
|
|
Ghon focus
|
TB
|
|
Glanzmann's thrombasthenia
|
Defect in platelet aggregation (2b-3a)
|
|
Goodpasture's syndrome
|
Autoantibodies against basement membrane proteins of:
1. Alveoli 2. Glomerulus |
|
Gower's maneuver
|
Seen w/Duchenne's
Use of patient's arms to help legs pick self off from the floor |
|
Guillian-Barre syndrome
|
Idiopathic polyneuritis
Distal --> Proximal |
|
Hair-on-end/Crew cut skull appearance on X-ray
|
Extramedullary hematopoiesis
Seen w/sickle cell, B-thalassemia |
|
Hand-Schuller-Christian disease
|
Chronic progressive histiocytosis
Diabetes insipidus + Exopthalmos + Lesions of skull |
|
HbF
|
Thalassemia major
|
|
HbS
|
Sickle cell anemia
|
|
hCG elevated
|
Choriocarcinoma, hydatiform mole
Pregnancy |
|
Heberden's nodes
|
Osteoarthritis
DIP swelling 2 to osteophytes |
|
Heinz bodies
|
G6PD deficiency
|
|
Henoch-Schonlein Purpura
|
#1 childhood vasculitis
A hypersensitivity vasculitis Associated w/URIs Causes 1. Hemorrhagic urticaria that appear and age together 2. Joints (arthritis) 3. GI (Intestinal hemorrhage) *Abdominal pain and melena Henoch = NOCH knees (joints) Schonlein = Stomach Purpura = Purpura |
|
Heterophil antibodies
|
Infectious mononucleosis (EBV)
|
|
High-output cardiac failure
|
Dilated cardiomyopathy
Seen w/Wet Beriberi (B1 deficiency) |
|
HLA-B27
|
PAIR:
Psoriasis Ankylosing spondylitis IBD Reiter's syndrome (See, Pee, Climb a tree/Bend the knee) |
|
HLA-B8
|
Skinny people......I wish they 8 more
Graves disease Celiac sprue |
|
HLA-DR2
|
1 representative from each hypersensitivity type:
Hay fever Goodpasture SLE Multiple sclerosis |
|
HLA-DR3
|
Diabetes mellitus type 1
|
|
HLA-DR4
|
Diabetes mellitus type 1
Rheumatoid arthritis *4 walls in a "rheum" |
|
HLA-DR5
|
5 = TIRED
Pernicious anemia (B12 def) Hashimoto's thyroiditis |
|
HLA-DR7
|
Steroid-responsive nephrotic syndrome
7 year olds... |
|
SLE antibodies
|
ANA
Anti-phospholipid: May cause false + for syphilus Very specific: Anti-dsDNA: Poor prognosis Anti-Smith (rna binding prot): no prognostic info Drug induced: Anti-histone (drug induced) |
|
Scleroderma antibodies
|
Anti-centromere = CREST
Anti-Scl-70/topoisomerase = Diffuse |
|
Primary biliary cirrhosis antibody
|
Anti-mitochondrial
|
|
Pemphigus vulgaris antibody
|
Anti-epithelial cell (desmosomes)
|
|
Hashimoto's thyroiditis antibodies
|
Hashes moto (microsome) and thyroiditis (thyroglobulin)
Anti-microsomal Anti-thyroglobulin |
|
Polymyositis, Dermatomyositis antibodies
|
Anti-Jo-1
|
|
Sjogren's syndrome antibodies
|
Anti-SS-A (anti-Ro)
Anti-SS-B (anti-La) *More specific than SSA |
|
Anti-U1 RNP antibody
|
Mixed connective tissue diseases
SLE, Scleroderma |
|
Autoimmune hepatitis antibody
|
Anti-smooth muscle
|
|
Type 1 diabetes mellitus antibody
|
Anti-glutamate decarboxylase
|
|
Wegener's granulomatosis antibody
|
c-ANCA
Binds proteinase 3 in neutrophil cytoplasm |
|
p-ANCA
|
Binds myeloperoxidase, which aggregates around neutrophil nucleus
|
|
Homer Wright rosettes
|
Neuroblastoma
|
|
Honeycomb lung on X-ray
|
Interstitial fibrosis
|
|
Horner's syndrome
|
Ptosis
Anhydrosis Miosis SC lesion above T1 |
|
Howell-Jolly bodies
|
Splenectomy or non-functional spleen
|
|
Huntington's disease
|
Caudate degeneration
Decreased GABA, Ach Autosomal dominant Chromosome 4 |
|
Hyperphagia + hypersexuality + hyperorality + hyperdocility
|
Kluver-Bucy syndrome (amygdala)
|
|
Hyperpigmentation of skin
|
Addison's (1 adrenal insufficiency)
|
|
Hypersegmented neutrophils
|
Megaloblastic/macrocytic anemia
|
|
Hypertension + Hypokalemia
|
Conn's syndrome (aldosterone secreting adenoma)
A form of primary aldosteronism HTN Hypokalemia Alkalosis |
|
Hypochromic microcytosis
|
Iron deficiency anemia
or Lead poisoning |
|
Increased alpha-fetoprotein in amniotic fluid/maternal serum
|
Neural tube defects
(Anencephaly, spina bifida) |
|
Increased uric acid levels
|
GoLLuM
Gout Lesch-Nyhan (HGPRT deficiency) Loop and thiazide diuretics Myeloproliferative disorders |
|
Intussusception: Cause
|
Adenovirus
Causes hyperplasia of Peyer's patches |
|
Janeway lesions
|
Endocarditis
Found on palms, soles |
|
Jarisch-Herxheimer reaction
|
Syphilis
Overaggressive treatment of an asymptomatic patient Symptoms are due to rapid bacterial lysis and toxin release |
|
Job's syndrome
|
Abnormalities w/neutrophil chemotaxis
|
|
Kaposi's sarcoma
|
AIDS in MSM
|
|
Kartagener's syndrome
|
Dynein defect (microtubules of cilia are missing dynein arms)
Situs inversus, infertility, etc. |
|
Kayser-Fleischer rings
|
Wilson's disease
|
|
Keratin pearls
|
Squamous cell carcinoma
|
|
Kimmelsteil-Wilson nodules
|
Diabetic nephropathy
|
|
Koilocytes
|
HPV
|
|
Koplik spots
|
Measles
|
|
Krukenberg tumor
|
Gastric adenocarcinoma that metastasizes to ovary
|
|
Kussmaul Hyperpnea
|
Diabetic ketoacidosis
|
|
Kussmaul Hyperpnea
|
Diabetic ketoacidosis
|
|
Lens dislocation
Aortic dissection Joint hyperflexibility |
Marfan's syndrome
|
|
Fibrillin deficit
|
Marfan's syndrome
|
|
Lesch-Nyhan syndrome
|
HGPRT deficiency
"He's got purine trouble" |
|
Lewy bodies
|
Parkinson's disease
Frontotemporal dementia (Pick's disease) Alpha synuclein |
|
Libman-Sacks disease
|
Endocarditis associated w/SLE
"LSE w/SLE" Verrucous (wart-like) lesions on both sides of mitral valve |
|
Lines of Zahn
|
Arterial thrombus
|
|
Lisch nodules
|
Neurofibromatosis
Von Recklinghausen's diease *17 letters = chromosome 17 Lisch = Hyperpigmented areas on iris |
|
Low serum ceruloplasmin
|
Wilson's disease
|
|
Lucid interval
|
Epidural hematoma
|
|
Lumpy bumpy appearance of glomeruli on immunofluorescence
|
Post-streptococcal glomerulonephritis
|
|
Lytic bone lesions on X-ray
|
Multiple myeloma
Met from lung |
|
Mallory bodies
|
Alcoholic liver disease
Eosinophilic |
|
Mallory-Weiss syndrome
|
Esophagogastric lacerations
PAINFUL (esophageal varices are not) |
|
McArdle's disease
|
Muscle phosphorylase deficiency
|
|
McBurney's sign
|
Appendicitis
Deep tenderness at McBurney's point (RLQ) |
|
MLF Syndrome
|
Multiple sclerosis
|
|
Monoclonal antibody spike
|
1. Multiple myeloma: IgG or IgA
*Called the "M protein" 2. Waldenstrom's macroglobulinemia: IgA 3. MGUS (Monoclonal gammopathy of undetermined significance) |
|
Myxedema
|
Hypothyroidism
|
|
Necrotizing vasculitis (lungs)
+ Necrotizing glomerulonephritis |
Goodpasture's syndrome
Wegener's |
|
Needle shaped, negatively birefringent (yellow) crystals
|
Gout
|
|
Negri bodies
|
Rabies
|
|
Nephritis
+ Cataracts + Hearing loss |
Alport's syndrome
|
|
Neurofibrillary tangles
|
Alzheimer's disease
|
|
Neimann-Pick disease
|
Sphingomyelinase deficiency
|
|
No lactation postpartum
|
Sheehan's syndrome (pituitary infarction)
|
|
Nutmeg liver
|
CHF
|
|
Occupational exposure to asbestos
|
Maligant mesothelioma
|
|
Orphan Annie nuclei
|
Papillary carcinoma of the thyroid
Lots of Orphans in the PAPulation |
|
Osler's nodes
|
Endocarditis
|
|
Owl's eye
|
CMV
|
|
Painless jaundice
|
Pancreatic cancer (head)
|
|
Pancoast's tumor
|
Bronchogenic apical tumor
*May cause Horner's sydrome |
|
Pannus
|
Rheumatoid arthritis
|
|
Parkinson's disease
|
Nigrostriatal dopamine depletion
Failure to excite the excitatory + Failure to inhibit the inhibitory Lewy bodies (Alpha synuclein) Depigmentation of the substantia nigra TRAP: Tremor at Rest Rigidity (cogwheel) Akinesia (impaired movement) Postural instability |
|
Periosteal elevation on X-ray
|
Pyogenic osteomyelitis
|
|
Peutz-Jegher's syndrome
|
Benign polyposis
|
|
Peyronnie's disease
|
Penile fibrosis
Bent penis |
|
Philadelphia chromosome
|
CML (sometimes AML)
|
|
Pick bodies
|
Pick's disease (Frontotemporal dementia)
|
|
Pink puffer
|
Emphysema
Centroacinar = smoking Panacinar = Alpha 1 def |
|
Centroacinar emphysema
|
Smoking
|
|
Panacinar emphysema
|
Alpha-1-antitrypsin deficiency
|
|
Pick's disease
|
Progressive dementia
Pathology similar to PD Progression similar to AD |
|
Plummer-Vinson syndrome
|
Plumber wearing a WIG:
Webs (Esophageal--dysphagia) Iron deficiency anemia Glossitis |
|
Podagra
|
Gout at the MP joint of big toe
|
|
Hallux
|
Big toe
|
|
Podocyte fusion
|
Minimal change disease/Lipoid nephrosis
|
|
Polyneuropathy
Cardiac pathology Edema |
Dry beriberi
(B1 deficiency) |
|
Polyneuropathy preceded by GI or respiratory infection
|
Guillain-Barre
|
|
Pompe's disease
|
Lysosomal glucosidase deficiency
Associated w/cardiomegaly *TV: Girl had progressive muscle weakness, tons of glycogen in muscle |
|
Port-wine stain
|
Hemangioma
(seen w/Sturge-Weber) |
|
Positive anterior drawer sign
|
ACL injury
|
|
Pott's disease
|
Vertebral TB
Considered a form of osteomyelitis |
|
Pseudopalisade tumor cell arrangement
|
GBM
|
|
Pseudorosettes
|
Ewing's sarcoma
Neuroectodermal origin |
|
Ptosis, miosis, anhidrosis
|
Horner's syndrome
Often Pancoast's tumor |
|
Rash on palms and soles
|
2 syphilis
Rocky mountain spotted fever |
|
Raynaud's syndrome
|
Recurrent vasospasm in extremities
|
|
RBC casts in urine
|
Acute glomerulonephritis
|
|
Recurrent pulmonary Pseudomonas and S. aureus infections
|
Cystic fibrosis
|
|
Red urine in the morning
|
Paroxysmal nocturnal hemoglobinuria
Complement disorder |
|
Reed-Sternberg cells
|
Hodgkin's lymphoma
|
|
Reid index
|
Increased w/chronic bronchitis
Mucus:Total thickness ratio |
|
Reinke crystals
|
Leydig cell tumor
(Testosterone) |
|
Reiter's syndrome
|
Can't see, pee, climb a tree/bend the knee
Conjunctivitis Urethritis Arthritis HLA-B27 (MHC1) association More common in males Happens after you've "REITED" an STD (chlamydia) Happens after you haven't been EITing (GI infection) |
|
Renal cell carcinoma
+ Cavernous hemangiomas + Adenomas |
Von hippel landau (chromosome 3)
|
|
Renal EPITHELIAL casts in urine
|
Acute toxic/viral nephrosis
|
|
Rhomboid crystals
Positively birefringent |
Pseudogout
Affects older people (>50) M=F Calcium pyrophosphate Usually affects the knee NO TREATMENT |
|
Rib notching
|
Coarctation of the aorta
Caused by enlarged intercostal collaterals |
|
Roth spots
|
Endocarditis
Retinal hemorrhages w/pale or white centers |
|
Rotor's syndrome
|
Congenital conjugated hyperbilirubinemia
Less severe than Dubin-Johnson No black liver |
|
Rouleaux formation
|
Multiple myeloma
Stacked RBCs |
|
S3
|
Increased volume within the ventricle
Left to right shunt Mitral regurgitation LV failure |
|
S4
|
Atria contracting forcefully to overcome stiff ventricle
Aortic stenosis Hypertrophic subaortic stenosis Long-standing HTN Fibrosis (post MI) |
|
Schiller-Duval bodies
|
Yolk sac tumor
|
|
Senile plaques
|
Alzheimer's disease
B-amyloid |
|
Sezary syndrome
|
Form of cutaneous T cell lymphoma
T cells have pathological quantities of mucopolysaccharides (The other form is Mycosis fungiodes) |
|
Sheehan's syndrome
|
Postpartum pituitary infarction/necrosis
|
|
Shwartzman reaction
|
Neisseria meningitidis
1st exposure: Inflammation, thrombosis (can be cleared) 2nd exposure: Necrosis |
|
Signet-ring cells
|
Gastric carcinoma
|
|
Simian crease
|
Down syndrome
|
|
Sipple's syndrome
|
Men Type 2a
Medullary Thyroid CA + Hyperparathyroidism Men 2B = Medullary thyroid CA + Pheochromocytoma |
|
Sjogren's syndrome
|
Dry eyes
Dry mouth Arthritis |
|
Skip lesions
|
Crohns
|
|
Slapped cheeks
|
Erythema infectiosum (5th's disease)
B19 Parvo |
|
Slapped cheeks
|
Erythema infectiosum (5th's disease)
B19 Parvo |
|
Smudge cell
|
CLL
|
|
"Soap bubble" on X-ray
|
Giant cell tumor of bone
|
|
Spike and dome on EM
|
Membranous glomerulonephritis
|
|
Spitz nevus
|
Benign juvenile melanoma
|
|
Splinter hemorrhages in fingernails
|
Endocarditis
|
|
Starry-sky pattern
|
Burkitt's lymphoma (EBV)
8-->14 translocation |
|
Strawberry tongue
|
Scarlet fever
|
|
Streaky ovaries
|
Turner's syndrome
|
|
String sign on X-ray
|
Crohn's disease
|
|
Subepithelial humps on EM
|
Post-streptococcal glomerulonephritis
|
|
Sub-occipital lymphadenopathy
|
Rubella
|
|
Sulfur granules
|
Actinomyces israelii
|
|
Swollen gums, bruising, poor wound healing, anemia
|
Scurvy
Vitamin C necessary for hydroxylation of proline and lysine in collagen synthesis |
|
Systolic ejection murmur
|
Aortic stenosis
|
|
8-->14 translocation
|
Burkitt's lymphoma
c-myc |
|
9-->22 translocation
|
Philadelphia chromosome
CML Bcr-abl fusion |
|
14 --> 18 translocation
|
Follicular lymphoma
Bcl-2 activation |
|
Tabes dorsalis
|
3 Syphilis
|
|
Tendon xanthomas
|
Familial hypercholesterolemia
|
|
Thumb sign on lateral x-ray
|
Acute epiglottitis
H. Influenzae |
|
Thyroidization of the kidney
|
Chronic bacterial pyelonephritis
|
|
Tophi
|
Gout
|
|
Tram-track appearance on LM
|
Membranoproliferative glomerulonephritis
Appearance: 2 glomerular basement membranes in parallel |
|
Trousseau's sign
|
Carpal spasm w/arm cuff
Visceral cancer Pancreatic adenocarcinoma Hypocalcemia |
|
Virchow's node
|
Left supraclavicular node enlargement
Metastatic carcinoma of the stomach |
|
Virchow's triad
|
Pulmonary embolism
1. Blood stasis 2. Endothelial damage 3. Hypercoagulation |
|
Von Recklinghausen's disease
|
Neurofibromatosis type 1
|
|
Von Recklinghausen's disease of bone
|
Osteitis fibrosa cystica
"Brown tumor" |
|
Wallenberg's syndrome
|
PICA thrombosis
|
|
Waterhouse-Friderichsen syndrome
|
Meningococcemia --> Adrenal hemorrhage
|
|
Waxy casts
|
Chronic end-stage renal disease
|
|
WBC casts in urine
|
Acute pyelonephritis
|
|
WBCs in urine
|
Acute cystitis
|
|
Wermer's syndrome
|
MEN type 1
Pituitary Parathyroid Pancreas |
|
Whipple's disease
|
Malabsorption syndrome
Caused by tropheryma whippelii |
|
Wilson's disease
|
a.k.a. hepatolenticular degeneration
|
|
Wire loop lesions on LM
|
Loop --> Loopus
Lupus nephropathy |
|
Worst headache of my life
|
Berry aneurysm
Associated w/adult PCKD |
|
Xanthochromia
|
Yellow CSF--processed RBCs
Subarachnoid hemorrhage |
|
Xerostomia
+ Arthritis + Keratoconjunctivitis sicca |
Sjogren's
|
|
Zenker's diverticulum
|
Upper GI diverticulum
Halitosis |
|
Zollinger-Ellison syndrome
|
Gastrin secreting tumor associate w/ulcers
|
|
Most common bacteremia/pneumonia
|
S. aureus
|
|
Most common bacteria associated w/cancer
|
H. Pylori
|
|
Most common bacteria in GI
|
#1 Bacteriodes
#2 E. coli |
|
Most common brain tumors (adults)
|
Mets
Astrocytoma (including GBM) Meningioma Schwannoma |
|
Most common brain tumor (kids)
|
Medulloblastoma (cerebellum)
|
|
Most common supratentorial brain tumor (kids)
|
Craniopharyngioma
|
|
Most common breast cancer
|
Infiltrating ductal carcinoma
US: 1 in 9 women will develop breast cancer |
|
Most common breast mass
|
Fibrocystic change
In post-menopausal women, carcinoma is the most common mass |
|
Most common breast tumor (benign)
|
Fibroadenoma
|
|
Most common bug in debilitated, hospitalized pneumonia patients
|
Klebsiella
|
|
Most common primary cardiac tumor (adults)
|
Myxoma--ball and valve
4:1 left atrium Ball and valve structure --> Blocking and syncopal episodes |
|
Most common primary cardiac tumor (kids)
|
Rhabdomyoma
Biggest association: Tuberous sclerosis (Ash, Green, CardiacRhab, Astrocytoma, Renal Angiomyolipoma) |
|
Most common cardiac tumor (adults)
|
Mets
|
|
Most common cardiomyopathy
|
Dilated
|
|
Most common chromosomal disorder
|
Down syndrome
Associations: *ALL *Alzheimer's disease *Endocardial cushion defects |
|
Most common chronic arrythmia
|
Atrial fibrillation
HIGH risk of emboli |
|
Most common congenital cardiac anomaly
|
VSD
|
|
Most common constrictive pericarditis
|
TB
|
|
Most common coronary artery involved in thrombosis
|
LAD > RCA > LCA
|
|
Most common early cyanosis
|
Tetralogy of Fallot
Transposition of great vessels Truncus arteriosus |
|
Most common late cyanosis
|
VSD, ASD, PDA
|
|
Patent ductus arteriosus
|
Close w/indomethacin
Keep open w/misoprostol (PGE1) |
|
Most common demyelinating disease
|
MS
|
|
Most common dietary deficit
|
Iron
|
|
Most common epiglottitis
|
H. influenzae type B
|
|
Most common esophageal cancer
|
Squamous cell carcinoma
|
|
Most common gene involved in cancer
|
p53
|
|
Most common group affected by cystic fibrosis
|
Caucasians
|
|
Cystic fibrosis complications
|
Fat soluble vitamin deficiencies
Mucous plugs --> Lung infections Cholesterol gallstones |
|
Gynecologic malignancy
|
Endometrial carcinoma
|
|
Most common heart murmur
|
Mitral valve prolapse
|
|
Most common heart valve in bacterial endocarditis
|
Mitral
|
|
Most common heart valve in bacterial endocarditis--IV drug abuser
|
Tricuspid
|
|
Most common heart valve affected by rheumatic fever
|
#1 Mitral valve
#2 Aorta |
|
Most common helminth infection (US)
|
#1 Enterobius vermicularis
*Pinworm #2 Ascaris lumbricoides *Roundworm |
|
Most common hereditary bleeding disorder
|
Von Willebrand's
|
|
Most common kidney stones
|
#1 Calcium --radiopaque
#2 Ammonium -- radiopaque *Urea --> Ammonia *Urease positive organisms such as Proteus, staphylococcus |
|
Most common liver disease
|
Alcoholic
|
|
Most common location of brain tumors (adults)
|
Supratentorial
|
|
Most common location of brain tumors (kids)
|
Infratentorial
|
|
Most common lysosomal storage disease
|
Gaucher's
Glucocerebrosidase deficiency |
|
Most common male cancer
|
Prostatic carcinoma
|
|
Most common malignancy associated w/noninfectious fever
|
Hodgkin's disease
|
|
Most common malignant skin tumor
|
Basal cell carcinoma (rarely mets)
|
|
Most common mets to brain
|
~50% of brain tumors are mets
Lots of Bad Stuff Kills Glia Lung Breast Skin (melanoma) Kidney GI |
|
Most common mets to liver
|
Liver metastases > Primaries
Cancer Sometimes Penetrates Benign Liver: Colon > Stomach > Pancreas > Breast > Lung or Please Get Back to CoLorado Pancreatic GI Breast Colon Lung |
|
Most common neoplasm (kids)
|
#1 ALL
#2 Cerebellar medulloblastoma |
|
Most common motor neuron disease
|
ALS
|
|
Most common nephrotic syndrome
|
Membranous glomerulonephritis
|
|
Most common obstruction of male urinary tract
|
BPH
|
|
Most common opportunistic infection in AIDS
|
Pneumocystis carinii pneumonia
|
|
Most common opportunistic infection in AIDS
|
Pneumocystis carinii pneumonia
|
|
Most common organ receiving mets
|
Adrenal glands (rich blood supply)
|
|
Most common organ sending mets
|
#1 Lung
#2 Breast and stomach (tied) |
|
Most common ovarian tumor (benign)
|
Serous cystadenoma
|
|
Most common ovarian tumor (malignant)
|
Serous cystadenocarcinoma
|
|
Most common pancreatic tumor
|
Adenocarcinoma @ head of pancreas
|
|
Most common patient w/ALL
|
Child
|
|
Most common patient w/CLL
|
Adult >60
|
|
Most common patient w/AML
|
Adult > 60
|
|
Most common patient w/CML
|
Adult 35-50
|
|
Most common patient w/Hodgkin's
|
Young male
Except nodular sclerosis type-female |
|
Most common patient w/minimal change disease
|
Young child
|
|
Most common patient w/Reiter's
|
Male
|
|
Most common pituitary tumor
|
#1 Prolactinoma
#2 Somatotropic "adicophilic" adenoma |
|
Most common preventable cancer
|
Lung cancer
|
|
Most common primary bone tumor (adults)
|
Multiple myeloma
|
|
Most common primary hyper PTH
|
#1 Adenomas
#2 Hyperplasia #3 Carcinoma *Adrenal adenoma will cause insufficiency (AI), while a parathyroid adenoma will cause a plethora (hyper PTH) |
|
Most common primary liver tumor
|
Hepatoma
|
|
Most common renal tumor
|
Renal cell carcinoma
Associations: *Von Hippel-Landau *Acquired polycystic kidney disease *Paraneoplastic syndromes (distant neoplasm secretes erythropoietin, renin, PTH or ACTH) |
|
Most common secondary hyper parathyroidism
|
Hypocalcemia of chronic renal failure
|
|
Most common sexually transmitted disease
|
Chlamydia
|
|
Most common site of diverticula
|
Sigmoid colon
|
|
Most common site of metastasis
|
#1 Regional lymph nodes
#2 Liver |
|
Most common sites of atherosclerosis
|
The first stops from the heart (aorta, coronary arteries)
Knee and neck #1 Abdominal aorta #2 Coronary arteries #3 Popliteal arteries #4 Carotid arteries |
|
Most common skin cancer
|
Basal cell carcinoma
|
|
Most common stomach cancer
|
Adenocarcinoma
|
|
Most common testicular tumor
|
Seminoma
|
|
Most common thyroid cancer
|
Papillary carcinoma
PAPillary has the biggest POP |
|
Most common tracheoesophageal fistula
|
Lower esophagus joins trachea/upper esophagus --> blind pouch
|
|
Most common tumor in men
|
Prostate carcionoma
|
|
Most common tumor in women
|
Leiomyoma (estrogen dependent)
|
|
Most common tumor of infancy
|
Hemangioma
|
|
Most common tumor of the adrenal medulla (adults)
|
Pheochomocytoma (benign)
Chromaffin cells (neural crest) release NE/E, DA Associated with MEN II, III Treatment: Phenoxybenzamine (irreversible alpha 1 and 2 blocker) 10% bilateral 10% malignant 10% extra-adrenal 10% calcify 10% kids 10% familial Symptoms = Spells of the 5 Ps: Pain (headache) Pallor Palpitations Perspiration Pressure (BP) |
|
Most common tumor of the adrenal medulla (children)
|
Neuroblastoma (malignant)
Tumors along the sympathetic chain HVA found in urine N-Myc gene |
|
Most common type of Hodgkins
|
Nodular sclerosis
(vs. Mixed celularity, lymphocytic predominance, lymphocytic depletion) |
|
Most common type of pituitary adenoma
|
Prolactinoma
|
|
Most common vasculitis
|
Temporal arteritis
Risk of ipsilateral blindness due to thrombosis of opthalmic artery |
|
Most common viral encephalitis
|
HSV
|
|
Vitamin deficiency
|
Folic acid
Body stores only a 3-4 month supply Pregnant women at high risk |
|
Most frequent cause of Addison's disease
|
AI (Adrenal insufficiency) is AI (autoimmune)
#1 Autoimmune #2 Infection |
|
Most frequent cause of aneurysm, dissecting
|
Hypertension
|
|
Most frequent cause of aortic aneurysm, ascending
|
Tertiary syphilis
|
|
Most frequent cause of bacterial meningitis (adults)
|
Streptococcus pneumoniae
|
|
Most frequent cause of bacterial meningitis (elderly)
|
Streptococcus pneumoniae
|
|
Most frequent cause of bacterial meningitis (kids)
|
Streptococcus pneumoniae
Neisseria meningitidis |
|
Most frequent cause of bacterial meningitis (newborns)
|
Groub B streptococcus
|
|
Most frequent cause of bacterial meningitis (newborns)
|
Groub B streptococcus
|
|
Most frequent cancers associated with AIDS
|
Kaposi's sarcoma
Malignant lymphoma (non-Hodgkins) *True of all immunodeficiency states |
|
Most frequent cause of congenital adrenal hyperplasia
|
21-hydroxylase deficiency
|
|
Most frequent cause of cretinism
|
Iodine deficit (hypothyroidism)
|
|
Most frequent cause of Cushing's syndrome
|
#1 Corticosteroid therapy
#2 ACTH secretion by pituitary |
|
Most frequent cause of death in CML
|
Blast crisis
|
|
Most frequent cause of death in CML
|
Blast crisis
|
|
Most frequent cause of death in SLE
|
Lupus nephropathy
|
|
Most frequent cause of dementia
|
#1 Alzheimer's
#2 Multi-infarct dementia |
|
Most frequent cause of DIC
|
#1 Gram-negative sepsis
#2 Obstetric complications #3 Cancer #4 Burn trauma |
|
Most frequent cause of ejection click
|
Aortic/pulmonic stenosis
|
|
Most frequent cause of food poisoning
|
Staph aureus
|
|
Most frequent cause of glomerulonephritis
|
IgA nephropathy (Berger's disease)
|
|
Most frequent cause of epidural hematoma
|
Rupture of middle meningeal artery
|
|
Most frequent cause of subdural hematoma
|
Bridging veins (due to trauma)
|
|
Most frequent cause of hemochromatosis
|
Multiple blood transfusions
Increased risk of CHF, hepatocellular carcinoma |
|
Most frequent cause of hepatic cirrhosis
|
Alcohol
|
|
Most frequent cause of hepatocellular carcinoma
|
Cirrhotic liver
Often associated w/Hep B, C |
|
Most frequent cause of holosystolic murmur
|
#1 VSD
#2 Tricuspid regurgitation #3 Mitral regurgitation |
|
Most frequent cause of secondary hypertension
|
Renal disease
|
|
Most frequent cause of hypoparathyroidism
|
Thyroidectomy
|
|
Most frequent cause of hypopituitarism
|
Adenoma
|
|
Most frequent cause of infection in blood transfusions
|
Hepatitis C
|
|
Most frequent cause of infection in burn victims
|
Pseudomonas
|
|
Most frequent cause of leukemia (adults)
|
AML
|
|
Most frequent cause of machine-like murmur
|
Persistent ductus arteriosus
|
|
Most frequent cause of mental retardation
|
#1 Down syndrome
#2 Fragile X |
|
Most frequent cause of MI
|
Atherosclerosis
|
|
Most frequent cause of mitral valve stenosis
|
Rheumatic heart disease
|
|
Most frequent cause of myocarditis
|
Coxsackie B
|
|
Most frequent cause of nephrotic syndrome (adults)
|
Membranous glomerulonephritis
|
|
Most frequent cause of nephrotic syndrome (kids)
|
Minimal change disease
Assoiated w/infections and vaccinations Treat w/corticosteroids |
|
Most frequent cause of opening snap
|
Mitral stenosis
|
|
Most frequent cause of osteomyelitis
|
S. Aureus
> Streptococcus, Neisseria |
|
Most frequent cause of osteomyelitis in patient w/sickle cell disease
|
Salmonella
|
|
Most frequent cause of osteomyelitis with IV drug abusers and diabetics
|
Pseudomonas
|
|
Most frequent cause of acute pancreatitis
|
Alcohol and Gallstones
|
|
Most frequent cause of chronic pancreatitis in adults
|
Alcohol
|
|
Most frequent cause of chonic pancreatitis in children
|
Cystic fibrosis
|
|
Most frequent cause of peau d'orange
|
Carcinoma of the breast
|
|
Most frequent cause of PID
|
Neisseria gonorrhoeae
Associated w/monoarticular arthritis |
|
Most frequent cause of hospital acquired pneumonia
|
Klebsiella
|
|
Most frequent cause of pneumonia in cystic fibrosis
|
Pseudomonas aeruginosa
|
|
Most frequent cause of pneumonia in burn infection
|
Pseudomonas aeruginosa
|
|
Most frequent cause of preventable blindness
|
Chlamydia
|
|
Most frequent cause of primary amenorrhea
|
Turner's syndrome
|
|
Most frequent cause of primary hyperaldosteronism
|
Adenoma of adrenal cortex
|
|
Most frequent cause of pulmonary hypertension
|
COPD
|
|
Most frequent cause of right heart failure due to a pulmonary cause
|
Cor pulmonale
|
|
Most frequent cause of sheehan's syndrome
|
Postpartum pituitary infarction due to hemorrhage
|
|
Most frequent cause of SIADH
|
Small cell carcinoma of the lung
|
|
Most frequent cause of UTI
|
E. coli (50-80%)
|
|
Most frequent cause of UTI in young women
|
E. coli
and Staphylococcus saprophyticus |
|
Sensitivity
|
Sensitivity =
True positives ------------- True positives + False negatives |
|
Specificity
|
Specificity =
True negatives ------------------ True negatives + False positives |
|
Positive predictive value
|
PPV =
True positives ---------------- True positives + False positives |
|
Negative predictive value
|
NPV =
True negatives ------------------- True negatives + False negatives |
|
Relative risk
|
Relative risk (applies in prospective studies)
Exposed w/disease --------------------- Total exposed / Unexposed w/disease ------------------------ Total unexposed |
|
Attributable risk
|
Exposed w/disease
--------------------- Total exposed - Unexposed w/disease ------------------------ Total unexposed |
|
Hardy Weinberg equilibrium
|
p^2 + 2pq + q^2 = 1
p+q = 1 |
|
Henderson-Hasselbach equilibrium
|
pH =
pKa + log [HCO3-]/0.03 PCO2 [H+] = 24 PCO2 ----------- [HCO3-] |
|
Volume of distribution
|
Vd =
Amount of drug in the body -------------------------------- Plasma drug concentration |
|
Clearance
|
Cl =
Rate of elimination of the drug ----------------------------------- Plasma drug concentration |
|
Half-life
|
t 1/2 =
0.7 x Vd --------- Clearance |
|
Loading dose
|
LD =
Cp x Vd/F |
|
Maintenance dose
|
MD =
Cp x CL/F |
|
Cardiac output
|
CO = HR x SV
CO = Rate of O2 consumption ----------------------------- Arterial O2 - Venous O2 |
|
Mean arterial pressure
|
MAP = CO x TPR
MAP = 1/3 systolic + 2/3 diastolic |
|
Stroke volume
|
SV =
End disatolic volume - End systolic volume |
|
Ejection fraction
|
EF =
End diastolic volume --------------------- x 100% End systolic volume Normally >55% |
|
Resistance
|
R =
Driving pressure ------------------- Flow R = 8 x viscosity x length ------------------------ Pi x r^4 |
|
Net filtration pressure
|
Pnet =
net Hydrostatic P - net Osmotic P Net ~ Capillary P - Interstitial P |
|
Glomerular filtration rate
|
Inulin: GFR = UV / P
GFR = K[(Pgc-Pbs) - (Tgc-Tbs)] U = Urine concentration V = Urine flow rate P = Plasma concentration |
|
Effective renal plasma flow
|
PAH: ERPF = UV/P
|
|
Renal blood flow
|
RBF = RPF / 1-Hct
|
|
Filtration fraction
|
FF = GFR/RBF
|
|
Free water clearance
|
H2O clearance =
Urine volume - Osmole clearance |
|
Physiologic dead space
|
Vd =
Vt x (PaCO2 - PeCO2) -------------------------- PaCO2 PaCo2 = Arterial PeCo2 = Expired CO2 |
|
Vitamin A: Alternative name
|
Retinol
|
|
Vitamin B1: Alternative name
|
Thiamine
|
|
Vitamin B2: Alternative name
|
Riboflavin
|
|
Vitamin B3: Alternative name
|
Niacin
|
|
Vitamin B5: Alternative name
|
Pantothenate
|
|
Vitamin B6: Alternative name
|
Pyridoxine
|
|
Vitamin B12: Alternative name
|
Cobalamin
|
|
Night blindness
Dry skin |
Vitamin A deficiency
|
|
Flu-like symptoms (arthralgia, fatigue, headache, sore throat)
Alopecia and other skin changes |
Vitamin A excess
|
|
Vitamin A: Source
|
Leafy vegetables
|
|
Vitamin A: Function
|
Constituent of visual pigments (retinal)
|
|
Vitamin B1: Function
|
COFACTOR
HMP shunt: Transketolase cofactor As TPP (thiamine pyrophosphate), a cofactor for: 1. Branched chain AA dehydrogenase 2. Oxidative decarboxylation of Pyruvate and Alpha-ketoglutarate |
|
Vitamin B1: Deficiency
|
BeriBeri (Ber1Ber1) and Wernike-Korsakoff syndrome
*Alcoholism *Malnutrition Dry beriberi: Symmetrical muscle wasting Polyneuritis Wet beriberi: High output cardiac failure Edema |
|
High output cardiac failure
Edema |
Wet beriberi
|
|
Vitamin B2: Function
|
Oxidation, reduction yielding 2 ATP:
*FADH2 (oxidation, reduction) *FMN |
|
Cheilosis (inflammation of the lips)
Corneal vascularization |
Vitamin B2 Deficiency
|
|
Vitamin B3: Function
|
Oxidation, reduction yielding 3 ATP:
*NAD *NADP |
|
Niacin synthesis
|
Made from tryptophan
REQUIRES vitamin B6 |
|
Diarrhea
Dermatitis Dementia |
The 3D's of pellagra
Vitamin D deficiency |
|
Causes of B3 deficiency
|
INHer Car
INH (decreases vitamin B6) Hartnup disease (tryptophan absorption) Carcinoid syndrome (uses tryptophan to make serotonin) |
|
Dermatitis, Alopecia
Enteritis Adrenal insufficiency |
Vitamin B5
No pantene? No hair (also true of vitamin A deficiency) |
|
Vitamin B5 function
|
1. Pantothen-A-te is in Co-A
*CoA used for ACYL transfers 2. Component of fatty acid synthase |
|
Vitamin B6 function
|
Pyridoxine--At the DOX, the NICE guy got THuGeD (THGD)
1. Required for NIACIN synthesis from tryptophan 2. Becomes pyridoxal phosphate (cofactor): *Transamination (AST, ALT) *Heme synthesis *Glycogen phosphorylase *Decarboxylations |
|
Hyperirritability
Convulsions Peripheral neuropathy |
Vitamin B6 deficiency
Causes: *INH *Oral contraceptives |
|
Vitamin B12 function
|
1. Cofactor for HOMOCYSTEINE METHYLTRANSFERASE
*Converts homocysteine --> Methionine *Folate also takes part in this rxn 2. Cofactor for METHYLMALONYL-COA MUTASE *Converts methylmalonyl-CoA --> Succinyl-CoA |
|
Macrocytic, megaloblastic anemia
Neurological symptoms |
B12 deficiency
Spinal cord demyelination: *Changes in dorsal columns *Changes in spinothalamic tract *May be due to decreased methionine (unable to build myelin proteins) or excess methylmalonic acid (toxicity) Primarily stored in liver (several years worth) Causes: *Malabsorption *Lack of intrinsic factor *Absence of terminal ileum (Crohn's) |
|
Most common VITAMIN deficiency in the US
|
Folic acid
|
|
Macrocytic, megaloblastic anemia
|
Folic acid deficiency
No neurologic symptoms |
|
Folic acid source
|
Leafy greens
FOLate from FOLiage B12 from BUFFALO |
|
Folic acid supply
|
Months
|
|
Folic acid: Function
|
As THF:
1. Participates in the conversion of HOMOCYSTEINE to METHIONINE 2. DNA, RNA synthesis (nitrogenous bases) |
|
Dermatitis
Enteritis |
Biotin deficiency
Causes: 1. Raw egg consumption: Avidin in egg whites AVIDly binds biotin 2. Antibiotics |
|
Biotin: Function
|
PAM in the PM when making eggs
Carboxylations P = Pyruvate --> Oxaloacetate AM = Acetyl-CoA --> Malonyl-CoA PM = Propional-CoA --> Methylmalonyl CoA |
|
Swollen gums
Bruising, anemia, poor wound healing |
Vitamin C deficiency (scurvy)
CDE: Collagen --> Hydroxylation of proline and lysine Dopamine-B-hydroxylase (converts DA to NE) Electrons on iron (keeps it reduced for good absorption) |
|
Vitamin C function
|
Collagen --> Hydroxylation of proline and lysine
Dopamine-B-hydroxylase (converts DA to NE) Electrons on iron (keeps it reduced for good absorption) |
|
Vitamin D function
|
D2 = Ergocalciferol (milk)
D3 = Cholecalciferol (sun) *Get D3 standing next to a tree Liver: D2/D3 --> 25-OHD (storage) Kidney: 25-OHD --> 1,25-OHD (active) |
|
Hypocalcemic tetany: Nutritional cause
|
Vitamin D deficiency
|
|
Loss of appetite
Stupor |
Excess Vitamin D
Seen in sarcoidosis (converts vitamin D to active form) |
|
Vitamin E function
|
Antioxidant
|
|
Fragile erythrocytes
Neurodysfunction |
Vitamin E
"E is for erythrocytes" |
|
Vitamin K function
|
Synthesized by INTESTINAL FLORA
K for Koagulation K for Karboxylation Catalyzed Gamma carboxylation of Glutamic acid residues on clotting factors 2, 7, 9, 10 + proteins C and S |
|
Increased PT: Nutritional cause
|
Vitamin K deficiency
Causes: *Neonate = Sterile intestines *Adult antibiotic use |
|
Hair loss (axillary, facial pubic)
Hypogonadism Delayed wound healing |
Zinc deficiency
Bone marrow transcription factor Testosterone transcription factor Alcohol dehydrogenase transcription factor |
|
Ethanol metabolism
|
Ethanol --> Acetaldehyde --> Acetate
1. Alcohol dehydrogenase *Fomepizole: Methanol, ethylene glycol antidote *ZERO order kinetics (not concentration dependent) 2. Acetaldehyde dehydrogenase *Disulfram Both reactions produce NADH NAD is the LIMITING REAGENT |
|
What alcohol processing enzyme has zero order kinetics?
|
Alcohol dehydrogenase
|
|
What is the limiting reagent in alcohol processing?
|
NAD+
|
|
Kwashiorkor
|
Results from protein-deficient MEALS:
*Malnutrition *Edema *Anemia *Liver (fatty) *Swollen belly |
|
Marasmus
|
Energy malnutrition
Tissue and muscle wasting Loss of subcutaneous fat Variable edema |
|
Ethanol hypoglycemia and fatty liver
|
High NADH/NAD ratio causes:
1. Pyruvate to be shunted to lactate (inhibits gluconeogenesis) 2. OAA to be shunted to malate (inhibits gluconeogenesis) 3. Liver: Glycolysis intermediates to be shunted to FA synthesis (fatty liver) GLUCONEOGENESIS INHIBITED |
|
Nucleosome
|
2 each of H2, H3, H4, H5
Wrapped twice by DNA |
|
Heterochromatin
|
Transcriptionally inactive
Condensed |
|
Euchromatin
|
Transcriptionally active
Not as condensed |
|
Purines
|
PURe As Gold --> A, G
|
|
Pyrimidines
|
CUT the PY --> C, U, T
1 ring Uracil = RNA Thymine = DNA |
|
High level of G-C bonds
|
Higher melting point
G-C associations have 3 hydrogen bonds |
|
Which nucleotide has a ketone?
|
Guanine
"GOLD key" |
|
Which nucleotide has a methyl?
|
Thymine
"THYmine has a meTHYl" |
|
Amino acids necessary for purine synthesis
|
Pure ppl make you GAG:
Glycine --> Icing Aspartate --> Sparring/fighting Glutamine --> Gluttony |
|
Antibiotics, antivirals and anti-fungals to avoid in pregnancy
|
SAFE Moms Take Really Good Care
Sulfonamides --> Kernicterus *Yellow like sulfer Aminoglycosides --> Ototoxicity, teratogen Fluoroquinolones --> Cartilage Erythromycin (acute cholestatic hepatitis in mom) + clarithromycin (embryotoxic) Metronidiazole--mutagenesis *M&M Tetracyclines--discolored teeth, inhibition of bone growth Ribavirin -- teratogenic *RSV, HCV Griseofulvin--teratogenic *Antifungal *Also carcinogenic Chloramphenicol--"chrome" (gray) baby *Low URP-uridyl transferase in premies |
|
Oocyte development
|
Primary oocytes are in PROPHASE 1
Secondary oocytes are in METAPHASE II Primary oocytes become secondary oocytes @ovulation (leave prOphase to Ovulate) Secondary oocytes become Ova w/sperm entry (leave METaphase when they MEET a sperm) No tetrads formed until after ovulation |
|
I band
|
Actin-only portion of the sarcomere
Shortens w/contraction |
|
H band
|
Myosin only portion of the sarcomere
Shortens w/contraction |
|
A band
|
Entire length of the myosin filament
Does NOT shorten w/contraction |
|
Sarcomere: Myosin measurements
|
"My-son? HA!"
H band: Myosin only A band: Entire myosin length (constant) *A ~ ALL of the myosin |
|
Premature heart beats are stronger/weaker than on-time ones
|
Weaker
Less time for filling --> decreased preload Less time for Ca2+ in sarcoplasmic reticulum to get to RELEASE SITE |
|
Prevalence
|
Prevalence =
Total cases in population at a given time --------------------------------- Total population at risk |
|
Incidence
|
Incidence =
New cases in population over a given period ----------------------------------- Total population at risk for a new case |
|
Systematic error
|
Reduced accuracy/validity
|
|
Random error
|
Reduced reliability/precision
|
|
Selection bias
|
Non-random assignment to a study group
|
|
Recall bias
|
Altered recall
Ex. Knowledge of presence of a disorder alters what is remembered |
|
Sampling bias
|
Subjects are not representative to the general pop
|
|
Late-look bias
|
Information gathered at an inappropriately late time
|
|
Procedure bias
|
Subjects in different groups are not treated the same
|
|
Positive/negative skew
|
Wherever the tail is going
Positive = Positive tail Mean > Median > Mode Negative = Negative tail Mean < Median < Mode |
|
Standard error of the mean
|
Used to calculate CI
Standard deviation ----------------------- (n)^1/2 |
|
CI
|
Mean +/- 1.96 (SE)
SE = Standard deviation ----------------------- (n)^1/2 |
|
Reportable diseases
|
Hep, Hep, Hep, Hooray, the SSSMMART CHICK is GONe
Hep A Hep B Hep C HIV Salmonella Shigella Syphilis Measles Mumps AIDs Rubella TB Chickenpox Gonorrhea Hep C and HIV might be exceptions in some states |
|
Leading causes of death 65+
|
Heart disease
Cancer Stroke COPD Pneumonia Influenza |
|
Leading causes of death 25-64
|
CHISSeling away at life
Cancer Heart disease Injuries Suicide Stroke *#1 and #2 are reversed for the 65+ crowd *Oldest group to feature injuries and suicide |
|
Leading causes of death 15-24
|
I finished HS and went to a College House (I HS CH)
Injuries Homicide Suicide Cancer Heart disease Injuries, homicide, suicide precede the top 2 for adults 25-64 Cancer Heart disease |
|
Leading causes of death 1-14
|
I have an ICCHH
Injuries Cancer Congenital anomalies Homicide Heart disease |
|
Leading causes of death in infancy
|
CLoSe your mouth, MR
(CLS MR) Congenital anomalies Low birth weight/short gestation SIDS Maternal complications RDS |
|
Therapeutic privilege
|
Witholding info when disclosure would severely harm the patient or undermine decision-making capacity
|
|
Usually required unless
|
Usually required unless:
1. Married or otherwise emancipated 2. Emergency situation 3. Treating STDs, providing counsel or contraception 4. Medical care during pregnancy 5. Management of drug addiction |
|
APGAR score
|
Evaluated at 1 minute and 5 minutes
*Each category: 0-2 points Appearance *Blue --> Pink trunk --> All pink Pulse *None --> <100 /> >100/min Grimace *None --> Grimace --> Grimace + cough Activity *Limp--> Some --> Active Respiration *None--> Irregular --> Regular |
|
Complications of low birth weight
|
<2500 g
TIRNIP Tiny tots Infections RDS Necrotizing entercolitis *No bacterial colonization ~ mucosal necrosis, esp in colon *Possible perforation Intraventricular hemorrhage Persistent fetal circulation |
|
Motor milestone: Birth
|
Rooting reflex
|
|
Milestones: 3 mo
|
3 things
Motor: *Holds head up *Moro reflex desappears Social: *Social smile |
|
Milestones: 4-5 mo
|
Propping (and rolling)
People Motor: *Rolls front to back *Sits when propped Social: *Recognizes peopl |
|
Milestones: 7-9 mo
|
Seven - 4 S's
Sit Scoots (or crawls) Stranger anxiety Spins around to see you (orients) Motor: *Sits alone *Crawls Social: *Stranger anxiety *Orients to voice |
|
Milestones: 12-15 mo
|
12-14 mo: Babinski disappears
15 mo: Can walk, but doesn't want to YOU to (walk away) *Walks *Separation anxiety *A few words |
|
Milestones: 3 years
|
Lots of 3's
Motor: *Stacks 9 blocks --> 3x3 years *Rides tricycle --> 3 wheels *Copies line or circle drawing Social: *Toilet training --> "Pee at 3" *Core gender identity (2-3 yr) *900 words *Complete sentences |
|
Milestones: 4 years
|
1. Can draw and play hopscotch
2. Can play w/others (even imaginary ones) 3. Can get ready for school (grooming) Motor: *Simple drawings (stick figure) *Hops on 1 foot Social: *Parallel play (2-4) *Cooperative play *Imaginary friends *Grooms, brushes teeth |
|
Milestones: 6-11 years
|
Reading
Understands death Conscience Same-sex friends Identification w/same-sex parent |
|
Milestones: Adolescence
|
Boys ~ 13
Girls ~ 11 Abstract reasoning Formation of personality |
|
Tanner stages
|
1= Childhood
2= Pubic hair begins to develop *Men: Testes *Women: Breast tissue elevation 3 = Pubic hair darkens, curls *Men: Penile length 4 = Men: Penile width, glans development Women: Raised areolae 5 = Adult *Areolae no longer raised |
|
BMI
|
Weight in kg
--------------- Height in m^2 < 18.5 = Underweight > 30 = Obese |
|
Sleep stages
|
BATS Drink Blood
Awake: High freq, low amp BETA: Alert ALPHA: Eyes closed Sleep: THETA waves: 5% SLEEP spindles + K complex: 45% DELTA: 25% *Low freq, high amp BETA: 25% *Sawtooth waves *Variable pulse, BP *Occurs every 90 min *Ach based -- REMACH 9000 |
|
Xeroderma pigmentosum
|
Defect in nucleotide excision repair system
Unable to repair thymidine dimers created by UV light |
|
HNPCC: Mutation type
|
DNA mismatch repair system
Enzymes can tell old vs. new based on what has been methylated (old ones) |
|
Death cap mushroom poison
|
Alpha-amantin
Inhibits RNA polymerase II (mrna) |
|
Prokaryotic vs. Eukaryotic ribosome
|
PrOkaryotes: 30 + 50 = 70
Eukaryotes: 40 + 60 = 80 *Even |
|
Energetics of mRNA synthesis
|
ATP = tRNA ACTIVATION (loading)
*2 phosphate bonds (AMP) GTP = GRIPING (ribosome) and GOING *1 GTP to bind A site *1 GTP to translocate = 4 Phosphate bonds per AA |
|
Rb and P53 prevent ___ to ___ transition
|
G1 to S
Because after DNA replicates, division is imminent Rb (13q mutation): Retinoblastoma Osteosarcoma p53 (17p mutation): Most human cancers Li-Fraumeni syndrome *Sarcoma before 45 + cancer under 45 (or sarcoma) in a first degree relative |
|
I cell disease
|
Often fatal in childhood
In GOLGI, failure of addition of mannose-6-phosphate to lysosome proteins Lysosomal proteins secreted outside cell... Coarse facial features Clouded cornea Restricted joint movement (inflammation) |
|
Drugs that act on microtubules
|
Mebendazole/thiabendazole (antihelminthic)
Paclitaxel (Taxol) --> Inhibits tubule breakdown Griseofulvin (anti-fungal) --> Fungal cell wall Vincristine/Vinblastine --> Inhibits microtubule formation Colchicine (anti-gout) inhibits WBC taxis |
|
Kartagener's syndrome defect
|
Dynein arm
Infertility Bronchiectasis Recurrent sinusitis Situs invertus |
|
Actin and myosin
|
MAC'kin the MUSCLE
Microvilli Adherens junctions Cytokinesis Muscle contraction |
|
Intermediate filaments
|
DC VeGaN
*Progressively squishier Desmin --> Muscle Cytokeratin --> Epithelial cells Vinmentin --> Connective tissue GFAP --> Neuroglia Neurofilaments --> Neurons |
|
Collagen
|
Be So Totally Cool, Read Baby Books
Collagen I (90%): Bone, skin, tendon Collagen II: Cartilage Collagen III: Reticulin--Blood vessels *Also, baby ~ uterus, fetal tissue Collagen IV: Basement membrane or basal lamina *Glomerulus, lung, lens |
|
Collagen synthesis
|
Pre-procollagen = Singles
Procollagen = Unmodified triple Tropocollagen = Trimmed triple Collagen = Cross-linked triple RER: 1. Alpha chains synthesized 2. Hydroxylation: Proline, lysine *VITAMIN C 3. Glycosylation: Lysines 4. Triple helix formation 5. Secretion Outside cell: 6. Cleavage of terminal regions 7. Cross-linking: Lysine, hydroxylysine *Lysyl oxidase |
|
Ehlers Danlos
|
Faulty collagen synthesis (no X-linking)
Type III usually affected *Blood vessel instability (bleeder) *Berry aneurysms *Stretchy skin *Hyperextensible joints |
|
Malate-aspartate shuttle
|
Heart and liver
32 ATP |
|
Glycerol-3-phosphate shuttle
|
Muscle
30 ATP |
|
What transfers methyl units?
|
S-adenosyl-methionine (SAM)
ATP + Methionine --> SAM |
|
NADPH: Functions
|
Anabolic processes
P-450 activation Respiratory burst (NADPH oxidase) |
|
Hexokinase vs. Glucokinase
|
Both catalyze:
Glucose --> Glucose-6-P Hexokinase: Ubiquitous *High affinity *Low capacity *G6P feedback inhibition gLucokinase: Liver and B cells of pancreas *Phosphorylates glucose after a meal to SEQUESTER it in the liver *Low affinity --> NO FEEDBACK *High capacity *Induced by insulin |
|
What regulates hexokinase?
|
(-) Glucose 6P
Glucose --> Glucose 6-P |
|
What regulates phosphofructokinase-1?
|
(+) Fructose 2,6 BP (PFK-2--fed state)
(-) ATP, Citrate Fructose-6P --> Fructose 1,6 BP |
|
What regulates pyruvate kinase?
|
(+) Fructose 1,6 BP
(-) ATP, alanine PEP --> Pyruvate |
|
What regulates pyruvate dehydrogenase?
|
(-) ATP, Acetyl CoA, NADH
Pyruvate --> Acetyl CoA |
|
Glycolytic enzyme deficiency
|
Hemolytic anemia from Na/K pump stalling in RBC
Pyruvate kinase |
|
Pyruvate dehydrogenase complex
|
B1, B2, B3, B5
+ Lipoic acid |
|
Arsenic
|
Vomiting
Rice water stools Garlic breath |
|
Pyruvate dehydrogenase deficiency
|
Lysine + Leucine (only purely ketogenic AAs)
|
|
TCA cycle
|
Citrate Is Kreb's Starting Substrate for Making Oxaloacetate
Per cycle (2x for glucose) 3 NADH, 1 FADH, 1 GTP 2 CO2 Isocitrate --> CO2, NADH Alpha keto --> CO2, NADH Succinyl CoA --> GTP, CoA Succinate --> FADH2 Malate --> NADH |
|
Gluconeogenesis enzymes
|
PPFG: Pathway Produces Fresh Glucose
Pyruvate carboxylase *Pyruvate --> OAA *Happens w/backup of TCA cycle (high levels of Acetyl-CoA) *Requires ATP -- no GNG w/o E to spare *Requires BIOTIN PEP carboxykinase *OAA --> PEP *REQUIRES GTP (2nd check of energy to spare) Fructose 1,6 bisphosphatase *Fructose 1,6 BP --> Fructose 6P Glucose 6 phosphatase *Glucose 6P --> Glucose |
|
G6PD
|
More prevalent among blacks
X-linked recessive Heinz bodies: Hb precipitates within RBCs Bite cells: Phagocytes remove Heinz bodies from RBCs Cell does a poor job of keeping glutathione reduced Oxidative damage to RBCs --> Hemolytic anemia Common causes: *Fava beans *TB drugs *Sulfonamides, primaquine |
|
Fructose intolerance
|
AR deficiency of ALDOLASE B
Buildup of fructose-1-phosphate *Steals/incapacitates tons of phosphate: as a result, inhibition of glucose pathways (glycogenolysis, gluconeogenesis) Symptoms: *Vomiting *Hypoglycemia *Cirrhosis, jaundice Treatment: Avoid fructose and SUCROSE (fructose + glucose) |
|
Essential fructosuria
|
Defect in FRUCTOKINASE
1st enzyme in fructose pathway Fructose does NOT enter cells --> only seen in blood in urine Benign, asymptomatic condition |
|
Galactosemia
|
AR absence of GALACTOSE-1-P URIDYLTRANSFERASE
Pathway backup --> Toxic substances including galactitol (toxic) Hepatosplenomegaly CATARACTS (Gonna "lack" seeing much") MENTAL RETARDATION Treatment: Exclude galactose + lactose (glucose + galactose) from diet |
|
Galactokinase deficiency
|
Causes galactosemia, galactosuria
Galactitol accumulation --> Toxicity, but not as severe as Galactosemia |
|
Acidic amino acids
|
The "tates"
Aspartate Glutamate |
|
Basic amino acids
|
Histidine
Lysine Arginine HISTIDINE LYS (ARG)! It's not positive/basic in the body That's why LYSINE and ARGININE are the dominant AAs in histones (+ charge to attract - DNA). |
|
Gluconeogenic AND Ketogenic essential amino acids
|
PITT (everybody likes him)
They all end in "ine" Phenylalanine Isoleucine Tyrosine Threonine |
|
Gluconeogenic essential amino acids
|
The most wasteful in terms of E: HAM-V
Or: HAm for growing kids *Histidine, arginine needed during periods of growth Histidine Arginine Methionine Valine |
|
Urea cycle
|
Excretes excess nitrogen
Ordinarily, Careless Crappers Are Also Frivolous About Urination Ornithine + Carbamoyl phosphate (i) *Acted on by Ornithine transcarbamoylase *Happens in mitochondrion (all other steps = cytoplasm) Citrulline + Aspartate (i) *Acted on by arginossucinate synthetase Arginosuccinate *Acted on by arginosuccinate synthetase Fumarate (o) + Arginine *Acted on by arginase Urea (o) *Made from arginine + H2O (via arginase) |
|
Derivatives of phenylalanine
|
Pound The Darn Donut No Earlier Than Mid-morning
Pound = Phenylalanine The = Tyrosine --> THYROXIN Darn = Dopa --> MELANIN Donut = Dopamine No = NE Earlier = Epinephrine Than = THYROXINE Mid-morning = MELANININ |
|
Phenylketonuria
|
Incidence: 1/10,000
*Screened for at birth Problem w/Phe --> Tyrosine either: 1. Phe hydroxylase defect 2. THB defect (reduces Phe using Phe hydroxylase as catalyst) Results: *Tyrosine becomes essential *Phe buildup --> Phenylketones in urine Findings: *Musty body odor --> AROMATIC defect *Retardation, eczema --> Phe buildup *Growth retardation --> Thyroxine *Fair skin --> Melanin |
|
Alkaptonuria
|
A.k.a. Ochonosis
Dark urine --> Like peeing "KAPTAN" (morgan) The captain was a TYRant (tyrosine) Congenital deficiency of HOMOGENTISIC ACID OXIDASE Used to degrade TYROSINE Buildup of alkapton bodies: *Urinary excretion (urine turns black) *Joint deposition (dark CT, +/- arthralgia) Considered a benign disease |
|
Albinism
|
Congenital deficiency of either:
1. Tyrosinase (AR): Tyr --> Melanin 2. Defective tyrosine transporters Possible mechanism: Poor neural crest migration Increased risk of skin cancer Variable inheritance (locus heterogeneity) |
|
Homocystinuria
|
Homocysteine has 2 breakdown pathways:
1. Cystathionine synthase *Homocysteine --> Cystathionine --> Cysteine *Requires B6 2. Homocysteine methyltransferase *Homocysteine --> Methionine *Requires B12/folate **3 forms of disease:** 1. Deficient cystathionine synthase *Decrease dietary MET, increase CYS *Increase dietary B12/folate 2. Inefficient cystathionine synthase (doesn't bind B6 well) *Increase dietary B6 3. Deficient homocysteine methyltransferase Result: *Excess homocysteine *Cysteine becomes essential *MENTAL RETARDATION *Bone problems: Tall stature, osteoporosis, kyphosis *Vessel problems (stroke, MI) *Lens subluxation (down and in) |
|
Cystinuria
|
Common 1/7000
Inherited defect of RENAL TUBULAR ABSORPTION in PCT + AA Transporter (NH3+): Histidine, lysine, arginine, ornithine, CYSTINE *Excess cystine in urine Complications: Cystine kidney STONES *Treat w/acetazolamide to alkalinize urine, prevent precipitation Cystine = 2 cysteines connected by disulfide bond |
|
Stones and pH
|
If it has a C in it, precipitates in ACIDIC urine
Ca2+ Uric acid Cysteine |
|
Maple syrup urine disease
|
Decreased alpha-KETOACID DEHYDROGENASE
Blocked degradation of branched amino acids *I Love Vermont maple syrup: Isoleu, LEU (most buildup), Val *Urine smells like maple syrup Complications: *Mental retardation *CNS defects *Death |
|
Maple syrup urine disease
|
Decreased alpha-KETOACID DEHYDROGENASE
Blocked degradation of branched amino acids *I Love Vermont maple syrup: Isoleu, LEU (most buildup), Val *Urine smells like maple syrup Complications: *Mental retardation *CNS defects *Death |
|
Lesch-Nyhan
|
X-linked recessive
HGPRT: "He's got purine recovery trouble" Absence of HGPRT--> purine salvage *Hypoxanthine --> IMP *Guanine --> GMP Result: Excess uric acid production Results: Mental: Retardation, self-mutilation, aggression (Lesch I lay a hand on you), choreoathetosis Urinary: Hyperuricemia, gout |
|
Adenosine deaminase deficiency
|
Adenosine --> Inosine
*Related to purine breakdown pathway *Backup ~ excess ATP, dATP Excess ATP, dATP causes feedback inhibition of RIBONUCLEOTIDE REDUCTASE *Less new nucleotides made for DNA syn *Rapidly multiplying tissues like marrow are affected --> Decreased LYMPHOCYTE COUNT (SCID--B and T cells) |
|
Insulin
|
DEphosphorylates glycogen synthatse
Required for skeletal MUSCLE and ADIPOSE uptake of glucose Synthesized in pancreatic BETA cells (buh-bye, glucose) from pro-insulin *By product = C-PEPTIDE Effects: 1. Glucose transport 2. Glycogen/TG/Protein synthesis 3. Na RETENTION (kidneys) *Concurrent cellular UPTAKE of K+ (to match increased extracellular Na_) |
|
GLUT 1 Transporter
|
RBCs
Brain Not responsive to insulin |
|
GLUT 2 Transporter
|
Bidirectional
Things which sample (islet), reabsorb (kidney), absorb (GI) or produce (liver) glucose B islet cells Liver Kidney GI enterocytes (blood side) Not Insulin responsive |
|
GLUT 4 Transporter
|
Muscle
Adipose INSULIN RESPONSIVE |
|
Things which don't need insulin for glucose intake
|
BRICK Layer
Brain RBCs Intestine Cornea Kidney Liver |
|
Von Geirke's Disease
|
Type 1 glycogen storage disease
Problem with GLUCOSE 6 PHOSPHATASE 1. No gluconeogenesis 2. G1P from glycogen phosphorylase gets stuck at G6P 3.Glucose from limit dextran metabolism (debranching enz) and lysosomal acid maltase pathway can be trapped if phosphorylated by Glucokinase Poor delivery to tissues: *Severe hypoglycemia *Increased blood lactate Backup of glycogen in liver: hepatomegaly |
|
Pompe's Disease
|
Deficiency of LYSOSOMAL ACID MALTASE (1,4 glucosidase)
*POMPOUS: the VIP/fast track enzyme Trashes the PUMP *Heart and other muscle --> Cardiomegaly, weakness *Liver damage |
|
Cori's disease
|
Deficiency of DEBRANCHING enzyme
Like mild Von Geirke: Mild hypoglycemia *But NORMAL blood lactate *But gluconeogenesis intact Some glycogen buildup, hepatomegal |
|
McArdle's disease
|
Deficiency of GLYCOGEN PHOSPHORYLASE in skeletal MUSCLE
Increased glycogen in muscle Strenuous exercise: Cramps, myoglobinuria |
|
Lysosomal storage disease: Tay sachs
|
*AR deficiency of HeXosaminidase A (Tay SaX)
GM2 ganglioside -> GM3 -> glucocerebroside Neural degeneration CHERRIES AND ONIONS: *Cherry red spot *Onion skin lysosomes |
|
Lysosomal storage disease: Fabry's
|
F = Female chromosome transmission
A = Alpha galactosidase B = Blood vessels (CV, renal) R = RASH (angiokeratoma) Y = 3 lines (Ceramide TRIhexoside) X-RECESSIVE deficiency of ALPHA-GALACTOSIDASE A Ceramide trihexoside --> Glucocerebroside Vascular issues leading to: *Cardiovascular, renal disease *Peripheral neuropathy *ANGIOKERATOMA (unique) |
|
Gaucher's
|
AR deficiency of B-GLUCOCEREBROSIDASE
Gluco cerebroside --> Ceramide OUCHER'S disease: *Aseptic necrosis of femur, bone crises *Macrophages = Crumpled tissue paper |
|
Neimann-Pick
|
AR deficiency of SPHINGOMYELINASE
*"Noman picks his nose w/his sphinger" Spingomyelin --> Ceramide A lot like Tay-Sachs: *Neurodegeneration *CHERRY red spot *FOAM cells Cherries + Onions (T-S) vs. CHERRIES + WHIPPED CREAM (which would you PICK?) |
|
Metachromic leukodystrophy
|
AR deficiency of Arylsulfatase A
*Sounds like ARICEPT Sulfatides/Cerebroside sulfate --> Galactocerebroside DEMENTIA Peripheral neuropathy (DEMYELINATION) --> Ataxia |
|
Krabbe's
|
AR deficiency of Galactocerebrosidase
Galactocerebroside --> Ceramide "A slow Krabbe w/little eyes" Peripheral neuropathy DEVELOPMENTAL DELAY OPTIC ATROPHY GLOBOID CELLS (like eyes) |
|
Lysosomal storage dieases: Mucopolysaccharidoses (2)
|
Both cause buildup of heparan sulfate, dermatan sulfate
Hurler's syndrome: AR *Alpha-L-iduronase *Gargoyle on a ledge (trying to get fresh air) that can't see (clouding)...hopefully won't HURL him/herself off *Gargoyle face *Airway obstruction *Corneal clouding *Developmental delay Hunter's syndrome: XR *Iduronate sulfatase *Mild Hunter's but NO CORNEAL CLOUDING *Good HUNTERS need to see clearly *AGGRESSIVE BEHAVIOR *Lesch-Nyhan and Hunter's are XR diseases of developmental delay and aggression |
|
What brings Acetyl-CoA out of the mitochondrion for FA synthesis?
|
Citrate shuttle
SYtrate = Synthesis |
|
What brings Acyl-CoA (long chain Fatty acids) into the mitochondrion for continued FA breakdown?
|
Carnitine shuttle
CARnitine = CARnage of fatty acids Carnitine deficiency = Inability to utilize LCFAs + toxic accumulation |
|
Ketone bodies
|
ACETOACETATE
B-HYDROXYBUTYRATE Made from HMG-CoA in liver Acetyl-CoA -> Acetoacetyl-CoA -> HMG-CoA Production stimulated by shut-down of TCA cycle (depletion of **OAA**) 1. Starvation 2. Diabetic ketoacidosis 3. Alcohol-related NADH (shunts OAA to malate) Breath smells fruity (acetone) |
|
Urine test for ketones does not detect...
|
B-hydroxybutyrate
|
|
Rate limiting step of cholesterol synthesi
|
HMG-CoA reductase
Inhibited by statins |
|
HDL
|
Mediates cholesterol transport from periphery to liver
Acts as a repository for Apo C-II and Apo E *Gives ApoE and C-II to chylomicrons and VLDL *Takes C-II from IDL *Takes ApoE from LDL Secreted from both liver AND intestine |
|
B-100
|
Lipoproteins originating from liver
(chylomicrons have B-48 for secretion) Aids in VLDL secretion Binds LDL receptor (even better w/ApoE) VLDL IDL LDL |
|
C-II
|
COFACTOR for LPL
TG delivery: Chylomicrons VLDL |
|
Signs of high cholesterol
|
AAX
Caused by excess LDL Atherosclerosis Arcus cornae --> White or gray opaque ring in the corneal margin Xanthomas --> Yellowish cholesterol deposits *Cholesterol-laden histiocytes *Can deposit in tendons |
|
Signs of high triglycerides
|
LEPtin
Lipema retinalis (>2000) *Excess chylomicrons *Veins and arteries of the retina appear milky ERUPTIVE xanthomas (>2000) *Excess chylomicrons Pancreatitis (>1000) *Excess VLDL or Chylomicrons |
|
Hyperchylomicronemia
|
Excess chylomicrons
C-II/LPL reaction not working well: *LPL deficiency *Altered C-II HYPER-TRIGLYCERIDE symptoms *Lipemia retinalis, Eruptive xanthoma, Pancreatitis Cholesterol also elevated |
|
Hypercholesterolemia
(Type 2a familial dyslipidemia) |
Excess LDL
Decreased LDL receptors Elevated cholesterol *Arcus senilis/corneae *Atherosclerosis *Xanthomas |
|
Hypertriglyceridemia
(Type 4 familial dyslipidemia |
Excess VLDL due to liver overproduction
Elevated TG's *Pancreatitis |
|
Heme synthesis
|
Succinyl-CoA + Glycine --> ALA
*ALA synthase *Requires B6 ALA --> Porphobilinogen *ALA dehydratase *Inhibited by LEAD Porphobilinogen ->-> Pre-uroporphyrinogen *Porphobilinogen deaminase *ACUTE INTERMITTENT PORPHYRIA Uroporphyrinogen III --> Co-pro-porphyrinogen *Uroporphyrinogen decarboxylase *PORPHYRIA CUTANEA TARDA Protoporphyrin + Fe2+ --> Heme *Ferrochelatase *Inhibited by LEAD |
|
Lead poisoning
|
1. Inhibits ALA DEHYDRATASE
*ALA ->-> Porphobilinogen *ALA buildup 2. Inhibits FERROCHELATASE *Protoporphyrin + Fe2+ --> Heme *CO-PRO-PORPHYRIN buildup |
|
Precipitated by drugs
Painful abdomen Polyneuropathy Pink urine Psychological disturbances |
Acute intermittent porphyria
|
|
Imprinting
|
Differences in phenotype exist depending on which parent the gene cam from
AngelMan --> Maternal deletion Prader-Willi --> Paternal deletion |
|
Adult PKD
|
90% are due to AD mutation of APKD1 (chromosome 16--legal adult?)
*Juvenile form is recessive A = ANEURYSMS (berry) P = Prolapse (mitral valve) K = Kidney failure (pain, hematuria, HTN) D = Dominant inheritance 1 = Liver disease (also polycystic) ALWAYS BILATERAL Large cysts --> Massive enlargement of kidneys |
|
FAP
|
FAP = Familial ADENOMATOUS POLYPOSIS
APC gene --> ADENOMATOUS POLYPOSIS of the colon 5 letters in polyp --> Chromosome 5q *Learn the 'APCs' when you're 5 Defect in MISMATCH REPAIR gene *Dominant phenotype (assume 100% 2nd hit) COLON becomes covered in polyps AFTER puberty --> Progression to CRC unless resected *Rectum always involved Gardner's syndrome: FAP + 1. Osseous and soft tissue tumors 2. Retinal hyperplasia Turcot's Syndrome: FAP + Glioblastoma |
|
Familial hypercholesterolemia: Genetics
|
AD mutation in LDL receptor
(absent, defective) Heterozygote (1/500): Cholesterol over 300 Homozygote: Cholesterol over 700 *Tendon xanthomas (Achilles) *MI may develop before age 20 |
|
Huntingtons
|
AD mutation of chromosome 4
*Hunting 4 food Triplet repeat disorder (CAG) *Anticipation Caudate atrophy Decreased GABA and Ach --> GAch it's bad Manifests between 20 and 50 *Depression *Progressive dementia *Choreiform movements |
|
Marfan
|
AD fibrillin gene mutation
Ocular: Subluxation of lenses Skeletal abnormalities *Tall w/long extremities *Pectus excavatum *Hyperextensive joints *Arachnodactyly Cardiovascular: *CYSTIC MEDIAL NECROSIS of aorta --> Dissecting aneurysm *Floppy mitral valve *Aortic regurgitation as a late complication |
|
Neurofibromatosis 1
|
a.k.a. Von Recklinghausen's disease
*Long name: LONG arm of chromosome 17(q) *17 letters in Von R AD mutation "Scalding coffee" *KyphoSCOLIOSIS *Cafe au lait spots Tumors: PALON *Pheos *All tumors (inc. skin fibromas) *Lisch nodules (pigmented iris hamartomas) *Optic gliomas *Neural tumors |
|
Neurofibromatosis 2
|
AD mutation of chromosome 22q
2 senses: *Hearing: Bilateral acoustic neuroma (schwannoma) *Eyes: Juvenile cataracts |
|
Tuberous sclerosis
|
AD mutation w/incomplete penetrance, variable penetration
White to green while in the CAR: *Facial angiofibroma *Ash leaf spots (depigmented skin) *Shagreen patch (orange peel skin) *Other skin lesions (facial adenoma sebaceum) *Cardiac rhabdomyoma *Astrocytoma *Renal angiomyolipomas |
|
VHL
|
AD mutation of chromosome 3 (3 parts to name)
HEMANGIO, HALF Hemangioblastomas (retina, brain--cerebellum, medulla) Half develop bilateral renal cell carcinomas |
|
Cystic fibrosis
|
AR defect in CFTR gene
*Most common lethal genetic disease of Caucasians Chromosome 7 deletion of Phe 508 *508 area code when I was 7 CFTR is a 2 way Cl- channel *Secretes Cl- in lungs, GI *Absorbs Cl- from sweat *Cl- sweat test is diagnostic Thick mucus that plugs: *LUNGS --> Pseudomonas, S. aureus, chronic bronchitis, bronchiectasis, meconium ileus *PANCREAS --> Insufficiency (malabsorption, steatorrhea), fat soluble vitamin deficiencies *LIVER Infertility in males: Bilateral agenesis of vas deferens Treatment: N-acetylCYSTeine to loosen mucous plugs (also an antidote for aspirin OD) |
|
X-linked recessive diseases
|
Be Wise, Fools GOLD Heeds False Hope
Bruton's agammaglobulinemia *BTK gene; no B lymphocytes Wiskott-Aldrich syndrome *Low IgM, high IgA Fragile X *FMR1 gene; MR, anticipation G6PD *Poor glutathione function Ocular albinism *Eye lacks melanin pigment Lesch-Nyhan syndrome *Collagen 3 Duchennes *Dystrophin gene deletion Hemophilia A and B *Hemophilia A = Factor 8 *Hemophilia B = Factor 9 Fabry's disease *Alpha-galactosidase A def --> Ceramide trihexoside Hunter's syndrome *Iduronate sulfatase def --> Heparan, dermatan |
|
Duchenne's
|
*XR
*Frame-shift mutation causing deletion of dystrophin Accelerated muscle breakdown *Onset before 5 years of age 1st = Pelvic girdle muscles *Gower's maneuver (using upper extremities to stand) Later: Superior muscles, cardiomyopathy Pseudohypertrophy of calf muscle *Fibrofatty replacement Diagnosis: **CPK** **MUSCLE BIOPSY** |
|
Becker's
|
XR
Mutated dystrophin gene Less severe than Duchenne's |
|
Fragile X
|
XR defect
Aberrant METHYLATION, expression of FMR1 *Chromosome becomes fragile *Triplet repeat: CGG *Expansion in females 2nd most common cause of genetic mental retardation (DS = #1) FragileX = eXtra-large testes, jaw, ears Association w/autism |
|
Trinucleotide repeat diseases
|
Try HUNTING for MY fried EXX
Huntingtons Myotonic dystrophy Friedrich's ataxia Fragile X +/- Anticipation |
|
Downs Syndrome
|
Downs ~ Drinking age (21)
1/700 (Most common chromosomal disorder) Increases w/maternal age *95% Nondisjunction *4% Robertsonian translocation *1% Mosaicism Decreased alpha fetoprotein Decreased Beta-HCG Nuchal translucency Life expectancy: 45-50 years ASSOCIATIONS: *ALL, AML *Alzheimer's disease > age 35 *Duodenal atresia (double bubble) *Hirschprung's diease Mental retardation (most common cause) Head: *Flat facial profile *Epicanthal folds Congenital heart defects: ASD *Endocardial cushion defects Hands: Simian crease Feet: Gap between 1st two toes |
|
Edward's Syndrome
|
Edwards ~ Election age (18)
1/8000 Increased risk w/maternal age No prenatal screening Life expectancy < 1 year Severe MR Low set ears + small jaw Heart defects Rocker bottom feet |
|
Patau's syndrome
|
Patau ~ Puberty age (13)
1/15,000 Increased risk w/maternal age No prenatal screening Life expectancy < 1 year Severe MR Holoprosencephaly Small eyes and cleft palate Polydactyly Heart defects Rocker bottom feet |
|
Cri-du-chat
|
Deletion of short (p) arm of chromosome 5
Severe MR --> Cat-like cry Microcephaly --> Cat-size head Epicanthal folds --> Cat-like eyes Cardiac abnormalities |
|
22q11
|
CATCH 22
Cleft palate Abnormal facies Thymic aplasia --> T-cell deficiency Cardiac defects Hypocalcemia (Parathyroid) DiGeorge: THC --> Thymic, parathyroid (hypocalcemia), cardiac defects Velocardiofacial: CAC--> Cleft palate, abnormal facies, cardiac |
|
Surface ectoderm derivatives
|
Adenohypophysis (anterior pituitary)
Everything exposed to air: *Epidermis *Lens of eye *Epithelial linings of eye, ear, nose |
|
Surface ectoderm derivatives
|
Adenohypophysis (anterior pituitary)
Everything exposed to air: *Epidermis *Lens of eye *Epithelial linings of eye, ear, nose |
|
Neuroectoderm
|
Neurohypophysis (posterior pituitary)
CNS neurons Oligodendrocytes Astrocytes Ependymal cells Pineal gland |
|
Neural crest derivatives
|
ABCCDE
LMOP ANS + Schwann cells Bones of the skull Parafollicular C cells (thyroid) DRG Enterochromaffin + Chromaffin cells Laryngeal cartilage Melanocytes Odontoblasts Pia (and arachnoid) |
|
Endoderm derivatives
|
Gut tube epithelium and derivatives
Lungs Liver Pancreas Thymus Thyroid (Follicular cells) Parathyroid |
|
Mesoderm
|
ABCD SLUM
Adrenal cortex Bone, blood Cardiovascular, CT Dura mater Spleen Lymphatics Urogenital structures Muscle |
|
Most common mesodermal defects
|
VACTERL
Vertebral defect Anal atresia Cardiac defects Tracheo-Esophageal fistula Renal defects Limb defects |
|
Tobacco during pregnancy
|
Pre-term labor
Placental problems ADHD |
|
Alcohol during pregnancy
|
#1 cause of congenital malformations in US
May involve migration errors HHeLL = *Head and heart *Limb and lung Head = Retardation, Microcephaly, Facial abnormalities Heart = Fistulas Lung = Fistulas Limb = Dislocation |
|
Twinning
|
Each fetus will always have its own amniotic sac
|
|
Fetal component of placenta
|
Chorionic villi
Outer layer = Syncytiotrophoblast *Secretes hCG Inner layer = Cytotrophoblast |
|
Bulbus cordis
|
Smooth parts of left and right ventricle
|
|
Primitive ventricle, primitive atrium
|
Trabeculated parts of left and right ventricle/atrium, respectively
|
|
Right horn of sinus venosus
|
Smooth parts of right atrium (and left atrium)
|
|
Fetal erythropoiesis
|
BSLY --> BeaSLY
Bone marrow: 28+ Spleen: 9-28 Liver: 6-30 Yolk sac: 3-8 |
|
Foramen ovale closure
|
1st breath: Resistance of pulmonary vasculature DECREASES --> Increased flow through lungs and into LA --> Increased LA pressure
Foramen ovale closes |
|
Umbilical vein becomes
|
Ligamentum teres hepatis
Hepatis --> Goes to liver region *Umbilicus to portal vein + ductus venosus Contained in falciform ligamen |
|
Ductus venosus becomes
|
Ligamentum venosum
Starts where umbilical vein sends a branch to liver Ends at IVC |
|
Ductus arteriosus becomes
|
Ligamentum arteriosum
|
|
Umbilical arteries become
|
Medial umbilical ligaments
From Internal iliacs to umbilicus |
|
Urachus becomes
|
Median umbilical ligamen
|
|
1st aortic arch: Derivatives
|
1st arch is MAXIMAL
Maxillary artery |
|
2nd aortic arch: Derivatives
|
STAPEDIUS IS SECOND
Stapedial artery Hyoid artery |
|
3rd aortic arch: Derivatives
|
C is the 3RD letter of the alphabet
COMMON CAROTID (and part of internal carotids) |
|
4th aortic arch: Derivatives
|
Blood gets to the 4 limbs
Left = Aortic arch Right = Proximal subclavian artery |
|
6th aortic arch: Derivative
|
Proximal pulmonary arteries
Left: includes ductus arteriosus |
|
Branchial apparatus: Germ layer origins
|
a.k.a Pharyngeal apparatus
Clefts --> Ectoderm Arches --> Mesoderm + Neural crest Pouches --> Endoderm |
|
Branchial cleft derivatives
|
Cleft 1: External auditory meatus
He had to EAt Meat so he CLEFT Clefts 2-4 --> Obliterated |
|
Branchial arch 1 derivatives
|
TTT MAD MOUTH
Innervated by CN V-2 and V-3 Muscles (TTT MAD): Tensor tympani Tensor veli palatini anterior Tongue (Two-thirds) Mylohyoid Anterior belly of Digastric Mouth =Mastication (Masseter, pterygoids, temporalis) Mouth =Meckel's cartilage Malleus (+incus) Mandible SphenoMANDIBULAR ligament |
|
Branchial arch 2 derivative
|
SSSecond arch
CN SSSeven The SS Faces the PD Innervated by CN SSSeven SS = Reichert's cartilage + mirror muscles *Stapes *Stylohyoid ligament AND attachments (Styloid process + hyoid: lesser horn) Stapedius muscle Stylohyoid muscle *FACE = Facial expression muscles PD = Posterior belly of digastric |
|
Branchial arch 3 derivatives
|
3x3 =9 --> Innervated by CN 9
3rd arch = 3 things to remember: Cartilage --> Greater horn of hyoid *Great enough to have its own arch Tongue: Posterior 1/3 (with arch 4) Muscle: Stylopharyngeus |
|
Branchial Arch 4
|
Superior laryngeal branch of CN X
TLC Please --> Take care of cricothyroid! Tongue--posterior 1/3 (w/arch 3) Levator veli palatini Constrictors (pharyngeal) Cricothyroid |
|
Branchial Arch 6
|
In the end, an I for an I
Inferior laryngeal branch of CN X Intrinsic muscles of larynx EXCEPT cricothyroid |
|
Branchial arch innervation
|
The only CNs with both SENSORY and MOTOR components
1 --> CN V-2, V-3 2 --> CN VII 3 --> CN IX 4 --> CN X (S. laryngeal branch) 6 --> CN X (I. laryngeal branch) |
|
Ear origins
|
Malleus/incus + tensor tympani
*Part of ARCH 1: TTT Mad Mouth *CN V-3 External auditory meatus: Cleft 1 Tympanic membrane: 1st branchial membrane Stapes + Stapedius *Part of ARCH 2: SS Faces PD *CN VII |
|
Tongue origins
|
Anterior 2/3:
*Part of ARCH 1: TTT Mad Mouth *CN V-3 --> Sensation ANTERIOR 2/3 TASTE IS CN VII Posterior 1/3 *Part of TLC-P: Arch 4 (AND 3) *CN 9 (most), CN X (posterior) Motor innervation: CN XII Muscle origin: Occipital myotomes |
|
Branchial pouch 1
|
Endoderm lined structures of the ear
MAC (n' cheese) ET MEC's: Mastoid air cells Eustachian tube Middle ear cavity |
|
Branchial pouch 2
|
Epithelial lining of palatine tonsil
|
|
Branchial pouches 3 + 4
|
3rd pouch:
*THree ~ THymus *INFERIOR parathyroids 4th pouch: *Superior parathyroids *Since it only gets 1 thing, it gets the SUPERIOR parathyroids DiGeorge: Malformation of 3rd and 4th pouches *THC: Thymic aplasia, hypocalcemia (no parathyroids), cardiac defects |
|
Cleft lip
|
Failure of PRIMARY palate
Failure of fusion of nasal processes: maxillary and medial |
|
Cleft palate
|
Failure of SECONDARY palate
Failure of ANY of the following to fuse: *Nasal septum *Palatine processes (lateral, medial) |
|
Pancreas structure
|
2 embryologic buds:
*VW: Ventral --> Head, Wirsung *Dorsal --> Everything else, Santorini Wirsung is the main duct Santorini is accessory duct *Santa's little helper Annular pancreas: Ventral pancreatic head can accidentally encircle duodenum |
|
Diaphragm origins
|
Several Parts Build Diaphragm
Septum transversum Pleuroperitoneal folds Body wall Dorsal mesentary of esophagus Diaphragmatic hernia --> abdominal contents herniate into thorax *May cause hypoplasia of thoracic organs (compression) |
|
Bladder or cloacal extrophy
|
Failure of caudal abdominal fold
|
|
Gastrochisis
|
Failure of LATERAL abdominal folds to fuse
Extrusion of abdominal contents |
|
Omphalocele
|
Peritoneum-enclosed organs
Herniation of abdominal contents into umbilical cord |
|
Mesonephros becomes
|
Male anatomy
Forms SEVE of SEVEN UP: Seminal vesicles Epididymis Vas deferens Ejaculatory duct Originally functions as secondary kidney Origin of metanephros |
|
Metanephros becomes...
|
Functional kidney
Starts as a bud from mesonephros Induces metanephric blastema Later changes attachment point to UG sinus (bladder, ureters, allantois) |
|
Allantois
|
Endodermic evagination of hidgut
Becomes surrounded by mesoderm that will form umbilical vasculature Endoderm + mesoderm becomes umbilical cord |
|
Paramesonephric/Mullerian duct becomes...
|
Fallopian tube
Uterus Upper vagina |
|
SRY
|
Gene that induces testes
|
|
MIF
|
Secreted by testes, along with androgens, to cause male development
|
|
Male vs. Female genital origins
|
Genital tubercle
*Glans penis *Glans clitoris Corpus cavernosum *Erectile tissue of penis *Erectile tissue of clitoris Urogenital sinus *Corpus spongiosum (urethra) *Vestibular bulbs *Bulbourethral glands of Cowper *Greater vestibular glands (Bartholin) *Prostate *Urethral, paraurethral glands of Skene Urogenital folds: *Ventral shaft of penis *Labia minora Labioscrotal swelling *Scrotum *Labia majora |
|
Techoic acid and LPS induce
|
TNF and IL-1
|
|
Anthrax capsule
|
D-glutamate
(All other encapsulated organisms have polysaccharide capsules) |
|
Spores
|
Provides resistance to dehydration, heat and chemicals
*Must autoclave to kill Autoclave ~ 1 hr >100C Keratin-like coat DiPIColinic acid in core = Keeps em from dying when life isn't a PICnic Gram POSITIVE organisms *Clostridium (Perf, Tet, Bot) *Bacillus anthracis |
|
Bad gram stainers
|
These Rascals May Microscopically Lack Color
Treponema (thin) Rickettsia (intracellular) Mycoplasma (no cell wall) Mycobacteria (lipids) *Acid fast Legionella (intracellular) *Silver stain Chlamydia (intracellular) |
|
What is the only gram (+) bacteria to have an ENDOtoxin?
|
Listeria
|
|
Endotoxins
|
Permanent structure on gram (-) bacteria
*AND LISTERIA LPS --> Stable at 100C for 1hr Induces fever, shock Induces TNF and IL-1 *So does Teichoic acid (Gram +) Poorly antigenic No vaccines |
|
Exotoxins
|
SECRETED from gram (+) and (-) bacteria
*Tetanus *Botulism *Diptheria *Staph Polysaccharide --> Destroyed at 60C *Except staph exotoxin DNA is NOT intrinsic to genome *Plasmid or bacteriophage HIGHLY toxic Induces ANTITOXINS (high titer Abs) Vaccines: Toxoids |
|
S. Aureus protein A
|
Binds the Fc region of IgG
A bacterial virulence factor |
|
IgA protease
|
Secreted by encapsulated bacteria, which already have a capsule to inhibit phagocytosis (Strep pneumo, H. Influenza, Neisseria)
Cleaves IgA |
|
Group A streptococcal M protein
|
Helps prevent phagocytosis
Mediator of rheumatic fever |
|
S. Aureus: Exotoxins and Virulence factors
|
Exotoxins:
TSST-1: Superantigen *Fever *Rash *Shock Enterotoxins --> Food poisoning Exfoliatin --> SCALDED SKIN Virulence factor = Protein A: Grabs Fc of immunoglobins |
|
TSST-1: Origin
|
Exotoxin (superantigen) from S. Aureus
|
|
Exfoliatin: Origin
|
Exotoxin from S. Aureus
Scalded skin syndrome |
|
S. Pyogenes: Exotoxins
|
1. Scarlet fever-erythrogenic toxin
*Superantigen *Toxic shock-like syndrome 2. Streptolysin O *Hemolysin *Diagnose rheumatic fever w/ASO Ab |
|
Streptolysin O: Origin
|
Exotoxin from S. Pyogenes
Causes hemolysis Diagnostic for rheumatic fever |
|
Corynebacterium diptheriae:
Exotoxins |
CD = EF
ELONGATION FACTOR 2 (EF-2) *A.k.a. Diptheria toxin EF-2 is ADP ribosylated *Inhibits protein synthesis Gram positive rods METACHROMATIC granules Causes pseudomembranous pharyngitis (grayish-white membrane) Lymphadenopathy ABCDEFG: ADP Ribosylation of EF-2 Beta-prophage encoding of exotoxin Corynebacterium Diptheriae EF-2 Granules (metachromatic) |
|
Vibrio cholerae: Exotoxins
|
Cholera toxin
G protein is liked to adenylate cyclase *Cholera toxin ADP ribosylates it Overactivity ensues: *Cl pumped into gut *Na+ absorption reduced RICE WATER DIARRHEA Comma shaped bacterium |
|
E. coli: Exotoxins
|
Both cause WATERY DIARRHEA
Labile like the AIR (Labile-A) Stable like the GROUND (Stable-G) Heat labile: Activates Adenylate Cyclase *Increases cAMP Heat stable: Activates Guanylate Cyclase |
|
Bordatella pertussis: Exotoxins
|
Pertussis toxin
Causes whooping cough Inhibits an inhibitory G protein *Increases cAMP Inhibits a chemokine receptor --> Lymphocytosis |
|
Clostridium perfringens: Exotoxins
|
Alpha toxin
Causes GAS GAGRENE DOUBLE ZONE of hemolysis on blood agar |
|
Clostridium tetani: Exotoxins
|
Tetanus toxin
Blocks release of inhibitory neurotransmitters (GABA, glycine) Causes "lockjaw" |
|
Clostridium botulinum: Exotoxins
|
Botulinum toxin
Blocks release of Ach --> CNS paralysis *Especially CRANIAL NERVES Spores in canned food, honey *Floppy baby |
|
Bacillus antrhacis: Exotoxins
|
Toxin COMPLEX exists
EDEMA FACTOR = adenylate cyclase *Increases cAMP |
|
Shigella: Exotoxin
|
Shiga toxin
1. Cleaves host cell rRNA 2. Enhances cytokine release *HUS = Hemolytic uremic syndrome |
|
E. coli 0157:H7: Exotoxin
|
Shiga toxin
1. Cleaves host cell rRNA 2. Enhances cytokine release *HUS = Hemolytic uremic syndrome |
|
Gram positive bacteria: Rods
|
Little Bacilli Compared to Cocci, No Argument
Listeria Bacillus Clostridium (anaerobe) Corynebacterium Norcardia Actinomyces *Acts like fungus, formes hyphae |
|
Gram positive bacteria: Cocci
|
Catalase test: Breaks down peroxide
Staph (+) Strep (-) Staph: Clusters Strep: Strips |
|
Staphylococcus
|
Catalase (+)
Clusters Coagulase test: Fibrinogen--> Fibrin S. Aureus (+) S. Saprophyticus (-) S. Epidermidis (-) S. Saprophyticus and S. Epidermidis can be distinguished using NOVOBIOCIN "NO StRES:" Saprophyticus = Resistant Epidermitis = Susceptible |
|
Catalase
|
H2O2 --> H2O
Differentiates Strep from Staph |
|
Coagulase
|
Fibrinogen --> Fibrin
Differentiates S. Aureus from other type of Staph |
|
Novobiocin
|
Differentiates Coagulase negative staph
NO StRES: Saprophyticus = Resistant Epidermidis = Susceptible Novobiocin and Staph: Think of a NOVICE STAFF |
|
Streptococcus
|
Catalase (-) strips/chains
Hemolysis differentiates: Partial hemolysis (green) = Alpha *Differentiate further using Optochinin Complete hemolysis (clear) = Beta *Beta clear out, people * Differentiate further using Bacitracin No hemolysis = Gamma |
|
Alpha Hemolytic Strep
|
Catalase (-) chains
Alpha hemolysis (green) Strep pneumoniae: *Optochinin sensitive *Capsule (and Quellung +) *Bile soluble Strep viridans *Optochinin resistant *No capsule *Not bile soluble OVRPS (Overpass): Viridans = Resistant Pneumoniae = Sensitive |
|
Beta Hemolytic Strep
|
Catalase (-) chains
Beta hemolysis (clear) *Beta clear out, people Group A (Pyogenes) *Bacitracin sensitive *M PROTEIN (prevents phagocytosis) *Erythrogenic toxin encoded by prophage Group B (S. agalactiae) *Bacitracin resistant BBRAS: B = Resistant A = Sensitive |
|
Gram + bacteria tests:
|
Catalase:
*Strep (-) *Staph (+) Coagulase: *S. Aureus (+) *S. Saphrophyticus/Epiderm (-) Novobiocin: NO StRES *S. Saprophyticus = Resistant *S. Epidermidis = Sensitive Optochinin: OVRPS S. Pneumoniae = Sensitive *Capsule, bile solubility S. Viridans = Resistant *No capsule, no bile solubility Bacitracin: B-BRAS *Group B = Resistant *Group A (pyogenes) = Sensitive |
|
Gamma hemolytic strep
|
No hemolysis
Enterococcus Peptostreptococcus |
|
Gram negative cocci
|
Neisseria meningitidis (Maltose + Glucose)
Neisseria gonorrhoeae (Glucose) |
|
Gram negative "coccoid rods"
|
Hang Between Balls and Pills
H. Influenza Bordatella --> Like "between" Brucella --> Doesn't have balls Pasteurella |
|
Gram negative rods: Lactose non-fermenters
|
2 S, 2 P
Oxidase +: Pseudomonas aeruginosa Oxidase (-): *Shigella *Salmonella *Proteus |
|
Gram negative rods: Lactose fermenters
|
Fast: EEK!
*E. Coli *Enterobacter *Klebsiella Slow: S sounds *Citrobacter *Serratia |
|
H. Influenzae culture
|
"Go to the 5&10 store for chocolate"
Chocolate agar w/ factors V and X |
|
N. Gonorrhoeae culture
|
Thayer & Gonorrhea are inexplicably linked...by a guy named Martin?
Thayer-Martin media |
|
Bordatella Pertussis culture
|
Bordat-Bordet
Bordet-Gengou (potato) agar |
|
C. Diptheriae culture
|
Double dipping with the letters
TeLLurite plate LoFFler's media |
|
M. Tuberculosis culture
|
Lownstein-Jenson agar
|
|
Lactose-fermenting enterics culture
|
Milky pink CONK shell
PINK colonies on MacConkey's agar |
|
Legionella culture
|
Charcoal yeast extract
Buffered w/iron and cysteine |
|
Fungus culture
|
Sabouraud's agar
|
|
Congo red stain
|
Used for amyloid
Apple-green birefringence in polarized light (B-pleated sheets) |
|
Geimsa's stain
|
BCT P ~ Bacteria + Protozoans
(Actually 2 + 2) *BORing CLAss--lets TRYP on PLASMA Borellia Chlamydia Trypanosomes Plasmodium |
|
PAS stain
|
Stains glycogen and mucopolysaccharides
Used to diagnose Whipple's disease |
|
Zeihl-Neelsen
|
Sounds like a fast European car
ACID-FAST STAIN Mycobacteria Cryptosporidium (Protozoan) |
|
India ink
|
Cryptococcus neoformans
|
|
Silver stain
|
Legionella
Fungi |
|
Conjugation
|
2 things make conjugation possible:
F+: Plasmid w/conjugation genes *Plasmid is what is transferred through pilus HFR: F+ plasmid has incorporated into bacterial chromosome *Transfer of plasmid + chromosomal genes |
|
Transduction
|
Introduction of new bacterial DNA via a virus
Generalized: Random parts of chopped up host DNA gets incorporated Specialized: Following lysogenic stage, flanking bacterial genes excised along w/viral DNA |
|
Exotoxins encoded in LYSOGENIC phages
|
ABCDE
ShigA-like toxin Botulinum Cholera Diptheria toxin Erythrogenic toxin (S. Pyogenes) |
|
Obligate aerobes
|
Nasty Pests Must Breathe
Norcardia Pseudomonas aeruginosa Mycobacterium TB Bacillus anthracis |
|
Obligate anaerobe
|
ABC
Actinomyces --> Soil Bacteriodes --> Gut Clostridium --> Soil Generally foul smelling (SCFAs) Produce gas in tissue --> Gas gangrene *H2 and CO2 *C. Perfringens |
|
Obligate intracellular bugs
|
Stay inside when its Really Cold (RC)
Obligate intracellular: Can't make ATP *Rickettsia *Chlamydia |
|
Facultative intracellular bugs
|
Some Nasty Bugs May Live FacultativeLY (8)
Salmonella Neisseria Brucella Mycobacterium Listeria Francisella Legionella Yersinia |
|
Encapsulated bacteria
|
Capsule = anti-phagocytic virulence factor
Capsular bacteria also have IgA protease POSITIVE QUELLUNG RXN =Capsular swelling when specific anticapsular sera are added SpINK Strep pneumo H. Influenza Neisseria meningitidis Klebsiella |
|
Urease positive bugs
|
Hockey PUK:
H. Pylori Proteus Ureaplasma Klebsiella Can cause struvite (ammonium magnesium phosphate) crystals by alkalinizing urine Treat w/acetazolamide |
|
Beta hemolytic bacteria (not just strep)
|
Strep:
*Strep pyogenes (Group A) *Strep agalactiae (Group B) STAPH AUREUS LISTERIA (Unpasteurized milk) |
|
Staph Aureus: Manifestations
|
Inflammatory manifestations:
*Skin infections, abscesses +/-MRSA *Pneumonia *Acute bacterial endocarditis *Osteomyelitis Toxin-mediated disease: *TSST1 *Scalded skin syndrome *Food poisoning |
|
Strep pyogenes
|
Inflammatory manifestations
*Pyogenic skin infections (impetigo, cellulitis) *Toxigenic skin infections (scarlet fever, toxic shock syndrome) IMMUNOLOGIC: *PHaryngitis: PHever, NePHritis *Rheumatic fever *Post-streptococcal Glomerulonephritis Bacitracin sensitive Antibodies to PROTEIN M (phagocytosis inhibitor) enhance host defenses, but can give rise to rheumatic fever ASO titer detects recent S. Pyogenes infection Rheum for SPECCulation *Subcutaneous nodules *Polarthritis *Erythema marginatum *Chorea *Carditis VS. FEVERSS: Fever ESR Valvular damage (Mitral > A > T) Erythema marginatum Red hot joints (polyarthritis) Subcutaneous nodules (Aschoff) + Anitz St. Vitus' dance (Chorea) Aschoff = Webby area that contains anitschow cells (nuclei look like a football stitch) |
|
Strep pneumoniae
|
Rusty sputum
Most common cause of MOPS: MENINGITIS OTITIS MEDIA PNEUMONIA SINUSITIS May cause SEPSIS w/no spleen (or sickle cell anemia) Encapsulated--IgA protease Optochinin sensitive |
|
Group B streptococci
|
B is for BABIES
Beta-hemolytic Bacitracin resistant Babies have PMS? Pneumonia Meningitis Sepsis |
|
Staph epidermidis
|
Infects prosthetic devices and catheters
Component of normal skin flora Contaminates blood cultures |
|
Enterococci
|
Part of Lancefield group D
*Subset of gamma-hemolyic strep *Based on C carbohydrate on cell wall *Variable hemolysis *Hardy: can grow in 6.5% NaCl UTI Subacute endocarditis Penicillin G resistant Some VANCOMYCIN resistant strains |
|
Viridans
|
Alpha hemolytic
Optochinin resistant Normal flora of oropharynx Strep mutans = CARIES Strep Sanguis = Subacute endocarditis *Sanguis = "Blood" *Lots of blood in HEART |
|
Clostridia
|
Gram positive
Spore forming Obligate anaerobe Tetani: Blocks glycine, GABA release from RENSHAW cells of spinal cord *Exotoxin encoded by prophage C. Botulinum: Inhibits Ach release @NMJ *Adults = Pre-formed toxin *Babies = Spores (honey, cans) *Exotoxin encoded by prophage C. Perfringens: Alpha toxin (lecithinase) *Myonecrosis (gas gangrene) *Hemolysis *Perfringens PERFORATES a gangenous leg C. difficile: Cytotoxin *Endotoxin that kills enterocytes *Pseudomembranous colitis *CLINDAMYCIN or AMPICILLIN use |
|
Renshaw cells
|
Inhibitory nerves emerging from spinal cord
C. Tetani blocks their release of glycine |
|
C. Difficile: Exotoxin
|
Cytotoxin
Kills enterocytes Causes pseudomembranous colitis Most often after AMPICILLIN OR CLINDAMYCIN *AMPed up necrosis = CLIND out Treat w/METRONIDIAZOLE |
|
Anthrax
|
Woolsorter's disease--spore inhalation
Caused by bacillus anthracis Gram positive Spore forming ONLY bacterium w/a PROTEIN capsule *D-glutamate Skin contact: 1. Malignant pustule (painless ulcer) 2. Black skin lesion *Vesicular pustule *Covered in black eschar Inhalation: 1. Flu-like symptoms 2. Massive pulmonary edema, hemorrhage 3. Mediastinitis, shock |
|
Listeria
|
Acquisition:
1. Birth (vaginal) 2. Unpasteurized dairy ACTIN ROCKETS to move between cells Healthy: Mild gastroenteritis Immunocompromised: Meningitis Pregnancy: pain in the ASS *Amnionitis *Septicemia *Spontaneous abortion Infancy: *Meningitis *Granulomatous infantiseptica |
|
Actinomyces israelii
|
Gram positive rod
Obligate anaerobe Forms long branching filaments (resembles fungi) NORMAL oral flora Can cause ORAL/FACIAL abscesses *Forms YELLOW sulfur granules in sinus tracts Treat w/PENICILLIN SNAP: Sulfa for Norcardia Actinomyces uses Penicillin |
|
Nocardia
|
Gram positive rod
Causes PULMONARY infection in immunocompromised patients SNAP: Sulfa for Norcardia Actinomyces uses Penicillin |
|
Neisseria
|
Gram negative cocci
BOTH produce IgA proteases Meningococci: *RESPIRATORY and ORAL secretions *Meningococcemia, Waterhouse-Freidrichson syndrome *Polysaccharide capsule --> Vaccine *Maltose + glucose fermentation Gonococci *Sexually transmitted *Gonorrhea + PID, septic arthritis, neonatal conjunctivitis *No capsule --> No vaccine *Glucose-only fermentation |
|
H. Influenza
|
Gram negative coccobacillus
Aerosol transmission Capsule--IgA protease Chocolate agar w/factors 5+10 *When you have the FLU, mom goes to the 5&10 to buy CHOCOLATE MOPE (vs. MOPS for Strep Pneumo) *Does NOT cause the flu Meningitis--ceftriaxone Otitis media Pneumonia Epiglottitis Vaccine: Given 2-18 months *Type B capsular plolysaccharide + protein (diptheria toxoid, etc.) |
|
Enterobacteria
|
All gram negative rods except PSUDOMONAS
*All ferment glucose *All are oxidase negative K antigen: virulence factor *Kapsular *KILLER factor O Antigen: POlysaccharide component of endOtoxin H antigen: Flagella *HUSTLE factor *Motile species |
|
Klebsiella
|
Currant jelly sputum
3 A's Alcoholics Abscess in lungs Aspiration pneumonia Also pneumonia in diabetics *Alcoholics + diabetics = People who hate their pancreas club |
|
Salmonella
|
Gram negative rod
Non-lactose fermenting Invades intestinal mucosa to cause BLOODY DIARRHEA Less virulent than Shigella (another non-lactose fermenting GNR that causes bloody diarrhea) STINKY SALMON SWIM: *H2S production *Animal reservoir *Flagella--can disseminate hematogenously Typhoid fever = *Diarrhea *Fever, headache *ROSE SPOTS on abdomen *Can remain in GB chronically Transmission via the 4 Fs: Food Fingers Feces Flies |
|
*Diarrhea
*Fever, headache *ROSE SPOTS on abdomen |
Typhoid fever
Salmonella typhi |
|
Shigella
|
Gram negative rod
Non-lactose fermenting Invades intestinal mucosa to cause BLOODY DIARRHEA More virulent than Salmonella (another non-lactose fermenting GNR that causes bloody diarrhea) Does not disseminate Propels itself via actin polymerization Transmission via the 4 Fs: Food Fingers Feces Flies |
|
Yersinia entercolitica
|
Transmitted via:
*PUPPIES (pet feces) *PORK *Milk Outbreaks common at DAY CARE centers Can mimic Crohn's or appendicitis |
|
Reheated rice food poisoning
|
Bacillus cereus
"Food poisoning from REHEATED RICE? B. CEREUS!" |
|
Custard food poisoning
Mayonnaise food poisoning |
S. Aureus
|
|
Seafood poisoning
|
Vibrio parahaemolyticus
Vibrio VULNificus *Skin is also VULNerable to infectio |
|
Meat food poisoning
|
S. Aureus
Salmonella C. Perfringens (if reheated) E. Coli O017:H7 (if undercooked) |
|
Poultry, egg poisoning
|
Salmonella
|
|
Pork food poisoning
|
Yersinia entercolitica
|
|
Milk food poisoning
|
Listeria
Yersinia entercolitica |
|
Bloody diarrhea
|
YE ESC, ESC
Yersinia entercolitica E. Coli O157:H7 *Makes shiga-like toxin *Can cause HUS Enteroinvasive E. coli (invades mucosa) Salmonella Campylobacter *S or comma shaped organism *CAMPS (grows) in your FRIDGE *Oxidase positive Entamoeba Histolytica (Protozoan) Shigella C. difficile *Can be bloody OR watery |
|
Watery diarrhea
|
They RAN to GUARD the CRYPTic PCD Emblem
RAN = Virusis *Rotavirus *Adenovirus *Norovirus Guard = Giardia (Protozoan) Cryptic = Cryptosporidium (Protozoan)--mild P = C. Perfringens C = Cholera *Comma shaped *Rice water diarrhea D = C. Difficile Emblem = E. coli (Enterotoxigenic) *Traveler's diarrhea *ST and LT toxins |
|
Bacterial cAMP modifiers
|
They increase camp somehow
3 ADP ribosylators: 1. Cholera: Stimulates Gs 2. Pertussis: Inactivates Gi 3. E. coli heat labile: Stimulates AC Anthrax: Actually IS an AC |
|
Legionella
|
Gram negative rod
Requires silver stain Requires charcoal yeast medium w/Fe, Cysteine Transmission = Aerosol from water source *No PERSON-TO-PERSON transmission Manifestations: 1. Legionnaire's disease = Severe pneumonia 2. Pontiac fever = Mild influenza Treatment: Erythromycin Picture: Legionnaire with his SILVER IRON dagger, sitting around a CHARCOAL fire. He's no SISSY (cysteine) |
|
Pseudomonas
|
Gram negative rod
OXIDASE (+) --> Aerobic Exotoxin A (like diptheria): Inactivates EF-2 Associations: Cystic fibrosis Burns Associations = PSEUDO P = Pneumonia (cystic fibrosis) S = Sepsis (w/BLACK lesions on skin) E = External otitis (swimmers ear) U = UTI D = Drug use O = Osteomyelitis (diabetic) *HOT TUB FOLLICULITIS Blue-green color (pyocyanin) GRAPELIKE odor Produces Exotoxin A (inactivates EF-2) Treat: Aminoglycoside + extended spectrum penicillin (piperacillin, ticarcillin) |
|
H. Pylori
|
Gram negative rod
Urease positive (neutralizes acid) Hangs out in the antrum Complications: *Type B gastritis --> AdenoCA, MALT lymphoma *~100% of duodenal ulcers *~70% of PUD Triple therapy: Make Tummy Better *Metronidiazole or PPI *Tetracycline or amoxicillin *Bismuth |
|
Cat scratch fever
|
Bartonella henselae
|
|
Brucella
|
Brucellosis/UNdulant fever
UNpasteurized dairy products Contact w/animals UNpasteurized dairy products ~ Undulant fever |
|
Francisella tularensis
|
Tularemia
Tick bite *Lives on deer and rabbits |
|
Gardnerella vaginalis
|
Gram VARIABLE rod
Sexually transmitted Gray vaginal discharge w/fishy smell CLUE cells (vaginal epithelial cells covered w/bacteria) Treat w/metronidiazole |
|
Primary TB
|
Nonimmune host (usually a child)
1. Ghon focus (granulomas) in lower lung 2. Lobar and perihilar node involvement Outcomes: 1. Healing (PPD+) *2nd exposure --> fibrocaseous cavitary lesion in UPPER lung 2. Progressive lung disease (death, rare) 3. Miliary TB (death) 4. Pre-allergic lymphatic dissemination --> Reactivation TB *CNS (parenchyma, meningitis) *POTT'S DISEASE (vertebral body) *Lymph nodes *Renal *GI *Lung --> Fibrocaseous cavitary lesion in upper lung |
|
Secondary TB
|
REACTIVATION
or 2nd INFECTION Fibrocaseous cavitary lesion UPPER LUNG (Ghon focus of primary TB is in lower lung) |
|
PPD+
|
Current infection
Past exposure BCG vaccinated FALSE POSITIVE: Anti-phospholipid antibody (SLE) |
|
PPD-
|
No infection
Anergic = SIMS * Sarcodosis *Immunocompromised *Malnutrition *Steroids |
|
Mycobacteria
|
TALKS
All are acid fast M. tuberculosis M. Avium-intracellulare *Avium ~ AIDS (Disseminated disease) *Often resistant to multiple drugs M. Leprae (Hansen's disease) *Infects skin and superficial nerves *Leonine facies: Lost eyebrows, nasal collapse, lumpy earlobe *Armadillo reservoir *Lepromatous = Worse; cell-mediated immunity, lethal *Tuberculoid = Self-limited *DAPSONE do be a dapper son again M. Kansasii *Pulmonary TB-like symptoms M. Scofulaceum *Cervical lymphadenitis in kids |
|
Hansen's disease
|
Leprosy
Not very HANSEM |
|
Leonine facies
|
Leprosy
Lost eyebrows Lumpy earlobe Nasal collapse |
|
Rickettsiae
|
Obligate intracellular parasites
Transmitted by arthropod vector *Except coxiella--aerosol CLASSIC SYMPTOMS: Headache Fever Rash: Differs by type *Rickettsia starts on HANDS + FEET (Rickettsia on the RISTS) *Typhus on the TRUNK RICKET --> TET (Tetracycline) PQR(S)T: Prowazekii = Epidemic typhus *Human body louse *PROWling around your BODY *(+) Weil-Felix Coxiella burnetti: Q fever Rickettsiii = Rocky Mtn spotted fever *Rash: Hands and feet *Endemic to EAST COAST *(+) Weil-Felix Typhi = Endemic typhus (fleas) *Rash on trunk *(+) Weil-Felix Erlichia: Erlichiosis (TICK) *Lick the tick |
|
Chlamydia
|
Obligate intracellular parasites
*Seen w/GEIMSA (BCTP) or fluorescent ab Unusual cell wall: lack muramic acid 2 forms: *ELEMENTARY BODY (small, dense): Enters cells via endocytosis *RETICULATE BODY = Replicates in cell Chlamydia trachomatis *Types A-C: Africa/blindness/chronic *Types D-K: Everything else *Urethritis and PID *Arthritis *Conjunctivitis Types L1-L3: Lymphogranuloma venereum *(+) Frei test (Ab from egg) C. Pneumoniae: Atypical pneumonia C. Psittaci: Atypical pneumonia *Avian reservoir |
|
Chlamydia serotypes A-C
|
Africa
Blindness Chronic |
|
Chlamydia serotypes D-K
|
Everything types A-C and L1-L3 aren't
Urethritis/PID Neonatal conjunctivitis Arthritis MOST COMMON CAUSE OF PREVENTABLE BLINDNESS |
|
Chlamydia serotypes L1-L3
|
Lymphogranuloma venereum
Positive Frei test (egg Ab) Rectal strictures |
|
Spirochetes
|
BLT, and B = Big
Borrelia (large) *Geimsa stain Leptospira Treponema *Dark field microscopy |
|
Leptospira interrogans
|
Question-mark shaped bacteria
Water contaminated w/animal urine Flu-like (Fever, Headache, Abdominal pain) + JAUNDICE Weil's disease: + Kidney dysfunction + Anemia, hemorrhage |
|
Lyme disease
|
Borrelia burgdorferi (Ixodes tick)
*Deer required for tick life cycle *Mice BAKED a key lime pie: Bell's palsy Arthritis Kardiac block Erythema migrans Doxycycline 1. Erythema chronicum migrans (bulls-eye rash) 2. Neurologic + cardiac symptoms 3. Arthritis (chronic mono, migratory poly) |
|
Treponema pertenue
|
YAWS
It's PERTINent that sex is not involved Tropical infection that is NOT an STD but VDRL test is positive |
|
VDRL
|
Syphilis test
(+) With either kind of Treponema *T. Pallidum: Syphilis *T. Pertenue: Tropical disease (non-STD) Not as good as FTA-ABS Possible false positives: VDRL V=Viruses D = Drugs R = Rheumatic FEVER L = Lupus and leprosy |
|
Syphilis
|
Primary = Painless chancre
Secondary = Disseminated disease *Constituional symptoms *Palm and sole rash *Condyloma lata (rash consolidations) Tertiary syphilus = More severe symptoms *GoT CRABS? *Gummas (inflammatory skin balls) *Tabes dorsalis (DC and DRG degeneration) *Charcot joints (lost proprio = degeneration) *Robertson (Argyll) pupil *Aortitis *Broad based gait *Stroke w/o HTN Treat w/Penicillin G |
|
PALM AND SOLE RASHES
|
ROCKY
SACKIE SYPHILUS Rickettsia rickettsii *Rocky Mtn spotted fever (E coast) Coxsackie A (Hand Foot and Mouth disease) Syphilus |
|
Congenital syphilis
|
SSHH
Saber shins (anterior bowing) Saddle nose Hutchinson teeth (small, widely spaced) Hearing problems (CNVIII deafness) |
|
Argyll-Robertson pupil
|
"Accomodates but doesn't react"
...EWW (Edinger-Westpal nucleus) Constricts w/accomodation Does not constrict in response to light |
|
FTA-ABS
|
Test for treponemes
More specific than VDRL (+) earlier (+) later (after treatment) If FTA-ABS is (-) while VDRL is (+), probably a false (+) |
|
Mycoplasma pneumoniae
|
No cell wall -- no gram staining
ONLY bacterium w/cholesterol in membrane Looks like fungus Classic cause of atypical (walking) pneumonia *Prisons, military *Insidious, w/non-productive cough *Diffuse INTERSTITIAL infiltrate High titer of COLD AGGLUTININS (IgM) Grown on Eaton's agar Treatment: Tetracyclin or erythromycin *No cell wall for penicillin to break down |
|
Eaton's agar
|
Medium for mycoplasma pneumoniae
|
|
Atypical pneumonia
|
"Walking pneumonia"
Interstitial infiltrate Mycoplasma pneumoniae Chlamydia psittaci Chlamydia pneumonia Treat w/erythromycin or tetracycline |
|
Candida
|
GERM TUBE TEST DIAGNOSTIC
May be superficial or systemic Transmission = Spore inhalation *No person-to-person spread 20C: Budding yeast w/pseudohyphae *Pseudohyphae = like incomplete buddings 37C: Germ tube formation *Look like BALLOONS *By 37, not many GERM (cells) in a fallopian TUBE IV drug users: Endocarditis Immunocomp: Thrush esophagitis Antibiotics, DM: Vaginitis Babies: Diaper rash |
|
Histoplasmosis
|
Systemic mycosis --> PNEUMONIA
Mississippi and Ohio river valleys Bird or bat droppings Invades MACROPHAGES *Histo HIDES *Tiny yeast can be seen within them |
|
Blastomycosis
|
Systemic mycosis
East of the Mississippi River Central america **East coast and Central america both got BLASTed by swine flu too** BROAD BASED BUDS BUMPS: Granulomatous nodules 1. Pneumonia 2. Skin and bone |
|
Coccidiomycosis
|
Systemic mycosis
a.k.a. San Joaquin or desert valley fever California (Southwestern US) Always a SPHERULE filled w/endospores *Coccidio CONSTANT 1. Pneumonia 2. Skin and bone 3. Meningitis |
|
Paracoccidiomycosis
|
Systemic mycosis
Rural Latin america Para ~ Pinweel *"Captain's wheel appearance" |
|
Cutaneous mycoses
|
1. Tinea versicolor
*KOH: Spaghetti and meatball *Malassezia FURFUR (affects head "fur") *Seen w/hot, humid weather *Tx: Miconazole, Selenium sulfide (Selsun) 2. Tinea EVERYTHING ELSE *Pruritic lesions w/central clearing *DERMATOPHYTES (Microsporum, Trichophyton, Epidermophyton) *KOH: Mold hyphae *Pets may be a reservoir (Microsporum) *Tx: Azoles |
|
Aspergillus fumigatus
|
ALWAYS A MOLD
*Septate hyphae *45 degree branching Allergic bronchopulmonary aspergillosis Lung cavity aspergilloma (fungus ball) Invasive aspergillosis *Immunocompromised *Chronic granulomatous disease/NADPH oxidase def |
|
Cryptococcus neoformans
|
Brink LATEX + SOAP to INDIA
Heavily encapsulated YEAST *Narrow based budding Found in pigeon droppings (and thus soil) Stains w/INDIA INK LATEX AGGLUTINATION TEST detects relevant capsular antigens Cryptococcal meningitis *SOAP BUBBLE lesions in brain Cryptococcosis (blood) |
|
Mucor and Rhizopus
|
Mold
*Non-septate hyphae *Branching at wide angles (>90) **Ketoacidotic diabetic and leukemic patients** 1. Rhinocerebral, frontal abscesses 2. Fungi proliferate in walls of blood vessels *Infarction of distal tissue |
|
Septate, 45 degree hyphae
|
AspergiLLus
|
|
Non-septate, wide branching hyphae
|
Mucor, rhizopus
|
|
Pseudohyphae
|
Candida
|
|
Pneumocystis jiroveci
|
Inhaled YEAST (not spore)
Most infections are asymptomatic Associated w/HIV, AIDS *Prophylaxis when CD4 <200 Diffuse interstitial pneumonia *Diffuse, bilateral CXR *Diagnose w/biopsy, lavage Stains w/METHENAMINE SILVER |
|
Pneumocystis jiroveci stain
|
Methenamine silver
|
|
Sporothrix schenki
|
Dimorphic fungus that lives on plants
*Cigar-shaped budding yeast *Unequal budding "Rose gardner's disease": *Local pustule/ulcer *Nodules along draining lymphatics Treat w/schenckII Itraconazole Potassium iodide |
|
Constant molds
|
MAD
Mucor Aspergillus Dermatophytes |
|
Constant yeasts
|
PC
Pneumocystis Cryptococcus |
|
Giardia
|
Protozoan
Cysts in water--when ingested: *Foul diarrhea *Bloating and flatulence Diagnosis: Trophozoites or cysts in stool *Look like double nuclei (2 eyes) Treat w/metronidiazole |
|
Trichomonas
|
Protozoan
Sexual transmision: *Vaginitis --> Greenish discharge w/itching, burning Diagnosis: Trophozoites on wet mount *THEY MOVE Treat w/metronidiazole |
|
Trypanosoma Cruzi
|
Protozoan
Chagas disease (SA) Transmitted via Reduvid bug: Dilated cardiomyopathy Megacolon Megaesophagus Diagnosis: Blood smear shows worm-like things w/flagella Treat w/Nifurtimox |
|
Trypanosoma gambiense
Trypanosoma rhodesiense |
Protozoan
African sleeping sickness Transmitted by TseTse fly Diagnosis: Blood smear Treat w/: Suramin -- blood borne disease Melarsoprol --CNS penetration |
|
Leishmania Donovani
|
Protozoan
Visceral Leishmaniasis *HOT in the DESERT Transmitted by Sandfly: *Hepatosplenomegaly --> Spiking fevers, pancytopenia Diagnosis: Blood smear *Macrophages w/amastigotes *Egypt: will they MASSACRE the GOATS in case they have disease inside? Treat w/Sodium stibogluconate |
|
Plasmodium
|
Protozoans
Malaria Transmitted by mosquito: *Splenomegaly --> Cyclic fever, headache, anemia P. malariae P. ViVax/OVale have dormant forms in liVer *Called hypnozoites *Relapsing malaria P. Falciparum is severe, possibly fatal *Don't FAL prey to falciparum Diagnosed w/blood smear: *RBCs w/TROPHOZOITE "ring form" (feeding stage, becomes a SHIZONT) *RBCs w/merozoites (after SHIZONT undergoes rapid replication) Treatment: *Primaquine to PREVENT (relapse) *Chloroquine *Sulfadoxine + pyrimethamine *Mefloquine *Quinine |
|
Babesia
|
Protozoan
Babesiosis Primarily in NE US (same as Lyme) Transmitted by Ixodes tick (same as Lyme) *Fever + hemolytic anemia (same as malaria) Diagnosis: Blood smear *RBCs w/ring trophozoites *RBCs w/MALTESE CROSS Treat w/Quinidine, Clindamycin *QUEEN CLINDA |
|
What protozoans cause diarrhea?
|
Watery:
Giardia Cryptosporidium Bloody: Entamoeba histolytica |
|
Cryptosporidium
|
Protozoan
Diarrhea Cysts in water--when ingested: *Mild watery diarrhea *AIDS: Severe diarrhea Diagnosis: Cysts on acid-fast stain NO TREATMENT |
|
Toxoplasma gondii
|
Protozoan
Brain abscess Birth defects: Ring-enhancing brain lesions Cysts in MEAT or CAT FECES: *Crosses placenta Diagnosis: Biopsy, serology Treat w/Sulfadiazine, Pyrimethamine *"Sulfa and its peer" |
|
Entamoeba Histolytica
|
Protozoan
Bloody diarrhea Liver abscesses (RUQ pain) Cysts in water--when ingested: *Bloody diarrhea *Liver abscesses (invades GI, stops @liver) Diagnosis: Stool *Trophozoites w/RBCs INSIDE *Cysts w/4 NUCLEI Treat w/: Metronidiazole Iodoquinol "IOD METRONIDIAZOLE one, because it treats so many things" |
|
Naegleria Fowleri
|
Entamoeba Histolytica
|
|
Trematodes (3)
|
a.k.a. flukes
Treat ALL w/Praziquantel Shistosoma: HSMEGALY *CERCARIAE penetrate skin *SNAIL host *Spleen + Liver: Granulomas, inflammation Clonarchis sinensis *Undercooked FISH *Enflames, CLOGS biliary tract *Pigmented gallstones *CHOLANGIOCARCINOMA Paragonimus westermani *Undercooked CRAB *Lung: Inflammation, 2 infection |
|
Praziquantel
|
Treatment for all TREMATODES
+ GI Taenia solium |
|
Cestodes (2)
|
a.k.a. tapeworms
*Cestode ~ Sticky *Sticky situations (Brain lesions, anaphylaxis) Treat both w/Albendazole *Praziquantel for intestinal taenia Taenia solium *Undercooked pork *Larvae (too big to cross GI) --> intestinal *Eggs --> Cysticercosis (inc BRAIN) *Neurocysticercosis: Swiss cheese Echinococcus granulosus: IgE, Eggs *Eggs in dog feces *Cysts in liver --> spontaneous anaphylaxis w/antigen release |
|
Nematodes treated w/Mebendazole
|
Pinworm (E)
Giant roundworm (E) Hookworm 1. Enterobius vermicularis (pinworm) *Food contaminated w/Eggs *GI infection only *Anal pruritis (SCOTCH TAPE TEST) 2. Ascaris lumbricodes: Giant roundworm *Eggs visible in feces *GI infection only 3. Ancylostoma dodenale (Hookworm) *Penetrate skin of feet *GI infection only *ANEMIA ("southern laziness") |
|
Nematodes treated w/Thiabendazole
|
Trichinella spiralis
*Undercooked pork *Larvae encyst in MUSCLE *Thiabendazole so you can BEND the THIGH again* Strongyloides stercoralis *Larvae in soil penetrate skin *"STAND-STRONG" *STRONG effect: N/V/D, Anemia |
|
Nematodes treated w/Ivermectin
|
IVER for RIVER
Onchocerca Volvulus: *Female blackflies *River blindness *Lizard skin (skin nodules) *IVAN the strong Strongyloides stercoralis *Larvae in soil penetrate skin *"STAND-STRONG" *STRONG effect: N/V/D, Anemia |
|
Nematodes treated w/Niridazole
|
Dracunculus medinensis
*In drinking water *Skin inflammation, ulceration *Dracula drank the water, then he leaked blood *But you'll never be RID of him (Niridazole) |
|
Nematodes treated w/Diethylcarbamazine
|
Loa Loa --> That's a grossa
*Transmitted by flies (deer, horse, mango) *Skin swelling *See worm CRAWLING in conjunctiva Wucheria bancrofti: *Female mosquito (W for woman) *Blockage of lymphatic vessels *ELEPHANTIASIS Toxocara canis *Food contaminated w/Eggs *Granulomas (possible blindness) *Visceral larva migrans |
|
Nematodes which infect via EGGS
|
EAT eggs:
Enterobius vermicularis (Pinworm)--GI Ascaris lumbricodes (Giant roundworm)--GI Toxocaris canis (granulomas, visceral migrans) |
|
Worm: Brain cysts, seizures
|
Taenia solium
Cestode Eggs cause cystercercosis Larvae = GI only Treat eggs w/Albendazole |
|
Worm: Liver cysts
|
Echinococcus granulosus
Cestode Eggs in dog feces Treat w/Albendazole |
|
Worm: B12 deficiency
|
Diphyllobothrium latum
|
|
Worm: Biliary tract disease
|
Clonarchis sinensis
Trematode Undercooked seafood Enflames biliary tract Pigment stones Cholangiocarcinoma Treat w/Praziquantel |
|
Worm: Hemoptysis
|
Paragonimus westermani
Trematode Undercooked crab Causes lung inflammation Secondary bacterial infection Treat w/Praziquantel |
|
Worm: Portal HTN
|
Shistosoma mansoni
Trematode Penetrates skin Snail host HSmegaly due to fibrosis, inflammation, granuloma formation Treat w/Praziquantel |
|
Worm: Hematuria and Bladder cancer
|
Shistosoma haematobium
Trematode Haema ~ Hematuria Bium ~ Bladder Treat w/Praziquantel |
|
Worm: Microcytic anemia
|
Anclyostoma (Nematode)
*Enters foot skin *Treat w/Mebendazole Strongyloides (Nematode) *Enters food skin *Treat w/Ivermectin (or thiabendazole) |
|
All DNA viruses are double stranded except _______
|
Parvovirus
Single stranded "Part of a virus" |
|
All DNA viruses are linear except...
|
POLYOMA got a PAPILLOMA and asked for HEP
She didn't follow the STRAIGHT AND NARROW (linear) Polyoma Papilloma Hepadnavirus (HPV) |
|
All RNA viruses are ssRNA except ___
|
Reovirus = REPEATOvirus
Double stranded |
|
Viral genomic material that is infectious by itself
|
ALL DNA viruses except HBV, Pox
*HBV and Pox have most complicated genomes ssRNA (+) |
|
Viral genomic material that needs viral enzymes to be infectious
|
Viral genomic material that is infectious by itself
|
|
Non-enveloped viruses
|
Naked CPR and PAPP smear
RNA: CPR Calicivirus Picornavirus Reovirus DNA: PAPP *Polyoma *Adenovirus *Papilloma *Parvovirus |
|
Viral envelopes: Source
|
Plasma membrane
Exception: HBV (nuclear membrane) |
|
All DNA viruses replicate in the nucleus except for...
|
Pox
Largest virus--needs room? POX likes to DOT the cytoplasm |
|
All RNA viruses replicate in the cytoplasm except for...
|
All DNA viruses replicate in the nucleus except for...
|
|
DNA viruses
|
HHAPPPPy viruses
Hepadnavirus (HBV) *Partial circular *Has reverse transcriptase (?) *Acute or chonic hepatitis *Vaccine available Herpes *HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-8 Adenovirus *Sore throat w/fever *Pneumonia *Pink eye (conjunctivitis) Polyoma *Circular DNA *"JC virus:" PML in HIV Papilloma (HPV) *Circular DNA *Warts, Cervical cancer Pox *Largest DNA virus *Replicates in cytplasm *Smallpox *Vaccinia--cowpox (milkmaid's blisters) *Molluscum contagiosum Parvovirus (B19) *Smallest DNA virus *Aplastic crisis in sickle cell disease *Hydrops fetalis *Slapped cheeks rash/5th's disease |
|
What virus has reverse transcriptase, even though it isn't a retrovirus?
|
HBV
|
|
HSV
|
DNA virus
Linear, enveloped HSV-1: Respiration, saliva *Oral > genital lesions *Keratoconjunctivitis *Temporal encephalopathy HSV-2: Sexual contact, perinatal *Genital > Oral lesions *Neonatal herpes VZV: Respiratory secretions *Chickenpox *Zoster *Shingles EBV: Respiratory secretions, saliva *Mononucleosis *Burkitt's lymphoma CMV: BODY FLUIDS (including urine) *Infection in immunosuppressed patients (esp after transplant) *Congenital defects HHV-6: Roseola (exanthem subitum) HHV-8: Sexual *Kaposi's sarcoma |
|
Icosahedral viruses
|
All SS (+) + Reovirus (ds)
POSITIVE ICOns CPR--No envelope FRT--Envelope Calicivirus: CRUISE SHIP hazards *Hepatitis E *Norwalk virus Picornavirus: PERCH *Poliovirus *Echovuris (aseptic meningitis) *Rhinovirus (common cold) *Coxsackie (Aseptic meningitis, febrile pharyngitis/herpangina, HFM disease) *Hepatitis A Reovirus (ds) *Rotavirus: #1 fatal diarrhea in children *Colorado tick fever Flavivirus *Hepatitis C *Yellow fever *Dengue *St. Louis encephalitis *West nile virus Retrovirus *HIV *HTLV Togavirus *Rubella (German measles) *EEE *WEE |
|
Helical RNA viruses
|
All SS (-) except for Coronavirus (SS +)
BAD COP FR sale *That's a NEGATIVE thing BAD = Circular B = Bunyavirus *Hantavirus (hemorrhagic fever, pneumonia) *California encephalitis *Rift valley fever/Sandfly fever *Crimean-Congo hemorrhagic fever A = Arenavirus: *LCV--lymphocytic choriomeningitis *Lassa fever encephalitis--spread by mice D = Deltavirus: Hepatitis D C = Coronavirus: "Common cold" + SARS O = Orthomyxovirus: Influenza P = Paramyxovirus: PaRaMyo (PRMM) *Parainfluenza (Croup) *RSV (bronchiolitis in babies) *Measles (Rubeola) *Mumps F = Filoviruses: Ebola/Marburg R = Rhabdovirus: Rabies |
|
Paramyxovirus
|
SS (-) Helical
Cause disease in CHILDREN PaRaMyxo = PRMM Parainfluenza (Croup) RSV (bronchiolitis in babies) Measles (Rubeola) *Buccal KOPLIK SPOTS (red w/white-blue) *Rash: HEAD --> TOE *3C's: Cough, Coryza (nasal congestion), Conjunctivitis Mumps *Makes parotids, testes swell like POM-POMs *POM: Parotitis, Orchitis, Meningitis |
|
Vaccines
|
Live attenuated: B and T cells
*MMR *Sabin (livin) *VZV *Yellow fever *Smallpox Killed: RIP Always *B cells only (but less dangerous) R = Rabies I = Influenza P = Polio--Salk (salK = Killed) A = Hepatitis A Recombinant: HBV (HBsAg) |
|
Viral reassortment
|
Occurs w/SEGMENTED genomes
BOAR: *Bunyavirus *Orthomyxovirus: Influenza *Arenavirus *Reovirus Viruses exchange segments Cause of worldwide influenza pandemics |
|
Hepatitis
|
HAV = Picornavirus
HBV = DNA HCV = Flavivirus *C how flavorful? HDV = Deltavirus HEV = Calicivirus *Cruise ships |
|
Phenotype mixing
|
Viral co-infection
DNA from one virus can be packaged in the capsid for another |
|
EBV diagnosis
|
Infects B CELLS
*Hodgkin's and Burkitt's lymphoma Spread via respiratory and saliva Peak age 15-20 Detect w/monospot test: *HETEROPHIL ANTIBODIES Presentation: *Abnormal circulating CD8 CELLS *Fever *HSmegaly *Pharyngitis *Lymphadenopathy (posterior auricular nodes) |
|
Yellow fever
|
Flavivirus
Aedes mosquitos Monkey or human reservoir...watch out John! Really YELLOW, BLACK and RED: Jaundice Black vomit Fever |
|
Rubella
|
a.k.a. German measles
*Togavirus Fine truncal rash (hidden under clothing...still look BELLA) + SUB-OCCIPITAL LYMPHADENOPATHY + Fever,arthralgia Children: Mild disease Congenital: Severe defects (PDA, Pulmonary artery stenosis, etc) |
|
Rotavirus
|
A reovirus...dsRNA
Major cause of acute diarrhea in US #1 cause of fatal childhood diarrhea worldwide VILLOUS DESTRUCTION *Decreased absorption of Na+, H20 |
|
Rabies
|
Rhabdovirus
SS (-) Helical Night creatures: Bat, racoon skunk Virus has BULLET shaped capsid NEGRI bodies: Cytoplasmic inclusions in affected neurons Presentation: 1. Siezures 2. Hyperactive oropharynx *Hypersalivation *Pharyngeal spasm --> Hydrophobia |
|
Hepatitis A
|
RNA Picornavirus
ASYMPTOMATIC ACUTE ALONE (no carriers) Fecal oral Short incubation (3 weeks) |
|
Hepatitis B
|
DNA virus
BLOOD BORNE (parenteral, sexual) Long incubation (3 months) Contains REVERSE TRANSCRIPTASE to circumvent cell transcription GROUND GLASS HEPATOCYTES |
|
Hepatitis C
|
RNA Flavivirus SS (+), Icosahedral
Chronic (80%) --> CIRRHOSIS, CA Transmitted primarily via BLOOD Most common hepatitis among IV drug user |
|
Hepatitis D
|
RNA Deltavirus SS (-), Helical
Requires HBsAg as its envelope Superinfection worse than coinfection |
|
Hepatitis B
|
RNA calicivirus SS (+), Icosahedral
Fecal-oral (water-born epidemics) Resembles HAV, except w/respect to PREGNANT WOMEN (high mortality): Acute Asymptomatic Alone (no carriers) HBsAg (surface) --> Carrier state HBcAg (core) --> Carrier state HBeAg (core) --> Active viral replication and TRANSMISSABILITY HBsAb (surface) -->Immunity *Recovery *Vaccination HbcAb (core) --> Infection happened *Seen almost immediately *Present in recovered OR carrier state *IgMcAb = Recent infection *IgGcAb = Awhile ago HBeAb --> Indicates low transmissability |
|
HIV surface proteins
|
Outside to inside:
gp120 = Envelope protein gp41 = Envelope protein (holds gp120) p17 = matrix protein p24 = Rectangular capsid protein Infection: *CD4 T cells: CXCR4 *CD5 Macrophages: CCR5 CCR5 mutation: *Heterozygous = Slower course *Homozygous = Immunity |
|
HIV, AIDS diagnosis
|
1. ELISA -- Low threshold
2. Western blot (protein) --High threshold False negatives: 1-2 mo post-infection False positives: Babies born to HIV-infected mothers (anti-gp 120 crosses placenta) AIDS = CD4 under 200 CD4:CD8 ratio under 1.5 HIV w/AIDS indicator (PCP) |
|
Chronic hepatitis states
|
Carrier state = No symptoms
Chronic persistent: *Minimal symptoms, LFTs *Portal inflammation but NO NECROSIS Chronic active: *Symptoms, LFTs *Portal inflammation and necrosis Cirrhosis: *Bridging fibrosis *Portal HTN *Ascites |
|
Low CD4 counts: Associated conditions
|
**Throat, lungs, brain**
Under 100: Candida esophagitis Histoplasmosis Toxoplasmosis Under 50: CMV retinitis and esophagitis M. avium-intracellulaire Cryptococcal meningoencephalitis |
|
Normal flora: Nose
|
Staph epidermidis (also normal on skin)
Staph aureus |
|
Normal flora: Oropharynx
|
Strep Viridans
Strep Mutans (subgroup of viridans) *Cavities, plaque |
|
Normal flora: Colon
|
Bacteriodes fragilis > E. coli
|
|
Normal flora: Vagina
|
LEG BS
LEG BS Lactobacillus > E. coli, Group B strep |
|
Neonatal pneumonia (<4 weeks)
Newborn meningitis (0-6 mo) |
Pathogens are vaginal flora:
E. coli Group B strep + Listeria (milk) for meningitis |
|
Pneumonia: Most common pathogens
|
Neonates (Up to 4 weeks):
*E. coli *Group B strep Non-neonate children (up to 18): *Runts May Cough Sputum RSV Mycoplasma C. Pneumoniae Strep pneumoniae Adults 18-40: Just remove RSV Adults 40-65: Remove C. pneumoniae *Add H. Influenzae *Add Anaerobes *Add Viruses Elderly: Remove mycoplasma *Add GNRs |
|
Meningitis: Most common pathogens
|
Up to 6 months:
*E. coli *Group B strep *Listeria (milk) 6 mo-6 years: HIB (v) + S.E.N. *Strep pneumo *Enteroviruses *Neisseria Adults 6-60: Remove HIB Adults 60: Listeria returns *Step pneumo only SEN remnant *Add GNRs |
|
UTIs
|
Risk factors:
*Flow obstruction/surgery/catheter *Gynecologic abnormalities *DIABETES *PREGNANCY (stasis) SSEEK PP *Atypicals are "nocosomial, drug resistant" S. Saprophyticus: #2 UTI cause in sexually active women Serratia marcesens: *Some produce red pigment E. Coli: #1 cause *METALLIC SHEEN on EMB AGAR Enterobacter cloacae Klebsiella: #3 cause *Mucoid capsule, viscous Proteus mirabilis: *Motile --> Swarming *Struvite stones Pseudomonas: Blue-green, fruity |
|
TORCHS
|
Toxoplasma:
*Intracranial CALCIFICATIONS (also CMV) *HYDROCEPHALUS *Chorioretinitis [Other] Rubella: Isolated *HEART defects (PDA, PA stenosis) *Mental retardation *Deafness *CATARACTS CMV: 90% asymptomatic at birth *CALCIFICATION (also toxo) *Mental retardation *HSmegaly, JAUNDICE, petechiae HSV-2: Often asymptomatic at birth *ENCEPHALITIS *Conjunctivitis *VESICULAR skin lesion HIV: *HSmegaly *Frequent INFECTIONS *Neurologic abnormalities Syphilis *Cutaneous lesions *HSmegaly, JAUNDICE *SADDLE NOSE *SABER CHIN *Hearing loss (CN VIII) *HUTCHINSON teeth |
|
Chancroid
|
Haemophilus ducreyi
Painful genital ulcer Inguinal lymphadenopathy |
|
PID: Most common causes
|
C. trachomatis (3-4 million cases/yr)
*Subacute, often undiagnosed *Chandelier sign (cervical motion tenderness) *Purulent discharge Neisseria Gonorrhoeae *Acute, high fever *Purulent discharge |
|
Most common nosocomial UTIs
|
Risk factor = Catheterization
E. coli --> Most common anyway Proteus --> Can swim |
|
Most common infection while on respiratory therapy equipment
|
Pseudomonas aeruginosa
|
|
Most common infection w/hyperalimentation (overfeeding)
|
Candida albicans
|
|
Most likely to infect pus, empeyema, abscess
|
S. Aureus
|
|
Traumatic open wound
|
Clostridium perfringens
|
|
Surgical wound
|
S. aureus
|
|
Sepsis/meningitis in a newborn
|
Group B strep
|
|
Bacteriostatic anti-microbials (5)
|
We're ECSTaTiC (ECSTTC) about bacteriostatics
Erythromycin --> 50s Clindamycin --> 50s SMP-TMX --> Nucleotide synthesis Tetracyclines --> 30s Chloramphenicol --> 50s |
|
Bacteriocidal anti-microbials
|
Very Finely Proficient At Cell Murder
Vancomycin --> Peptido synthesis Fluoroquinolones --> DNA toposomerase Penicillin --> Peptidoglycan X-linking Aminoglycosides --> 30S Cephalosporins --> Peptidoglycan X-linking Metronidiazole |
|
Penicillin
|
Prototype B-lactam
Penicillin G (IV) Penicillin V (oral) --> Packman mouth Binds PENICILLIN BINDING PROTEINS *Blocks TRANSPEPTIDASE cross-linking of cell wall Activates autolytic enzymes Uses: Bactericidal *Gram (+) organisms *Gram (-) cocci (Neisseria) *Spirochetes (Borellia, Leptospira, SYPHILUS) SE: *Hypersensitivity (all B-lactams) *HEMOLYTIC ANEMIA |
|
Penicillinase resistant penicillins
|
Methicillin, Nafcillin, Dicloxacillin
*On the MeND **Use NAF for STAPH** Bulkier R group = Penicillinase resistance Use: STAPH *Not MRSA; altered penicillin binding site SE: *Hypersensitivity (all B-lactams) *Methicillin: Interstitial nephritis |
|
Aminopenicillins
|
Ampicillin
Amoxicillin (more oral bioavailability) Penicillinase sensitive: combine w/clavulanic acid (penicillinase inhibitor) Uses: HELPS *H. Influenza *E. coli *Listeria *Proteus *Salmonella SE: *Hypersensitivity (all B-lactams) *Ampicillin: Rash *C. DIFFICILE |
|
Antipseudomonal penicillins
|
TCP: Takes Care of Pseudomonas
Ticarcillin Carbenicillin Piperacillin Penicillinase sensitive: combine w/clavulanic acid (penicillinase inhibitor) Use: PSEUDOMONAS SE: *Hypersensitivity (all B-lactams) |
|
Cephalosporins: General info
|
B lactam drugs that inhibit cell wall cross-linking
*Less susceptible to penicillinases Bactericidal SE: All about other drugs 1. 5-10% cross reactivity w/penicillins 2. Alcohol: Disulfram-like reaction 3. Aminoglycosides: > nephrotox *Take Aminoglycosides w/Aztreoam instead (synergistic) |
|
1st generation cephalosporins
|
B lactams
CefaZOlin, CefaLEXin *Zoe and Lexi Uses: Gram (+) cocci + PEcK *Proteus *E. coli *Klebsiella |
|
2nd generation cephalosporins
|
B lactams
CeFAClor, CeFOXitin, CeFURoxime *FAKE FOX FUR Uses: Gram (+) cocci + HEN PEcKS *H. Influenza *Enterobacter aerogenes *Neisseria *Proteus *E. coli *Klebsiella *Serratia |
|
3rd generation cephalosporins
|
B lactams
CefTriaxone, CefoTaxime, CeTazidime *Cef-T Uses: *Meningitis (crosses BBB) *Serious/resistant gram (-) infections (Pseudomonas, gonorrhea |
|
4th generation cephalosporins
|
B lactams
CefiPime ~ Pseudomonas Uses: PSEUDOMONAS (just like 4th class of penicillins) |
|
Aztreonam
|
Monobactam
Binds to PBP3, but resistant to B lactamases Synergistic w/aminoglycosides No penicillin cross-reactivity Uses: Gram negative rods *PEcKS without the E --> Proteus, Klebsiella, Serratia |
|
Imipenem/Cilastatin, Meropenem
|
Carbapenems
B-lactamase resistant Imipenem always administered w/CILASTATIN *Inhibits renal dihydropeptidase I *Prevents inactivation in renal tubules Uses: ENTEROBACTER *IMIpenem--if death is IMInent *MEROpenem--merrier option SE: *SEIZURES (more w/Imipenem) *GI distress, skin rash |
|
Vancomycin
|
Bactericidal
Inhibits cell wall MUCOPEPTIDE: *Binds D-ala D-ala portion of cell wall *Resistance: D-ala changed to D-lac Use: GRAM (+) multidrug resistant *MRSA *Clostridium difficile SE: N.O.T. many problems N = Nephrotoxicity O = Ototoxicity T = Thrombophlebitis + Red man Red man = Diffuse flushing *"Red man VANquished by dz" *Prevented w/antihistamines |
|
Aminoglycosides
|
Bacteriocidal--binds 30s subunit
Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin *GNATS Inhibits formation of initiation complex --> misreading if mRNA Synergistic w/B-lactams, but DON'T take w/cephalosporins Use: Severe GNR infections *Bowel surgery = Neomycin *Requires O2 for uptake: ineffective against anaerobes SE: "Mean GNATS can NOT kill anerobes" *N = Nephrotoxicity (esp. w/cephalosporins) *O = Ototoxicity (esp. w/loop diuretics *T = Teratogen |
|
Tetracyclines
|
Tetracyclines--bacteriostatic
The CYCLINES: Tetracycline, doxycycline, demeclocycline, minocycline 30S binder Blocks subsequent tRNA binding after Met *Limited CNS penetration: doesn't affect the "tet" *Doxycycline--OK w/renal failure *Dimeclocycline--SIADH (ADH antagonist) *Absorption VERY susceptible to Ca2+, Fe2+ in stomach Uses: VACUUMS THe Bed Room *Vibrio cholerae *A = Acne *Chlamydia *Ureaplasma *Urealyticus *Mycoplasma *S = SIADH (Dimeclocycline) *Tularemia (francisella) *H. Pylori *Borellia burdorferi *Rickettsia Tox: *Contraindicated in pregnancy *GI distress *Photosensitivity *Discoloration of teeth *Inhibits bone growth in children |
|
Macrolides
|
THROMYCINs (remember that aminoglycosudes have "mycins")
*Erythromycin *Azithromyin *Clarithromycin Bacteriostatic Binds to 50s subunit and blocks translocation *Macrolides = NO SLIDES Use: Gram (+) cocci + MLCN it (Milkin it) *Mycoplasma *Legionella --> Fac intracellular *Chlamydia --> Ob intracellular *Neisseria --> Fac intracellular SE: "No slide" = Friction = IRRITATION *Eosinophilia and rashes *GI DISCOMFORT (#1 noncompliance) *Acute CHOLESTATIC hepatitis --> Theophyllines, Anticoagulants higher |
|
Chloramphenicol
|
Bacteriostatic
Binds to 50s subunit and blocks PEPTIDYLTRANSFERASE Uses: MENINGITIS, including HIB *Conservative (toxicity) *HIB, S. Pneumo, Neisseria SE: 1. CLORAMPHENICOL CLEANS OUT the marrow: *Dose-dependent anemia *Dose-independent aplastic anemia 2. GRAY BABY (chrome) *Premature infants lack UDP-glucuronyl transferase |
|
Clindamycin
|
Bacteriostatic
Binds to 50S subunit and blocks peptide bond Uses: CLINDA in the CLOUDS (treats inf above diaphragm), but no AIR (anaerobes) *Actinomyces *Bacteriodes *Clostridium SE: Treats above the diaphragm, but SE are below *Pseudomembranous colitis *Fever |
|
Sulfonamides
|
Bacteriostatic
Sulfamethoxasole, sulfisoxazole, triple sulfas, sulfadiazine Inhibits (folate) nucleotide synthesis: DihydroPTEROATE SYNTHETASE Uses: Simple UTI *HUGE RANGE (gram +/-) *Norcardia *Chlamydia SE: *Hypersensitivity reactions *Tubulointerstitial nephritis *Photosensitivity *HEMOLYSIS w/G6PD *KERNICTERUS (infants) *Interactions w/warfarin (albumin) |
|
Trimethoprim
|
Basteriostatic
Inhibits (folate) nucleotide synthesis: DihydroFOLATE REDUCTASE Uses: Recurrent UTI + Super Serious Problems (SSP) *Shigella *Salmonella *Pneumocystis jirovecii pneumonia SE: TMP =TREATS MARROW POORLY *Megaloblastic anemia *Leukopenia *Granulocytopenia Try supplemental folinic acid |
|
Sulfa drug allergies
|
Celecoxib--Cox 2 inhibitor
Sulfonamides --Broad spectrum antibiotic Sulfasalazine (5-ASA) -- IBD Sulfonylureas -- Induce Beta cell insulin release in DM II (K+ channel) Thiazide diuretics -- BP, urine Ca2+ loss, nephrogenic DI Loop diuretics Acetazolamide -- Glaucoma, altitude sickness, uric acid stones |
|
Flurodoquinolones
|
Bactericidal
The FLOXACINS + nalidixic acid (quinolone) Inhibits DNA topoisomerase II *Must not be taken w/antacids Use: GNRs, Neisseria SE: QUINOLONES hurt attachments to BONES *Adults = tendonitis, rupture *Children = leg cramps, myalgias *Pregnancy = cartilage damage Superinfection GI upset --> DON'T take antacid! Skin rash Headache, dizziness |
|
Metronidiazole
|
Bactericidal
Forms toxic metabolites--damage bacterial DNA Uses: GET GAP on the Metro, not trashed! GET = Protozans G = Giardia E = Entamoeba T = Trichomonas GAP = Bacteria G = Gardnerella A = Anaerobe (Acti, Bacteri, Clostridi) P = H. Pylori Part of "make tummy better" *Metronidiazole or PPI *Tetracycline (or amOxicillin) *Bismuth SE: *Disulfram-like reaction *Metallic taste (metro~metal) |
|
Polymixins
|
Polymixin B and E
Cationic, basic proteins that act like detergent POSITIVE MOLECULES that kill GRAM NEGATIVE bacteria SE: NRTN (norton) *Neurotoxicity *Renal tubular necrosis (RTN) |
|
TB drugs
|
INH-SPIRE
Ethambutol = ETHICAL, but the world may not look as BUTIFUL *No hepatotoxicity *Red-green color blindness All others = Hepatotoxicity INH: PROPHYLAXIS and treatment *INH ~ injures neurons + hepatocytes Streptomycin (aminoglycoside) *NOT: Neurotoxicity, Ototoxicity, Teratogen Pyrizinamide Rifampin--treats all mycobacteria *Rapid resistance if used alone Ethambutol *Red-green color blindness |
|
INH
|
soniazid
Decreases synthesis of mycolic acids Uses: TB treatment + prophylaxis INH ~ injures NEURONS + HEPATOCYTES *Prevent neurotoxicity w/B6 *Highly variable t1/2 (acetylation) Anion gap metabolic acidosis G6PD hemolysis SLE-like syndrome |
|
Rifampin
|
Inhibits DNA-dependent RNA polymerase
4R's: *RNA polymerase inhibitor *RAPID resistance if used alone *REVS up p-450 (minor hepatotox) *RED/orange body fluids Uses: Always in combo (rapid resistance) 1. All mycobacteria (TB, leprosy, MA-I) 2. Meningitis prophylaxis: Neisseria, HIB SE: *REVS up p-450 (minor hepatotox) *Red/orange body fluids |
|
Most common form of resistance to macrolides
|
Methylation
|
|
Most common form of resistance to tetracyclines
|
Transport
Increased removal or decreased uptake |
|
Drug of choice for meningococcal prophylaxis
|
Rifampin
|
|
Drug of choice for gonorrhea prophylaxis
|
Ceftriaxone
Don't even TRI |
|
Drug of choice for prevention of recurrent UTIs
|
TMP-SMX
|
|
Drug of choice for Pneumocystis jirovecii prophylaxis
|
TMP-SMX
|
|
Drugs of choice for VRE
|
Very pristine striped linoleum
*Very = VRE *Pristine = Pristins *Striped = Streptogramins *Linoleum = Linezolid Linezolid Streptogramins (PRISTINS) |
|
Amphotericin B
|
AmphoTERicin TEARs holes:
*Binds ERGOSTEROL (unique to fungi) *Forms a membrane PORE Does not cross BBB Uses: *Systemic mycoses, Candida, Crypto *ASPERGILLIS, MUCOR *Give intrathecally for meningitis Liposomal amphotericin reduces toxicity SE: "Amphoterrible" *SHAKE and BAKE (fever, chills) *Nephrotoxicity: Reduce w/H2O *Hypotension, phlebitis *ANEMIA, arrhythmia |
|
Nystatin
|
*Binds ERGOSTEROL (unique to fungi)
*Forms a membrane PORE Too toxic for systemic use Uses: Topical candida *Oral candidiasis (swish and swallow) *Diaper rash *Vaginal candidiasis |
|
Azoles
|
AZOLES
Inhibit fungal ergosterol SYNTHESIS Uses: Doesn't get aspergillus, mucor *Fluconazole: Candida + Cryptococcal meningitis in AIDS patients (crosses BBB) *CloTRIMazole, MIconazole: Topical *Ketoconazole: Systemic mycoses, candida SE: *Also SHAKE and BAKE (like ampho) *DESMOLASE inhibition (Cholesterol --> Pregnenolone); gynecomastia *Inhibits p-450 |
|
Flucytosine
|
Inhibits fungal DNA synthesis by conversion to FLUOROURACIL
*Competes w/uracil Uses: Add-on to amphotericin B SE: *Bone marrow suppression (w/AmphoB = 2 hits toward anemia) *N/V/D |
|
Caspofungin
|
Inhibits cell wall synthesis
ASPERGILLUS SE: GI upset, FLUSHING (not like casper) |
|
Turbinafine
|
"Squealing turbine"
Inhibits SQUALENE EPOXIDASE DERMATOPHYTES Esp. Onychomycosis (toe fungus |
|
Griseofulvin
|
Interferes w/microtubule function
"GREASY NAILS": Deposits in keratin-containing tissues Use: Oral treatment of superficial infections *Tinea, ringworm, etc. SE: *CARCINOGEN *Teratogen *P-450, warfarin metabolism stimulator *Confusion, headaches |
|
Amantidine
|
Influenza A drug
90% resistance |
|
Zanamivir, Oseltamivir
|
Inhibit influenza NEURAMINIDASE
*Both influenza A and B Decreases RELEASE of progeny virus Mivir ~ Come here (don't go out) |
|
Ribavirin
|
Inhibits IMP DEHYDROGENASE
*Guanine synthesis ~ GIMP Uses: RSV, Chronic HCV SE: Hemolytic anemia Severe teratogen Before birth --> Teratogen After birth --> Cure RSV, but may lower RBCs |
|
Acyclovir, Famciclovir
|
Needs to be phosphorlyated by HSV/VZV THYMIDINE KINASE
*No thymidine kinase ~ resistance Inhibits viral DNA polymerase by chain termination Not effective on latent forms Acyclovir: EBV, HSV (lesions, encephalitis) Famiciclovir: VZV SE: Well tolerated |
|
Ganciclovir
|
Needs to be phosphorlyated by CMV VIRAL KINASE (or HSV/VZV thymidine kinase)
Inhibits viral DNA polymerase Uses: CMV (esp. w/transplant) SE: Worse than acyclovir, famciclovir *Bone marrow suppression *Renal toxicity |
|
Foscarnet
|
VIRAL DNA POLYMERASE inhibitor that does NOT require phosphorylation (acyclovir, famciclovir, and gancyclovir all do)
PyroFOSphate analog: Binds to the pyrophosphate binding site of VIRAL DNA POLYMERASE Uses: BACKUP *CMV retinitis when Gancyclovir fails *Acyclovir-resistant HSV SE: NeFron --> Renal toxicity |
|
HIV therapy types (3)
|
Protease inhibitors
*Prevents assembly of a new virus Reverse transcriptase inhibitors *Nucleosides *Non-nucleosides Fusion inhibitors (Enfuvirtide) *Bind GP41--block fusion w/CD4 |
|
Protease inhibitors
|
HIV treatment
"NAVIRs" --> NAVIR TEASE a proTEASE Inhibit assembly of a new virus SE: GILTY *GI intolerance *Lipodystrophy *Thrombocytopenia (indinavir) *hYperglYcemia Use: HAART therapy (RTI + PI) *CD4 < 500 *High viral load |
|
Reverse transcriptase inhibitors
|
HIV treatment
Inhibit reverse transcriptase Prevent viral incorporation into genome Nucleosides: Lactic acidosis *Competitive inhibitors of RT Zidovudine (ZDV a.k.a. AZT) *Pregnancy prophylaxis *Megaloblastic anemia Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) Lamivudine (3TC) Abacavir Non-nucleosides: Rash **Never Ever Deliver nucleosides** *NON-competitive inhibitors of RT *Nevirapine *Efavirenz *Delavirdine Use: HAART therapy (RTI + PI) *CD4 < 500 *High viral load SE: *Bone marrow suppression *Peripheral neuropathy |
|
Fusion inhibitors
|
HIV therapy
**EnFUvirtide** Bind viral gp41 to prevent fusion w/CD4 Use: 2nd line--persistent viral replication despite anti-retroviral therapy SE: *Hypersensitivity *Bacterial pneumonia |
|
Lymph node structure
|
Secondary lymphoid organ
*Many afferents (enter cortex) *1+ efferent (exits by artery, vein) **BTMP** (Cortex to medulla) Cortex: B cells *Primary follicles are dense, dormant *Secondary follicles (active) have pale germinal centers Paracortex: T-cells and HEVs *HEV: Where B and T cells enter from blood *Not well-developed w/DiGeorge Medulla: Medullary cords and sinuses *Cords = Plasmas, lymphocytes *Sinuses = Macrophages, reticular cells Macrophages ~ Mobile (sinuses) |
|
Stomach lymphatic drainage site
|
Celiac nodes
Cecelia, you're breakin my STOMAC |
|
Duodenum, jejunum lymphatic drainage site
|
Superior mesenteric nodes
DJ = Tallest (superior) sister |
|
Sigmoid, rectum and anal canal lymphatic drainage
|
Signmoid: Colic nodes --> Inferior mesenteric nodes
Sigmoid says there's an INFERIORITY complex behind the COLIC Rectum and upper anal canal (above pectinate line): Internal iliac nodes Lower anal canal: Superficial inguinal nodes |
|
Scrotum, superficial thigh and lower anal canal lymphatic drainage
|
Superficial inguinal nodes
|
|
Lateral dorsum of foot lymphatic drainage site
|
Popliteal nodes
|
|
Right lymphatic duct drainage
|
Right arm
Right half of head |
|
Thoracic duct drainage
|
Everything except what right lymphatic duct drains (right arm, right half of head)
|
|
Primary and secondary lymphoid organs
|
Primary: Lymphoid organs that develop early immune cells
Bone marrow Thymus Secondary: Lymphoid organs that house mature immune cells Lymph nodes --> Encapsulated Spleen --> Encapsulated MALT, GALT --> Unencapsulated |
|
Spleen structure
|
MBTA (Outside to inside)
MACROS, APCs, T cells--red pulp B cells (Follicles)--white pulp T cells (PALS) Central arteriole Red pulp: *Vascular channels w/fenestrated BM ("BARREL HOOP") *Macrophages (remove encapsulated bacteria) PALS = Periarterial lymphatic sheath Arises from dorsal mesentary but fed by branches of the celiac artery (splenic a) |
|
"Barrel hoop" basement membrane
|
Red pulp of the spleen
|
|
Thymus
|
3rd branchial pouch origin
Encapsulated Cortex = Immature T cells Corticomedullary junction *Positive selection (MHC restriction) *Negative selection (nonreactive to self) Medulla = Mature T cells (pale) *Epithelial reticular cells *HASSALL'S CORPUSCLES (granular cell center, concentric epithelial layers) |
|
Differentiation of T cells
|
After creation in marrow DIRECTLY to thymus
*No receptors or other defining features Thymus: 1. CD4+ CD8+ 2. CD4+ OR CD8+ (cytotoxic) 3. CD4+ T cells further differentiate: *IL-12 --> TH1 *IL-4 --> TH2 |
|
TH1 cells
|
Differentiation induced by IL-12
*Origin: B cells and macrophages Secretes: IL-2 *Stimulates CD8 cells *Autostimulation IFN-gamma *Stimulates MACROS Inhibits TH2 cells via: IFN-gamma |
|
TH2 cells
|
Differentiation induced by IL-4
*Origin: Other TH2 cells Secretes: IL-4 *Activates B cells *Induces class switching to IgE > IgG IL-5 *Promotes differentiation of B cells *Induces class switching to IgA *Stimulates eosinophils (production, activation) Inhibited by: IFN-gamma EOSINOPHIL STIMULATION AND IGE CLASS SWITCHING ARE NOT PART OF THE SAME IL FUNCTION |
|
What cells control TH1 differentiation?
|
B cells and macrophages (secrete IL-12)
|
|
What cells control TH2 differentiation?
|
TH2 cells
|
|
MHC-1
|
Encoded by 3 genes:
HLA-A HLA-B HLA-C Expressed on almost all nucleated cells Reflects material from RER *Mostly intracellular MEDIATES VIRAL IMMUNITY Pairs w/B2 MICROGLOBULIN to form complete receptor |
|
MHC-II
|
Encoded by 3 genes:
HLA-DP HLA-DQ HLA-DR Expressed only on APCs *B cells *Macrophages *Dendritic cells Reflects material from acidified endosome *Extracellular material Receptor has alpha and beta subunits *Roughly equal in size |
|
Immune cells and hypersensitivity
|
Type 1 = IgE (B cells)
Type 2 = IgG (B cells) Type 3 = IgG (B cells) Type 4 = CD8 T cells |
|
APCs
|
My BaD (MBD)
Macrophages B cells Dendritic cells Have MHC II complexes Bind to CD4 T cells |
|
CD4 T cells: Costimulatory signa
|
After binding to MHC II...
CD28 on CD4 cell + B7 on B cell (or other APC) (7 x 4 = 28) |
|
CD8 T cells: Costimulatory signal
|
After binding to MHC 1...
Cytotoxic T cell needs IL-2 from a TH1 helper cell |
|
Antibody structure
|
2 light chains + 2 heavy chains
*Each have variable (antigen-recognizing) and constant regions *Each have inter-chain and intra-chain disulfide bonds Fab = Upper half *Binds antigen *Amino end Fc = Lower half *Completely constant (vs. partially) *Carboxy terminal *COMPLEMENT binding (IgG + IgM only) *Carbohydrate chains |
|
Antibody diversity
|
Recombination of VJ (light chain) or VDJ (heavy chains) genes
*Addition of nucleotides occurs via terminal DEOXYNUCLEOTIDYL TRANSFERASE Random combination of established heavy and light chains Somatic hypermutation (post-antigen recognition) |
|
Isotype switching is mediated by...
|
Cytokines
CD40 ligand *Midlife crisis? |
|
Complement binding Abs
|
IgG
IgM Driving a GM gets you COMPLEMENTS? |
|
Mature B cells originally express what Abs?
|
IgM
IgD |
|
IgG
|
Crosses the placenta (UNIQUE)
Fixes complement (IgG + IgM only) Promotes opsonization Neutralizes bacterial toxins and viruses |
|
IgA
|
Monomer or dimer found in secretions
Prevents attachment of bacteria/viruses to mucous membranes Picks up SECRETORY COMPONENT from epithelial cells before secre |
|
IgM
|
Monomer on B cell
Pentamer in serum Produced in the PRIMARY response to an antigen (IgG later) Fixes complement (IgG + IgM only) |
|
IgD
|
Unclear function
Found on surface of many B cells and in serum |
|
IgE
|
Lowest concentration in serum
1. Activates mast cells and basophils (induces mediator release) *Type 1 hypersensitivity reactions 2. Activates eosinophils during parasitic infection |
|
Ig Allotype
|
POLYMORPHISM
Immunoglobin epitope that differs among members of the same species Constant regions of light chains or heavy chains |
|
Ig Isotype
|
Immunoglobin epitope that is common to a class
IgA, IgM, IgG, etc. Determined by heavy chain |
|
Ig Idiotype
|
Determined by VARIABLE REGION
Immunoglobin epitope determined by antigen binding site |
|
Cytokines released by macrophages
|
IL-1
IL-6 (also TH cells) IL-8 IL-12 (also B cells) TNF |
|
Cytokines secreted by B cells
|
IL-12 (also macrophages)
|
|
Cytokines secreted by regulatory T cells
|
IL-10
|
|
Cytokine released by both cytotoxic and helper T cells
|
IL-3
|
|
Cytokine released by all helper T cells
|
IL-6 (also macrophages)
|
|
IL-1
|
Secreted by macrophages
*Possibly in response to techoic acid or LPS ACUTE INFLAMMATION *Induces chemokines --> WBC taxis *Induces endothelium to express adhesion molecules |
|
TNF
|
Secreted by macrophages
*Possibly in response to techoic acid or LPS Mediates SEPTIC SHOCK *WBC recruitment *Vascular leak |
|
IL-2
|
Secreted by TH1 cells
Stimulates growth of CD8 and TH1 cells |
|
IL-3
|
Secreted by activated T cells
Supports growth and differentiation of BONE MARROW |
|
IL-4
|
Secreted by TH2 cells
Promotes B cells Class switching to IgE, IgG *IgE > IgG |
|
IL-5
|
Secreted by TH2 cells
Promotes B cells Class switching to IgA Promotes Eosinophils |
|
IL-6
|
Secreted by TH cells and macrophages
Stimulates acute-phase reactants and immunoglobins Anemia of chronic disease: IL-6 increases liver production of Hepcidin *Hepcidin stops ferroportin from releasing iron stores |
|
IL-8
|
Secreted by macrophages
Neutrophil recruitment "Clean-up on aisle 8" *Neutrophils recruited by IL-8 to clear infections |
|
IL-10
|
Secreted by regulatory T cells
Inhibits all other T cells |
|
IL-12
|
Secreted by B cells and macrophages
Activates TH1 cells Activates NK cells |
|
IFN-gamma
|
Secreted by TH1 cells
Activates macrophages |
|
Helper T cell surface proteins
|
TCR/CD3 --> T cell
CD4 --> HELPER T cell *Binds to MHC II CD28 --> HELPER T cell *Costimulatory signal CD40L --> HELPER T cell *General APC activation *B cell class switching |
|
CD8 cell surface proteins
|
TCR/CD3 --> T cell
CD8 --> Cytotoxic T cell |
|
B cell surface proteins
|
Unique:
IgM CD 19-21 Others are in common w/macrophage: MHC II *APC B7: Costimulatory signal CD40 *Class switching |
|
Macrophage surface proteins
|
Unique:
CD14 Receptors for Fc and 3b Others are in common w/B cell: MHC II *APC B7: Costimulatory signal CD40 *Activation by TH cell |
|
NK cell surface proteins
|
Unique:
CD16 CD56 MHC I |
|
Opsonins in bacterial defense
|
IgG
C3b THAT'S IT |
|
Decay accelerating factor
|
Deficiency leads to complement-mediated lysis of RBCs
Paroxysmal nocturnal hemoglobinuria (PNH) Paroxysmal ~ I don't get it *Are you DAFt? |
|
C1 esterase
|
Inhibitor of complement activation
Protects self cells along w/DAF Deficiency causees HEREDITARY ANGIOEDEMA *Aunt ESTER and ANGIE in the HEREDITARY tree |
|
Anaphylaxins
|
C3a, C5a
C5a also participates in neutrophil chemotaxis |
|
Neutrophil chemotaxis
|
IL-8 (macrophages)
C5a (complement) |
|
C3 deficiency
|
Severe, recurrent pyogenic sinus and respiratory tract infections
|
|
Deficiency of C6-8
|
Neisseria bacteremia
6-8 is never a NICE time to call |
|
C5b-9
|
MAC
Responsible for complement-induced lysis |
|
C1-4
|
Responsible for viral neutralzation
|
|
Classic complement pathway
|
C1 binds to Ag-Ab complex (IgG or IgM)
C1-C4b-C2a-3b-5b-6789 The only #out of place is 4 The only "a" is w/complement #2 *"B usually STAYS; A usually floats AWAY" The point where 3b attaches is where opsonization (viral neutralization) can occur |
|
Lectin complement pathway
|
Lectin binds to mannose on pathogen
Lectin-4b-2a-3b-5b-6789 |
|
Alternative complement pathway
|
C3 w/B and D bind to endotoxin or other part of microbial surface
C3b-Bb-C3b-5b-6789 DOUBLE C3b |
|
Interferons
|
Put uninfected cells in an antiviral state
Induce ribonuclease that degrades viral mRNA Increase activity of NK cells Gamma interferon: Increase all MHC I, II expression and antigen presentation Alpha: Alpha BC, KLM *Hep B/C *Kaposi's *Leukemia *Malignant melanoma Beta: Multiple sclerosis Gamma: NADPH oxidase deficiency (Chronic Granulomatous Disease) Inferferon SE = NEUTROPENIA |
|
Passive immunity
|
Preformed Abs given after exposure to:
Tetanus toxin Botulinum HBV Rabies "TO BE HEALED RAPIDLY |
|
Type 1 Hypersensitivity: Examples
|
AAA:
Anaphylaxis Atopy Allergic rhinitis |
|
Type 2 Hypersensitivity
|
Cy-2-toxic
IgM, IgG bind to fixed antigen on "enemy" cell --> Complement-mediated lysis or phagocytosis Vascular: *Hemolytic anemia *Idiopathic thrombocytopenic purpura *Erythroblastosis fetalis Heart: Rheumatic fever Kidney, Lung: Goodpasture's Skin: Bullous Pemphigoid (BM) Thyroid: Grave's disease NMJ: Myasthenia gravis |
|
Type 3 Hypersensitivity
|
Immune complex mediated
*Immediately attracts COMPLEMENT, which attracts NEUTROPHILS SHARPPS SLE Hypersensitivity pneumonitis Arthus reaction: Local, subacute *Intradermal injection of Ag Rheumatoid arthritis Post-streptococcal glomerulonephritis Polyarteritis nodosa Serum sickness: Abs form in 5 days *Usually caused by drugs *IC's deposited systemically |
|
Type 4 Hypersensitivity
|
Sensitized T cells encounter antigen, activate macrophages
Examples: 5 T's TB (PPD test) Thyroid (Hashimoto) Touching (Contact dermatitis) Transplants (Graft vs. host) Type 1 diabetes + MSG: MS + Guillain Barre |
|
Bruton's agammaglobulinemia
|
X-linked recessive
Defect in a tyrosine kinase gene **Low B cells** **Low levels of all Abs** Infections after 6 months of age (maternal IgG declines) |
|
Thymic aplasia
|
Feature of DiGeorge syndrome (22q11)
THC: T = Thymus --3rd pharyngeal pouch *Viral and fungal infections H = Hypocalcemia *Parathyroids --3rd (inf) and 4th (sup) pouch C = Cardiac defects *Tetralogy *Truncus arteriosus |
|
SCID
|
Low B cells and T cells
Defect in stem-cell differentiation due to one of several causes *MHC II presentation defect *Defective IL-2 receptors *Adenosine deaminase deficiency (Purine pathway--toxic accumulations kill lymphocytes) Recurrent infection of all kinds (bacterial, viral, fungal, protozoal, etc) |
|
IL-12 receptor deficiency
|
Diminished TH1
DISSEMINATED MYCOBACTERIAL INFECTION |
|
Hyper IgM syndrome
|
Defect in CD40 ligand (CD4 T helper cells)
*No CD40-CD40L binding =inability to class switch *B cells make only IgM Severe PYOGENIC infections early in life |
|
Wiskott-Aldrich syndrome
|
X-linked recessive
Inability to mount an IgM response to capsular polysaccharides *Low IgM *High IgA Wiscott = WIPE *W= Wiscott *I = Infections (pyogenic) *P =Purpura (thrombocytopenic) *E = Eczema Aldrich = IgA (very high) |
|
Job's syndrome
|
Failure if IFN-gamma production by TH1 cells
*Responsible for stimulating macrophages Poor macrophage function --> Low IL-8 --> Poor neutrophil response FATED: F = Facies (coarse) A = Abscesses (cold, noninflamed) T = Teeth (retained primary) E = IgE (high) D = Dermatologic prob (eczema |
|
Leukocyte adhesion deficiency
|
LFA-1 integrin defect
Recurrent bacterial infections NO PUS DELAYED SEPARATION OF UMBILICUS LAD: Lots of infections Absent pus Delayed separation of umbilicus |
|
Chediak Higashi diease
|
Autosomal recessive
Defect in microtubular function Poor lysosomal emptying of phagocytic cells Recurrent pyogenic infections *Staph, strep Partial ALBINISM (pigment release) Peripheral NEUROPATHY (axonal transport) |
|
Chronic granulomatous disease
|
Lack of NADPH oxidase (or similar enzymes) --> Defect in phagocytosis
Marked susceptibility to opportunistic infection *S. aureus *E. coli *Aspergillus Diagnosis = Negative TETRAZOLIUM dye reduction test Treatment: Gamma interferon |
|
Chronic mucocutaneous candidiasis
|
T cell dysfunction against CANDIDA
Skin and mucous membrane candida infections |
|
Selective Immunoglobin Deficiency
|
Deficiency in a specific Ig class
IgA most common *Sinus and lung infections *Milk allergies *Diarrhea *DEATH POSSIBLE W/TRANSFUSION |
|
Ataxia-telangiectasia
|
DNA repair enzymes defect
**Associated w/IgA deficiency** Ataxia (cerebellar) Telangiectasia (spider angiomas) |
|
Common variable immunodeficiency
|
B cells don't MATURE into plasma cells
*Normal B cell #s *Low plasma cells and Igs Can be acquired in 20s-30s |
|
Cyclosporine
|
Immunosuppressant
Binds to cyclophilins --> Inhibits CALCINEURIN --> IL-2 inhibition Use: TRANSPLANTS Viral infection Lymphoma Nephrotoxicity --> Prevent w/MANNITOL |
|
Tacrolimus
|
Immunosuppressant
Similar to cyclosporine (IL-2 inhibition) *Binds to FK-BINDING PROTEIN rather than calcineurin Use: TRANSPLANTS SE: Significant Nephrotoxicity Peripheral neuropathy HTN, pleural effusion Hyperglycemia No lymphoma risk like cyclosoprine, but the nephrotox isn't preventable w/mannitol |
|
Azathioprine
|
Anti-metabolite precursor of 6 mercaptopurine
*Interferes w/purine metabolism *Toxic to lymphocytes *ALLOPURINOL PROLONGS (does the same thing to 6-MP, which treats all leukemia except CLL and all lymphoma except Hodgkins) Uses: Kidney transplantation Glomerulonephritis Hemolytic anemia SE: Marrow suppression |
|
Muromonab
|
A.k.a. OKT3
CD3 antibody Blocks T cell signal transduction Uses: Kidney transplantation SE: Cytokine release syndrome Hypersensitivity |
|
Sirolimus
|
a.k.a. Rapamycin
Binds to mTOR Inhibits T cell prolif in RESPONSE to IL-2 *IL-2 is calling, but T cells not there for ROL call Use: Kidney transplantation SE: *"Rolls" --> Hyperlipidemia *Thrombocytopenia, leukopenia |
|
Mycophenolate mofetil
|
GUANa tell the story of Ms. Mofet?
Inhibits guanine synthesis Block lymphocyte production |
|
Daclizumab
|
IL-2 receptor antibody
|
|
Filgrastim
|
G-CSF
Used for BM recovery |
|
Sargramostin
|
GM-CSF
Used for BM recovery |
|
Oprelvekin
|
a.k.a. IL-11
Thrombocytopenia |
|
Aldesleukin
|
IL-2 activator
Metastatic renal cell carcinoma Metastatic melanoma |
|
Hyperacute rejection
|
Pre-formed ANTIBODIES in the transplant recipient
Occurs within minutes |
|
Acute rejection
|
Occurs weeks after transplantation
Cytotoxic T CELLS react against foreign MHCs REVERSIBLE w/cyclosporine, OKT3, etc. |
|
Chronic rejection
|
Occurs within months to years
ANTIBODY mediated vascular damage --> Fibrinoid necrosis IRREVERSIBLE |
|
Graft vs. host disease
|
Transplanted T cells attack the host
Maculopapular rash Jaundice, hepatomegaly Diarrhea |
|
Types of necrosis
|
*Coagulative (Heart, liver, kidney)--tons of blood in all of these organs
*Liquifactive (Brain) *Caseous (TB) *Fat (pancreas) *Fibrinoid (blood vessels) *Gangrenous (limbs, GI) |
|
Caspases mediate...
|
Apoptosis
|
|
Irreversible cell injuries
|
CMPLN --> Complain
Ca2+ influx Mitochondrial permeability Plasma membrane damage Lysosomal rupture Nuclear changes (pyknosis, karyolysis, karyorrhexis) |
|
Granulomas
|
May feature granulomas = Nodular collections of epithelioid MACROPHAGES and GIANT CELLS
STBL CSF --> STaBLe CSF Syphilis TB Bartonella Leprosy Crohn's disease Sarcoidosis Fungal pneumonias (some) |
|
Leukocyte activation
|
LEUKOCYTE FACTORS HAVE CAPITAL L IN THEM
Emigration: 1. Rolling *Endothelial E-selectin, P selectin *Sialyl Lewis-X on leukocyte 2. Binding *Endothelial ICAM-1 *Leukocyte LFA-1 (Integrin) 3. Diapedesis: Exits blood vessel 4. Migration/Chemotaxis |
|
Granulation tissue
|
Highly vascularized
Fibrotic |
|
Abscess
|
Fibrosis surrounding pus
|
|
Fistula
|
Abnormal communication
|
|
Scarring
|
Collagen deposition resulting in an altered structure and function
|
|
Transudate
|
TRANSFORMED from source composition
Due to: *Increased hydrostatic P *Increased oncotic P *Na+ retention Hypocellular Protein poor --> SG <1.012 |
|
Exudate
|
Merely EXITS the source
Due to: *Lymphatic obstruction *Inflammation Cellular Protein rich --> SG >1.020 |
|
Amyloidosis
|
All cause apple-green birefringence of Congo red stain under polarized light
Secondary (AA) *AA = Acute phase reactant *From serum amyloid-associated protein (SAA) *Seen w/chronic inflammatory disease Medullary thyroid carcinoma (A-CAL) *CAL = Calcitonin DM Type 2 (AE) *E = Endocrine *Derived from Amylin Senile cardiac (AF) *F =Fogies (familial) *Derived from transthyretin Primary (AL) *L = Light chain (Bence-Jones) *Light chains derived from IgG *Seen w/multiple myeloma (bone lesions) Alzheimer's disease (APP) *APP= Amyloid precursor protiein *Derived from B-amyloid Dialysis-associated (B2-microglobulin) *Derived from MHC-I |
|
Dysplasia
|
Abnormal proliferation of cells w/loss of size, shape and orientation
Often pre-neoplastic |
|
In situ carcinoma
|
Monoclonal neoplastic cells encompass entire thickness, but do not invade BM
High nuclear/cytoplasmic ratio Clumped chromatin |
|
Tumor invasion enzymes
|
Collagenases
Hydrolases |
|
Reversible plasias
|
Hyperplasia (number)
Dysplasia (size, shape, orientation) Metaplasia (tissue type) |
|
Irreversible plasias
|
Anaplasia (lack differentiation)
Neoplasia ("uncontrolled and excessive" proliferation) Desmoplasia (Fibrous tissue formation in response to neoplasm) |
|
Tumor grade
|
Degree of cellular DIFFERENTIATION
Based on histologic appearance of tumor Usually graded I-IV based on: *Degree of differentiation *# of mitoses per HPF LESS PROGNOSTIC than tumor stage |
|
Tumor stage
|
Degree of spread
TNM description Based on: *Site and size of primary tumor *Spread to lymph nodes *Presence of distant mets MORE PROGNOSTIC than grade |
|
Epithelial neoplasms: Nomenclature
|
Benign --> Malignant
Adenoma --> Adenocarcinoma Papilloma --> Papillary carcinoma |
|
Multi-cell type neoplasms
|
Benign = Mature teratoma (women)
Malignant: *Immature teratoma *Mature teratoma (men) |
|
Skeletal muscle neoplasms
|
Benign = Rhabdomyoma
Malignant =Rhabdomyosarcoma *Most common soft tissue tumor of childhood |
|
Malignancies associated w/Down synrome
|
ALL
AML |
|
Malignancies associated w/Xeroderma pigmentosum and albinism
|
#1 Squamous cell carcinoma
Others: *Melanoma *Basal cell carcinoma |
|
Malignancies associated w/atrophic gastritis
|
Gastric adenocarcinoma
|
|
Malignancies associated w/pernicious anemia
|
Gastric adenocarcinoma
|
|
Malignancies associated w/postsurgical gastric remnants
|
Gastric adenocarcinoma
|
|
Barrett's Esophagus
|
Associated w/esophageal carcinoma
Stratified (esophagus) --> Columnar (stomach) epithelium due to acid exposure BARR = Becomes Adenocarcinoma, Results from Reflux |
|
Malignancies associated w/Plummer-Vinson syndrome
|
Squamous cell carcinoma of the esophagus
P-V: *Glossitis (atrophic) *Iron deficiency anemia *Esophageal webs |
|
Malignancies associated w/ulcerative colitis
|
Colonic adenocarcinoma
|
|
Malignancies associated w/Paget's disease of bone
|
Osteosarcoma and fibrosarcoma
|
|
Malignancies associated w/Immunodeficiency states
|
Malignant lymphomas
|
|
Malignancies associated w/autoimmune diseases (Hashimoto's thyroiditis, myasthenia gravis)
|
Lymphomas
|
|
Malignancies associated w/Acanthosis nigricans
|
= Hyperplasia of stratum spinosum
Visceral malignancy, esp. stomach cancer Acanthosis nigricans = Hyperpigmentation and epidermal thickening (stratum spinosum) |
|
Malignancies associated w/radiation exposure
|
Sarcoma
|
|
Malignancies associated w/erb-B2
|
B2 ~ 2 breast-related cancers
erb ~ HERB in your stomach Breast carcinoma Ovarian carcinoma GASTRIC carcinoma |
|
Malignancies associated w/ras
|
Colon cancer
RASpberry in the colon |
|
Malignancies associated w/L-myc
|
Lung tumor
|
|
Malignancies associated w/N-myc
|
Neuroblastoma
|
|
Malignancies associated w/ret
|
MEN are RETten
MEN II and III MEN II: The pear (parathyroids) pheals (pheo) good + medullary MEN III: Pheo + mucosal medullary + nodular disease |
|
MEN
|
MEN II and III associated w/ret gene (Autosomal DOMINANT)
MEN 1 (WERMER'S): Pitt (pituitary) the pear (parathyroids) and put it in the pan (pancreas) 1. Parathyroid 2. Pituitary (Prolactinoma) 3. Pancreas (Z-E, Insulinoma, VIPoma) MEN II (SIPPLE'S): The pear (parathyroids) pheals (pheo) good + medullary thyroid CA 1. Parathyroid 2. Pheochromocytoma 3. Medullary Thyroid CA MEN III: Pheo + medullary + mucosal neuromas 1. GI ganglioneuromatosis (mucosal neuromas) 2. Pheochromocytoma 3. Medullary Thyroid CA |
|
Malignancies associated w/c-kit
|
C? KIT gets the GIST of it
Gastrointestinal stromal tumor (GIST) |
|
BRCA mutations
|
TUMOR SUPPRESSORS
BRCA1 = Breast and ovarian cancer *#1 fear (more cancer risk) *Chomosome 17q (same chrom as p53) BRCA 2= Breast cancer *Chromosome 13q (same chrom as Rb) |
|
Malignancies associated w/p16
|
TUMOR SUPPRESSOR
Chromosome 9p Melanoma |
|
Malignancies associated w/WT1
|
TUMOR SUPPRESSOR
Chromosome 11p *111 (WT 1, Chrom 11) Wilm's tumor |
|
Malignancies associated w/DPC
|
TUMOR SUPPRESSOR
Chromosome 18q *Went to the DNC when I was 18 Pancreatic cancer DPC = "Da pancreatic cancer" |
|
Malignancies associated w/DCC
|
TUMOR SUPPRESSOR
Chromosome 18q *Went to the DNC when I was 18 Colon cancer DCC = "Da colon cancer" |
|
Prostate cancer markers
|
PSA
Prostatic acid phosphatase |
|
Elevated CEA
|
Nonspecific
C = Colon (70%) and gastric EA = BrEAst, PancrEAs (70%) |
|
Elevated alpha fetoprotein w/o pregnancy may indicate...
|
Yolk sac tumor
Hepatocellular carcinoma |
|
Elevated B-hCG may indicate...
|
Hydatifrorm moles
Choriocrcinoma Gestational trophoblastic tumors |
|
CA-125 may indicate...
|
Ovarian
Malignant epithelial tumors |
|
S-100 may indicate
|
Brain (neural tumors, astrocytomas)
+ #1 metastasis to brain--Melanoma |
|
Alkaline phosphatase may indicate...
|
Mets to bone
Paget's disease of bone (nl Ca2+, PO4, PTH) Obstructive biliary disease |
|
Bombesin may indicate...
|
When a bomb goes off...
Headache --> NeuroBLASToma Air quality --> Lung Nervous --> Gastric cancer |
|
CA 19-9 may indicate...
|
Pancreatic adenoacarinoma
|
|
Nasopharyngeal carcinoma can be caused by what virus?
|
EBV
|
|
Cervical carcinoma can be caused by what virus?
|
HPV (16, 18)
|
|
Aflatoxins can cause...
|
Hepatocellular carcinoma
|
|
Vinyl chloride can cause...
|
Angiosarcoma of the liver
"Vinyl vessel" |
|
CCl4 can cause...
|
CL ~ CentriLobular necrosis of the liver
Fatty change in the liver |
|
Cigarette smoke can cause...
|
Larynx
Lung Renal cell Transitional cell (bladder, ureters, renal pelvis) |
|
Asbestos can cause...
|
Bronchogenic carcinoma
Mesothelioma |
|
Aresnic can cause...
|
Squamous cell carcinoma
|
|
Aklylating agents can cause...
|
Leukemia
|
|
Napthalene (aniline) dyes can cause..
|
Transitional cell carcinoma (bladder, ureters, renal pelvis)
|
|
Paraneoplastic effects: Small cell lung carcinoma
|
ACTH
ADH Ab's against NMJ Ca2+ channels (presynaptic) *Lambert-Eaton syndrome |
|
Paraneoplastic effects: Intracranial neoplasms
|
ADH
|
|
Paraneoplastic effects: Squamous cell lung carcinoma
|
Hypercalcemia: PTH-related peptide
Or possibly TGF-beta, TNF, IL-1 |
|
Paraneoplastic effects: Renal cell carcinoma
|
EPO
Hypercalcemia due to PTHrP, TGF-beta, TNF, or IL-1 |
|
Paraneoplastic effects: breast carcinoma
|
Hypercalcemia due to PTHrp, TGF-beta, TNF or IL-1
|
|
Paraneoplastic effects: Thymoma
|
Abs against NMJ Ca2+ channels (presynaptic)
a.k.a. Lambert-Eaton syndrome Can also cause Myasthenia |
|
Paraneoplastic effects: Leukemia and lymphoma
|
Hyperuricemia due to cytotoxic therapy --> excess nucleic acid turnover
Gout Urate nephropathy |
|
Most common mets to bone
|
Bone metastases > Primaries
PT(t) Barnum Loves Kids Prostate Testes Thyroid Breast Lung Kidney Most likely: PB (Prostate and breast) Lung lesions = Lytic Prostate = Blastic Breast = Both |
|
Psammoma bodies
|
Laminated, CONCENTRIC, CALCIFIC spherules
PSAMM P = Papillary adenocarcinoma--thyroid SA = Serous papillary cystAdenocarcinoma of the ovary M = Meningioma M = Mesothelioma (malignant) |
|
Cancer epidemiology shortcuts
|
Male:
~1/3 Prostate --> Deaths < 50% *32% --> 13% ~1/6 Lung --> Deaths 2x *16 --> 32 Colon cancer: ~13% for both men and women Women: ~1/3 Breast --> Deaths >50% *32% --> 18% Lung and colon are tied--13% *Lung deaths almost 2x (23%) |
|
Carotid sheath
|
Contains 3 structures (follows VAN rule)
Internal jugular vein Common carotid artery VAGUS nerve |
|
Left coronary artery
|
1. Left anterior descending (LAD)
*MOST LIKELY TO OCCLUDE *Apex *Anterior interventricular septum 2. Circumflex artery *Supplies posterior LV 3. 20%: CFX gives off PD artery *Supplies posterior septum *Supplies inferior LV *In 80%, PD artery comes from RCA |
|
Right coronary artery
|
1. Supplies SA and AV nodes
2. Acute marginal artery *Supplies right ventricle 3. 80%: Posterior descending/IV artery *Supplies posterior septum *Supplies inferior LV "That's a RAP": RCA, Acute marginal, PD/interventricular |
|
Where are septal defects heard?
|
Right heart
Atrial septal defect = Pulmonic Ventricular septal defect = Tricuspid |
|
Cardiac output during exercise: what increases first?
|
STROKE VOLUME
HR increases after prolonged exercise |
|
Factors influencing myocardial O2 demand
|
~CO
HR SV: *Contractility *Afterload *Preload VIA hypertrophic wall tension |
|
Factors influencing stroke volume
|
SV CAP
*Contractility and preload increase SV *Afterload decreases SV 1. Contractility + = High Ca2+ (i), low Na+ (o) - = B1 block, low O2, high Co2, acidosis 2. Afterload ~ MAP *VaZodilators decrease afterload (HydralaZine) 3. Preload ~ ventricular EDV *Venodilators decrease preload (VeNo-Nitroglycerin) |
|
Factors influencing contractility
|
CANa Increase contractility:
High intracellular Ca2+ *Catecholamines (stimulate Ca2+ pump in sarcoplasmic reticulum) Low extracellular Na+ *Digitalis/digoxin blocks Na+ pump, causing higher intracellular Ca2+ Decrease: GAB *Gases (low O2, high CO2) *Acidosis *B1 and Ca2+ channel blockers |
|
Starling curve
|
Force of contration is proportional to INITIAL LENGTH of cardiac muscle fiber
CO vs. Preload/Ventricular EDV |
|
Hydralazine reduces...
|
Afterload
HydralaZine = VaZodilator |
|
Nitroglycerin reduces...
|
Preload
VeNodilator: VeNo-Nitro |
|
Resistance and viscosity
|
ARTERIOLES are the greatest contributor to PVR
R = P/Q (If you don't want R, mind your P's and Q's) R = 8nl/(Pi)(r^4) *n = viscosity (usually ~Hct) Increased viscosity states: *Lots of RBCs: Polycythemia *Fat RBCs: Hereditary spherocytosis *Lots of protein: Multiple myeloma, etc |
|
S1 and S2
|
S1: Mitral and tricuspid valve closure
Loudest at mitral valve (higher P) S2: Aortic and pulmonary valve closure Loudest at L STERNAL BORDER |
|
S3
|
Ken-tuck-y (S1-S2-S3)
Occurs in early diastole *RAPID ventricular filling phase Associated w/increased filling pressures *Dilated ventricle NORMAL FINDING in children |
|
S4
|
Tenn-ess-ee (S4-S1-S2)
Occurs in late diastole *SLOW ventricular filling phase Sound is from atrial kick (high atrial P) *Hypertrophied/stiff ventricle |
|
Jugular venous pulse
|
Occur in alphabetical order
A wave (A is for ATRIA): Atrial contraction C wave (C is for CLOSED): RV contraction Even though flow from RV to jugular vein is blocked, the tricuspid valve BULGES into atrium V wave (V is for VOLUME): Increased atrial P as it fills w/blood |
|
Wide S2 splitting: Cause
|
Splitting w/o inspiration is wide
Splitting w/inspiration is even wider Still A2 P2 PULMONIC STENOSIS |
|
Fixed S2 splitting: Cause
|
Splitting is constant
Still A2 P2 ATRIAL SEPTAL DEFECT (extra volume of inspiration gets evenly dispersed between L and R heart) |
|
Paradoxial S2 splitting:
|
Splitting is P2 A2
Split SHRINKS w/inspiration AORTIC STENOSIS |
|
Mitral/Tricuspid regurg
|
Occurs during systole
Immediate, holosystolic High pitched blowing murmur Mitral regurg *Loudest at apex *Radiates to axilla Tricuspid regurg *Loudest at tricuspid area *Radiates to right sternal border |
|
Ventricular septal defect
|
Occurs during systole
Immediate, holosystolic Harsh sounding murmur Heard best in R heart (tricuspid area) |
|
Aortic stenosis
|
Occurs during systole
Ejection click + Crescendo-decrescendo sound PULSUS PARVUS ET TARDUS--> Pulses weak and late compared to heart sounds |
|
Mitral valve prolapse
|
Occurs during LATE systole
Mid-systolic click + Crescendo sound that stops @S2 Most common valvular lesion |
|
Aortic regurg
|
Occurs during diastole
Immediate High pitched blowing murmur Presents w/wide pulse pressure when chronic |
|
Mitral/Tricuspid stenosis
|
Occurs during diastole
Opening snap + murmur Tricuspid stenosis gets LOUDER w/inspiration |
|
Navigating heart sounds
|
Systole (4), diastole (2) or continuous (1)?
Continuous = PDA *Machine-like murmur Diastole: *Immediate, HP blowing --> Aortic regurg *Opening snap --> Mitral/TC stenosis *Louder during inspriation --> TC stenosis Systole: *Immediate, HP blowing --> Mitral/TC regurg *Immediate, harsh, louder at TC --> VSD *Ejection click, cres/decres --> Aortic stenosis *Mid-systolic click --> MVP |
|
Ventricular action potential
|
Phase 0 = Rapid upstroke
*Voltage-gated Na+ channels open Phase 1=Initial repolarization *Inactivation of voltage-gated Na+ channels *Voltage-gated K+ channels open Phase 2: Plateau *Voltage-gated Ca2+ channels *Balance w/K+ efflux *Ca2+ gated Ca2+ release (SR) Phase 3: Rapid depolarization *Slow voltage-gated K+ channels *Voltage-gated Ca2+ channels close Phase 4: Resting potential *High K+ permeability |
|
Pacemaker action potential
|
Occurs in SA and AV nodes
Phase 0: Upstroke *Voltage gated Ca2+ channels Phase 3: *Inactivation of Ca2+ channels *Voltage-gated K+ channels Phase 4: Slow diastolic depolarization *I-f channel (Na+) *Slope determines heart rate |
|
Electrocardiogram
|
P wave = Atrial depolarization
*Repolarization masked by QRS PR interval = Conduction delay through AV *Includes P wave, ends at QRS *< 200 msec QRS complex: Ventricular depolarization *< 120 msec QT interval: Ventricular contraction *Includes QRS and T wave ST segment: Ventricles depolarized *Isoelectric *From end of QRS to beginning of T wave *Elevation: Pericarditis or transmural MI *Depression: Subendocardial MI T wave: Ventricular repolarization Isoelectric line: After T wave U wave: Hypokalemia, bradycardia, transmural MI |
|
Torsades de Pointes
|
A type of ventricular tachycardia
Shifting SINUSOIDAL waveforms Can progress to ventricular fibrillation Treat w/Mg2+ Risk factors: Long QT 1. Class IA--Na+ (quinidine) antiarrythmics 2. Class III--K+ (sotalol) antiarrythmics 3. Cisapride (5HT4 agonist, a gastroprokinetic agent) |
|
Wolf-Parkinson-White syndrome
|
Wolff, Parkinson and White from Kent (snobby county) to try to BYPASS the rules
Caused by a BUNDLE OF KENT *Accessory conduction pathway *Bypasses AV node Ventricles partially depolarize earlier --> DELTA WAVE on ECG May lead to RE-ENTRY current --> SUPRAVENTRICULAR tachycardia Treatment: Amiodarone |
|
Atrial fibrillation
|
No P waves
Irregularly irregular QRS complexes |
|
Prolonged PR interval
|
1st degree AV block
No dropped QRS complexes |
|
1st degree AV block
|
Asymptomatic
PR interval is prolonged *Normally < 200 msec Repolarization of P wave visible NO DROPPED QRS COMPLEXES |
|
2nd degree AV block type 1: Wenckebach
|
A.k.a. Mobitz type 1
Usually asymptomatic Progressive lengthening of PR interval until a beat is DROPPED |
|
2nd degree AV block type 2
|
Pathologic/Symptomatic
No change in the PR interval (<200 ms) QRS complexes abruptly dropped Often 2 P waves to 1 QRS |
|
3rd degree AV block
|
Atria and ventricles beat independently of one another
Atrial rate > Ventricular rate Treat w/pacemaker |
|
Ventricular fibrillation
|
COMPLETELY ERRATIC RHYTHM
No identifiable waves FATAL arrhythmia w/o CPR, defibrillation |
|
Baroreceptors
|
Aortic arch --> INCREASED BP
*BP will never really be low here *CN X --> Near the heart anyway Carotid sinus --> High or Low BP *CN IX --> In the neck anyway *NINE IN THE NECK |
|
Chemoreceptors
|
Aortic arch and carotid BODY
*High CO2 *Low O2 (< 60 mm Hg) *Low pH Brain chemoreceptors: *CO2 *pH *NOT O2 (can be naturally low in brain) *Responsible for CUSHING RXN |
|
Cushing reaction
|
Inciting event: Increased ICP
Brain Ischemia = Sympathetic activation *Vasoconstriction --> Systemic HTN Peripheral baroreceptors detect HTN and induce bradycardia Result = CUSHING'S TRIAD *HTN (from brain ischemia) *Bradycardia (from periphery) *Resp depression (brainstem hypoperfusion) |
|
Normal heart pressures
|
RA: < 5 mm Hg
RV Diastolic: < 5 mm Systolic: < 25 mm Hg Pulmonary artery Diastolic: < 10 mm Hg Systolic: < 25 mm Hg LA: 12 LV: Diastolic: 10 Systolic: 130 |
|
Hypoxia causes vasoCONSTRICTION in the...
|
Lungs
|
|
Congenital heart disease: Right to Left shunts
|
Causes early cyanosis (blue babies)
Children may squat --> increase PVR (compress femoral arteries), which allows L heart P to approach R heart P --> directs more blood to lungs The 5 T's: 1. Tetralogy of Fallot *Most common *22Q 2. Transposition of great vessels *Maternal diabetes *Not compatible with life unless there is 2nd mutation (VSD, PDA, patent foramen ovale) 3. Truncus arteriosus *22Q 4. Tricuspid atresia 5. Total anomalous pulmonary venous return (TAPVR) |
|
Congenital heart disease: Left to Right shunts
|
Late cyanosis (blue kids) w/clubbing and polycythemia
*Cyanosis only after R--> L transition (Eisenmenger's) Pumping extra fluid into RV --> Increased pulmonary resistance --> ARTERIOLAR THICKENING --> R to L shunt In order of frequency: VSD --> Down ASD --> Down *Fixed split S2 PDA --> Rubella *Close w/indomethacin |
|
Tetralogy of fallot
|
Anterosuperior displacement of the infundibular septum
Cyanotic spells PROVe: Pulmonary artery stenosis *MOST important determinant for prognosis RVH (boot heart) Overriding aorta VSD |
|
Coarctation of the aorta: Infantile
|
INfantile = IN close to the heart
Aortic stenosis is proximal to insertion of ductus arteriosus |
|
Coarctation of aorta: Adult type
|
ADult = Distal to Ductus
Associated w/Turner's syndrome Associations: *Notching of the ribs (overuse of collateral circulation) *HTN in upper extremities *Weak pulse in lower extremities (check femoral pulse) |
|
Patent ductus arteriosus
|
Direction of flow in fetal period: R --> L
Direction of flow post-natally: L --> R *Extra blood in pulmonary outflow means increased RV pressure --> RVH Continuous machine-like murmur *Loudest at S2 (highest P time) Close w/indomethacin Keep open w/PGE *May be necessary w/transposition of GV |
|
HTN
|
BP > 140/90
Controllable factors: *Smoking *Obesity, DM Uncontrollable factors: *Age *Race/Genetics: Black > White > Asian 90% of HTN is primary (CO, PVR) 10% is secondary to renal disease Complications: *Atherosclerosis *Stroke *CHF *Renal failure *Retinopathy *Aortic dissection |
|
Monckeberg arteriosclerosis
|
"PIPESTEM ARTERIES"
CALCIFICATION in the media of the arteries Usually benign |
|
Arteriolosclerosis
|
Complication of primary HTN
Hyaline thickening of the small arteries Malignant HTN --> hyperplastic onion skinning |
|
Arteriolosclerosis vs. Atherosclerosis
|
Arteriolosclerosis:
*Small vessels *THICKENING of vessel walls Atherosclerosis: *Medium and large arteries *PLAQUES (atheromas) |
|
Aortic dissection
|
Longitudinal intraluminal tear
*Forms a false lumen *TEARING chest pain radiating to BACK CXR shows mediastinal WIDENING Associations: *HTN *Cystic medial necrosis (Marfan's) |
|
Atherosclerosis
|
Disease of elastic arteries + large and medium muscular arteries
Possible symptoms: *Angina *Claudication (cramping pain in legs) Risk factors: *HTN (Obesity, DM, Smoking, Genetics) *Hyperlipidemia Process: *Endothelial dysfunction *Macrophage and LDL accumulation *Foam cell formation *Fatty streaks *Smooth muscle migration *Fibrous plaques *Complex atheroma Complications: ANEURYSMS Ischemia Infarcts Peripheral vascular disease Thrombus Emboli |
|
Angina
|
CAD narrowing >75%
Stable: ATHEROSCLEROSIS *Retrosternal chest pain w/exertion Prinzmetal's variant: SPASM *Occurs at rest Unstable/Crescendo: THROMBOSIS *Activity-independent worsening chest pain *No necrosis (otherwise would be an MI) |
|
Most common cause of sudden cardiac death
|
Arrhythmia
Death from cardiac causes within 1 hour of symptoms |
|
Chonic ischemic heart disease
|
Progresive onset of CHF over many years
Due to chronic ISCHEMIC myocardial damage |
|
Red "hemorrhagic" infarcts
|
Loose tissues w/collaterals
"a LIL red" --> *Liver *Intestine *Lung |
|
Pale infarcts
|
Tissues w/single blood supply
"SHeiK" --> Spleen Heart Kidney |
|
Coronary artery occlusions: Frequency
|
"The LAD wanted an RCA CFX radio"
LAD > RCA >CFX |
|
Coronary artery occlusions: Symptoms
|
Pain:
*Retrosternal *L arm *L jaw Adrenergic symptoms: *Diaphoresis *N/V Hypoxic symptoms: *SOB *Fatigue |
|
MI: First day
|
2-4 hours: NO visible change on LM
4+ hours: Initial necrosis and contraction bands *Coagulative necrosis *CONTRACTION BANDS Gross appearance: *Dark mottling *Tetrazolium stain: Light |
|
MI: 2-4 days
|
ARRHYTHMIA RISK
**Acute inflammation and more necrosis** Dilated vessels Neutrophil emigration Extensive coagulative necrosis Gross appearance: Hyperemia *Due to inflammation |
|
MI: 5-10 days
|
FREE WALL RUPTURE RISK
**Macrophages (the new red) surround neutrophils** Gross appearance: *Red border *Yellow-brown center |
|
MI: 7 weeks
|
VENTRICULAR ANEURYSM RISK
Contracted scar complete Gross appearance: Gray-white |
|
MI diagnosis
|
0-6 hours: ECG
*Transmural: ST elevation, Q waves *Subendocardial: ST depression Troponin I: *1st to rise (4 hours) *1 origin (heart) CK-MB: *2nd to rise *2 origins: Heart, skeletal muscle AST: *3rd to rise *3 origins: Heart, skeletal muscle, liver |
|
MI Complications
|
DR. SALAD
D = Dressler's syndrome: *Autoimmune fibrinous pericarditis *Several weeks post-MI *Fibrinous pericardis can also occur 3-5 d post-MI (friction rub) R = Rupture (5-10 days) *Ventricular free wall --> Tamponade *Interventricular septum --> VSD *Papillary muscle --> Mitral regurg S = Shock (cardiogenic) A = Arrhythmia (2-4 days) L = LV failure and pulmonary edema A = Aneurysm (7 wks) *Decreased CO *Risk of arrythmia *Mural thrombi D = Death |
|
Dilated (CONGESTIVE) cardiomyopathy
|
#1 cardiomyopathy (90%)
SYSTOLIC DYSFUNCTION Heart looks like a balloon on CXR Causes: ABCCCD Alcohol abuse Beri-Beri (B1) Coxsackie B virus Cocaine Chagas Doxorubicin toxicity Peripartum cardiomyopathy |
|
Dilated/congestive cardiomyopathy features systolic or diastolic dysfunction?
|
Systolic
S3 may be heard during diastole (blood rushing in quickly from atrium) |
|
Hypertrophic cardiomyopathy
|
50% genetic (autosomal dominant)
Cause of sudden death in young athletes Diastolic dysfunction Normal heart size, but inside: *Hypertrophy *Often involves IV septum Findings: *Loud S4 *Apical impulses Treatment: REDUCE CONTRACTILITY *Beta blocker *Ca2+ blocker (Verapamil) |
|
Hypertrophic cardiomyopathy features systolic or diastolic dysfunction?
|
Diastolic
Loud S4 |
|
Restrictive/Obliterative cardiomyopathy
|
Restrictive ~ Fibrosis
Obliterative ~ Deposits Causes: Deposits: *Sarcoidosis *Amyloidosis *Hemochromatosis Fibrosis: *Post-radiation *Endocardial fibroelastosis (kids) *Loffler's (prominent eosinophil infiltrate) |
|
CHF Features
|
Dyspnea on exertion
*Failure of LV output to increase Pulmonary edema *LV failure --> Increased pulmonary venous pressure --> Transudation of fluid HEMOSIDERIN-LADEN MACROPHAGES IN LUNG *"Heart failure cells" Orthopnea *Increased venous return in supine position worsens pulmonary vascular congestion Hepatomegaly/Nutmeg liver *Increased central venous pressure --> Increased resistance to portal flow Edema and JVD: *RV failure increases peripheral venous pressure *Edema = transudation |
|
Emboli
|
An embolus moves like a FAT BAT
Fat --> Long bone fracture, liposuction Air Thrombus Bacteria Amniotic fluid --> DIC risk Tumor 95% of PEs arise from deep leg veins Symptoms: *Chest pain *Tachypnea *Dyspnea |
|
Bacterial endocarditis
|
Acute = S. Aureus
*Large vegetations on previously normal valves *Rapid onset Subacute = Strep viridans *Smaller vegetations on abnormal/diseased valves *Insidious onset *Associated w/DENTAL procedures Bacteria FROM JANE: Fever Roth spots (white spots on retina) Osler's nodes (finger/toe pad bumps) Murmur Janeway lesions (red lesions on palm/sole) Anemia Nail-bed/splinter hemorrhage Emboli |
|
Rheumatic heart disease
|
Consequence of pharyngeal S. Pyogenes (Group A Beta-hemolytic) infection
Type 2 hypersensitivity reaction FEVERSS: F = Fever E = Erythema marginatum V = Valvular damage *Mitral > aortic >> tricuspid E = ESR R = Red hot joints (polyarthritis) S = Subcutaneous nodules (Aschoff bodies) + Anitchkow's cells S = St. Vitus' dance (chorea) ASCHOFF BODY = granuloma w/giant cells ANITSCHKOW'S cells = activated histiocytes |
|
Cardiac tamponade
|
Compression of heart by fluid in pericardium
EQUILIBRATION of diastolic pressures in all 4 chambers Findings: *PULSUS PARADOXUS: Decreased strength of pulse during inspiration *Hypotension *JVD *Soft heart sounds *ELECTRICAL ALTERNANS (height of QRS complex varies) |
|
Pulsus Paradoxus
|
Decreased strength of pulse during inspiration
Seen with: *Pericardial issues --> Tamponade, pericarditis *Esophageal inflammation --> Asthma, croup |
|
Electrical alternans
|
Seen in cardiac tamponade
Height of QRS changes |
|
Pericarditis
|
3 types:
*Serous --> Uremia, RA, SLE, Virus *Fibrinous --> Uremia, RF, Dressler *Hemorrhagic --> TB, neoplasm Findings: *PULSUS PARADOXUS *ST segment ELEVATION *FRICTION RUB *Pericardial pain *Soft heart sounds +/- Chronic adhesive/constrictive pericarditis |
|
Syphilus and the heart
|
Tertiary syphilis disrupts the vasa vasorum of the aorta
Dilation of the aorta and valve +/- Calcification ("tree bark") Possible complications: Aneurysm of the ascending aorta Aortic valve incompetence |
|
Kussmaul
|
Kussmaul's Sign: Increase in JVP w/inspiration
Cardiac tumor Kussmaul's Pulse: Pulsus paradoxus Decrease in pulse strength w/inspiration Pericarditis, tamponade, asthma, croup |
|
Telangiectasia
|
SMALL VESSELS
Arteriovenous malformations that look like dilated capillaries May present as part of Osler-Weber-Rendu syndrome: *AD *Nosebleeds *Skin discolerations |
|
Wegener's granulomatosis
|
SMALL VESSELS
c-ANCA (+) *CANCA sores will put a WEGE in your relationship Focal necrotizing: 1. Vasculitis 2. Granulomas in lung, upper airway *Perforation of nasal septum *Otitis media (up Eustachian?) *Chronic sinusitis *Cough, dyspnea *Hemoptysis *CXR: Possibly NODULAR DENSITIES 3. Glomerulonephritis *Hematuria *Red cell casts Treatment: *Cyclophosphamide *Corticosteroids |
|
Sturge-Weber disease
|
Congenital SMALL VESSEL DZ (Capillary size)
Sturge --> Sturgeon --> Port *PORT WINE STAIN on face Web --> in brain *INTRACEREBRAL AVM (leptomeningeal angiomatosis) |
|
Henoch Schonlein Purpura
|
SMALL VESSELS
#1 childhood systemic vasculitis Common triad of symptoms AFTER URI: 1. Skin (purpura--appear + age together) 2. Joints (arthritis) 3. GI (Intestinal hemorrhage) *Abdominal pain and melena Henoch = NOCH knees (joints) Schonlein = Stomach Purpura = Purpura |
|
Microscopic polyangitis
|
SMALL VESSELS
Like Wegeners, but LACKS granulomas P-ANCA (+) Lung and UR symptoms Glomerular disease |
|
Primary pauci-immune crescentic glomerulonephritis
|
SMALL VESSELS
Vasculitis LIMITED to kidney Pauci immune = Paucity of Abs ANCA (+) |
|
Churg-Strauss Syndrome
|
SMALL VESELS
p-ANCA (+) GRANULOMATOUS vasculitis w/EOSINOPHILIA *Strauss~spouse of Wegeners (only 2 small vessel vasculitis diseases to form granulomas) **Churg ~ Urg to scratch** (Seen in atopic patients) Affects lungs, heart, skin, kidneys, nerves |
|
Kawasaki disease
|
Kawasaki ~ Coronary
Red motorcycle ~ Strawberry tongue SMALL AND MEDIUM VESSELS ACUTE necrotizing vasculitis Affects infants and kids *More dangerous than Henoch-Shonlein Purpura CORONARY ANEURYSMS + Very inflammatory: *Strawberry tongue *Fever, lymphadenitis *Congested conjunctiva |
|
Polyarteritis Nodosa
|
MEDIUM VESSELS
*Only disease to affect strictly mediums **Unique** Immune complexes 30% HBV seroposiitive Kind of an adult version of Henoch-Schonlein purpura + necrotizing, aneurysm features of Kawasaki *Myalgia (vs. arthritis) *GI damage, melena *Skin eruptions (BUT age differently) Tx: Same as that of Wegeners Cyclophosphamide Corticosteroids |
|
Takayasu's arteritis
|
MEDIUM AND LARGE ARTERIES
a.k.a. Pulseless disease Primarily Asian females <40 Granulomatous thickening of the aortic arch and/or proximal vessels *Increased ESR (lg artery involvement) FAN MY SKIN on Wednesday: Fever Arthritis Night sweats MYalgia SKIN nodules Ocular disturbances Weak pulses in extremities |
|
Temporal arteritis
|
MEDIUM AND LARGE ARTERIES
Primarily affects elderly females Granulomatous inflammation of (usually) carotids *Increased ESR (lg artery involvement) *50% of patients have systemic involvement, polymyalgia rheumatica Unilateral headache Jaw claudication Opthalmic artery occlusion Treat w/high dose steroids |
|
Hydralazine
|
Vasodilates arterioles > veins
*Increases cGMP (sm relaxation) Uses: *Severe HTN (1st line in pregnancy) *CHF SE: *LUPUS LIKE SYNDROME *Compensatory tachycardia (bad w/angina) *Fluid retention |
|
Minoxidil
|
Vasodilates
*Opens K+ channels (sm relaxation) Uses: *Severe HTN *Baldness SE: *Hair overgrowth (hypertrichosis) *PERICARDIAL EFFUSION *Compensatory tachycardia (bad w/angina) *Fluid retention |
|
Ca2+ channel blockers
|
We FED at the FRAPPE MILL until DIL was TIAd of ZEM
Nifedipine Verapimil Diltiazem Block L-type (voltage-gated) channels in: *Smooth muscle (vessels) *Cardiac muscle *Cardiac AV nodal cells Vessel effect: N > D >V *Nice if you are doing something to vessels Heart effect: V > D > N Uses: 1. Vascular relaxation: HTN + Raynaud's 2. Heart: Decrease rate and contractility *Angina (even Prinzmetals) *SVT (not N--too weak) SE: *Heart: CARDIAC DEPRESSION (AV block, bradycardia, CHF) *CUTANEOUS FLUSHING *Vascular: Fluid retention, dizziness |
|
Nitroglycerin, Isosorbide dinitrate
|
Releases nitric oxide
*Venodilation > Arteriolar dilation Uses: APE Vasodilation: Angina, Erections Preload reduction: Pulmonary edema SE: *Reflex tachycardia, flushing, headache *Industrial tolerance: MONDAY DISEASE |
|
Malignant HTN: Treatments
|
Malignant HTN is a FieND (FND)
1. Fenoldopam Dopamine D1 receptor agonist Relaxes renal vascular smooth muscle 2. Nitroprusside Directly releases NO *Increases cGMP --> sm relaxation SE: CYANIDE TOXICITY 3. Diazoxide: Like minoxidil *K+ channel opener |
|
Beta blockers + Nitrates
|
When taken together, the following are lowered:
**Heart rate** **Blood pressure** **MVO2** BP EDV Contractility HR Ejection time MVO2 Nitrates lower everything except HR and contractility (increased as a reflex response) Beta blockers lower everything except EDV and ejection time |
|
Statins
|
HMG-CoA reductase inhibitors
*Prevent synthesis of MEVALONATE (cholesterol precursor) Affects all 3 lipids in a good way, but major effect is LDL Side effects: Elevated LFTs (reversible) Myositis |
|
Niacin
|
Inhibits lipolysis in adipose tissue
Reduces hepatic VLDL secretion into circulation Affects all 3 lipids in a good way, but major effect is HDL Side effects: FLUSHING (part of VANC) |
|
Cholestyramine, Cholestipol
|
a.k.a. Bile acid resins
Prevents intestinal reabsorption of bile acids ONLY CONTRAVERSIAL EFFECT *Slight increase in TGs LDL significantly lowered HDL rises slightly SE: Patients hate it *Tastes bad *GI discomfort *Possible ADEK deficiency |
|
Ezetimibe
|
E ~ Early, Easy (1 effect)
Prevents reabsorption of cholesterol @brush border 1 effect: Decreases LDL 1 SE: Rare LFTs |
|
Fibrates
|
Gemfibrozil, Clofibrate, Bezafibrate, Fenofibrate
Upregulates LPL to increase TG clearance Good effects on all 3 lipids, but main effect is TGs SE: Like statins *Myositis *LFTs |
|
Mg2+
|
Torsades de pointes
*Class 1A: Quinidine *Class IC: Sotalol *5HT4 agonist/prokinetic: Cisapride Digoxin antidote |
|
Adenosine
|
Very short-acting (15 seconds)
Use: 1st line for AV nodal arrhythmias Causes K+ to leave cells --> hyperpolarization *AV node cells *Vascular smooth muscle cells SE: Flushing, hypotension, chest pain |
|
Amiodarone
|
Class I-IV Antiarrhythmic (Na+, K+, Ca2+)
Used for Wolf-Parkinson-White syndrome SE: PULMONARY FIBROSIS PHOTOSENSITIVITY **MAKE SURE TO CHECK:*** PFTs (risk of fibrosis) LFTs (risk of hepatotoxicity) TFTs (risk of hypo/hyperthyroid) |
|
Class III Anti-arrhythmics
|
Decreases myocyte activity
K+ channel blockers BIAS: *Bretylium *Ibutilide *Sotalol *Amiodarone --> WPW Block K+ channel, but act like 1A antiarrhythmics *Increased AP duration *Long QT, ERP Uses: Atrial and ventricular arrhythmias (backup) SE: *Bretylium = Arrhythmia, hypotension *Ibutilide = TDP *Sotalol = TDP, excessive B block *Amiodarone--> Photsensitivity, pulmonary fibrosis, PFTs, LFT,s TFTs |
|
IC Anti-arrhythmics
|
PROP, FLECK and ENter the goal
Propafenone Flecainide Encainide As with all Class I drugs, slow rate of CONDUCTION of the action potential, but no effect on AP duration Really good at prolonging refractory period in the AV node Last resort: Ventricular arrythmias SE: C is for contradiction *Actually pro-arrhythmic (esp post-MI) |
|
IB Anti-arrhythmics
|
I'd Buy LIDdy's MEXican Tacos
I'd buy = IB L = Lidocaine M = Mexiletine T = Tocainide Binds both activated and inactivated Na+ channels --> K+ can flow in unchallenged, and AP is SHORTENED *Decreased AP (and QT, ERP) *Acts on Purkinje fibers in ventricle Uses: Ventricular arrhythmia (esp w/MI) Digitalis arrhythmia SE: U feel numb when UR depressed *Local anaesthetic *Cardiac depression |
|
1A Anti-arrhythmics
|
QUeen AMy PROClaims DISO's PYRAMID
Quinidine Amiodarone--class 1-4, actually Procainamide Disopyramide Increase AP duration --> long QT *Increased effective refractory period *Caused by prolonged phase 0 AND prolonged phase 3 via a small interaction with K+ channels Use: Atrial arrhythmias Ventricular arrhythmias SE: Quinidine = Cinched belt, pale *Cinchonism (headache, tinnitus) *Thrombocytopenia *Torsades de pointes (from long QT) Procainamide = SLE-like syndrome |
|
Lipophilic/Steroid hormones
|
PET CAT:
Progesterone Estrogen Testosterone Cortisol Aldosterone Thyroxine and T3 Vitamin D is also a steroid hormone! |
|
Adrenal cortex layers
|
GFR:
Glomerulosa --> Salt (Aldosterone) *Angiotensin II regulates Fasciculata --> Sugar (Cortisol) *ACTH (CRH) regulates Reticularis --> Sex (Aldosterone) *ACTH (CRH) regulates Medulla: Secretes catecholamines (E, NE) *Preganglionic sympathetic fibers *Ach w/nicotinic receptors |
|
Pituitary hormones
|
FLAT PiG
Beta cells --> FH LH ACTH TSH Alpha cells --> Prolactin GH |
|
Hormone Subunits
|
1. Alpha = "All the same" for the FLAT (Beta cell) hormones where A is replaced by HCG
FH LH HCG TSH Beta = "Be specific" --> Each hormone has its own beta subunit |
|
Pancreas cell types
|
Alpha cells: Release glucagon when the sugar is All gone
*Alpha--> ALL gone Beta cells: Release insulin when some sugar needs to go Bye bye *Beta --> BYE bye Delta cells: Release somatostatin to slow the digestive system Down *Delta --> slow DOWN |
|
Hypothalamic hormone control
|
(+) effects:
GnRH --> FSH, LH CRH --> ACTH TRH --> TSH, Prolactin GHRH --> GH (-) Effects: Dopamine --> Prolactin |
|
Adrenal Steroid Synthesis: Starting reaction
|
Cholesterol --> Pregnenolone
Catalyzed by DESMOLASE *ACTH stimulates *Ketoconazole inhibits |
|
Mineralocorticoid excess:
17B-hydroxylase deficiency |
17B-hydroxylase handles:
Pregnenolone --> 17OH-Pregnenolone Progesterone --> 17OH-Progesterone Result: Mineralocorticoids --> Increased Na+ resorption in DCT (HTN, Hypokalemia) x-Glucocorticoids x-Sex hormones: Female phenotype w/o maturation |
|
Adrenal Hyperplasia (sex hormone excess):
21-OH hydroxylase deficiency |
21-OH hydroxylase handles:
Progesterone --> 11-deoxycorticosterone 17-OH progesterone --> 11-deoxycortisol Result: x-Mineralocorticoids --> No Na+ resorption in DCT (hypotension, Na+ wasting, hyperkalemia) x-Glucocorticoids Sex hormones --> Masculinization, female pseudohermaphrodism |
|
Adrenal Hyperplasia (sex hormone excess
+ 1 mineralocorticoid): 11-OH deficiency |
11-deoxycorticosterone --> Corticosterone
11-deoxycortisol --> Cortisol Result: Mineralocorticoids: A lot of 11-deoxycorticosterone (HTN) x-Glucocorticoids Sex hormones --> Masculinization |
|
PTH release
|
Chief cells of parathyroid gland respond to low serum [Ca2+]
Bone: Overall resorption to release Ca2+, PO4 *Direct stimulation of osteoblasts *Indirect stimulation of osteoclasts Kidney: 1. Ca2+ sparing with PO4 excretion 2. Vitamin D (1,25 OH-D) *Increased intestinal absorption of Ca2+ and PO4 *Bone resorption to release Ca2+ and PO4 (Not significant?) |
|
Hyperparathyroidism:
Ca2+, PO4, PTH, AP findings |
Ca2+: High
PO4: Low AP: High PTH: High |
|
Vitamin D excess:
Ca2+, PO4, PTH, AP findings |
Ca2+: High
PO4: High AP: Normal PTH: Low |
|
Osteomalacia:
Ca2+, PO4, PTH, AP findings |
Ca2+: Low
PO4: Low AP: High PTH: High |
|
Osteoporosis:
Ca2+, PO4, PTH, AP findings |
Ca2+: Normal
PO4: Normal AP: Normal PTH: Normal |
|
Paget's disease:
Ca2+, PO4, PTH, AP findings |
Ca2+: Normal
PO4: Normal AP: VERY HIGH PTH: Normal |
|
Calcitonin
|
Parafollicular cells (C cells, thyroid gland) in response to high serum Ca2+
Result: Reduced Ca2+ loss from bone |
|
Alkaline phosphatase: Sources
|
Bone: Osteoblasts
Liver: Cells lining bile ductules |
|
Effect of SHBG
|
Binds testosterone --> Reduces effect
Males: Increased SHBG causes gynecomastia Females: Reduced SHBG causes hirsutism (PCOS) |
|
Functions of T3
|
T4 converted to T3 in periphery
The 4 B's: 1. Brain maturation 2. Bone growth 3. Beta adrenergic effects *HR, SV, contractility 4. Basal metabolic rate *Encourages IMMEDIATE E: Gluconeogenesis, glycogenolysis, lipolysis |
|
T4 synthesis
|
1. Thyroglobulin (TG) and I2 made by follicular cell, released into lumen
2. TG + I2 --> MIT or DIT 3. DIT + DIT/MIT --> T4/T3 4. Cell re-entry and secretion in to blood 5. Most grabbed (inactivated) by TBG *Reduced TBG: Liver failure *Increased TBG: Pregnancy (Estrogen) 5. T4 converted to T3 in periphery |
|
Functions of cortisol
|
BIMB
1. Bone breakdown 2. Immunodeficiency 3. Metabolic effects: Immediate E *Gluconeogenesis, glycogenolysis, lipolysis, PROTEOLYSIS 4. Blood pressure maintenance (increase) Thus, symptoms of Cushing's disease: BIMBO Bone: Osteoporosis Immune: Immunosuppression Metabolic: Weight gain, insulin resistance, truncal obesity, moon facies, buffalo hump Blood pressure: HTN Other: Purple striae |
|
Hormones using cGMP mechanisms
|
Vasodilators --> cANE
ANP NO EDRF |
|
4 causes of Cushing Syndrome
|
. Pituitary tumor (Cushing's DISEASE)--> ACTH
(HD Dexamethasone suppressible) 2. Ectopic tumor (SSLC) --> ACTH (Not suppressible) 3. Primary adrenal tumor --> Cortisol (Not suppressible) 4. Exogenous cortisol --> Cortisol |
|
What can low dose dexamethasone suppress?
|
Pituitary ACTH tumors only
Not ectopic ACTH secreting tumors N/A cortisol secreting tumors or exogenous cortisols |
|
Lab finding that distinguishes primary and secondary aldosteronism
|
Plasma renin levels
Primary (Conn's syndrome): Low renin Secondary: High renin (kidney perceives low intravascular vol) |
|
Hyperaldosteronism treatment
|
Spironolactone
|
|
Addison's disease
|
Loss of adrenal cortex
AAA: Atrophy All cortical layers lost --> No hormones ACTH high (along with MSH--pigmentation) |
|
Hyperthyroid vs. Hypothyroid
|
Temperature: Cold intolerance, cool dry skin
Energy: Fatigue, hypoactivity, weakness GI: Decreased appetite, weight gain, constipation Hair: Coarse and brittle Myxedema: FACIAL, PERIORBITAL Temperature: Heat intolerance, warm moist skin Energy: Hyperactivity GI: Weight loss, diarrhea Hair: Fine B agonist: Chest pain/palpitations, ARRHYTHMIA, REFLEXES Myxedema: PRETIBIAL (Graves) |
|
Thyroid Storm
|
Graves disease + Stress -->
Catecholamines --> Arrhythmia --> Deat |
|
Graves symptoms
|
GOP:
Goiter Opthalmopothy (proptosis, EOM swelling) Pretibial myxedema |
|
Hashimoto's thyroiditis
|
Hashimoto's Thyroiditis: Slow autoimmune hypothyroidism
Thyroid moderately enlarged, NONTENDER during lymphocyte invasion *HURTHLE cells *Germinal centers AUTOANTIBODIES: Antimicrosomal + Anti-TG Associated with LYMPHOMA Distinguish from Lymphocytic subacute thyroiditis (variant of Hashimotos?) which does not feature FOLLICLES and SCARRING Distingish from Subacute Thyroiditis (deQUervain's), which is painful, features granulomas instead of lymphocytic invasion and follows flu-like illness |
|
Toxic Multinodular Goiter Features
|
Hyperthyroidism following iodine repletion
Iodine restoration--T3/T4 release In the context of relocation--Jod-Basedow phenomenon |
|
Thyroid cancers
|
FLUMP
FLUMP: 1. Follicular: Good prognosis (follicles) 2. Lymphoma: Assoc. w/Hashimotos 3. Undifferentiated: Older ppl, bad 4. Medullary: Parafollicular C cells *Calcitonin *MEN II and III 5. Papillary: Excellent prognosis *Ground glass/orphan annie *Psammoma *Childhood Radiation |
|
5P's of Cretinism
|
Pale
Puffy Face Pot bellied Protruding umbilicus Protuberant tongue Matches w/Marasmus in a lot of ways (not protuberant tongue, retardation) |
|
Acromegaly
|
GH excess:
Large tongue, hands, feet Deep voice Coarse features IMPAIRED GLUCOSE TOLERANCE |
|
Growth hormone regulators
|
Stress
Exercise Hypoglycemia |
|
Primary hyperparathyroid
|
"Bones, stones and groans," but often asymptomatic
1. Bone breakdown raises Ca2+, PO4 *Alkaline phosphatase high *Causes cystic bone spaces filled w/brown fibrous tissue (OSTEITIS FIBROSA CYSTICA/Von Recklinghausen's) 2. Ca2+ retained, while PO4 excreted *Enough Ca2+ in urine --> stones *Hypophosphatemia 3. Weakness, constipation --> groans |
|
Secondary hyperparathyroid (CRF)
|
PTH's objectives are reversed by kidney, even though PTH levels are high
Ca2+: Low PO4: High AP: High PTH: High Leads to RENAL OSTEODYSTROPHY (bone lesions due to 2 hyperparathyroidism) |
|
Hypoparathyroid signs
|
Signs: Low Ca2+ tetany
*Chvostek's --> Facial tapping *Trusseau --> BP cuff causes carpal spasm |
|
Pseudohypoparathyroid
|
It's as if PTH wasn't there...
Autosomal dominant Kidney ignores PTH --> Hypocalcemia Shortened stature and 4th/5th digits |
|
Hypercalcemia: Causes
|
CHIMPANZEES:
Calcium (milk-alkali) Hyperparathyroid Hyperthyroid Iatrogenic (Thiazides) Multiple Myeloma Paget's disease Addison's disease Neoplasms Z-E Excess vitamin D Excess vitamin A Sarcoidosis |
|
Prolactinoma
|
Galactorrhea
GnRH inhibition: Amenorrhea/infertility Bitemporal hemanopsia Treatment: Bromocriptine (DA agonist) |
|
Diabetes tests
|
Fasting serum glucose
Glucose tolerance test HbA1c (long-term control) |
|
Diabetes: Chronic vessel sign
|
Mechanism: Nonenzymatic glycosylation
1. Small vessels: -Retinopathy -Glaucoma -Nephropathy *Ateriosclerosis --> HTN, Kimmelstiel-Wilson nodules *Progressive Proteinuria --> CRF 2. Large vessels: -CAD -Cerebral vessels -Peripheral vascular disease --> Gangrene |
|
Diabetes: Signs of osmotic damage
|
Neuropathy (motor, sensory and autonomic)
Cataracts (Sorbitol accumulation) |
|
Zollinger-Ellison Syndrom
|
Gastrin secreting tumor in pancreas or duodenum
May be responsible for recurrent ulcers |
|
Type 1 vs. Type 2 diabetes
|
Insulin dependence: Always vs. Sometimes
Age: < 30 vs. >40 Genetics: Weak vs. Strong (both polygenetic) HLA association: DR-3, DR-4 vs. none B cell numbers: Low vs. variable Insulin levels: Low vs. variable Coma: DKA vs. Hyperosmolar Hyperosmolar coma: Presence of SOME insulin inhibits ketone synthesis, but it's not enough to keep sugars low--> diuresis, volume contraction, hemo concentration |
|
SIADH: Causes
|
1. Ectopic ADH (small cell LC)
2. CNS release (head trauma, PULMONARY stressors) 3. Drugs (cyclophosphamide) |
|
SIADH: Signs
|
**Urine osmolality > Serum osmolality**
Hyponatremia Excessive water retention (oliguria) Tx: Dimeclocycline or H20 restriction |
|
Ketoacidosis
|
Stress (infection) --> GH --> IR --> Increased insulin demand --> Inability to suppress lipolysis --> B-hydroxybutyrate (ketone) synthesis
Labs: Ketoacids --> Anion gap acidosis Leukocytosis Hyperkalemia --> K+ leaves cells w/low insulin Kussmaul respirations: Hyperventilation N/V and abdominal pain Dehydration from polyuria Fruity breath odor |
|
Ketoacidosis: Complications
|
Mucormycosis and Rhizopus
Cerebral edema (osmotic changes) Arrhythmia and heart failure (hyperkalemia) |
|
Ketoacidosis treatment
|
WIP it good:
"Water" to reverse dehydration Insulin to reduce glucose levels Potassium to replete intracellular store |
|
Diabetes insipidus: Causes
|
Central: No ADH secreted
*Tumor/trauma *HISTIOCYTOSIS X Tx: Desmopressin (ADH analog) Nephrogenic: *Hereditary *High Ca2+ *Lithium *Dimeclocycline (tx for SIADH) Tx: Hydrochlorothiazide, indomethacin, amiloride |
|
Diabetes insipidus: Labs
|
Urine specific gravity under 1.006
Serum osmolality over 290 Water deprivation test--> does urine concentrate? *If no, DI Give desmopressin--does it concentrate now? *If no, nephrogenic |
|
Carcinoid syndrome
|
NEUROENDOCRINE cell tumor
--> GI (usually SI) DENSE CORE secretory bodies (vesicles) seen on EM Often releases serotonin: **URINE 5-HIAA** ForWaRD to problems: Flushing RH valvular damage/murmur Wheezing (Bronchoconstriction) Diarrhea Treatment: OCTREOTIDE (Somatostatin) 1/3 met 1/3 present w/2nd malignancy 1/3 multiple carcinoids |
|
Insulin
|
S = Short acting: LiSpro,ASpart
Intermediate: NPH Long acting: Lente, Ultralente All cause anabolism via Tyrosine Kinase receptor: glycogen synthesis (liver, muscle), protein synthesis (muscle), TG storage (adipose) |
|
Sulfonylureas
|
sulFONamides: Not much FON (1st gen), then the glucose is GON (2nd gen)
Sulfa drug Type 2 diabetes only (need some islet function) 1st generation: Tolbutamide, Chlorpropamide *DISULFRAM-LIKE REACTION 2nd generation: GL__IDE Glyburide, Glimepride, Glipizide *HYPOGLYCEMIA Binds to Beta cell K+ channel to increase Ca2+ Promotes depolarization and release of Insulin |
|
Biguanides
|
Metformin
Met-formula (lactic acidosis) Used as an oral sugar-dropper Can be used +/- islet function Probably reduces gluconeogenesis SE: Lactic acidosis |
|
Glitazones
|
Glit ~ Glutton (weight gain)
DMII Not really used anymore due to SE Pioglitazone Rosiglitazone Increases cell response to insulin (think GLIT-->GLUT) Hepatotoxicity, CV toxicity, Weight gain |
|
Alpha-glucosidase inhibitors
|
DMII
Acarbide Miglitol Inhibit brush border alpha-glucosidase to slow sugar spike Possible GI disturbances |
|
Orlistat
|
Long-term obesity management
Inhibits pancreatic lipase SE: GI discomfort, steatorrhea, reduced ADEK absorption, headache |
|
Sibutramine
|
"Boot camp" for the brain (and heart)
SSRI and NERI Long-term obesity management SE: Hypertension, tachycardia |
|
Anti-thyroids
|
Propylthiouracil, methimazole
Both inhibit T4/T3 synthesis Propylthiouracil ALSO decreases peripheral conversion of T4 --> T3 |
|
Somatostatin/Octreotide: Use
|
Shuts down GH and the GI
PGA: Pancreas: Z-E (gastrinoma), Glucagonoma GI: Carcinoid Acromegaly (inhibition of GHRH) |
|
Somatostatin/Octreotide: Use
|
Shuts down GH and the GI
PGA: Pancreas: Z-E (gastrinoma), Glucagonoma GI: Carcinoid Acromegaly (inhibition of GHRH) |
|
Prostaglandins
|
Inhibits the CLAP:
Cox-2 expression Leukotrienes Phospholipase A2 Prostaglandins Toxic CUD: Cushing's syndrome Ulcers (peptic) Diabetes (chronic use) |
|
Abdominal Layers: Skin--> Peritoneum
|
Susan Sarandon Eats Italian Toddlers To Enlarge Peritoneum
Skin Superficial fascia External oblique Internal oblique Transversus abdominis Transversalis fascia Extraperitoneal tissue Peritoneum |
|
Lower back muscles
|
Ventral
Quadratus Psoas Psoas Quadratus Lats Erector Spinae Erector Spinae Lats Dorsal |
|
Retroperitoneal Structures (10)
|
GI: Parts of duodenum, ascending colon, descending colon, rectum
Kidneys, adrenals, ureters Pancreas (except tail) Aorta and IVC |
|
Foregut --> Hindgut
|
Foregut: TUMMY AT TWELVE
Start: Stomach End: Ampulla of Vater (duodenum) Includes liver, pancreas, GB Artery: Celiac Parasympathetics: Vagus Spinal levels: T12/L1 Midgut: Start: Ampulla of Vater (duodenum) End: 2/3 point of transverse colon Artery: Superior mesenteric Parasympathetics: Vagus Spinal levels: L1 Hindgut: Lets 3 things out (L3) Start: Last 1/3 of transverse colon End: Upper rectum Artery: Inferior mesenteric Parasympathetics: Pelvic Spinal levels: L3 |
|
Celiac artery: Branches
|
Calmly (COM LE) splain (SPLEN)
Common hepatic artery *Hepatic proper --> R gastric, R/L hepatic *Gastroduodenal --> R epiploic, Panc-duod Left gastric artery Splenic artery *Short gastric branches *Splenic branches *L gastroepiploic *Cystic artery comes off the R hepatic proper |
|
Celiac anastamoses
|
L and R gastric
L and R gastroepiploic |
|
Abdominal anastamoses (matter when abdominal aorta is blocked)
|
Anterior diaphragm and abdomen: Superior + Inferior epigastrics
*Superior epigastric from Internal thoracic/mammary (a branch of the subclavian) *Inferior epigastric from External iliac Head of the pancreas: Superior + inferior pancreaticoduodenal *Superior is from celiac trunk *Inferior is from SMA 3. Transverse colon Middle + Left colic *Middle colic is from SMA *Left colic is from IMA 4. Rectum: Superior and Middle rectal *Superior is from IMA *Middle is from internal iliac |
|
Portal-systemic venous anastamoses
|
Butt, gut, caput
Butt: Hemorrhoids Superior rectal vein <----> Middle and inferior rectal veins Gut: Esophageal varices Left gastric <----> Esophageal Belly: Caput medusae Paraumbilical <----> SUPERFICIAL and inferior epigastric |
|
Surgical tx for portal hypertension
|
Shunt between splenic vein (portal circulation) and renal vein (systemic)
|
|
Centrilobular vs. Periportal zone
|
Centrilobular zone: Zone surrounding the hepatic vein
PITA: P-450 system location Ischemia (most susceptible) Toxic injury (most susceptible) Alcaholic hepatitis site Periportal zone: Zone surrounding portal vein, hepatic artery, and bile duct Affected 1st by viral hepatitis |
|
Splenorenal ligament
|
The name LIES!
Contains splenic artery and vein Connects spleen to posterior abdominal wall |
|
Greater curvature ligaments
|
Structure named first = contains artery coming from there
Only the falciform and splenorenal ligament are not omental Gastrocolic: Contains gastroepiploic arteries and connects to transverse colon (part of greater omentum) Gastrosplenic: Contains short gastrics and connects to spleen (separates greater and lesser sacs) |
|
Hepatic Ligaments
|
Structure named first = contains artery coming from there
Only the falciform and splenorenal ligament are not omental 1. Falciform: Contains ligamentum teres (former umbilical vein) and connects anterior liver to abdominal wall 2. Hepatoduodenal: Contains HEPATIC ARTERY, portal vein, bile duct; separates greater and lesser omental sacs *Pinch in epiploic foramen of Winslow to control bleeding 3. Gastrohepatic: Contains gastric arteries (lesser curvature), separates greater and lesser omental sacs |
|
Gut wall layers
|
MSMS
Mucosa Submucosa (w/Meissner's) Muscularis externa Serosa/adventitia Mucosa = ELM Epithelium --> Absorption Lamina propria --> Support Muscularis mucosa --> Motility |
|
Meissner's and Auerbach's plexi
|
Meissner (A.k.a. Submucosal)
*meiSSner *Located between mucosa and inner circular layer *Secretions/absorption, blood flow Auerbach (A.K.A. Myenteric) *Located between inner circular and outer longitudinal layers *Motility along entire gut wall |
|
Arteries, veins, and innnervation of rectum
|
**Above pectinate line**
Vessels: Superior rectal a/v (IMA) Innervation: Visceral (no pain) Internal hemorrhoids Adenocarcinoma **Below pectinate line:** Vessels: Inferior rectal a/v *From internal pudendal, a branch of the internal iliac External hemorrhoids (painful) Squamous cell carcinoma |
|
Femoral triangle
|
Borders: Sartorius muscle (lateral), Adductor longus muscle (medial), inguinal ligament (superior)
Contents: NAVEL Femoral nerve, artery, vein Empty space Lymphatics The L side is NOT lateral! |
|
Femoral sheath
|
_AVEL
Femoral artery, vein and lymphatics (deep inguinal LN drainage) NOT THE FEMORAL NERVE |
|
Diaphragmatic hernia
|
Most common pop = Infants (pleuroperitoneal membrane development)
Most common form = hiatal hernia *Sliding: Most common; GE junction intact *Paraesophageal: GE junction is normal, but cardia has moved into thorax (blood supply?) |
|
Indirect vs. direct inguinal hernia
|
Indirect: Most common pop = Infants (failure of processus vaginalis to close), males
Travels through deep inguinal ring (LATERAL to inferior epigastrics) --> Scrotum Direct: Most common pop = Older males Protrusion through inguinal (Hasselbach's) triangle: *Rectus abdominis (medial) *Inguinal ligament (inferior) *Inferior epigastric artery (lateral) Covered in transversalis FASCIA |
|
Femoral hernia
|
Most common pop = Women
Most common cause of bowel incarceration/trapping Protrusion through femoral canal (below inguinal ligament) |
|
Peyer's patches
|
Unencapsulated collections in lamina propria and submucosa
M cells take up antigen Activated B cells travel to mesenteric LN's and differentiate into IgA plasma cells Return to epithelial cells via Poly-Ig receptor (attaches secretory component) |
|
Salivary glands
|
Sympathetic (T1-T3)
Parasympathetic (VII, IX) Serous on the SIDES Mucinous in the MIDDLE High flow = Isotonic (Highsotonic) LOw flow = HypOtonic Parotid (most serous) *CN VII runs through it Submaxillary Submandibular Sublingual (most mucinous) |
|
THe ONLY GI submucosal gland
|
Brunner (bicarbonate)
Connect to crypts of Leiberkuhn in the mucosa |
|
Parietal cells
|
1. Intrinsic Factor (for vitamin B12 absorption)
*No regulation 2. Gastric acid (for digestion) *Tons of regulation Acid regulators: HAG GIPPSy Increase: HAG Histamine Ach (vagus) Gastrin Decrease: GIPPSSy GIP Prostaglandin Secretin Somatostatin |
|
Chief cells
|
Pepsinogen --> Pepsin
Released in response to: 1. Vagal (the "man upstairs" 2. Local H+ (the "locals)) |
|
Gastrin
|
Released by G cells in stomach antrum
Gastrin's effects: GAS Growth--of the gastric mucosa Acid--H+ secretion by parietals Smooth muscle--Gastric motility Postivie reg: Think of GAS again Stomach distention Amino acids (Phe, Trp) Vagal stimulation Negative reg: pH <1.5 |
|
Small intestine hormones
|
SIK MV = SIcK MoVe:
S cells --> Secretin *Acids I cells --> CCK *Fatty acids + amino acids K cells --> GIP *Fatty acids + amino acids + glucose also Motilin from "Small intestine" VIP from Parasympathetic ganglia |
|
Somatostatin
|
Released by D cells in GI and PANCREATIC islets
Regulation: Same factors as chief cells, but different effects 1. Local acid increases (same as Chiefs) 2. Vagal input DECREASES Functions: 1. Anti-growth hormone 2. Shuts down: A. Stomach (parietal, chief cells) B. SI mucosal secretion C. Gall bladder contraction D. Pancreas (enzymes, insulin, glucagon) Used to treat VIPoma and carcinoid tumors |
|
Secretin
|
**BICARBONATE and BILE**
Makes every organ secrete something Released from S cells in Duodenum Regulation: Increased by local Acids (including fatty acids) Actions: 1. Stomach: Inhibits parietal cells, increases bicarbonate 2. SI: Increases bicarbonate 3. GB/Liver: Increases bile 4. Pancreas: Increases bicarbonate |
|
Cholecystokinin
|
**SI DIGESTION**
Released from I cells of Duodenum, Jejunum Regulation: Fatty acids Amino acids Actions: 1. Stomach: Decreases gastric emptying 2. SI mucosa: None 3. GB: Increased contraction 4. Pancreas: Increased secretion |
|
GIP
|
*Insulin*
Secreted from K cells of duodenum and jejunum Regulation: Fatty acids Amino acids Oral glucose (used faster than IV glucose) Actions: 1. Stomach: Inhibits parietal cells 2. SI: None 3. GB: None 4. Pancreas: Insulin release |
|
What does the LES need to avoid achalasia?
|
NO
Smooth muscle relaxation at LES Loss of nitric oxide @ LES --> achalasia |
|
VIP
|
Released from parasympathetic ganglia:
1. Sphincters 2. Small intestine 3. GB Positive Regulation: Like GASTRIN 1. Distention 2. Vagal stimulation Negative regulation: Adrenergic input Actions: 1. Sphincter relaxation 2. Water and electrolyte secretion VIPoma (pancreas) = Copious diarrhea |
|
Enterokinase/Enteropeptidase
|
Duodenal mucosa enzyme that converts trypsinogen (from pancreas) --> trypsin
Trypsin activates more trypsin Trypsin activates other zymogens |
|
Pancreatic and salivary amylases
|
NOT rate limiting
Alpha amylases: Hydrolyze alpha-1,4 linkages *Unable to hydrolyze alpha-1,6 linkages (branches) Starch --> Maltose (2 glucose), maltotriose (3 glucose), limit-dextrans, other oligo and disaccharides The rest is taken care of by oligosaccharide hydrolases from the BRUSH BORDER |
|
Sugar absorption
|
GI lumen to enterocyte:
1. Glucose/galactose --> SGLT-1 *Na+ dependent 2. Fructose --> GLUT-5 Enterocyte to blood: GLUT-2 for fructose, glucose and galactose |
|
What makes a bile salt water soluble?
|
Congugation with glycine or taurine
|
|
Bilirubin cycle: Reabsorption sites
|
RES + liver enzyme products --> Biliverdin --> Indirect Bilirubin (insoluble)
Liver adds glucuronic acid (conjugation) --> Excretion as Direct Bilirubin Bile salts partially reabsorbed by the distal ileum Urobilinogen (some) and Uncongugated bilirubin reabsorbed in colon Absorbed urobilinogen --> Urobilin (urine) Non-absorbed urobilinogen --> Stercobilin (feces) |
|
Achalasia-like syndrome
|
Part of scleroderma or CREST
Esophagus features smooth muscle atrophy and fibrous replacement of CT Result: "Tightening" that resembles, but is not related to a Myenteric plexus defect LOW PRESSURE proximal to the LES rather than high |
|
Achalasia
|
Dysfunctional myenteric plexus
1. High LES opening pressure 2. Uncoordinated peristalsis Barium swallow = bird's beak (dilated esophagus w/distal stenosis) ESOPHAGEAL CARCINOMA RISK |
|
Mallory-Weiss
|
Mallory, why do you drink/purge?
Severe vomiting lacerates the GEJ PAINFUL + Hematoemesis Alcoholics and bulemics |
|
Boerhaave syndrome
|
VIOLENT retching causes transmural esophageal rupture
Severe pain, often vomiting, possible mediastinitis (dyspnea) and septic shock |
|
Esophageal strictures: Cause
|
Lye (base) ingestion
|
|
Esophagitis: Causes
|
Irritants: Reflux, chemicals
Infection (CatCH): Candida CMV HSV-1 |
|
Tracheoesophageal fistula
|
Abnormal connection between esophagus and trachea
Most common: Upper esophagus = Blind pouch Lower esophagus = Connected to trachea AIR BUBBLE on CXR Polyhydramnios in utero Cyanosis Choking and vomiting w/feeding |
|
Congenital pyloric stenosis
|
1/600 live births, especially 1st born males
Hypertrophy of the pylorus causes obstruction Epigastric OLIVE MASS (hypertrophied pylorus) Nonbilous projectile vomiting @ 2 weeks Tx =Surgical incision |
|
Esphageal cancer risk factors
|
ABCDEF
Alcohol/Achalasia Barrett's esophagus Cigarettes Diverticuli Esophageal webs, Esophagitis Familial Squamous = Upper 2/3 *Most common worldwide *50% in US AdenoCA = Lower 1/3 (closer to glandular tissue of stomach) |
|
Tropical Sprue
|
Like celiac sprue but is caused by bacteria (treatable w/antibiotics)
Affects WHOLE small bowel, rather than just jejunum |
|
Whipple's disease
|
Tropheryma Whippelii (gram +)
Most often in older men CAN be CANned as typical "older man" complaints: 1. Cardiac symptoms 2. Arthritis 3. Neurological symptoms Look for PAS POSITIVE macrophages in lamina propria + mesenteric LN's |
|
Pancreatic insufficiency
|
Obstruction (CYSTIC FIBROSIS, stones), or pancreatic damage (pancreatitis) leads to low enzymes
Malabsorption: 1. Protein 2. Fat 3. Fat-soluble vitamins |
|
Celiac sprue
|
HLA-DQ 8
Most common in N. European pops Gliadin + MHCII --> B and T cell activation Elevated GLIADIN AB and TISSUE TRANSGLUTAMINASE Primarily jejunum Blunted villi w/decreased absorption Lymphocytes in lamina propria Steatorrhea Dermatitis herpetiformis Increased risk of T cell lymphoma |
|
Acute gastritis vs. Chronic gastritis: Which is erosive?
|
Acute gastritis
|
|
Causes of acute gastritis (5)
|
Things that disrupt the mucosal barrier in some way
1. NSAIDs (reduce Cox-1 PGs) 2. Alcohol (erodes lining) 3. Uricemia (Hypoxanthine --> free radical damage) 4. Curling's ulcer (burns) --> NECROSIS *Low plasma volume, ischemia, sloughing 5. Cushing's ulcer (ICP, brain injury) --> Vagal stimulation of H+ SECRETION |
|
Chronic gastritis type A + B
|
Type A(B): Autoimmune ABs to parietal cells
*Gastritis *Pernicious anemia (low IF) *Achlorhydria (low H+) Type B(A): Bacteria in the Antrum *H. Pylori |
|
Menetrier's disease
|
"Might rain" mucus...
Increased mucus cells Atrophy of parietal cells Rugae enlarge to look like brain gyri PRECANCEROUS CONDITION |
|
Stomach Cancer (AdenoCA): Features and risk factors
|
Aggressive with early spread
Virchow's node: Left supraclavicular node (indicates stomach met) Krukenberg's tumor: BILATERAL ovarian met w/signet cells Risk factors: MOM (type A blood, gastritis), eating beef jerky Type A blood Chronic gastritis (esp if type A, which features achlorhydria) Nitrosamines (smoked food) |
|
Linitis plastica
|
Diffusely infiltrative stomach cancer
"Leather, not plastic" --> Leather bottle appearance of stomach lining Nuclei LINE the edges of signet cells Skin LINING affected: Acanthosis nigricans (hyperpigmentation of body folds also seen w/IR) |
|
PUD
|
Pain GREATER w/meals --> Weight loss
H. Pylori (70%) and NSAIDS |
|
DUD
|
Pain REDUCED with meals --> weight gain
H. pylori (100%) and Z-E Brunner's glands hypertrophy to counteract poor protection (HP) or increased acid (ZE) Studded appearance ("DUD WILL STUD") --> clean, regular margins |
|
PUD and DUD: Causes
|
PUD: H. pylori (70%) + NSAIDS
*Pain increased w/meals DUD: H. pylori (100%) + ZE *Pain reduced w/meals |
|
Crohn's disease
|
Postinfectious ("CATCH Crohn's")
Any age, but peaks = 13-30, 50-80 3x risk in smokers ANYWHERE IN GI, but usually: Terminal ileum (absorption probs) Colon TRANSMURAL inflammation Creeping fat Granulomas Skip lesions (not continuous) Linear ulcers (+ fissures, fistulas) Cobblestone mucosa "String sign" on barium swallow xray "CATCH a FAT GRANny SKIPping down a LINEAR COBBLESTONE path with an old crone, away from the REC" Diarrhea: Bloody OR nonbloody Joints: Migratory polyarthritis, ankylosing spondylitis Skin: Erythema nodosum Eye: Uveitis Gallbladder: Cholesterol STONES Tx: *Sulfasalazine *Infliximab (pain on TNF) *Corticosteroids |
|
Ulcerative colitis
|
Autoimmune
Peaks 15-25, 60-70 Reduced risk in smokers Colon only Continuous and retroactive from rectum Mucosal and submucosal inflammation only *Creates hanging polyps *Lead pipe appearance on imaging Instead of creeping fat --> Friable pseudopolyps Instead of granulomas --> Crypt abscesses and ulcers Instead of skip lesions --> Continuous Diarrhea: ALWAYS BLOODY PSC: Bile ductule (intrahepatic) and bile duct (extrahepatic) onion skinning and beading (2x men) Skin: Pyoderma gangrenosum (deep, necrotic leg ulcers) Tx: Sulfasalazine |
|
Appendicitis
|
Occurs in all age groups
Elderly: Similar to diverticulitis Women: Similar to ectopic pregnancy (check B-hCG) Symptoms: Periumbilical pain --> McBurney's point (RLQ) once infection has irritated the peritoneum Nausea, fever |
|
Diverticulum
|
True = 3 layers
*Mucosa *Submucosa *Muscularis externa False = 2 layers *Muscularis externa reduced or absent *Likely in places where vasa recta perforate muscularis externa |
|
Diverticulosis vs. Diverticulitis
|
DIVERTICULA USUALLY IN SIGMOID COLON
Diverticulosis = Many diverticula *50% of people over age 60 *Low fiber diets --> intraluminal P Diverticulitis: Bacterial infection of diverticulum *LLQ pain, fever, WBCs |
|
Zenker's diverticulum
|
FALSE DIVERTICULUM
Herniation of mucosal tissue @pharynx, esophagus junction Dysphagia, obstruction Bacterial accumulation --> HALITOSIS |
|
Meckel's diverticulum
|
MOST COMMON CONGENITAL ANOMALY OF THE GI (2% of pop)
Persistent vitelline duct/yolk sac The five "2's" --> 1. 2 inches long 2. 2 feet from the ileocecal valve 3. 2% of pop 4. Presents in 1st 2 years of life 5. 2 possible types of epithelia inside (gastric, pancreatic) Complications: Obstruction, volvulus, intussusception |
|
Intussusception
|
"Telescoping" of proximal bowel segment into distal one
Usually infants w/an intraluminal mass Possible blood supply issue |
|
Volvulus
|
Twisting of bowel (around mesentary)
Obstruction, infarction SIGMOID COLON (redundant mesentary) |
|
Hirschprung's Disease
|
Missing plexi (Auerbach + Meissner) due to poor NEURAL CREST MIGRATION
Increased risk with Down Syndrome Creates: 1. Constricted segment (at site of missing plexus) 2. Dilated megacolon (proximal) |
|
Duodenal atresia
|
Early BILOUS vomiting
"Double bubble" --> Duodenal distention + proximal stomach distention Assoc w/Down Syndrome: "DOUBLE DOWN" |
|
GI adhesion
|
Acute bowel obstruction
Most common cause is surgery |
|
Angiodysplasia
|
Usually seen in elderly patients
Ascending colon and cecum --> "ANGels ascend" Tortuous vessel dilation --> bleeding |
|
Sigmoid colon problems
|
Polyps (rectosigmoid)
Volvulus Diverticuli |
|
Colon polyps
|
90% benign hyperplastic hamartomas (benign, focal growth that resembles a neoplasm of that tissue)
10% malignant Tubular: Rounded Villous (more likely to be malignant): Fingerlike projections *Villous = Villainous |
|
Colorectal cancer
|
3rd most common cancer
APPLE CORE lesions on barium enema X-ray (narrowing from either side--like a C ring) Risk factors: Age >50 PMH: Previous CRC or villous polyps Ulcerative colitis Family history: FAP, HNPCC, P-J |
|
Portal HTN: Classic signs
|
1. Butt, gut, caput:
*Esophageal varices --> Hematemesis, melena *Hemorrhoids *Caput medusae 2. Splenomegaly (backup into splenic vein) 3. Ascites 4. Peptic ulcer --> Melena *Stasis of L gastric vein? |
|
Liver failure: Signs
|
Liver failure signs
Fetor hepaticus: Mecaptan backup into lungs Bilirubin: Jaundus, scleral icterus Hepatoencephalopathy: Asterixis, coma Decreased prothrombin, clotting factors, erythropoietin: Bleeding, anemia Diminished andostenodione catabolism: Spider nevi, testicular atrophy, gynecomastia |
|
Micronodular vs. Macronodular cirrhosis
|
Micronodular = METABOLIC INSULTS
*Chemicals or deposits Alcohol Wilson's disease Hemochromatosis Macronodular = LIVER INJURY *> 3 mm Infection Drug toxicity Increased risk of hepatocellular carcinoma |
|
Hepatocellular carcinoma: Causes (7)
|
Causes --> AB(H)C
Alcohol Anti-trypsin def Aflatoxin Hepatitis B, C Hemochromatosis Copper (Wilson's disease) Symptoms: Hepatomegaly Function: Hypoglycemia, ascites Ischemia --> Erythropoietin |
|
Causes of increased AST or ALT
|
Viral hepatitis (ALT > AST)
Alcoholic hepatitis (AST > ALT) *ToASTed Myocardial infarction |
|
Causes of increased Alkaline Phosphatase
|
BOB:
Bone degeneration Obstructive liver disease (CA) Bile duct disease |
|
Causes of increased serum amylase
|
Acute pancreatitis (pancreatic amylase)
Mumps (salivary amylase) |
|
Causes of increased serum lipase
|
Acute pancreatitis
Serum amylase is also elevated--but both pancreas and parotids secrete it |
|
Reye's syndrome pathogenesis
|
Viral infection (VZV, Influenza B)
+ Salicylates Result: Hepatoencephalopathy *Fatty liver *Hypoglycemia *Coma |
|
Hepatic steatosis
|
Stage preceding hepatitis
Moderate alcohol intake + Cessation Result: Macrovesicular fatty change (reversible) |
|
Alcoholic hepatitis
|
Stage preceding cirrhosis
Long-term alcohol intake Cells feature cytoplasmic inclusions --> Mallory bodies NECROSIS has started --> Neutrophils |
|
Alcoholic cirrhosis
|
Long-term alcohol intake
Zone III (around central vein) Add FIBROSIS to ongoing cell death --> "HOBNAIL" appearance Symptoms (jaundice, low albumin, etc.) |
|
Budd-Chiari syndrome
|
Vascular OUTPUT of the liver is obstructed
*Hepatic vein *IVC Causes: Pregnancy, hepatocellular carcinoma, polycythemia vera Centrilobular congestion, ischemia and necrosis *Hepatomegaly, varices + visible stomach/back veins *Ascites, liver failure **NO JVD** |
|
Urine bilirubin levels w/hyperbilirubinemia:
Hepatocellular, Obstructive, and Hemolytic |
Hepatocellular = Conjugated bilirubin
Obstructive = Conjugated bilirubin Hemolytic = Unconjugated bilirubin Urine bilirubin: *Only conjugated can be secreted in urine Hepatocellular: High Obstructive: High Hemoltyic: Absent Urine urobilinogen: *Must go to GI and be reabsorbed Hepatocellular: Normal or low Obstructive: Low Hemolytic: High |
|
Gilbert's syndrome
|
Benign congenital UNCONJUGATED hyperbilirubinemia
During stress --> 1. Decreased w/bilirubin uptake or 2. Decreased UDP-glucuronyl transferase No clinical consequences |
|
Dubin-Johnson syndrome
|
Problem with bilirubin excretion
Elevated CONJUGATED bilirubin Black liver, but asymptomatic |
|
Wilson's Disease
|
Copper does not enter circulation as ceruloplasmin --> poor excretion
ABCD: Asterixis Basal ganglia degeneration *Parkinsonian symptoms *Chorea Ceruloplasmin (low), Cirrhosis/Carcinoma, Corneal deposits Dementia |
|
Hemochromatosis
|
Association with HLA-A3
Hemochromatosis Can Cause Crappy Deposits (HCCD): CHF Cirrhosis Carcinoma Diabetes Treatment: Phlebotomy, DeFERoxamine (chelator) |
|
Primary Sclerosing Cholangitis
|
2x Men:Women
Associated w/ulcerative colitis Intrahepatic (ductules) and extrahepatic (duct) fibrosis of bile ducts *Concentric layers --> Onion skinning BEADING on ERCP (endoscopic retrograde cholangiopancreatography) Increased ALP |
|
Primary biliary sclerosis
|
9x Women
Associated w/scleroderma, CREST INTRAHEPATIC (ductules) autoimmune reaction causing severe OBSTRUCTION Increased ALP Anti-mitochondrial antibodies (AMA) |
|
Secondary biliary sclerosis
|
Extrahepatic biliary obstruction
Often causes ascending cholangitis Increased ALP |
|
Intrahepatic vs. Extrahepatic biliary diseases
|
Primary sclerosing cholangitis: Both
Primary biliary cirrhosis: Intrahepatic Secondary biliary cirrhosis: Extrahepatic |
|
Gallstone pathogenesis
|
Promote Solubility: Bile acids + lecithin
Promote Insolubility: Cholesterol, bilirubin Stones: Cholesterol, bilirubin > Bile salts, lecithin The 4 "F's" of cholesterol stones: Female --> Estrogen Fat --> Obesity, rapid wt loss, Clofibrate (cholesterol) Fertile --> Multiparous Forty --> Age (also a RF for pigment stones) + Crohn's + Cystic fibrosis + Native American Pigment stones: HIGH CONCENTRATIONS OF BILIRUBIN, ESP UNCONJUGATED RBC hemolysis Biliary infection (stasis?) Alcoholic cirrhosis (predisposes to > unconjugated bilirubin in bile duct) |
|
Acute pancreatitis
|
Many more causes than chronic (alcohol, gallstones)
Symptoms: *Epigastric abdominal pain radiating to BACK *Anorexia, nausea Causes = GET SMASHeD Gallstones Ethanol Trauma Steroids Mumps *Take amylase seriously--not just parotid Autoimmune disease Scorpion bite Hypercalcemia *Modifies secretion, predisposes to plugs Hyperlipidemia Drugs (sulfa) Complications are SAD: Soap deposits --> Hypocalcemia ARDS--> Direct leakage DIC --> Direct leakage |
|
Pancreatic cancer
|
Aggressive cancer--usually spread by discovery
Risk factors: Jewish, African american descent Cigarettes (but not EtOH) CEA and CEA 19-9 markers Pancreas pain: Epigastric abdominal pain radiating to BACK Weight loss (malabsorption + anorexia) TROUSSEAU's syndrome: Extremity redness and tenderness (due to venous thrombosis) COURVOISIER'S sign: Palpable gallbladder (implies quick obstruction) |
|
H2 blockers
|
Take H2 before you DINE: Cimeditine, Ranitidine, Famotidine, Nizatidine
Uses: Gastritis, GERD, PUD SE: Cimeditine sucks: *P450 (Inhibitor) *Anti-androgen (GYNECOMASTIA) *Crosses BBB, placenta Increase serum CReatinine: Cimdeditine and Ranitidine |
|
PPIs
|
PRAZOLES: Omeprazole, lansoprazole
Block parietal H+/K+ ATPase Uses: Gastritis, GERD, PUD ZOLLINGER-ELLISON SE: None listed |
|
Bismuths
|
Bismuth, Sucralfate
Healing: Protect mucous layer and promote HCO3- secretion SE: None listed Uses: Ulcer healing, traveler's diarrhea |
|
Traveler's diarrhea
|
Bismuths (Bismuth, Sucralfate)
E. coli (Enterotoxigenic) *Traveler's diarrhea *ST and LT toxins |
|
Misoprostol
|
PGE-1 analog
Uses: 1. PUD prevention: Replaces the COX-1 PG's lost by taking an NSAID 2. Maintains a patent ductus arteriosus 3. Abortifacient, Induces labor Decreases acid production Increases mucus production --> Diarrhea |
|
Muscarinic antagonists for PUD
|
PR__ine
Pirenzipine, propantheline: Use = PUD treatment Bind to M3 receptor of parietal cells (stop H+) Bind to M1 receptor of ECL cells (stop histamine) SE: Just like atropine, they inhibit DUMBBELSS --> Diarrhea Urination Miosis Bradycardia Excitation (CNS) Lacrimation Salivation Sweating |
|
Antacids (3)
|
Aluminum Hydroxide
Magnesium Hydroxide Calcium Carbonate ALL CAUSE HYPOKALEMIA Aluminum --> Constipation, Phosphate binding (bone loss, proximal muscle weakness, seizures) Magnesium --> Diarrhea, Muscle depression (Hyporeflexia, Hypotension, Cardiac arrest) Calcium --> Acid rebound, hypercalcemia, CHELATION (tetracycline--part of H. Pylori treatment) |
|
What SE can all antacids cause?
|
Hypokalemia
|
|
Infliximab
|
Anti-TNF antibody
Uses: *Crohn's disease *Ulcerative colitis *Rheumatoid arthritis *Ankylosing spondylitis *Psoriasis SE: *"Serum sickness" (hypotension, fever) *Predisposition to infection, esp respiratory (TB reactivation) Alternative = Etanercept (recomb TNF receptor-binds TNF) |
|
Sulfasalazine
|
Sulfapyridine (antibacterial) + mesalamine (anti-inflammatory)
*Melasamine is activated to 5-ASA in colon Activated by colonic bacteria Uses: Crohn's, Ulcerative colitis SE: Oligospermia Sulfonamide toxicity Malaise, nausea |
|
Odansetron
|
Dancing from 5 to 3...weak in the knee
5-HT3 antagonist --> Acts at central emetic center *"Go dancing" Uses: Chemotherapy, post-operative vomiting prevention SE: Constipation (GI suppression), headach |
|
Metoclopramide
|
Prokinetic agent: D2 antagonist
*Increased tone and motility *Increased LES tone *SAME TRANSIT TIME in colon Uses: Gastroparesis, either post-surgery or due to diabetes SE: CNS: PD, restlessness, fatigue, depression GI: Nausea, diarrhea "D CONFLICTS" *D2 receptor (antagonist) *Digoxin/Digitalis *Diabetes medications |
|
Metoclopramide
|
Prokinetic agent: D2 antagonist
*Increased tone and motility *Increased LES tone *SAME TRANSIT TIME in colon Uses: Gastroparesis, either post-surgery or due to diabetes SE: CNS: PD, restlessness, fatigue, depression GI: Nausea, diarrhea "D CONFLICTS" *D2 receptor (antagonist) *Digoxin/Digitalis *Diabetes medications |
|
Cisapride
|
Prokinetic agent: 5HT4 agonism --> Ach at myenteric plexus
*NOT USED ANYMORE (Torsades) *Increased tone and contractility *Increased TRANSIT TIME Interactions: Ketoconazole/Fluconazole Nefazodone |
|
Erythrocyte formation
|
Pluripotent hematopoietic stem cell
--> Proerythroblast --> Reticulocyte --> Erythrocyte |
|
Granulocyte formation
|
Neutrophil, Eosinophil, Basophil
Pluripotent hematopoietic stem cell --> Myeloid stem cell --> Myeloblast --> Promyelocyte --> Myelocyte --> Metamyelocyte --> Band/Stab cell --> Neutrophil/Eosinophil/Basophil |
|
Progeny of a hematopoietic stem cell
|
Myeloid stem cell --> Neutro, Eos, Baso
Lymphoid stem cell --> B, T cells Pro-Erythroblast --> Erythrocyte |
|
RBC energy source
|
Glucose (via GLUT-1)
90% fermented 10% used in HMP shunt |
|
Chloride shift
|
Chloride/Bicarbonate transporter in RBCs
When bicarbonate (CO2) needs to diffuse out, Cl- keeps it isoelectronic |
|
Basophil properties
|
Exist in BLOOD
Bilobed nucleus Basophilic granules contain: Heparin (anticoag)* Histamine, etc. (vasodilators)* LTD-4 * = Mast cells too |
|
Mast cell properties
|
Exist in TISSUE
Bind IgE Basophilic granules contain: Heparin (anticoag)* Histamine (vasodilators)* Eosinophil chemotactic factors *Basophils too Mast cell degranulation is prevented by Cromolyn sodium |
|
Prevents mast cell degranulation
|
Cromolyn Sodium (Asthma)
|
|
Eosinophil properties
|
EOSINOPHIL EATS
Defends against helminthic, protozoan infections Rapidly phagocytoses antigen-antibody complexes Bilobed nucleus Uniform granule size Granules contain: Major basic protein Histaminase Arylsulfatase Causes of high eosinophils: NAACP Neoplasm Asthma Allergic process Collagen vascular diseases Parasites (Protozoans, helminths) |
|
Allergic cells
|
Basophils
Eosinophils Mast cells (Type I) |
|
Neutrophils
|
Acute inflammation response:
1. Granule release 2. Phagocytosis Multilobed nucleus Hypersegmented w/B12, folate deficiency Granules ("lysosomes", azurophilic): *Hydrolytic Enzymes *Lysozyme *Lactoferrin *Myeloperoxidase |
|
Large cell w/FROSTED GLASS cytoplasm
Kidney shaped nucleus |
Monocyte
|
|
Macrophage
|
Arrive after neutrophils
1. Phagocytosis, antigen presentation 2. Cleanup (debris, senescent red cells) Activated by gamma-interferon Long life in tissue |
|
Dendritic (Langerhan's-skin) cells
|
Act solely as APCs
Responsible for primary antibody response |
|
Plasma cells
|
Plasma cell malignancy is responsible for MULTIPLE MYELOMA (bone)
Appearance: Off-center nucleus "Clock face" chromatin Well-developed RER and Golgi |
|
Extrinsic pathway
|
A sole EXILED clotting factor
Tissue factor converts 7 --> 7a 7a then converts 10 --> 10a 10 --> 10a (5a joins) 2 --> 2a (thrombin) 1 --> 1a (fibrin) 13a produces cross-links in fibrin Fibrinogen (1) bridges platelets via GP2b/3a --> converted to fibrin (1a) in place |
|
Factor 12
|
1st step of intrinsic pathway (PTT)
2 things convert it to 12a: 1. Injured endothelium (collagen, BM, activated platelets) 2. HMW Kinin Factor 12a has 2 functions: 1. 11 --> 11a 2. Pre-kallikrein --> Kallikrein |
|
Intrinsic pathway
|
12 --> 12a (by endothelium or HMWK)
11 --> 11a 9 --> 9a (8a joins) 10 --> 10a (5a joins) 2 --> 2a (thrombin) 1 --> 1a (fibrin) 13a produces cross-links in fibrin Fibrinogen bridges platelets via GP2b/3a --> converted to fibrin in place |
|
Protein C
|
1. Thrombomodulin converts Ci --> Ca
2. Protein S joins Protein C and S are vitamin K dependent Ca inactivates joiners (5a, 8a) to affect both intrinsic and common pathway Resistance = Factor V Leiden |
|
Anti-thrombin III activation
|
Heparin converts ATIIIi ---> ATIIIa
ATIII inactivates thrombin (2a), 9a, 10a, 11a |
|
Plasmin activation
|
Tissue plasminogen activator (or kallikrein) converts plasminogen --> plasmin
Cleaves fibrin clots Converts C3 to C3a (complement) |
|
HMWK and Kallikrein
|
HMWK:
*Converts Factor 12 --> 12a *Kallikrein converts HMWK to Bradykinin Kallikrein (from Prekallikrein, catalyzed by factor XIIa): *Converts HMWK to Bradykinin *Converts Plasminogen ---> Plasmin (like tPA) |
|
Stages of thrombogenesis
|
1. Adhesion: Platelet GP1B bonds to endothelial vWF
2. Aggregation: TXA2 from platelets *Inhibited by endothelial NO, PGI2 3. Swelling: ADP and Ca2+ released to strengthen plug Fibrin deposition can now occur |
|
Spherocytosis: Causes
|
Hereditary spherocytosis
Autoimmune hemolysis |
|
Elliptocytosis: Causes
|
Hereditary elliptocytosis
|
|
Macro-ovalocytes: Causes (2)
|
Megaloblastic anemia
Marrow failure |
|
Helmet cells/Shistocytes: Causes
|
DIC, traumatic hemolysis
Fibrin severs RBCS |
|
Bite cells: Cause
|
G6PD (Heinz body removed by spleen)
|
|
Teardrop cells: Cause
|
MYELOID METAPLASIA w/myelofibrosis
Squeezing through fibrous marrow causes shape |
|
Target cells: Causes (4)
|
Ring of pallor around central Hb
HALT, said the hunter to his target Hemoglobin C (abnormal beta chains that precipitate) Asplenia (weird cells not removed) Liver dz (low LCAT causes high cell cholesterol, big plasma membranes) Thalassemia (low Hb levels |
|
Poikilocytes: Causes
|
Poikilocytes --> Different sizes
Fibrin: DIC, trauma TTP/HUS (ADAMTS13 deficiency --> vWF clumps) |
|
Basophilic stippling: Causes (4)
|
TAIL = The 3 microcytic anemias + Anemia of Chronic disease
Thalassemia Anemia of chronic disease Iron deficiency Lead poisoning |
|
Microcytic anemias
|
ALL are HYPOCHROMIC
MCV < 80 Causes: TAIL w/o the A Thalassemia --> Target cells Iron deficiency Lead poisoning, sideroblastic anemias |
|
Iron-moving compounds
|
Ferroportin: moves iron through cells
*Inhibited by hepcidin Transferrin: Carries iron around in blood Stored iron (in cell): Ferritin, hemosiderin |
|
Signs of hemolysis
|
Decreased serum HAPTOGLOBIN
*Haptoglobin binds free Hb in blood --> Overwhelmed INCREASED SERUM LDH *Lactate dehydrogenase *RBCs get nutrition anaerobically |
|
Aplastic anemia
|
NORMAL looking cells, just not enough of them
Bone marrow is hypocellular *Stem cells have been lost *Stem cells that remain are not producing/releasing enough Causes: Radiation Virus: B19, EBV, HIV Fanconi's anemia (AR, assoc. w/short stature and other malignancies) Drugs: Antimetabolites Alkylating agents Propylthiouracil (anti-thyroid, prevents iodination of thyroglobulin --> thyroxine) Methimazole (anti-thyroid, prevents iodination of thyroglobulin --> thyroxine) NSAIDS Chloramphenicol (Bacteriostatic 50S inhibitor) *Meningitis: HIB, Neisseria, Strep pneumo Benzene (various materials) |
|
"Crew cut skull"
|
Sign of increased erythropoeisis (marrow expansion) on X-ray
Sickle cell Thalassemias |
|
Sickle cell anemia
|
8% of AA population = Trait
0.2% = Disease Complications: SARVS Salmonella osteomyelitis (vs. S. Aureus) Aplastic crisis (B19) Renal papillary necrosis Veno-occlusive crises Spleen destruction, sequestration Treatments: Bone marrow transplant HYDROXYUREA (increases HbF) |
|
TTP/HUS: Cells
|
Burr cell (really looks like a burr)
Poikilocytes |
|
Alpha thalassemia
|
Asian and African populations
3 missing copies = Hemoglobin H *H4 tetramers seen 4 missing copies = Hemoglobin Barts *Hydrops (cardiac overpumping) *Intrauterine death |
|
Beta thalassemia
|
Mediterranean populations
Fetal hemoglobin becomes elevated in either case 1 missing copy = Minor Both copies missing = Major *Severe anemia requiring transfusions *Hemochromatosis --> heart failure |
|
Hemolytic anemia: Types
|
All cases:
**Increased serum bilirubin (unconjugated) --> Jaundice, pigment gallstones** **Increased reticulocytes** 1. Autoimmune (EV)--extravascular *Coomb's positive *Warm/Cold agglutinins *Erythroblastosis fetalis--Rh+ baby w/Rh- mother 2. Hereditary spherocytosis (EV) *Extravascular *Spectrin or ankyrin defect *Small, round cells --> High MCHC, RDW 3. Paroxysmal nocturnal *Intravascular *DAF 4. Microangiopathic: Shistocytes/helmets *DIC, TTP/HUS, Malignant HTN *SLE *Intravascular EV: Spleen and Kuppfer cell destruction |
|
Autoimmune hemolytic anemia
|
Coombs positive, Extravascular
Warm weather is GGGreat (IgG) MMM (IgM), cold icecream 1. Warm agglutinins: "Silly (SLE) dope (dopa), cold (CLL) is warm!" SLE CLL Alpha methyldopa 2. Cold: MMM IgM Mononucleosis Mycoplasma bacterium 3. Eryhroblastosis fetalis: Maternal Ab attack fetal RBCs |
|
Paroxysmal Nocturnal Hemoglobinuria
|
Intravascular hemolysis
Membrane defect in RBC increases susceptibility to complement Increased urine HEMOSIDERIN Commonly a problem w/ the GPI anchor (allows Decay Accelerating Factor to attach, which then inhibits alternative complement pathway) |
|
DIC: Causes and Labs
|
STOP Making New Thrombi!
Sepsis (gram NEGATIVE) Trauma Obstetric complications Pancreatitis (acute) Malignancy Nephrotic syndrome Transfusion Labs: Microthrombi --> consumption of platelets and coagulation factors Elevated PT, PTT Elevated fibrin split products (D-dimers) Low platelets Helmet cells and schistocytes |
|
Platelet problem signs
|
MICROhemorrhage
Mucous membrane bleeding (including epistaxis--nosebleed) Petechiae (pin), Purpura (larger) |
|
Clotting factor problem signs
|
MACROhemorrhage
Increased PTT and/or PT Hemarthroses Easy bruising |
|
Platelet problems
|
Platelet deficiency/malfunction = increased bleeding time
PTT/PT do not change! Bernard Soulier disease (GP 1b) *Defect of platelet ADHESION *Low platelets (?), high bleeding time Glanzmann's (AgGregation, GP2b-3a) *High bleeding time ITP (antiplatelet Abs) *Low platelets, high bleeding time TTP (platelet aggregation) *Low platelets, high bleeding time DIC *Low platelets, high bleeding time *CF consumption: High PTT, PT Aplastic anemia *Low platelets, high bleeding time Drugs *Low platelets, high bleeding time |
|
Clotting factor problems
|
Hemophilia A --> Factor 8 deficiency
*Increased PTT Hemophilia B --> Factor 9 deficiency *Increased PTT Von Willebrand's disease *Shortened factor 8 survival --> PTT *Poor platelet adhesion --> Bleeding time |
|
Hodgkin's Lymphoma vs. Non-Hodgkin's Lymphoma
|
Req R-S cells (CD15, CD30) vs. No cells req'd
Localized node group w/continuous spread (often Mediastinal) vs. Multiple nodes w/non-contiguous spread Common constitutional B symptoms vs. Fewer constitutional symptoms 100% B cell origin vs. mostly B cell origin Associated w/EBV (50%) and men (ex.nodular sclerosing) vs. HIV and immunosuppression Bimodal (15-30, 55+) vs. Peak 20-40 |
|
Hodgkin's lymphoma vs. non-hodgkin's
|
All tumors feature lymphocytes and R-S cells
Nodular sclerosing (65-75%) *Excellent *Young WOMEN *Collagen banding *LACUNAR CELLS (R-S variant) seen Mixed cellularity (25%) *Intermediate *NUMEROUS R-S cells Lymphocyte predominant (6%) *Excellent *Young MEN Lymphocyte depleted (rare) *Poor *Older men w/disseminated disease |
|
Multiple myeloma
|
Most common bone tumor >40-50
*Always originates from bone Malignant PLASMA cells release IgG (55%) or IgA (25%) --> Monoclonal Ab spike Complications of bone lesions: *Punched-out lesions on X ray *Hypercalcemia --> Renal insufficiency *Rouleaux formations (stacked RBCs) and anemia IgG or IgA output: *Primary amyloidosis (light chains) --> renal insufficiency *Susceptibility to infection |
|
Non-hodgkins Lymphomas
|
"The San Francisco MD's BilL" --> SF MD BL
Small lymphoblastic (Adults, B) *Low grade *Like CLL with a mass Follicular (Adults, B) *Most common *Low grade, but often incurable *Involves bcl-2 activation (14;18) Mantle cell (Adults, B) *High grade, poor prognosis *CD5+ *11:14 Diffuse large cell (80% adult, 80% T) *High grade, but up to 50% curable *Mature T cells Burkitt's (Children, B cell) *8:14 (c-myc --> Ig heavy chain gene) *Starry Sky: Macros in lympho sea *Associated w/EBV *Endemic/African--Jaw lesion *Sporadic--Pelvis or abdomen Lymphoblastic (Children, T cells) *Very aggressive *Immature T cells *Often presents w/ALL *Often presents w/mediastinal mass |
|
11:14 Translocation
|
Mantle cell lymphoma
Adult, B cell CD5 Poor prognosis |
|
11-->22 translocation
|
Ewing's Sarcoma
|
|
14 --> 18 Translocation
|
Follicular lymphoma
Mutation in Bcl-2 inhibits apoptosis Adult, B cell Low grade but often incurable |
|
Leukemoid reaction: Features
|
Response to stress or infection
Bands (left shift) **High Leukocyte alkaline phosphatase** *Low w/CML |
|
ALL
|
Children <15
LymphoBLASTS = Tdt+ (Pre-B, Pre-T) ALL: BRAINS to BALLS *High level of spread to CNS, testes Prognosis: Most responsive |
|
AML
|
Children and adults 5-40
MyeloBLASTS: Several subtypes M3 type (promyelocytic) features 15 --> 17 translocation *Auer rods *Responsive to ALL-TRANS RETINOIC ACID |
|
CLL
|
Adults > 60
B Lymphocytes (no Ab made) SMUDGE cells (fragile) WARM Ab autoimmune hemolytic anemia *Silly (SLE) dope (methyldopa), cold (CLL) is warm! |
|
CML
|
Adults 30-60
Philadelphia chromosome 9-->22 *Bcl-Abl fusion Myeloid stem cells --> Neutrophils, Metamyelocytes (mature cells found too) Possible blast crisis (acceleration to AML) |
|
Hairy cell leukemia
|
"TRAP a Hairy animal"
Elderly population B cells w/HAIRLIKE FILAMENTS inside Stains TRAP+ (tartrate-resistant acid phosphatase) |
|
B cells w/ hairlike filaments inside
|
Hairy cell leukemia
|
|
Histiocytosis X
|
Malignancy of the MONOCYTE lineage affecting YOUNG adults
Langerhans cells (usually in skin) infiltrate lung *Worse with SMOKING; pro-monocyte/macrophage environment Cells contain Birbeck granules (tennis rackets) on EM |
|
What is a histiocyte?
|
A type of monocyte
|
|
Heparin
|
Catalyzes the formation of ATIII
*Immediate anticoagulation *Factors 2a (thrombin) and 10a are the most important reductions *LMW Heparins more selectively reduce 10a Uses: CLOT BREAKUP or PREVENTION Pulmonary embolism Stroke Angina, MI DVT Obstetric problems (doesn't cross placenta) Toxicity: Bleeding OSTEOPOROSIS Drug-Drug interactions HIT: Heparin-induced TCP *Heparin + platelet = Hapten *Destroyed platelets *Remaining platelets activated (hypercoagulable) |
|
Heparin: Monitoring
|
Regular heparin must be monitored by watching PTT
Low molecular weight heparins (Enoxaparin) are administered subQ w/o monitoring *Better bioavailability *Longer t1/2 (2-4x) *Also work more selectively on Xa |
|
Lepirudin, Bivalirudin
|
Hirudin derivatives
Directly inhibit thrombin Do not cause HIT: Use as heparin alternative |
|
Warfarin/Coumadin
|
Warfarin/Coumadin
The "EX-PaTriot went to WAR(farin) and came back w/scars (necrosis" Vitamin K antagonist: Interferes w/synthesis and gamma-carboxylation of 2, 7, 9, 10, C, S *Consider EXTRINSIC the only pathway affected Long, and extremely VARIABLE t 1/2 *Metabolized by P-450 Use: Chronic anticoagulation *Crosses placenta--TERATOGENIC Toxicity: Skin/tissue NECROSIS, drug-drug interactions |
|
Heparin vs. Coumidin
|
Large acidic anion polymer (t 1/2=hours) vs. Small, lipid soluble molecule (t 1/2=days)
Parenteral (IV, SQ) vs. oral Acts in blood vs. in liver Monitor PTT vs. PT/INR No placental crossing vs. Placental crossing + teratogen |
|
Thrombolytics
|
Increases PLASMIN
*Breaks up fibrin clots *Breaks down fibrinogen (prevents more fibrin) Increases PT, PTT (not bleeding time) Uses: Early MI Early stroke APSAC: Complex of Streptokinase + Plasminogen |
|
Aspirin (ASA)
|
Aspirin: Irreversibly acetlyates COX-1, COX-2
*Prevents conversion of arachidonic acid to TXA2 (needed for aggregation step) Bleeding time is increased (platelet-only effect) Uses: Inhibit many COX-2 products *TXA2: Anti-platelet *Anti-pyretic *Anti-inflammatory *Analgesic SE: COX-1 inhibition: Gastric ulcers Metabolic acidosis: hyperventilation Reye syndrome (+VZV, Influenza) Tinnitus (CN VIII) |
|
Clopidogrel, Ticlopidine
|
CLOPIDogrel, TiCLOPIDine
Interferes w/the 1st (GP1B) and 3rd (ADP, Ca2+) steps of aggregation 1. Irreversibly blocks ADP receptors 2. Blocks GP2b/3a expression Uses: *Acute coronary syndromes, stenting *Thrombotic stroke prevention Toxicity: Ticlopidine causes neutropenia |
|
Abciximab
|
AbCIXimab keeps em from sticking so bad
Binds GP2b/3a receptor on platelets Uses (A+A): Acute coronary syndrome, coronary Angioplasty |
|
Abciximab
|
AbCIXimab keeps em from sticking so bad
Binds GP2b/3a receptor on platelets Uses (A+A): Acute coronary syndrome, coronary Angioplasty |
|
Cell cycle specific anti-cancer drugs
|
By 56, a M wants to BE a VP
5-FU --> Thymidine synthesis 6-MP --> Purine synthesis Methotrexate --> Thymidine synthesis Bleomycin --> DNA breakage Etoposide --> DNA breakage (T2 inh) Vinca alkaloids --> MT synthesis Paclitaxel --> MT disassembly Microtubule drugs --> M phase Antimetabolites (56M) --> S phase DNA breakage --> S and G2 |
|
Methotrexate
|
FOLIC ACID analog -->
"tricks" dihydrofolate reductase Reduced dTMP --> Reduced DNA Non-cancer uses (immune): Psoriasis, RA Cancer uses: BM: Leukemia, lymphoma Muscle: Sarcoma Uterus: Choriocarcinoma, abortion, ectopic pregnancy Toxicity: THE THREE M'S Myelosuppression --> LEUCOVORIN RESCUE Mucositis Macrovesicular liver changes |
|
5-FU
|
Pyrimidine (URACIL) analog that forms 5F-duMP in vitro, then grabs FOLIC ACID
*THYMIDYLATE SYNTHASE is inhibited --> low dTMP --> low DNA *Synergy with methotrexate Uses: Colon cancer (+ other solid tumors) Basal cell carcinoma (topical) Toxicity: Myelosuppression --> THYMIDINE RESCUE Photosensitivity |
|
Leucovorin rescue
|
Myelosuppression associated w/Methotrexate
Folic acid analog, DHF reductase inhibitor BM: Leukemia, lymphoma Muscle: Sarcoma Uterus: Choriocarcinoma, abortion, ectopic pregnancy |
|
Thymidine rescue
|
5-FU (fluorouracil)
Uracil analog that grabs folic acid ~ inhibits thymidylate synthase Colon cancer + other solid tumors Basal cell carcinoma (topical) Photosensitivity |
|
6-MP
|
6-mercaptoPURINE
Activated by HGPRTase to block purine synthesis (A, G) Uses: Leukemia (not CLL) Lymphoma (not Hodgkins) Toxicity: Bone marrow, GI, liver 6-MP is metabolized by xanthine oxidase *Allopurinol (XO inhibitor) is bad |
|
Cytarabine (ara-C)
|
Inhibits DNA polymerase
Uses: AML (little beans/kids) Toxicity: Pancytopenia *Anemia is megaloblastic |
|
Alkylating agents
|
DNA CROSS LINKERS
Biased Christian News Channel (the 700 club) 1. Busulfan 2. Cyclophosphamide, ifosfamide 3. Nitrosureas: Carmustine, Lomustine, Semustine, Streptozocin 4. Cisplatin, carboplatin *"Act" like alkylating agents Only 1 group causes myelosuppression: cyclophosphamide, ifosphamide 2 groups need bioactivation: Nitrosureas, cyclophosphamide + ifosphamide |
|
Cyclophosphamide, Ifosfamide
|
*Crosslink interstrand DNA at guanine N-7
Uses: "Women's issues" Lymphoma (non Hodgkins) Breast and ovarian cancer Wegeners, polyarteritis nodosa SE: Myelosuppression Hemorrhagic cystitis (take MESNA) Can cause SIADH |
|
Nitrosureas
|
Alkylating agent
*Requires bioactivation like cyclophosphamide, but NO myelosuppression Carmustine Lomustine Semustine Streptozocin Use: Brain tumors (crosses BBB) SE: CNS effects (dizziness, ataxia) |
|
Cisplatin, Carboplatin
|
LIKE alkylating agents
Uses: BOLT Bladder Ovarian Lung Testicular Toxicity: Acoustic nerve damage Renal damage |
|
Busulfan
|
Alkylating agent
CML Pulmonary fibrosis Hyperpigmentation Busulfan: While riding the CML... *You might get a tan (hyperpigment) *You might want a fan (cause it's hard to breathe) |
|
Doxorubicin/Adriamycin
Daunorubicin |
1. DNA Intercalation
2. Generate free radicals --> Breakage Uses: ABVD regimen HMS LOB: *Hodgkin's lymphoma *Myeloma *Sarcoma *Lung *Ovary *Breast Toxicity: CARDIOTOXICITY MYELOSUPPRESSION Alopecia Toxic extravasation |
|
Dactinomycin
|
A.k.a. Actinomycin D
DNA intercalator Uses: CHILDHOOD tumors (children ACT out) *Ewing's sarcoma *Wilm's tumor *Rhabdomyosarcoma SE: Myelosuppression |
|
SE Common to all intercalators
|
Myelosuppression
Intercalators = Doxorubicin/Adriamycin Daunorubicin Dactinomycin |
|
SE common to all anti-metabolites
|
Myelosuppression
Methotrexate 5-FU 6-MP |
|
Bleomycin
|
Induces free radicals --> DNA breakage
Uses: ABVD cancers (HMS LOB) + Testicular Toxicity: Same as bisulfan Pulmonary fibrosis Skin changes |
|
Hydroxyurea
|
Inhibitor of RIBONUCLEOTIDE REDUCTASE
*DNA synthesis (S phase) reduced Non cancer use: Sickle cell (fetal Hb) Cancer uses: Melanoma *HYDROXYtone: Save the skin CML *HYDROXYcut: Fight the CreaML cheese Toxicity: Marrow suppression |
|
Etoposide
|
Inhibitor of topoisomerase II (DNA breakage/degradation)
Uses: "Men's cancers" Prostate Testicular Small cell lung (historically >men get lung cancer) Toxicity: Like Doxo/Dauno but with no cardiotoxicity Myelosuppression Alopecia |
|
Prednisone and cancer
|
Fights cancer by triggering apoptosis
Uses B CELLS: CLL, Hodgkins |
|
Imatinib
|
Ab to Bcr-abl tyrosine kinase
Uses: CML GI stromal tumor! Toxicity: Fluid retention |
|
Vinblastine, Vincristine
|
Block polymerization of microtubules
*Bind to TUBULIN Uses: MOPP regimen Choriocarcinoma Wilm's Lymphoma Toxicity depends on drug: Vinblastine "BLASTS" the marrow Vincristine causes neurotoxicity: arreflexia, peripheral neuritis, paralytic ileus |
|
Paclitaxel (and other taxols)
|
Block breakdown of mitotic spindle
*Bind to TUBULIN Uses: Ovarian and breast carcinoma Toxicity: PACks a punch against marrow (Myelosuppression) |
|
ABVD regimen
|
Adriamycin/Doxorubicin
Bleomycin Vincristine/Vinblastine Dacarbazine HMS LOB: Hodgkin's Myeloma Sarcoma Lung Ovarian Breast |
|
MOPP regimen
|
B cell things: CLL, lymphoma
Choriocarcinoma, Wilm's tumor Mustardgen (Nitrosurea) Oncovin (Vincristine) Prednisone Procarbazine |
|
Epithelial cell junctions:
|
Sides = Cadherin
Bottom = Integrin Top = Actin Bottom = Keratin (intermediate filament) |
|
Paclitaxel
|
Block breakdown of mitotic spindle
*Bind to TUBULIN Uses: Ovarian and breast carcinoma Toxicity: PACks a punch against marrow (Myelosuppression) |
|
Trastuzumab
|
a.k.a. Herceptin
Monoclonal Ab against HER-2 Ab-dependent cytotoxicity? Used for metastatic breast cancer CARDIOTOXICITY |
|
Skin layers
|
Californians like girls in string bikinis
Stratum corneum Stratum lucidum *Thick skin only Stratum granulosum Stratum spinosum Stratum basalis |
|
Macula adherens
|
3rd highest part of epithelial junction
Consists of DESMOSOMES CADHERIN bridges across KERATIN (intermediate filament) and Desmoplakin plaque anchor Desmoplakin --> Desmosome |
|
Hemidesmosomes
|
Connects keratinocyte to basement membrane
INTEGRIN bridges across *LAMIN on BM side *Keratin on cell side |
|
Knee injury from lateral clipping
|
MCL
Medial meniscus ACL |
|
Rotator cuff muscles
|
SItS
Supraspinatous --> Abduction Infraspinatous --> Lateral rotation Teres minor --> Adduction, lateral rotation Subscapularis --> Adduction, medial rotatio |
|
Brachial plexus
|
Roots: C5-T1
Trunks: Upper (C5-C6) Middle (C7) Lower (C8-T1) Divisions Cords Lateral Posterior Medial Branches Musculocutaneous (LC) Medial (LC, MC) Ulnar (MC) Axillary (PC) Radial (PC) |
|
Brachial plexus problems
|
Upper cord: Erb's palsy (waiter's tip)
Lower cord: Klumpke's palsy (claw hand) Posterior cord: Wrist drop Axillary: Deltoid muscle Radial: Wrist drop (Sat night palsy) Musculocutaneous: Trouble flexing elbow, variable sensory loss Median: Can't make a "thumbs up" (Pope's blessing) *Unopposed radial n action Ulnar: Intrinsic hand muscles (Claw hand) *Weakness of index, middle interosseous muscles causes them to curl *Can't make a "four" (adduct thumb, adduct/abduct fingers) |
|
Winged scapula
|
Problem with long thoracic nerve (C5-C7)
SERRATUS ANTERIOR |
|
Erb-Duchenne palsy
|
Loss of upper cord of the brachial plexus
Deltoid Lateral rotators (infraspinatus, teres minor) Biceps |
|
What protects the brachial plexus from injury, even if clavicle is broken?
|
Subclavius muscle
|
|
Shoulder dislocation
|
Inability to abduct the arm >90 degrees
|
|
Mid-shaft humeral fracture
|
Extensor: Rradial n
Wrist drop Sensory deficit in posterior arm, dorsal hand (grabs the back of median n fingers) Flexor: Musculocutaneous n Can't flex elbow Sensory deficit in lateral arm |
|
Fracture around elbow condoyles or wrists
|
Flexor: Median n
MEDIAN NERVE MAKES A THUMBS UP: Can't flex fingers Can't abduct/oppose thumb Sensory deficit on palm + dorsal tips of 3.5 fingers OR Flexor: Ulnar n ULNAR NERVE MAKES A WIGGLY 4: Can't adduct thumb *Move thumb toward ulnar side Can't adduct or abduct remaining fingers Sensory deficit on palm + dorsal tips of 1.5 fingers |
|
Klumpke's palsy/Thoracic outlet syndrome
|
Congenital/embryologic defect
Compression of lower trunk (C8, T1) *Thenar and hypothenar atrophy *Interosseous atrophy *Sensory deficits on ulnar forearm, 1.5 fingers Compression of subclavian artery *Radial pulse disappears when head turned toward opposite side (increases compression) |
|
Radial nerve structures
|
GREAT EXTENSOR NERVE
Innervates the BEST: Brachioradialis Extensors of wrist and fingers Supinator Triceps |
|
Thenar and hypothenar muscles
|
OAF:
Opponens pollicis/digiti minimi Abductor pollicis/digiti minimi brevis Flexor pollicis/digiti minimi brevis *Joint thenar innervation Thenar = Thumb *Median nerve innervates all 3 muscles *Ulnar nerve innervates flexor Hypothenar = Pinkie *Ulnar n innervates all |
|
Interosseus muscles of the hand
|
Innervated by ulnar nerve
DAB: Dorsal = ABduction PAD: Palmar = ADduction |
|
Anterior hip dislocation
|
Obturator nerve injury:
External obturator Adductor longus/brevis/magnus Gracilis Can't adduct thigh Sensory deficit in medial thigh |
|
Posterior hip dislocation
|
Superior gluteal or inferior gluteal nerves
No sensory deficits Superior: gluteus MEDIUS, MINIMUS *Iliac crest to greater trochanter *Can't abduct thigh (Trendelenberg sign) Inferior: gluteus MAXIMUS *Lumbar fascia to iliotibial tract (mid femur) *Can't climb stairs, rise from seated position, jump |
|
Lateral leg injury (fibular neck)
|
Common peroneal nerve injury
PED: PERONEAL EVERTS, DORSIFLEXES *As a result, food is droPED Can't extend toes Sensory deficit in anterolateral leg, dorsal foot |
|
Knee trauma
|
Tibial nerve injury
TIP= Tibial Inverts, Plantar flexes NO BALLET W/O A TIBIAL NERVE Can't flex toes Sensory deficit on sole of foot |
|
Pelvic fracture
|
Femoral nerve
No more ROCKETTES practice Can't flex thigh or extend leg Sensory deficits: Anterior thigh Medial leg (medial thigh covered by obturator nerve) |
|
Peroneal vs. Tibial nerves
|
PED: Peroneal Everts and Dorsiflexes
*If injured, foot is dropPED TIP: Tibial Inverts and Plantarflexes *If injured, unable to TIPtoe |
|
Ca2+ coupling in muscle cells
|
Voltage gated Ca2+ channel (DIIHYDROPYRIDINE receptor) in T tubule membrane
Ca2+ gated Ca2+ channel (RYANODINE) in sarcoplasmic reticulum |
|
Skeletal, Cardiac muscle contraction
|
Ca2+ binds to troponin C
Tropomyosin complex moves out of actin's myosin binding groove Myosin, w/ADP and Pi present, attaches Pi is spent on power stroke Myosin head is not released until ADP traded for ATP ATP --> ADP + Pi to achieve "cocked" state |
|
Smooth muscle contraction
|
Voltage gated Ca2+ channels
Ca2+ binds Calmodulin Calmodulin-Ca2+ activates MLCK (myosin light chain kinase) MLCK converts Myosin + actin --> Myosin-P + actin (contraction) MLC Phosphatase returns to Myosin + Actin |
|
Endochondral ossification
|
Longitudinal bone growth
Cartilage (chondrocytes) --> Woven bone (osteoblasts/clasts) --> Lamellar bone |
|
Membranous ossification
|
Flat bone growth
*Skull and facial bones *Axial skeleton (skull, ribcage, SC) Woven bone formed directly (no preceding cartilage) Remodeling to lamellar bone (like endochondral) |
|
Achondroplasia
|
Achondroplasia
AD mutation in FGF (fibroblast growth factor) receptor Poor endochondral ossification --> Short limbs Membranous ossification is okay --> Normal lifespan and fertility |
|
Osteoporosis: Features
|
Definition: Reduction in bone mass DESPITE normal mineralization
*Sparse trabeculae *Susceptibility to fracture Type 1: Postmenopausal (low E2) Type 2: Senile (age >70) Typical consequences: *Vertebral crush fractures (height, pain, kyphosis=hump) *Vertebral wedge fractures *Colles' (distal radius) fractures Prophylaxis: Exercise and Ca2+ before age 30 Treatment: *Estrogen (controversial) *Calcitonin *Severe: BISPHOSPHONATES (encourage osteoclast apoptosis) or pulsatile PTH |
|
Colles fractures
|
Osteoporosis-associated
Distal radius |
|
Osteopetrosis
|
Genetic deficiency of CARBONIC ANHYDRASE II
*Used by osteoclasts Poor OSTEOCLAST function --> bone buildup *Thickened, dense bones *"Erlenmeyer flask" epiphyses Complications: *Marrow space lost --> pancytopenia *Narrowed foramina --> CN palsies |
|
Osteomalacia/Rickets
|
Defective mineralization of osteoid (soft bones)
Osteomalacia in adults Rickets in children Cause = Vitamin D deficiency Low Vitamin D --> low Ca2+ --> high PTH --> low serum P --> not enough P to build bone |
|
Osteitis Fibrosa Cystica
|
a.k.a. Brown tumor of bone
a.k.a. Von Recklinghausen's disease of BONE *Osteolytic cysts (brown due to hemorrhage--fibrous stroma or blood inside) Lined w/OSTEOCLASTS High serum Ca2+, low serum P PTH high ALKALINE PHOSPHATASE HIGH |
|
Paget's disease
|
Cause = unknown (possibly viral)
Osteoblastic and osteoclastic activity is abnormally HIGH ALKALINE PHOSPHATASE HIGH *Distinguishes Paget's from osteopetrosis, another bone expanding disease Blood levels of Ca2+, P, and PTH are normal *Also true of osteopetrosis Features: *Mosaic bone pattern w/chalk-stick fractures (cut across lamellae) *High output CHF (pumping blood to affected bone) *Osteogenic sarcoma and fibrosarcoma *Hearing loss (foramen narrowing) |
|
Mosaic bone pattern w/chalk-stick fractures (cut across lamellae)
High output CHF Osteogenic sarcoma and fibrosarcoma Hearing loss |
Paget's disease
Also: High AP w/normal Ca2+, P, PTH CHF = Pumping blood to affected bone Hearing loss = foramen narrowing |
|
Polyostotic fibrous dysplasia
|
McCune-Albright syndrome (sporadic mutation in GNAS1) is an example
Areas of bone lesion replaced by fibroblasts, collagen, irregular trabeculae Cafe-au-lait/Coast of Maine spots Precocious puberty |
|
Benign bone tumors
|
1. Osteoma: New (skull) bone on old
*Gardner's (FAP; features other tissue tumors) 2. Osteoid osteoma: Men under 25 *Woven bone surrounded by osteoblasts *< 2cm *Usually in diaphysis of tibia, femur 3. Osteoblastoma ("blastoma in the back") *An osteoid osteoma bigger than 2 cm *In VERTEBRAL column 4. Osteochondroma/Exostosis: Men under 25 *CHONDROMA COMMON *Most common tumor *Metaphysial *Mature w/cartilaginous cap *Malignant transformation rare 5. Osteoclastoma/Giant cell tumor (20-40) *Aggressive epiphyseal tumor *Occurs near KNEE --> double bubble/soap bubble *Giant cells + spindle cells 6. Enchondroma *Cartilaginous/Intramedullary *DISTAL extremities |
|
Malignant bone tumors
|
Chonology and Diaphysis --> Metaphysis
1. Ewing's sarcoma--Men <15>s triangle, sunburst *Risks: Paget, infarct/radiation, familial RETINOBLASTOMA 3. Chondrosarcoma (Men 30-60) *Cartilaginous/Intramedullary *Glistening mass *PROXIMAL skeleton + humerus, femur, tibia |
|
Osteoarthritis
|
Causes: Weight-bearing wear + tear
*Many years *Many pounds *Joint deformity Articular CARTILAGE only destroyed: *Subchondral cysts (cartilage breakdown) *Slerosis (bone hardening) *Osteophytes (bone spurs) *Eburnation (reactive bone w/abrasion) *Thickened capsule w/slight synovial hypertrophy Heberden's nodes = DIP Bouchard's nodes = PIP *Neither of these have weird punctuation (accents, hyphens like RA does) |
|
Rheumatoid arthritis
|
Classic presentation: 4 S's
*Stiffness (morning) *Symmetric involvement *Systemic symptoms: fever, fatigue *Serositis included in systemic symptoms--pleuritis, pericarditis Joints show pannus formation Subcutaneous rheumatoid nodules Ulnar deviation Subluxation (joint dislocation, slippage) Swan-neck deformity: Hyperextended PIP, hyperflexed DIP *Comes w/Z-thumb deformity: hyperextended PIP Boutonniere deformity: Hyperflexed PIP, hyperextended DIP |
|
Sjogren's
|
When estrogen gets the AXX (age 40-60)
Ribonucleoporotein antibodies: SS-A (ro) and SS-B (la) + *Remember B cell lymphoma assoc A = ARTHRITIS (rheumatoid) X = Xerostomia *Dry mouth, dysphagia *Dental caries *Parotid enlargement X = Xeropthalmia *Dry eyes *Conjunctivitis |
|
Sicca Syndrome
|
Overlap w/Sjogren's
DRYNESS OF ALL MUCOUS MEMBRANES EXPOSED TO AIR Dry eyes Dry mouth Dry nasal passage Dry bronchi --> chronic bronchitis Dry esophagus --> reflux esophagitis Vaginal dryness |
|
Gout
|
Monosodium urate crystals deposited in body
Asymmetric swollen, red joint(s) *MTP of foot often involved --> PODAGRA TOPHI (crystal deposits) in joints, ACHILLES, EXTERNAL EAR Crystals: Needle shape, negatively birefringent **SHAPED LIKE MINUS SIGNS** **YeLLow when paraLLel to light** URIC ACID buildup: *Increased cell turnover (tumor lysis syndrome of leukemia, lymphoma) *Decreased excretion (THIAZIDES, LOOPS) *Lesch-Nyhan (HGPRT deficiency) |
|
Gout: Treatments
|
Allopurinol (Xanthine oxidase inh)
*Affects PURine breakdown *Lymphoma/Leukemia: Prevents tumor lysis syndrome nephropathy Probenecid *Competes w/uric acid for anion channel reabsorption in PCT *SE: Inhibits secretion of penicillin *Probenecid --> Prevents reentry Colchicine *Depolymerizes MTs to stop leukocyte chemotaxis, degranulation *SE: GI *Colchicine: Stops WBCs from coming NSAIDS for inflammation, pain *Indomethicin w/acute gout |
|
Chronic Infectious arthritis
|
TB
Lyme |
|
Psoriatic arthritis
|
HLA-B27 (MHC1) association
More common in males < 1/3 of patients w/psoriasis Papules and plaques w/silvery scaling on EXTENSOR surfaces Acanthosis *Decreased stratum granulosum *Increased stratum spinosum Parakeratosis (hypertrophied corneum w/retained nuclei) --> Scales Auspitz sign: Bleeding when scales are scraped off PSoriasis: Pain Pencil in cup deformity (xray) *Erosion@DIP Stiffness Sausage fingers (Dactylitis) *Entire nail bed may be lost |
|
Sausage fingers
|
Psoriatic arthritis
|
|
Pencil in cup deformity
|
Psoriatic arthritis
|
|
Ankylosing spondylitis
|
HLA-B27 (MHC1) association
More common in males "Bamboo spine": Inflammation of spine + sacroiliac joints Uveitis Aortic regurgitation (aortitis) |
|
SLE
|
90% female
Black = More common, severe Age 14-45 I'M DAMN SHARP Immunoglobins (ds, sm, pl, nuc) Malar rash Discoid rash ANA Mucositis (oropharyngeal ulcers) Neurologic disorders Serositis (pleuritis, pericarditis) HEMATOLOGIC/HILAR/HEART *Hilar adenopathy *Verrucous endocarditis (LSE) Arthritis Renal disorders/Reynaud's *Wire loops, ICs + nephrotic syndrome Photosensitivity |
|
Sarcoidosis
|
Young adults (esp black females)
MAShED GRAIN + Uveitis Macrophages-epitheliod Asteroid bodies in macros ScHaumann bodies in macros (Ca2+, protein inclusions w/large empty space around debris) Erythema nodosum D-Vitamin D activation Gammaglobinemia Rheumatoid arthritis ACE increase Interstitial fibrosis-hilar adenopathy Noncaseating granulomas |
|
Polymyalgia rheumatica
|
Adults >50
Mimics rheumatoid arthritis of the shoulder, hips, but NO BONE EROSION *Stiffness and pain *Symmetrical *Systemic symptoms (fever, malaise, weight loss) No bone or muscle damage: just inflammation *ESR elevated (inflammation) *CK normal (no muscle damage) ASSOCIATED W/TEMPORAL ARTERITIS *Also causes high ESR |
|
Shawl and face rash
Heliotrope rash (whole orbital area) |
Dermatomyositis
= Polymyositis (Proximal muscle weakness) + Rash |
|
Polymyositis + Dermatomyositis
|
CD8 T cells attack myofibers
Increased CK, aldolase (muscle enzymes) + ANA + Anti-Jo-1 (a type of ANA) Polymyositis --> Proximal muscle weakness Dermatomyositis --> Polymyositis + rashes *Heliotrope rash (whole orbital area) *Shawl and face rash (V-shaped rash over anterior neck, chest) Treat w/steroids |
|
Polymyositis + Dermatomyositis: What cell attacks myocytes?
|
CD8
|
|
Myasthenia gravis
|
Antibodies against Ach receptor at NMJ
*Treat with AchE inhibitor May be caused by a thymoma Symptoms worsen w/use: *Ptosis *Diplopia *General weakness Treat w/indirect cholinergics (Ach inhibitors): Neostigmine (bowels and bladder) Pyridostigmine (crosses BBB, glaucoma) Edrophonium (short-acting) |
|
Lambert-Eaton syndrome
|
Antibodies to NMJ presynaptic Ca2+ channel
*Reduced Ach release May be caused by small cell lung cancer (or thymoma) Muscle weakness improves w/use *AchE inhibitors alone will not help |
|
CREST
|
CREST
Cacinosis Reynaud's Esophageal dysmotility Sclerodactyly Telangiectasia |
|
Diffuse Scleroderma
|
FIBROSIS and COLLAGEN deposition
Diffuse: Anti-scl-70 Widespread skin involvement (taut) Rapid progression VISCERAL involvement *Kidneys, Lungs, GI, CV Crest: Anti-centromere Calcinosis Reynaud's Esophageal dysmotility Sclerodactyly *Skin involvement = face + hands Telangiectasia |
|
Rhabdomyosarcoma
|
Most common soft tissue tumor of childhood (soft tissue = muscle, fat, CT?)
SKELETAL muscle origin Usually head/neck |
|
Macule
|
FLAT discoloration < 1 cm
If >1 cm = patch |
|
Papule
|
ELEVATED lesion < 1 cm
If > 1 cm = plaque |
|
Vesicle
|
SMALL FLUID containing blister
If TRANSIENT = wheal If LARGE = bulla If it contains PUS = pustule |
|
Keloid
|
Scar tissue hypertrophy forming an IRREGULAR, RAISED lesion
Especially common w/African Americans |
|
Crust
|
Dried exudates from a BLISTER *vesicle, bulla or pustule
|
|
Hyperkeratosis vs. Parakeratosis
|
Hyperkeratosis: Increased thickness of the stratum CORNEUM (top layer)
Parakeratosis: A.k.a. psoriasis Increased thickness of the stratum CORNEUM (hyperkeratosis) + Retention of NUCLEI in the stratum corneum Causes SCALES |
|
Acantholysis
|
Separation of epidermal cells
|
|
Acanthosis
|
Epidermal hyperplasia
All 5 layers |
|
Verrucae
|
Warts: Cauliflower-like, tan, soft
Acanthosis w/hyperkeratosis Koilocytosis Hands: Verruca vulgaris Genitals: Condyloma accuminatum (HPV) |
|
Urticaria
|
Hives
Mast cell degranulation --> Pruritic wheals |
|
Urticaria
|
Hives
Mast cell degranulation --> Pruritic wheals |
|
Ephelis
|
Freckles
Dark color = Increased melanin pigment |
|
Seborrheic keratosis
|
Common benign neoplasm in older ppl
Flat, pigmented epithelial proliferation that looks "pasted on" *Greasy appearance *Microscopic keratin filled cysts (horn cysts) |
|
Pigmentation disorders
|
Albinism: Defective melanin production
Vitiligo: Irregular areas of complete depigmentation *Loss of melanocytes Melasma: Hormonally-driven hyperpigmentation *Pregnancy *OCP use |
|
Impetigo
|
Very superficial skin infection--> highly contagious
**S. aureus or S. pyogenes** HONEY COLORED CRUSTING |
|
Cellulitis
|
Acute, spreading infection
Dermis and subcutaneous tissue *Reaches the "cellulite" S. Aureus and S. pyogenes (same as impetigo) |
|
Necrotizing Fasciitis
|
Deep tissue injury
Lower O2 content: S. pyogenes and ANAEROBES Methane and CO2 production --> CREPITUS *Flesh-eating bacteria is CREEPY |
|
Scalded skin syndrome
|
Seen in newborns and kids
Staph aureus exotoxins (A, B) responsible Stratum GRANULOSUM keratinocyte attachments are destroyed by exotoxin *Granulosum = Highest layer w/nuclei that is guaranteed to be there Fever Erythemetous rash w/sloughing |
|
Hairy Leukoplakia
|
Seen w/HIV
Caused by immunodeficiency (EBV) White, painless plaques on tongue CAN'T be scraped off |
|
Bullous pemphigoid
|
He got a HEMI? That's BULL
IgG antibody against HEMIDESMOSOMES *Subepidermal bullae Linear immunofluorescence below epidermis Oral mucosa NOT involved |
|
Pemphigus vulgaris
|
Vulgar mouth
IgG antibody against DESMOSOMES *Acantholysis --> Intraepidermal bullae Immunogluorescence throughout epidermis Oral mucosa IS involved |
|
Dermatitis herpetiformis
|
Dermal deposits of IgA --> Pruritic papules and vesicles
IgA is deposited at tips of dermal PAPILLAE (highest point of dermis) Associated w/celiac disease |
|
Erythema multiforme
|
Associated w/many causes and takes on many forms
Causes: Infections, drugs, cancers, autoimmune disease Forms: All SMALL Macules (vs. patches) Papules (vs. plaques) Vesicles (vs. bullae) TARGET lesions (red papule w/pale center) |
|
Stevens-Johnson
|
Adverse drug reaction
Fever Bulla formation --> necrosis --> sloughing High mortality rate, but not as severe/not as much epidermal involvement as TOXIC EPIDERMAL NECROLYSIS |
|
Lichen planus
|
Lymphocytes infiltrate the DEJ
4Ps: Pruritic Purple Polygonal papules |
|
Squamous cell carcinoma
|
RED
Caused by SUN and ARSENIC exposure Precursor is ACTINIC KERATOSIS Rarely metastasizes RED lesion w/microscopic keratin pearls |
|
Basal cell carcinoma
|
Caused by SUN
Almost never metastasizes Pearly lesion Rolled (raised) edges w/central ulceration |
|
Melanoma
|
Caused by SUN
More common in fair-skinned people S-100 tumor marker Dark w/irregular borders Precursure is DYSPLASTIC NEVUS DEPTH of tumor correlates w/risk of metastasis |
|
PGI2
|
"Platelet gathering inhibitor"
Stops platelet aggregation and promotes vasodilation Stops thromboxane production in platelets (same step as aspirin) |
|
Leukotrienes
|
LTB4 --> Neutrophil chemotactic agent
*Neutrophils arrive "B4" others LTC4, LTD4, LTE4: *Contraction of smooth muscle: vasoconstriction, bronchoconstriction *Increased vascular permeability |
|
Prostacyclins
|
Soothing
Decrease everything: Platelet aggregation Smooth muscle (broncho, vasoconstriction) Uterine tone |
|
Prostaglandins
|
Decrease:
Smooth muscle (broncho, vasoconstriction) Increase (get a glandular organ going): Uterine tone |
|
Thromboxane
|
"Upper for the blood":
Platelet aggregation Smooth muscle (broncho, vasoconstriction) |
|
Zileuton
|
5-Lipoxygenase inhibitor
*Prevent leukotrienes from being synthesized Asthma prophylaxis SE: P-450 induction, leukopenia (1%) |
|
Zafirlukast, Montelukast
|
Antibodies to leukotriene receptor
Asthma prophylaxis |
|
Zafirlukast, Montelukast
|
Antibodies to leukotriene receptor
Asthma prophylaxis |
|
NSAIDS
|
Ibuprofen, naproxen, indomethacin, ketorolac
Block COX-1 and COX-2 Objective: Inhibits PG synthesis Uses: Antipyretic, anti-inflammatory, analgesic *Indomethacin: Close PDA Toxicity: RAG *RENAL DAMAGE *APLASTIC ANEMIA *GI distress, ulcers |
|
Acetaminophen
|
Reversibly inhibits COX
*Mostly in CNS, due to peripheral activation Uses: Antipyretic, analgesic *NOT AN ANTI-INFLAMMATORY (aspirin and NSAIDS are) Tox: Hepatic necrosis following depletion of glutathione *N-acetylcysteine = antidote |
|
Astrocyte functions
|
Support/repair
K+ metabolism BBB Marker: GFAP |
|
Microglia
|
Macrophages of the brain
Mesodermal (like macrophages) Multinucleated giant formation (HIV) Small nuclei Little cytoplasm --> Ameboid with injury Not very visible on Nissl stain |
|
Oligodendrocytes
|
Myelinates up to 30 axons
Destroyed in MS Small nuclei w/little cytoplasm Fried eggs on H&E stain Visible on Nissl stain |
|
Peripheral nerve wrappings
|
Endoneurium = Single axon
Perineurium = Bundle of axons *PERMEABILITY BARRIER *Rejoin during surgery Epineurium = Vessels and bundles |
|
Blood brain barrier layers (3)
|
1. Endothelial cells (tight junctions)
*Damage/destruction = vasogenic edema 2. Basement membrane 3. Astrocyte processe |
|
Areas w/o blood brain barrier (2)
|
Area postrema (informational blood sampling)
Neurohypophysis/PP: Excretion of oxytocin, ADH |
|
Hypothalamic functions
|
The hypothalamus wears TAN HATS:
Thirst --> Supraoptic nucleus *ADH also secreted from here Adenohypophysis Neurohypophysis + median eminance Hunger and satiety *Ventromedial = Satiety *Hunger = Lateral Autonomic regulation, circadian rhythm *pArasympathetic = Anterior *Sympathetic = Posterior *Circadian = Suprachiasmatic Temperature regulation *Cooling = Anterior (A/C) *Heating = Posterior (pH) Sexual urges and emotions *Septal nucleus = Control |
|
Posterior pituitary hormone sources
|
Oxytocin: Paraventricular
Vasopressin/ADH: Supraoptic *Area controlling thirst |
|
Thalamus supplying arteries
|
1. Posterior communicating arteries
2. Posterior cerebral 3. Anterior choroidal |
|
Thalamus functions
|
LGN --> "Light" (visual relay)
MGN --> "Music" (audio relay) VA/VL --> Motor VPL --> Body sensation *From dorsal columns + spinothalamic tract VPM --> Face sensation *From CN V *"Makeup on your face" |
|
Limbic system
|
CHFM
Cingulate gyrus Hippocampus Fornix Mammillary bodies The 5 F's: Fight, Flight Feeding, feeling... |
|
Cerebellar fibers
|
Climbing, mossy = Input
Purkinje = Output |
|
Basal ganglia: Excitatory pathway
|
D1 receptor binding = Excitement of excitatory pathway
1. Striatum (caudate, putamen) inhibits GPi 2. GPi stops inhibiting thalamus 3. Thalamus can stimulate cortex Striatum (-) --> GPi (-) ---> Thalamus |
|
Basal ganglia: Inhibitory pathway
|
D2 receptor binding = Inhibition of inhibitory pathway
1. Striatum is inhibited from inhibiting GPe 2. GPe is free to inhibit STN 3. STN stops stimulating GPi 4. GPi stops inhibiting Thalamus 5. Thalamus can stimulate cortex Striatum(-) --> GPe (-) --> STN (+) --> GPi (-) --> Thalamus |
|
Primary auditory cortex location
|
Heschl's gyrus
Just under posterior Sylvian fissur |
|
Wernike's area is...
|
Associative auditory cortex
Superior temporal gyrus |
|
"Arteries of stroke"
|
Lateral striate arteries (from MCA)
Supply striatum (caudate, putamen), globus pallidus, internal capsule |
|
Most common sites of aneurysm
|
Anterior communicating artery
*Most common circle of Willis aneurysm site *May cause visual field defects Posterior communicating artery *May cause CNIII palsy |
|
Anterior cerebral artery stroke
|
Anterior circle = Sensory and motor dysfunction:
*ACA: Leg-foot area sensory and motor deficits *MCA: *Trunk-arm-face sensory and motor deficits + Wernike's area + Broca's area Posterior circle = *CN deficits: Ocular (CNIII), vertigo *Visual disturbances *Cerebellar deficits *Coma |
|
CSF path through ventricles
|
Lateral ventricles --> 3rd ventricle
*Via foramen of Monro 3rd ventricle --> 4th ventricle *Via cerebral aqueduct 4th ventricle --> Subarachnoid space *Lateral = Luschka *Medial = Magendie Monro vs. Magendie: Shorter name for smaller ventricle # (ventricle 3 vs. 4) |
|
Most common site of vertebral disk herniation
|
L5-S1
Why don't you balance a circle on a triangle! |
|
Lumbar puncture
|
L3-5 keeps the spinal cord alive
SC extends to lower border of L1-L2 CSF extends to lower border of S2 Ligaments pierced in the following order: Supraspinous, interspinous, ligamentum flavum |
|
Arachnoid granulations
|
Allow CSF to travel through arachnoid + meningeal layer of dura (periosteal layer not crossed)
|
|
Fasciculus gracilis
|
Allow CSF to travel through arachnoid + meningeal layer of dura (periosteal layer not crossed)
|
|
Fasciculus cuneatus
|
Arms, upper body
Dorsal, lateral placement |
|
Spinothalamic tract and corticospinal tract vs. posterior columns
|
Posterior columns: Gracilis is MEDIAL
Everywhere else: Legs are lateral while arms are medial |
|
Path of a dorsal column signal
|
Sensory nerve (CB @ dorsal root):
*1 end connects to sensory site *Other end ascends ipsilateral cord and synapses in ipsilateral medulla *Synapse site: Nucleus cuneatus or gracilis 2nd neuron decussates travels from nucleus cuneatus/gracilis to VPL of thalamus 3rd neuron travels from VPL to cortex |
|
a spinothalamic tract signal
|
Sensory nerve (CB @ dorsal root):
*1 end connects to sensory site *Other end stops in ipsilateral gray matter 2nd neuron travels from ipsilateral gray matter across anterior white commissure and up cord to VPL 3rd nerve travels from VPL to thalamus |
|
Path of a corticospinal signal
|
UMN ~ Unitary neuron
UMN leaves cortex and descends ipsilaterally through brain Decussation at the caudal medulla and continuation to the anterior horn 2nd cell starts at anterior horn (LMN) and continues to NMJ |
|
Cervical dermatome landmarks
|
C2: Posterior 1/2 of a "skull cap"
*Includes most of ear and underneath chin C3: Neck of a turtleneck shirt C4: Turleneck - Boat neck shirt |
|
Thoracic dermatome landmarks
|
T4: "teat pore" (nipple)
T7: Xiphoid process T10: Belly butTEN (Umbilicus) *Detection of early appendicitis |
|
Lumbar/Sacral dermatome landmarks
|
L1: Inguinal ligament
L4: Includes the kneecaps S2,3,4: Erection and sensation of genitals, anal zone *"S2-4 keeps the penis off the floor" |
|
Gall bladder pain referral
|
Right shoulder
Via phrenic nerve (C3-5) |
|
Golgi tendon organ
|
Found at muscle insertion points
Monitors tension --> if too high, sends inhibitory feedback to alpha motor neurons **Drop the suitcase that is going to tear the muscle** |
|
Muscle spindle
|
Found in parallel with regular muscle fibers
Spindles = Intrafusal *Intrinsic tension is guided by gamma motor neurons *Gamma neuron stimulation increases the sensitivity of reflex arc Stretch causes 1a sensory transmission to cord --> returns an alpha motor neuron signal to contract Regular muscle fibers = Extrafusal |
|
Biceps reflex: Involved spinal levels
|
C5 --> C6
Think about musculocutaneous nerve damage: trouble flexing elbow (problem w/biceps) |
|
Triceps reflex: Involved spinal levels
|
C7 --> C8
Think about radial nerve: damage causes problems w/arm extensors (wrist drop, elbow extension) |
|
Patellar reflex: Involved spinal levels
|
L4 --> L3
L4: L is 4 for Leg |
|
Achilles reflex: Involved spinal levels
|
S1 --> S2
Achilles: "All the way down" |
|
Cranial nerve placement
|
Most medial: All motor
3 (x2) 6 (x2) 12 Midbrain: 3-4-5 *Just anterior to cerebellum Pons: 6-7-8 *Just behind cerebellum Medulla: 9-10-11-12 *Down sides brainstem |
|
Superior colliculus function
|
Conjugate vertical gaze center
Lesion (such as pinealoma) --> Vertical conjugate gaze palsy Conjugate gaze palsy: Inability to move both eyes in a particular direction |
|
Only CN without a thalamic relay to cortex
|
CN 1
|
|
Cranial nerves: Sensory and Motor
|
1: Some --> Smell
2: Say --> Sight 3: Marry --> Eye 4: Money --> Eye 5: But --> Mastication, facial and anterior 2/3 tongue sensation 6: My --> Eye movement 7: Bro --> Facial movement, taste (anterior 2/3), etc 8: Says --> Hearing, vestibular 9: Big --> Pharynx movement, taste (posterior 1/3), etc. 10: Brains --> Pharynx, taste (pharynx), etc. 11: Matter --> Head turn, shrug 12: Most --> Tongue |
|
Cranial Nerve 2
|
Optic nerve
Entirely sensory Enters brain between anterior communicating artery and MCA |
|
Cranial Nerve 3
|
Oculomotor nerve
Entirely motor Enters brain behind PCA 1. All oculomotor muscles EXCEPT: *Lateral rectus (CN VI) *Superior oblique (CN IV) 2. Pupil constriction (Sphincter Pupillae) 3. Accomodation (Ciliary muscle) 4. Eyelid opening (Levator Palpebrae) Loss: Eye appears "down and out" *Pupil dilation *Poor accomodation *Drooping eyelid |
|
Cranial Nerve 4
|
Trochlear nerve
Entirely motor Superior oblique muscle: AIDs the eye *Abducts *Intorts *Depresses Loss: *DEFECTIVE downward gaze *Diplopia |
|
Cranial Nerve 5
|
Trigeminal nerve
Sensory and motor Sensory: Facial sensation (includes CORNEA) Palate/teeth/gums Parts of meninges Motor: Muscles of TTT MAD MOUTH TTT MAD: Tensor tympani Tensor veli palatini anterior Tongue (Two-thirds) Mylohyoid Anterior belly of Digastric Mouth =Mastication (Masseter, pterygoids, temporalis) [Mouth =Meckel's cartilage Malleus (+incus) Mandible SphenoMANDIBULAR ligament] |
|
Cranial nerve 9
|
Glossopharyngeal
Sensory and motor Sensory: Pharynx Posterior 1/3 of tongue Carotid body and sinus Salivation (Parotid) Branchial arch 3: Cartilage --> Greater horn of hyoid *Great enough to have its own arch Tongue: Posterior 1/3 (with arch 4) Muscle: Stylopharyngeus |
|
Cranial Nerve 7
|
Facial nerve
Sensory and motor Sensory: Taste from anterior 2/3 of tongue Lacrimation Salivation (submandibular, sublingual) Motor: SS FACES the PD (branchial arch 2) Stapedius Stylopharyngeus (w/LH, styloid process) Facial muscles --> EYELID CLOSURE Posterior belly of the digastric |
|
Cranial Nerve 10
|
Vagus nerve
Sensory and motor Sensory: Somatic: Posterior 1/3 tongue (w/9) Taste from epiglottis region Thorax/abdomen (visceral) Aortic arch chemo/baroreceptors Branchial arch 4 structures: S. recurrent laryngeal nerve *Posterior 1/3 of tongue *Levator veli palatini: palate elevation *Constrictors: Swallowing *Cricothyroid: Talking Branchial arch 6 structures: I. Recurrent laryngeal nerve *Internal muscles of larynx: Talking |
|
Cranial nerve 11
|
Spinal accessory nerve
Purely motor SCM Trapezius |
|
Clinical reflexes
|
Corneal: 5(1) --> 7 (Orb oris)
Lacrimation: 5(1) --> 7 Pupillary: 2 --> 3 (sphincter pupillae) Jaw jerk: 5(3) --> 5(3) Gag: 9 --> 9, 10 |
|
Vagal nuclei
|
Nucleus Solitarius: SPECIAL SENSORY 7, 9, 10
*Taste *Baroreceptors *Visceral sensory (gut distention) Nucleus ambiguus: 9, 10, 11 *Motor innervation of pharynx, larynx, upper esophagus Dorsal motor nucleus: 10 only *The CRANIO of craniosacral *Parasympathetic fibers *Heart, lungs, upper GI |
|
Skull foramina
|
Optic canal:
*CN II *Opthalmic artery *Central retinal vein Superior orbital fissure: *CN 3, CN 4, CN 5-1, CN 6 *Opthalmic vein Foramen rotundum: CN V-2 Foramen ovale: CN V-3 Foramen spinosum: Middle meningeal artery *SPIN a MENINge Internal auditory meatus: CN VII-VIII Jugular foramen (CN 9-11) Hypoglossal canal CN 12 Foramen magnum: *Spinal roots of 11 *Brainstem *Vertebral arteries CN V mnemonic: *SRO (standing room only) or *V-1 for your S.O.F. eyes *V-2 for your ROUND cheeks *V-3 for your OVAL mouth |
|
Muscles of mastication
|
CN V-3
M's munch Medial pterygoid TeMporalis Masseter Lateral lowers: Lateral pterygoid |
|
KLM Sounds
|
Kuh = Palate elevation = CN X
La = Tongue = CN 12 Mi = Lips = CN |
|
Glossus and Palat rules
|
All muscles w/GLOSSUS in the name are innervated by CN 12
Exception: PALATOGLOSSUS *Fight between palat and glossus rules--CN X wins All muscles w/PALAT in the name are innervated by CN 10 Exception: TENSOR VELI PALATINI (too "tense" to go to vagus) *CN V-3 |
|
Sensory corpuscles (4)
|
1. Free nerve endings (A-delta, C)
*Pain, temp *All skin 2. MeiSSner's corpuscles (40% fingertip) *SMOOTH SKIN (glabrous) *Dynamic fine touch (impeded by hair?) 3. Pacinian corpuscles (15% fingertip) *Feels powerful forces (VIBRATION) *Deep skin layers, ligaments, joints 4. Merkel's disks (25% fingertip) *STATIC TOUCH *Cup-shaped --> hair follicle |
|
Inner ear components
|
Outer shell = Bony labyrinth *3 compartments: cochlea, vestibule, semicircular canals
*Filled with perilymph (ECF, Na+) Membranous labyrinth = cochlear duct, utricle, saccule, semicircular canals *Filled w/endolymph (ICF, K+) STRIA VASCULARIS makes endolymph Utricle/Saccule: Otolith organs *Maculae --> Thickened platforms *Detect LINEAR acceleration Semicircular canals *Ampullae: Cupula sitting over hair cells *Detect angular acceleration Organ of corti: Contains hair cells Cochlear membrane: Scuba flipper *High frequency = base |
|
Hearing loss: Conductive vs. Sensorineural
|
CONDUCTIVE LOSS: Sounds louder when it's touching
Weber *Conductive: louder on affected side *Sensorineural: softer on affected side Rinnie: Conductive: bone > air Sensorineural: air > bone |
|
Canal of Schlemm
|
Collects aqueous humor from front chamber of eye and delivers to blood
|
|
What enters eye w/the optic nerve?
|
Central retinal artery and vein
Optic nerve, opthalmic artery and central retinal vein go through the optic canal *Central retinal artery is a branch of the opthalmic artery |
|
Ocular testing
|
Look lateral = Lateral rectus
Look medial = Medial rectus Look up and lateral = Superior rectus *Lateral circumvents influence of inferior oblique Down up and lateral = Inferior rectus *Lateral circumvents influence of superior oblique |
|
Ocular testing
|
Look lateral = Lateral rectus
Look medial = Medial rectus Look up and lateral = Superior rectus *Lateral circumvents influence of inferior oblique Down up and lateral = Inferior rectus *Lateral circumvents influence of superior oblique |
|
Pupillary light reflex
|
CN II sends a signal to pretectal (before Sup Colliculus) nuclei in midbrain
Pre-tecal nuclei activate Edinger-Westphal nuclei Bilateral accomodation via CN III *Ciliary ganglion (lens), sphincter pupillae muscle (pupil) |
|
Visual field defects
|
Optic nerve: 1 entire eye
Optic chiasm: Bitemporal hemanopsia Optic tract (past chiasm): L/R field from EACH eye Dorsal optic radiations (parietal lobe): Lower L/R quadrant of EACH eye *Dorsal down Meyer's loop (temporal lobe): Upper L/R quadrant of EACH eye *Temoral upper: Mrs. Meyers bought TUPperware Late Meyer's loop (Calcarine fissure): Everything EXCEPT for macula |
|
Internuclear opthalmoplegia
|
Defects associated w/MS
When looking left, the left eye lateral rectus muscle fires Signal is sent to MLF of the right eye Tells Medial Rectus Subnucleus of CN III to contract R medial rectus If this does not happen, laterally looking eye has nystagmus |
|
Spina bifida: Subtypes
|
All feature elevated alpha-fetoprotein
OCCULTA: Failure of bony spinal canal to close, but NO structural herniation *TUFT OF HAIR on back *Dura is intact (others are not totally enclosed by dura) MENINGOCOELE: Failure of bony spinal canal to close + Meninges herniate through defect MENINGOMYELOCOELE: Failure of bony spinal canal to close + Meninges AND spinal cord herniate through defect |
|
Brain derivatives
|
Telencephalon
*Cerebral hemispheres *Lateral ventricles Diencephalon: *Thalamus, hypothalamus *3rd ventricle Mesencephalon: *Midbrain *Cerebral aqueduct (along w/pons) Metencephalon: pons + cerebellum MEET *Pons, cerebellum *Pons --> Cerebral aqueduct (along w/midbrain) *Cerebellum --> 4th ventricle |
|
Holoprosencephaly
|
Failure of hemispheres to separate
May cause cyclopia Causes: Fetal alcohol syndrome Trisomy 13 (Patau's syndrome) |
|
Multiple sclerosis: SC Damage
|
Random damage
Usually in the CERVICAL cord Motor: UMNs and LMNs can be affected Sensory: Dorsal columns and spinothalamic |
|
ALS: Spinal cord lesions
|
Motor only
UMNs and LMNs |
|
Poliomyelitis
Werdnig-Hoffmann disease (Infantile Spinal Muscular Atrophy) |
Anterior horn destruction: LMNs
Wednig-Hoffmann disease is a genetic (AR) disease (a.k.a. Infantile Spinal Muscular Atrophy, or SMA Type 1) *SMN gene *Floppy baby w/tongue fasciculations *Median age of death = 7 months |
|
Anterior spinal artery occlusion
|
Atrophy of all neurons in cord EXCEPT:
*Dorsal columns |
|
Tabes dorsalis
|
Tertiary syphilis
Dorsal roots AND dorsal columns destroyed Diminished sensation: *Proprioception/touch below highest lesion point --> locomotor ataxia *P/T information at every level of dorsal root destruction |
|
Syringomyelia
|
Enlargement of the central canal of the spinal cord
*Associated w/Arnold-Chiari formation *Most common in C8-T1 Damages anterior white commissure *Local (extremities) bilateral loss of pain and temperature sensation |
|
Horner's Syndrome
|
Occurs w/CERVICAL lesions
(lesions above T1) 1. Descending sympthatic input from hypothalamus synapses in lateral horn of T1 2. 2nd neuron enters cervical chain (adjacent to cord) and synapses in superior cervical ganglion (at level of T2) 3. 3rd neuron goes to: *Eyelid --> Ptosis if lost *Facial sweat glands --> Anhidrosis if lost *Pupil --> Constriction if lost "PAM is horny" Pancoast's tumor (superior lung) Brown sequard Sever syringomyelia |
|
Symptoms of arcuate fasciculus lesion
|
Arcuate fasciculus connects Broca's and Wernike's area
Conduction aphasia = Poor repetition Good comprehension Fluent speech |
|
Re-emergency of primitive reflexes
|
Frontal lobe lesion
|
|
Cerebellar structure and defects
|
Hemispheres: IPSILATERAL limb effects
*Intention tremor Vermis lesion = TRUNCAL effects *Dysarthria (speech) |
|
Subthalamic nucleus
|
Contralateral hemiballismus (violent thrashing movements)
|
|
PPRF lesions and FEF lesions
|
PPRF
Paramedian pontine reticular formation (PPRF) lesions: Eyes look AWAY from lesion ("blemish")...only wants to see PPRFect things FEF lesions: Eyes look TOWARD lesion Saccades, eye movements |
|
Broca's area
Wernike's area |
Inferior frontal gyrus
Superior temporal gyrus |
|
Alzheimer's: What correlates w/the degree of dementia?
|
Neurofibrillary tangles
Phosphorylated Tau Intracellular |
|
Alzheimer's Disease
|
Diffuse CORTICAL atrophy
Extracellular: B-amyloid plaques Intracellular: Neurofibillary tangles *Abnormally phosphorylated Tau protein *CORRELATES w/degree of dementia Down syndrome Familial (10% of cases) *APO-E: Chromosomes 1, 14, 19 *p-App gene: Chromosme 21 |
|
Alzheimer's Disease
|
Diffuse CORTICAL atrophy
Decreased Ach Extracellular: B-amyloid plaques Intracellular: Neurofibillary tangles *Abnormally phosphorylated Tau protein *CORRELATES w/degree of dementia Down syndrome Familial (10% of cases) *APO-E: Chromosomes 1, 14, 19 *p-App gene: Chromosme 21 |
|
Pick's Disease
|
Frontotemporal lobe atrophy
*Pick bodies (aggregated TAU) Dementia Parkinsonism (Basal ganglia) APHASIA (Broca involvement) |
|
Lewy body dementia
|
Dementia
Parkinsonism HALLUCINATIONS Lewy bodies are made of Alpha synuclein |
|
Huntington's
|
Chromosome 4 (Hunting 4 food)
Autosomal dominant CAG triplet repeat: *Caudate atrophy *Anticipation *GABAergic neurons lost *Decreased Ach |
|
Freidrich's Ataxia
|
AR mutation of chromosome 9 (FRATAXIN)
*Increased trinucleotide repeats Seen in children 5-15 years old 1. Posterior column, corticospinal and spinocerebellar degeneration *Gait ataxia (seen early) *Kyphoscoliosis, PES CAVUS (fixed plantar flexion), hammer toes 2. >50% develop hypertrophic cardiomyopathy *Arrhythmias *CHF 3. ~10% develop DM |
|
MS
|
PERIVENTRICULR plaques: Oligodendrocyte loss and reactive gliosis
Classic symptoms: GOSHIN *IgG in CSF *Optic neuritis *Scanning speech *Hemiparesis/sensory *Intention tremor *Incontinence *Internuclear opthalmoplegia *Nystagmus Treatment: Beta interferon or immunosuppressants |
|
Albuminocytologic dissociation
|
CSF finding w/Guillian Barre
Probably due to Ab content *High Protein *Normal WBCs (no "pleocytosis") *Papilledema |
|
Partial Seizures
|
Involve 1 region of the brain
Can secondarily generalize Simple = Consciousness intact *Motor, sensory *Autonomic *Psychic Complex: Impaired consciousness |
|
Generalized seizures
|
Diffuse involvement
*Tonic ~ stiffening *Clonic ~ movement 1. Absence (petit mal) = blank stare 2. Myoclonic = Quick, repetitive jerks 3. Tonic-clonic (grand mal) = Alternating stiffening and movement 4. Tonic = Stiffening 5. Atonic = Drop seizures *Commonly mistaken for fainting |
|
#1 Causes of seizures
|
Children: Genetics
Adults: Tumor Elderly: Stroke |
|
Epidural hematoma
|
Middle meningeal artery
Often after fracture of temporal bone Biconvex disk DOES NOT cross suture lines |
|
Subdural hematoma
|
Bridging veins
Less pressure than epidural hematoma --> Delayed onset of symptoms Crescent-shaped hemorrhage that crosses suture lines Risk factors: Brain atrophy, shaking, whiplas |
|
Subarachnoid hematoma
|
Aneurysm or AVM rupture
"Worst headache of life" Spinal tap: Bloody or yellow (Xanthochromic--broken down RBCs) |
|
Parenchymal hematoma
|
Vessel issues:
*HTN *Amyloid angiography *DM Tumor |
|
Charcot-Bouchard Microaneurysms
|
Associated with chronic HTN
Affects small vessels |
|
Berry Aneurysms
|
Occur at bifurcations in the Circle of Willis
*Most commonly ACA Rupture --> SAH Risk factors: 1. HTN + smoking 2. Advanced age Populations: 1. More common in blacks 2. Diseases: *Adult PCKD --> Generalized collagen and ECM abnormality *Ehlers-Danlos --> Collagen 3 *Marfan --> Fibrillin |
|
Normal pressure hydrocephalus
|
No obstruction = communicating
*Arachnoid GRANULATION prob NORMAL opening pressure Enlarged ventricles Symptoms: "Weird GAIT, can't WAIT, and a little CRAZED" *Gait problems *Urinary incontinence *Dementia |
|
Adult brain tumors: Supra or infratentorial?
|
Supratentorial
Adults are taller than kids (infratentorial) |
|
Adult brain tumors
|
Supratentorial
GOP MS G > M > S > O 1. Glioblastoma multiforme: *Grade IV Astrocytoma (stains GFAP) *CEREBRAL HEMISPHERES *PSEUDOPALISADING cells border areas of necrosis, hemorrhage 2. Oligodendroglioma *Rare, slow growing *FRONTAL LOBES *Chicken-wire capillary pattern *OLIGO ~ OCTAGON (chicken-wire capillaries) 3. Pituitary adenoma (Rathke's pouch) *Usually prolactinoma *Bitemporal hemanopsia *Hyper or hypoactive 4. Meningioma (Arachnoid origin) *Found on surface of brain *Concentric, whorled spindle cells *Psammoma bodies (concentric calcifications) 5. Schwannoma (Schwann cells) *Often CN VIII *NF2: Bilateral schwannomas |
|
Childhood primary tumors (5)
|
CHEMP
FIRST AND LAST are supratent, benign Hydrocephalus ~ Rosettes 1. CranioPHARYNGIOMA (benign) *Most common childhood supratentorial *Origin: RATHKE'S POUCH remnants *Tooth enamel-like calcification *Confused w/pituitary tumor 2. Hemangioblastoma *Cerebellar *FOAMY cells w/high vascularity *EPO SECRETION --> Polycythemia *VON-HIPPEL-LANDAU 3. Ependymoma (Poor prog) *Usually in 4th ventricle --> hydroceph *Perivascular pseudorosettes 4. Medulloblastoma (Poor prog) *Cerebellar: can compress 4th ventricle *Considered a PNET tumor *Rosettes or perivascular pseudorosettes 5. Pilocytic astrocytoma (benign) *PILE OF STARS *Posterior fossa (but supratentorial) *ROSENTHAL fibers (pink, corkscrew) |
|
Posterior fossa malformation
|
Arnold chiari malformations:
Small posterior fossa --> Cerebellar displacement, medulla deformity Chiari 1: Often asymptomatic *Tonsils descend *Medulla compressed (CSF flow) Chiari 2: Fatal *Tonsils and VERMIS descend *MEDULLA descends Dandy walker: *Large posterior fossa *Cerebellum replaced by cyst |
|
Physical signs and cranial nerve lesions
|
Ipsilateral (4):
CN 12: Tongue deviates TOWARD lesion *"Lick your wounds" CN 11: Shoulder droops on SAME side *Trouble turning head toward contralateral side CN V: Jaw deviates toward SAME side Cerebellum: Patients fall TOWARD lesion Contralateral signs (1) CN X: Uvula deviates AWAY from lesion |
|
Bell's Palsy
|
Facial motor nucleus has BILATERAL input for upper face (ipsilateral intact) but CONTRALATERAL input for lower face and orbicularis oris (lost)
UMN: Lost movement on contralateral side, LOWER FACE ONLY *Includes ability to close eye LMN: Hemiparesis of face Causes: ALexander (BELL) has an STD: AIDS Lyme Sarcoidosis Tumors Diabetes |
|
Cingulate herniation
|
A.k.a. subfalcine herniation
Herniation through falx cerebri May compress anterior cerebral artery |
|
Uncal herniation
|
A form of transtentorial herniation
Uncus = Medial temporal lobe/hippocampus DURET hemorrhages *Paramedian artery rupture *Caused by caudal displacement of brainstem Signs: TRUST THE EYES Ipsilateral dilated pupil/ptosis *Stretching of CNIII Contralateral homonymous hemanopia *Compression of ipsilateral PCA Ipsilateral paresis *FALSE localizing sign *Contralateral crus cerebri are compressed *KERNOHAN'S notch (indentation in peduncle) is formed |
|
Opiod analgesics
|
Methodone - addiction maintenance
DEXTROmethORPHAN - cough *Sick right-handed orphan Loperamide - diarrhea DIPHENOXYLATE - diarrhea Morphine FENTANYL Codeine Heroin MEPERIDINE General uses: 1. Pain 2. Acute pulmonary edema (respiratory depression) Toxicity: Miosis (PINPOINT) Constipation Respiratory depression CNS depression Addiction Antidote: Naloxone, naltrexone |
|
Topiramide
|
Anti-seizure med
Increases GABA action (like benzodiazepines, phenobarbitol) Blocks Na+ channels (like Lamotrigine) Uses: Partial and tonic-clonic seizures SE: Part of GTP Sedation Kidney stones (toppling stones) Weight loss (good if you top scales) |
|
Lamotrigine
|
Blocks Na+ channels (like Topiramide)
Uses: Partial and tonic-clonic seizures SE: Stevens-Johnson |
|
Gabapentin
|
Anti-seizure and neuropathy med
Increases GABA release (unique) Uses: 1. Partial and tonic-clonic seizures 2. Peripheral neuropathy (pain) SE: Gab that AS Ataxia Sedation (part of GTP) |
|
Valproic acid
|
Anti-siezure med
Increases GABA concentration (unique) Inactivates Na+ channels (like carbamazepine, phenytoin) Uses: *Partial and tonic-clonic seizures *Myoclonic seizures *Absence seizures (2nd line) SE: *Hepatotoxicity (like carbamazepine) *Not for use in pregnancy (like carbamazepine, phenytoin)--NTD defects *Weight gain (gain VALume), despite GI effects *Tremor |
|
Carbamazepine
|
Inactivate Na+ channels (like phenytoin, valproic acid)
Uses: 1. Partial and tonic-clonic seizures 2. Trigeminal neuralgia SE: *DAP: Diplopia, Ataxia, P-450 *Hepatotoxicity (like valproic) *Teratogen (valproic, phenytoin) *Blood changes (like phenytoin), including aplastic anemia, agranulo |
|
Phenytoin
|
Inactivates Na+ channels (like carbamazepine, valproic acid)
*USE-DEPENDENT Uses: 1. Partial and tonic-clonic seizures 2. Class IB anti-arrhythmic 3. Prevention of status epilepticus SE: *DAPS: Diplopia, ataxia, P-450, sedation *Teratogen (like carba, valproic)-Fetal Hydantoin *Blood changes (like carba): MB anemia *Phenny looking: Nystagmus, SLE-like, Hirsutism, Gingival hyperplasia |
|
Ethosuxamide
|
Anti-seizure drug
Blocks T-type Ca2+ channels *Thalamus Uses: 1st line for absence seizures SE: EFGHIJ Fatigue GI distress Headaches Itching (urticaria) J: Stevens-Johnson |
|
Anaesthetics: Influential properties
|
BlOOd solubility ~ SlOwness of induction, recovery
LiPid solubility ~ Potency *Proportional to 1/MAC (minimum alveolar concentration) |
|
IV anaesthetics
|
B.B. King on OPIATES PROPOses FOOLishly
Barbiturate: Thiopental *Induction: high potency, short acting Benzo: Midazolam *Most common drug for ENDOSCOPY: "Midazolam to look at your MIDDLE" *Used in conjunction w/gaseous anesthetics and narcotics Ketamine/Arylcyclohexylamines *PCP analog --> dissociative *Disorentation, hallucination *Bad dreams *Cardiovascular stimulant --> INCREASES cerebral blood flow like an inhaled anaesthetic would Opiates: Used during general anesthesia Propofol: *Short acting *Less nausea than thiopental |
|
Parkinson's drugs
|
BALSA:
1. Bromocriptine, pramipexole, ropinirole --> DA agonists (also used for prolactinoma) 2. Amantadine --> Increase DA release *Influenza A and rubellA (90% resistance) *Ataxia (cerebellA) 3. Levodopa--> Converted to DA in CNS *Carbidopa = peripheral decarboxylase inhibitor (increases CNS availability) *Peripheral conversion ~ arrhythmia 4. Selegiline (MAO-B inhibitor) Entacapone, tolcapone (COMT inhibitor) --> Prevent DA breakdown *Both may increase L-dopa SE 5. Antimuscarinics (Benztropine) *BenzTROPine: calm your TREMOR before you PARK your BENZ *Calms excess Ach activity in CNS *Parkinson's disease--tremor, rigidity *Has little effect on bradykinesia |
|
Sumatripan
|
5HT-1D agonists
*D for heaDache Short-term vasoconstrictor *T1/2 = < 2 hours SSS: Sumatripan --> Like serotonin --> Makes vessels SMALL Uses: 1. Acute migraine 2. Cluster headache attacks SE: *Vasospasm (not for CAD/Prinzmetal) *Mild tingling *Hypertensive emergencies |
|
Infant deprivation
|
Severe deprivation --> Possible death
Deprivation > 6 mo --> Irreversible changes 4 W's: Weak *Muscle tone *Physical illness, weight loss Wordless *Poor language skills Wanting *Poor socialization skills Wary *Basic lack of trust |
|
Regression: Children
|
Regression: Children
Younger behavior under conditions of STRESS Physical: Physical illness, fatigue Emotional: Punishment, new sibling |
|
ADHD treatment
|
Methylphenidate (Ritalin)
|
|
Conduct disorder
|
Converts to antisocial personality disorder @18
REQUIRES CRIMINALITY *Otherwise, oppositional defiant Aggression (including physical) Destruction Deceit Serious rule breaking <13 yoa |
|
Tourette's Syndrome
|
***Onset <18***
Motor/vocal tics Involuntary profanity Associated w/OCD Treatment: Haloperidol |
|
Separation Anxiety Disorder
|
Onset usually 7-8
Factitious physical complaints to avoid school Fear of loss of attachment figure |
|
Autism and Aspergers
|
DR CUB
Difficulty forming relationships Repetitive behavior Communication problems Unusual abilities Below normal intelligence (usually Aspergers: DR 1. Difficulty w/relationships 2. Repetitive behavior |
|
Rett's disorder
|
RETT-WRINGING
X-linked disorder --> FEMALES only *Males die in utero Age 4: *Loss of development --> MR *HAND WRINGING |
|
Childhood disintegrative disorder
|
A lot like AUTISM, but accompanied by loss of muscle control
Onset age 2-10 Multiple areas of REGRESSION Some autistic-like symptoms: *Difficulty w/relationships (social skills, adaptive behavior, play) *Communication (expressive and/or receptive language) + NEUROLOGICAL symptoms: *Motor control *Bladder/bowel control |
|
Abuse
|
Physical: Female abusers
Sexual: Male abusers *Peak 9-12 |
|
Neurotransmitter changes w/disease
|
DOPAMINE DISEASES:
Schizophrenia: (+) DA Parkinsons: (+) DA, (-) ACH ACH DISEASES: AD: (-) Ach Huntingtons: (-) Ach, (-) GABA SEROTONIN DISEASES Depression: (-) 5HT, (-) NE Anxiety: (-)5HT, (+) NE, (-) GABA |
|
Delirium
|
Knowledge of:
Time Place Person Also lost in that order |
|
Anosognosia
|
Defect in orientation
Me, sick? Ah, NO SO! Lack of awareness that one is ill |
|
Autotopagnosia
|
Defect in orientation
Inability to locate one's own body |
|
Depersonalization
|
Defect in orientation
Body seems unreal or dissociated |
|
Delirium
|
"Changes in sensoRIUM"
Most common psychiatric illness on medical and surgical floors *RAPID *Often reversible *Often caused by drugs w/anticholinergic effects (mimics etiology of Alzheimers Disease) ABNORMAL EEG Varying levels of consciousness Signs: 1. Disorganized thinking/cognitive dysfunction 2. Hallucinations/Illusions/Misperception 3. Disturbance in sleep-wake cycle |
|
Dementia
|
"DeMEMtia characterized by MEMory loss"
Gradual decline in cognition Usually irreversible NO CHANGE in CONSCIOUSNESS/ALERTNESS |
|
Pseudodementia
|
Depression in an elderly patient that presents like dementia
NORMAL EEG |
|
Hallucination vs. Illusion vs. Delusion
|
H: Perception in the ABSENCE of external stimuli
I: Misperceptions of ACTUAL external stimuli D: False beliefs D: Not shared w/other members of culture/subculture AND Firmly maintained in spite of obvious proof to the contrary |
|
Schizophrenia: Hallucination types
|
Visual and auditory
|
|
Psychomotor epilepsy hallucination types
|
Olfactory
|
|
Delirium Tremens and cocaine withdrawal hallucination types
|
Tactile--formulations
*Sensation of ants crawling on skin |
|
Schizophrenia
|
Lifetime prevalence = 1.5%
*Presents earlier in men, but M=F Genetic factors > Environmental Schizophrenia: At least 2 of the possible 5 symptoms for 6 MONTHS 1-6 months: Schizophreniform disorder < 1 month: Brief psychotic episode *Usually stress-related 1. Delusions 2. Hallucinations 3. Disorganized THOUGHT 4. Disorganized or catatonic BEHAVIOR *Catatonic: No activity, waxy paralysis, automatisms possible 5. Negative symptoms *Flat affect *Social withdrawal *Lack of motivation *Lack of speech or thought Subtypes: *Paranoid *Disorganized *Catatonic *Undifferentiated (elements of all types) Residual (diminished symptoms compared to acute) |
|
Schizoaffective disorder
|
Schizophrenia (2+ weeks) +
Manic episode = Bipolar schizoaffective +Depressive episode = Depressive Schizoaffective |
|
Manic episode
|
3+ symptoms for 1 WEEK
DIG FAST: Distractibility Irresponsibility (hedonistic) Grandiosity (inflated self-esteem) Flight of ideas (racing thoughts) Agitation/Increased Activity (goal directed) Sleep--decreased need Talkativeness/pressured speech |
|
Bipolar disorder
|
Lithium is the drug of choice
1 manic or hypomanic episode + 1 major depressive episode Manic = Bipolar type 1 Hypomanic = Bipolar type 2 |
|
Cyclothymic disorder
|
2 YEARS of:
Hypomanic episodes + Depressive symptoms *Does not qualify as depressive episode If depressive episode achieved --> Bipolar 2 |
|
Major depressive episode
|
Major depressive disorder: 2+ depressive episodes SEPARATED by 2+ months
5+ for 2 weeks: SIG E CAPS(D) Sleep disturbance Interest--loss of Guilt or feelings of worthlessness Energy--loss of Concentration--loss of Appetite/weight--change Psychomotor retardation/agitation Suicidal ideations Depressed mood |
|
Dysthymia
|
Depressive symptoms (not episodes) lasting 2+ years
|
|
Sleep changes w/depression
|
REM:
*Starts earlier *More of it *SWS: Less by default Awakenings: *More throughout night *Early morning --> start the day |
|
Panic disorder
|
1+ panic attacks
Panic attack = 4+ symptoms *Peaks in 10 minutes Palpitations Paresthesia Abdominal distress Nausea Intense fear of dying/losing control LIght-headedness Chest pain Chills Choking disConnectedness Sweating Shaking Shortness of breath |
|
Phobias
|
Fear of a specific object/situation that:
1. Is excessive 2. Interferes w/normal routine Person RECOGNIZES the fear as uncalled for, yet still experiences it Treatment: Systematic desensitization Gamophobia = Fear of marriage Algophobia = Fear of pain (algesics) Acrophobia = Fear of heights Agoraphobia = Public places |
|
PTSD
|
2-4 weeks of symptoms = Acute Stress Disorder
4+ weeks of symptoms = PTSD Process: Nightmares and/or flashbacks Acute fear, helplessness, horror Avoidance of triggers, persistent arousal Distress, impairment |
|
Adjustment disorder
|
Psychosocial stressor (divorce, moving)
< 6 months of emotional symptoms: *Anxiety, depression *Causes IMPAIRMENT |
|
Generalized anxiety disorder
|
At least 6 months of UNCONTROLLABLE anxiety
Unrelated to a specific event/situation Sleep disturbance --> Fatigue Difficulty concentrating |
|
Factitious disorder
|
Munchausen's Syndrome (or by proxy)
Faking a medical problem for "primary gain" (medical attention) Reward = sick role Willingness to receive INVASIVE procedures |
|
Types of gain
|
Types of gain
Primary: What the symptom does for patient's internal psychic economy Secondary: What the symptom gets for the patient (sympathy, attention, money) Tertiary: What the caretaker gets |
|
Somatiform disorders
|
Conversion disorder: Stressor --> specific motor/sensory symptoms
*Tests and physical exam negative *Paralysis, pseudoseizure Somatization disorder: Variety (non-specific) of complaints involving multiple organ systems *Tests and physical exam are negative Pain disorder --> Pain disproportionate to illness Hypochondriosis --> Proccupation, fear of serious illness Body dysmorphic disorder: Preoccupation w/minor or imagined physical flaws *Frequent cosmetic surgery Pseudocyesis *False belief of being pregnant *Accompanied by some physical signs |
|
Cluster A personality disorders
|
"Weird"
Genetics --> Schizophrenia Odd or eccentric demeanor Cannot develop meaningful social relationships Paranoid: *Distrust and suspiciousness *Main defense mechanism: PROJECTION *Accuse others of having/carrying out own temptations Schizoid *Social withdrawal --> Content *Limited emotional expression Schizotypal (Schizoid +) *Schizoid behavior (social withdrawal, limited emotional expression) *Interpersonal awkwardness *Eccentric appearance *Odd beliefs or magical thinking |
|
Cluster B personality disorders
|
Wild ~ "Rule" breaking (crime, sexual boundaries, mean)
Genetics --> Mood disorders, substance abuse Dramatic, emotional OR erratic Antisocial (sociopaths; > males) Borderline (> females) *Unstable moods featuring feelings of emptiness *Impulsivity, splitting --> Unstable relationships *Main defense mechanism: SPLITTING Histrionic *Attention seeking *Sexually provocative, overly concerned w/appearance *Excessive emotionality Narcissistic *Sense of entitlement --> Grandiosity *May react to criticism w/RAGE *May demand "top" medical personnel |
|
Cluster C personality disorders
|
"Worried"
Genetics --> Anxiety disorders Anxious or fearful Avoidant *Sensitive to rejection *Socially inhibited, timid --> Not content *Feelings of inadequacy Obsessive-Compulsive Dependent *Fear of abandoment --> Submissive, clinging *Low self-confidence --> Excessive need to be taken care of |
|
Anorexia
|
Primarily adolescent girls
Commonly coexists w/depression Behaviors: *Abnormal eating *Body image distortion *Exercise Signs: *Metatarsal stress fractures *Anemia *Severe weight loss, amenorrhea *Electrolyte disturbances (also seen w/bulimia) |
|
Bulimia nervosa
|
Individuals of normal body weight
Behaviors: *Binge eating *Self-induced vomiting or laxitive use Signs: *Parotitis *Enamel erosion *RUSSELL'S SIGN: Dorsal hand calluses *Electrolyte disturbances *Alkalosis (Loss of H+ from stomach) |
|
Russell's sign
|
Dorsal hand calluses (from vomiting)
Bulimia |
|
Substance Dependence vs. Substance abuse
|
Physical dependence:
1. Tolerance 2. Withdrawal Use wins out over desire: 3. Substance used in larger amounts or for longer time than desired 4. Persistent desire or attempts to cut down Problems and spite: 5. Significant energy spent obtaining, using or recovering from substance 6. Important social, work or recreational activities reduced 7. Continued use in spite of knowing problems it causes SIMILARITIES to substance abuse: Continued use in spite of problems How substance abuse differs: NEVER MET CRITERIA FOR DEPENDENCE No physical dependence (T/W) Okay with level of use: *No attempts/desire to cut down *No use in excess of desires Must feature recurrent use in presence of BIG problems: *Major obligations missed (vs. activities reduced) *Physically hazardous *Legal problems |
|
Alcohol withdrawal
|
Intoxication:
*Slurred speech **SERUM GGT** Withdrawal: *Delirium tremens, seizures *Tachycardia (unique as a WD symptom) |
|
Opiod intoxication and withdrawal
|
Seizures --> n/a
n/a --> Piloerection (cold turkey) Pinpoint pupils --> Dilated pupils Vomiting, constipation --> Diarrhea |
|
Amphetamine intoxication and withdrawal
|
Prolonged wakefulness --> Hypersomnolence
*Also cocaine Dilated pupil, hallucinations --> n/a *Also Cocaine/LSD/Marijuana Cardiac arrhythmia --> n/a *Also Cocaine/Caffeine/Nicotine No cocaine "euphoria" |
|
Cocaine intoxication and withdrawal
|
Euphoria --> Depression and suicidality
*Marijuana has euphoria Arrhythmia --> n/a *Also amphet/nicotine/caffeine Dilated pupil, hallucinations --> n/a *Also amphet/lsd/marijuana |
|
PCP Intoxication and Withdrawal: Most important features
|
Nystagmus
Hallucinations/PsychosisBelligerence/Homicidality Withdrawal: Recurrence as drug is reabsorbed in GI |
|
Marijuana Intoxication and Withdrawal:
Most Important features |
Euphoria --> n/a
*Cocaine also has euphoria, but followed by severe crash/suicidality Dilated pupil, Hallucinations *Amphet/Cocaine/LSD Slowed time Social withdrawal Appetite Withdrawal: None listed |
|
LSD
|
Marked anxiety or depression --> n/a
Dilated pupil, Hallucinations *Also Amphet/Cocaine/LSD |
|
Barbiturate Intoxication and Withdrawal: Most important features
|
Respiratory depression --> Life-threatening cardiovascular collapse
*Benzos do not cause CV collapse n/a --> Delirium *Benzos do not cause delirium n/a --> Seizures *Also alcohol, benzos |
|
Benzodiazepine intoxication and withdrawal: Most important features
|
Amnesia --> n/a
Mild respiratory depression --> n/a *Barbiturates cause much more depression n/a --> Seizures *Also alcohol, barbiturate withdrawal n/a --> Insomnia *Also opiate WD |
|
Caffeine Intoxication and Withdrawal: Most important features
|
Intoxication:
*Diuresis (unique) *Muscle twitching *Arrythmia (also Amphet/Cocaine/Nicotine) Withdrawal: *Weight gain (also nicotine) |
|
Nicotine Intoxication and Withdrawal: Most important features
|
Intoxication:
*Arrhythmia (alsp amphet/cocaine/caffeine) *Anxiety (also a WD SYMPTOM) Withdrawal *Wieght gain (also caffeine) *Anxiety |
|
Delirium tremens
|
Peaks 2-5 days after cessation
First: Autonomic hyperactivity *Tachycardia *Tremors *Anxiety Second: Psychotic symptoms *Delusions *Hallucinations *Confusion |
|
Operant conditioning
|
Particular ACTION produces a REWARD
Positive reinforcement: Press button to get food *ELICITS button pressing Negative reinforcement: Press button to avoid shock *ELICITS button pressing Punishment: Shock when button is pressed *EXTINGUISHES button pressing |
|
Transference/Countertransference
|
Involves PROJECTION of feelings
about formative/important person onto another Transference: Physician ~ parent (etc.) from the PATIENT'S perspective Countertransference: Patient ~ parent (etc) from the PHYSICIAN'S perspective |
|
Social learning
|
A.k.a. modeling
Behavior acquired by watching others and assimilating actions into ones own repertiore |
|
Immature ego defenses:
Acting out Dissociation Denial Displacement Fixation Identification Isolation |
Acting out: The unacceptable is expressed (ex. tantrum)
Dissociation: Effort to avoid emotional stress *Temporary, drastic change *Personality, memory, consciousness, motor *Extreme = multiple personality/ dissociative identity disorder Denial: Occurs w/painful reality *Avoidance of awareness *Ex. Cancer and AIDS patients Displacement: Avoided ideas and feelings *Neutral target receives them (vs. true target) *Ex. Angry at A, yells at B Fixation: REMAINING, in part, at a more childish level of development *This part never "grew" *Men fixating on sports games Identification: Modeling behavior *Modelee is powerful (+/- liked) *Ex. Abused child --> abuser Isolation: Feelings removed *Recount a murder w/o emotion |
|
Primitive Ego Defenses:
Projection Rationalization Reaction formation Regression Repression Splitting |
Projection: Accuse/suspect others of your own unacceptable temptations
*Man who wants to cheat accuses wife of cheating Rationalization: Changing the reasons behind an event to something w/less self-fault *Fired --> Didn't want job Reaction formation: Unacceptable idea/feeling spurs UNCONSCIOUS emphasis on opposite *Sexual thoughts --> join monastery Regression: Progressing beyond a developmental point, then returning there w/stress *Dialysis patient --> Crying Repression: Idea/feeling kept out of conscious awareness INVOLUNTARILY *Voluntary = Suppression (mature) Splitting: Belief that ppl are 100% good or bad |
|
Mature Ego Defenses:
Sublimation Altruism Suppression Humor |
Sublimation: Unacceptable wish replaced by similar, but acceptable one
*Aggressive impulses --> business ventures Altruism: Performing acts of unsolicited charity to alleviate guilty feelings Suppression: VOLUNTARY repression *Idea kept out of conscious awareness on purpose Humor: Anxiety-provoking or adverse situation --> Appreciate amusing aspects |
|
Alcohol Withdrawal: Treatment
|
Benzodiazepines
|
|
Anorexia/Bulimia: Treatment
|
SSRI
|
|
OCD: Treatment
|
SSRI
|
|
Anxiety: Treatment
|
Benzodiazepines
Barbiturates Busiprone (5HT1A agonist) Nonselective MAOI (Phenelzine, tranylcypromine) |
|
Panic disorder: Treatment
|
Busiprone (5HT-1A agonist)
TCA |
|
Atypical depression: Treatment
|
Nonselective MAOI (Phenelzine, tranylcypromine)
|
|
Typical depression
|
SSRI
TCA (MAOI reserved for atypical) |
|
Depression w/insomnia
|
Mirtazapine
*Alpha-2-antagonist --> NE, 5HT *5HT2, 5HT3 antagonist *Sedation, weight gain Trazodone *SSRI w/sedation, vasodilation, priapism (normally, SSRIs and TCAs used) |
|
Antipsychotics
|
D2 blockers (also Ach, NE, Histimine)
Haloperidol + "-AZINES" *THIORIDazine, CHLORPROMazine --> Low potency, no neurological SE HALOPERIDOL, TRIFLUPERazine --> High potency, neurological SE Uses: Schizophrenia Tourettes (Haloperidol) Psychotic episodes/acute mania SE: 1. Extrapyramidal *4h = Dystonia (muscle spasm, stiffness, oculogyric crisis) *4d= Akinesia (reduced movement, parinksonism) *4 wk = Akathisia (urge to move) *4 mo = Tardive dyskinesia (DA receptor sensitization --> stereotypic oral-facial movements) 2. DA blockade --> Prolactinemia 3. Ach muscarinic blockade --> Dry mouth, constipation 4. NE alpha blockade --> hypotension 5. Histamine blockade --> Sedation |
|
Atypical antipsychotics
|
Block DA AND 5HT-2 receptors
It's not ATYPICAL for OLd CLOsets to RISPER QUIETly *Risper --> Zipra Olanzapine, Clozapine,Risperidone, Ziprasidone, Qietapine, Ariprazole Uses: 1. Schizophrenia (+ and -) 2. Olanzepine: *Tourettes (not 1st line) *Psychosis/Mania *Replaces MAOI? Anxiety *Replaces SSRI? Depression, OCD SE: *Less EPS and anticholinergic effects *CLOZAPINE = AGRANULOCYTOSIS (weekly WBC monitoring) |
|
Lithium
|
Mechanism not clear
Clinical use: Bipolar disorder SE: LMNOP L = Lithium M = Movement (tremor) N = Nephrogenic diabetes insipidus O = HypOthyroid P = Pregnancy problems (teratogen) |
|
Busiprone
|
Mechanism: Stimulates 5HT-1A receptors
Uses: Anxiety or panic disorder No sedation, addiction No interaction w/alcohol |
|
SSRIs
|
Fluoxetine, paroxetine, citalopram, sertraline
Serotonin-specific reuptake inhibitors Uses: *Depression *OCD *Anorexia/bulimia SE: Better than TCAs *GI distress *Sexual dysfunction *Interaction w/MAOIs: Serotonin syndrome Serotonin syndrome: Hyperthermia and muscle rigidity, cardiovascular collapse |
|
Antidepressants
|
Block reuptake SSRI and NE
*An SSRI and then some The PRAMINES, TRIPTYLINES and Doxepin, Amoxapine Secondary = DNA *Desipramine *Nortriptyline *Amoxapine Uses: Major depression *Imipramine = Bedwetting *Clomipramine = OCD SE: 1. Toxicity = The TRI-C's *Convulsions (from hyperpyrexia) *Coma (from resp depression) *Cardiotoxicity (from arrhythmia) 2. Sedation (Desipramine least) 3. NE (alpha) blocking --> Hypotension 4. Ach (muscarinic) blocking: *Tachycardia *Urinary retention *Elderly: Confusion, hallucinations *Tertiary > Secondary |
|
MAOIs
|
Nonselective MAO inhibition
(MAO-B inhibitor gets DA--Selegiline for PD) Accomplishes the same thing as TCAs: increased NE, 5HT levels Phenelzine, Tranylcypromine Use: Atypical depression *Mood reactivity *Sensitivity to rejection *Hypersomnia *Anxiety *Hypochondriosis SE: 1. Hypertensive crisis *TYRAMINE ingestion (wine, cheese) *Beta agonists 2. Serotonin *SSRIs *Meperidine (opiod) |
|
Methylphenidate
|
ncreases PRESYAPTIC NE release (same w/amphetamines)
Use: ADHD Mechanism unknown |
|
Other antidepressants
|
You need BUtane in your VEINs to MURder for a MAP of alcaTRAZ
All are sedating except for bupropion (stimulant) #neurotransmitters declines! Buproprion (unknown mech): *Uses: Depression, Smoking cessation SE: STIMULANT, SEIZURES (if bulimic) Venlafaxine: *Triple reuptake block: Dopamine, Serotonin, NE *Uses: Depression *SE: Sedation AND Stimulant *Constipation Mirtazapine: 1. NE alpha-2 antagonist --> Increases release of NE and 5HT 2. 5HT-2 and 5HT-3 antagonist Uses: Depression w/insomnia SE: SEDATION, Appetite, WEIGHT GAIN Maprotiline: Blocks NE reuptake *Sedation, orthostatic hypotension Trazodone: SSRi + viagra *Use: Insomnia *SE: Sedation, priapism, hypotension |
|
Nephrotic syndrome is caused by loss of basement membrane ___
|
Negative charge
Heparan sulfate |
|
If clearance is < GFR...
|
There is net tubular reabsorption of X
|
|
Proximal tubule activities
|
ISOTONIC ACTIVITY
CABANG Cl/Base antiport Ammonia (SECRETED as H+ buffer) Bicarbonate (absorbed as CO2, H20) AA carrier system Na/Glucose symport + Na/H antiport Glucose/Na symptort |
|
Renin-Angiotensin system
|
JG cells secrete renin in response to:
*Low BP *Low Na+ *Increased sympathetic tone Renin cleaves angiotensinogen (from liver) to ATI ACE (in lungs) converts ATI to ATII Actions of ATII: HEAt 1. Hypothalamus: ADH, thirst 2. Efferent arteriole: Vasoconstriction 3. Adrenal cortex: Aldosterone |
|
Kidney endocrine functions
|
PERP
Prostaglandins *Vasodilate afferent arterioles Erythropoietin *Secreted by endothelial cells of PERITUBULAR capillaries during hypoxia Renin: Activates Angiotensinogen to yield AT1, then ATII *ADH, thirst *Efferent arteriole constriction *Aldosterone PTH-mediated activation of 25-OHD to 1,25-OHD *Converting enzyme = 1-alpha-hydroxylase |
|
The 2 ways aldosterone can be secreted
|
1. Angiotensin II
2. High plasma K+ *Aldosterone facilitates Na+/K+ trade in collecting tubule |
|
Parathyroid actions on kidney
|
PTH is released in response to low Ca2+
Induces 1-alpha-hydroxylase *Conversion of 25-OHD to 1,25-OHD Promotes Ca2+ resorption in the early DCT Inhibits phosphate absorption in the PCT |
|
The 2 ways ADH can be secreted
|
ATII
Senses increased plasma osmolarity *ADH has a diluting effect on plasma |
|
Horseshoe kidney
|
2 kidneys are fused at inferior pole
During ascension, they get stuck under INFERIOR MESENTERIC ARTERY |
|
Nephritic syndromes: Symptoms
|
BAHO
NephrItic = INFLAMMATION Blood in urine Azotemia Hypertension Oliguria |
|
Nephrotic syndromes: Symptoms
|
NephrOtic = PrOteinuria
PAL Proteinuria Albumin (low--edema) Lipids (high) |
|
Nephritic syndromes
|
GRAMPI
Goodpasture's syndrome *Linear anti-GBM antibodies *Hemoptysis accompanies hematuria Rapidly proliferative (crescentic) glomerulonephritis *Renal failure *Crescent-moon shapes (LM, IF) Alport's syndrome *Genetic collagen mutation --> Split BM *Nerve deafness, ocular disorders Membranoproliferative *Subendothelial humps (EM): TRAM TRACK *Renal failure Post-streptococcal (acute) *Lumpy-bumpy w/neutrophils (LM) *Subepithelial humps (EM) *Children; spontaneous remission IgA nephropathy (Berger's) *Most com rec. hematuria in young pts *Mesangial IgA (IF and EM) *Mild, usually post-infectious |
|
Nephrotic syndromes
|
DAMSFL (Like damsel) but missing the bottom of the E
Diabetic nephropathy *LM: Kimmelsteil-Wilson nodular lesions *Basement membrane thickening Amyloidosis: Apple-green birefringence *Associated w/multiple myeloma, chronic conditions, TB, RA Membranous glomerulonephritis *Most common adult nephrotic syndrome *EM: Subepithelial deposits, spike + dome SLE: 5 patterns of involvement *Membranous = subepithelial deposits w/WIRE LOOP lesions *Can also be subendothelial Focal segmental: *Focal = certain glomeruli *Segmental = Only part of the glomerulus *LM: Sclerosis and hyalinosis *More severe: HIV and IV drug users Lipoid nephsosis: *#1 cause of childhood nephrotic syndrome *EM: Podocyte foot effacement *Responds well to steroids |
|
Kidney stones
|
Stones SUCC
C = CAN see it (even if faint) U = Can't see U Struvite (Ammonium Mg Phosphate) *#2 kidney stone; +/- radiopaque *Urease + inf: Proteus, Staph, Kebsiella *STAGHORN CALCULI --> UTIs *Worsened w/alkaluria (opp of cystinuria) Uric Acid: *CAN'T SEE U (radiolucent) *Hyperuricemia: Gout, cell turnover Cystine: *FAINTLY radiopaque *Usually occurs w/cystinuria *Hexagonal shape *Treat w/acetazolamide (alkalinize urine) Calcium (Oxalate, Phosphate) *#1 stone (75-85%); seen clearly *Ca-Oxalate, Ca-P or both *Ca: Cancer, PTH, Vitamin D, milk-alkalai *Oxalate: Vitamin C abuse, antifreeze |
|
Renal cell carcinoma
|
Cancer of renal tubule cells
Most common renal malignancy Risk factors: *VHL (chromosome 3) *Most common in men 50-70 *Smoking and obesity Course: 1. Tubule cells become POLYGONAL CLEAR CELLS *Tendency to cause paraneoplastic syndromes (EPI, ACTH, PTHrP, prolactin) 2. Invade IVC and spread hematogenously Symptoms: *Hematuria *"Pyelonephritis": Flank pain, fever *Polycythemia |
|
Wilm's Tumor
|
#1 renal malignancy of early childhood
*Children 2-4 *Often part of WAGR complex Caused by deletion of WT1 (tumor suppressor) on chromosome 11 LARGE palpable flank mass *Recapitulation of embryonic kidney: Glomerular structures WAGR: DOUBLE DOWN ON 11 *Wilm's tumor *Aniridia (no iris) *Genitourinary malformation *Retardation (mental-motor) |
|
WAGR complex
|
DOUBLE DOWN ON 11
Caused by deletion of several genes on chromosome 11, including WT1 (Wilm's tumor suppressor gene) *Wilm's tumor *Aniridia (no iris) *Genitourinary malformation *Retardation |
|
Transitional cell carcinoma
|
#1 tumor of the urinary tract system
*Bladder *Ureters, renal pelvis, calyces Associated w/Pee SAC (PSAC) risk factors: *Phenacetin (withdrawn from market) *Smoking *Aniline dyes *Cyclophosphamide (Leukemia/lymphoma, SLE) Painless hematuria --> Bladder CA |
|
Acute pyelonephritis
|
Glomeruli/vessels are SPARED
*Scarred in chronic pyelonephritis **WBC casts in urine** *NEUTROPHIL-filled abscesses in INTERSTITIUM (chronic = lymphos) *Abscesses can rupture into tubules Fever, CVA tenderness |
|
Chronic pyelonephritis
|
Glomeruli/vessels are SCARRED (vs. spared w/acute), and so is cortex
Primarily lymphocytes (vs. neutrophils for acute) Eosinophilic casts THYROIDIZATION of the kidney *Fibrosis |
|
Diffuse cortical necrosis
|
Acute generalized infarction of the cortex (both kidneys)
Vasospasm + DIC Associations: *Septic shock *Obstetric catastrophes (abruption) |
|
Drug-induced interstitial nephritis
|
Type 1 Hypersensitivity reaction
*Acute interstitial inflammation Caused by drugs: *NSAIDs *Methicilln *Loop diuretics Hematuria 2 weeks after administration Eosinophil based : *Rash *Fever |
|
Acute tubular necrosis
|
#1 cause of ACUTE renal failure
*Reversible (in 2-3 weeks) *Fatal if untreated (usually initial oliguric stage) Causes: *Renal ischemia *Crush injury (myoglobinuria) *Toxins Course: 1. Inciting event *Loss of cell polarity + necrosis *Epithelial detachment --> Granular/muddy brown casts 2. Maintenance (low urine) 3. Recovery |
|
Acute renal failure: How to decide
|
1. Look at urine osmolality or Na+
If osmolality 500+ --> Azotemia If Na under 1%: Azotemia 2. Look at BUN/Cr If under 15 --> Intrinsic renal If over 15 --> Post-renal |
|
Consequences of renal failure
|
HTN possible (renin)
Chronic pyelonephritis (stasis) Hormone functions of kidney: *EPO --> Anemia *1-alpha-hydroxylase --> Renal osteodystrophy Failure to filter: 1. K+ --> Hyperkalemia -->Arrhythmias 2. H+ --> Metabolic acidosis (also less HCO3 prod) 3. BUN, Creatinine --> Encephalopathy 4. Na, H2O --> CHF, Pulmonary edema |
|
Most common causes of chronic renal failure
|
Diabetes
HTN |
|
Fanconi's syndrome
|
Defect in proximal tubule transport of...everything
AA's, glucose, phosphate, uric acid, protein, electrolytes 1. Hypothosphatemic rickets/osteomalacia 2. Hypokalemia 3. Metabolic acidosis due to BICARBONATE wasting (like type 2 renal tubular acidosis) |
|
RTAs
|
Type 1: Failure of H+ secretion
*Hypokalemia Type 2: Bicarbonate wasting *Associated w/Fanconi's syndrome Type 3: HypOaldosteronism *Hyperkalemia |
|
Juvenile PKD
|
Infantile presentation of cysts in kidney parenchyma
Liver involvement too Autosomal RECESSIVE |
|
Simple cysts
|
Simple cysts = Surface cysts
Cortex only Incidental finding |
|
Medullary sponge vs. cystic disease
|
Medullary cystic disease
*Parenchyma *Poor prognosis Medullary sponge disease *Cortical collecting duct *Good prognosis |
|
Na+
|
ALL NEUROLOGIC
BOTH HIGH AND LOW --> COMA High = Irritability, delirium, coma Low = Disorientation, stupor, coma |
|
K+ disturbances
|
ALL MUSCULAR
BOTH HIGH AND LOW --> Arrhythmia Low ~ muscle depression *Flattened T waves *U waves *Paralysis *Arrythmia High ~ Muscle excitement *Big T waves *Wide QRS *Arrhythmia |
|
Ca2+ and Mg2+ disturbances
|
Low ~ Hyperactive muscle
*Tetany/NM irritability *Arrythmia High ~ Delirium + deposits (Ca2+) *Abdominal pain *Stones + muscle depression (Mg2+) *DTRs reduced *Cardiopulmonary arrest |
|
PO4- disturbances
|
Low = Bone loss
High = Metastatic calcification Stones (Calcium phosphate) |
|
Ovary/Testicular lymphatic drainage
|
Peri-aortic nodes
|
|
Contents of suspensory ligament of ovary
|
Ovarian a/v
|
|
Contents of transverse cervical/cardinal ligament
|
Uterine artery and vein
|
|
Contents of inguinal canal: males vs. females
|
Males: Spermatic cord (external fascia, cremaster muscle, internal fascia)
Females: Round ligament of the uterus (connects area near start of fallopian tube to labia majora)--NO STRUCTURES CONTAINED |
|
Sperm origins and properties
|
Uses FRUCTOSE as fuel
Mitochondria in MIDDLE piece Acrosome = Golgi apparatus Tail = Centriole |
|
Sperm origins and properties
|
Uses FRUCTOSE as fuel
Mitochondria in MIDDLE piece Acrosome = Golgi apparatus Tail = Centriole |
|
Spermatogenesis
|
Spermatogonium in basal (bottom, sealed off by sertoli cells) compartment
*These germ cells are always unreplicated (2N vs. 4N) Development occurs in adluminal compartment |
|
Sperm path
|
SEVEN UP
Seminiferous tubules Epididymis Vas deferens Ejaculatory duct (Nothing) Urethra Penis |
|
Leydig vs. Sertoli secretions and feedback
|
Leydig: Induced by LH
*Secretes testosterone *Feeds back at hypothalamus (a LITTLE HIGHER up than FSH) Sertoli: Induced by FSH *Secretes ABP and inhibin *Feeds back (via inhibin) at anterior pituitary |
|
Testosterone types and function
|
Testes: Testosterone, DHT
Adrenals, theca cells: Androstenedione 5-alpha reductase converts testosterone to DHT Aromatase converts testosterone and androstenedione to estrogen Development: 1. Differentiation of Wolffian duct 2. Secondary sexual characteristics Adulthood: 1. Spermatogenesis 2. Libido 3. Muscle, RBCs (increased hematocrit) |
|
Estrogen types and functions
|
Potency:
Estradiol (ovary) > Estrone > Estriol (placenta) Estradiol and estrone --> 50x in pregnancy Estriol --> 1000x in pregnancy Menstrual Cycle: Follicle development and endometrial proliferation Hepatic synthesis of transport proteins (such as SHBG) Myometrial excitability Better lipids: Increased HDL, lower LDL |
|
Progesterone
|
Produced by corpus luteum (and later placenta if pregnancy)
Adrenal cortex, Testes *Part of testosterone synthesis Menstrual cycle: Secretory development and spiral arteries + thick cervical mucus (inhibits sperm entry) DECREASES myometrial excitability Feedback on LH, FSH INCREASES BODY TEMP |
|
Oocyte development
|
Primary oocytes are in PROPHASE 1
Secondary oocytes are in METAPHASE II Primary oocytes become secondary oocytes @ovulation (leave prOphase to Ovulate) Secondary oocytes become Ova w/sperm entry (leave METaphase when they MEET a sperm) No tetrads formed until after ovulation |
|
B-hcg
|
Secreted by syncytiotrophpblast
Maintains corpus luteum (and thus progesterone production) until placenta can make enough progesterone for itself Detectable in blood by 1 week, urine by 2 weeks after conception HcG peaks in 1st trimester Elevated w/hydatiform mole or choriocarcinoma |
|
Menopause
|
Average age: 51
Hormone changes: GnRH, FSH, LH high (unresponsive ovaries) Symptoms = HAVOC Hot flashes Atrophy of the vagina (AV) Osteoporosis CAD |
|
Bicornuate uterus: Cause
|
Incomplete fusion of paramesonephric ducts
Possible UT abnormalities Possible infertility |
|
Hypospadias vs. Epispadias
|
Hypospadias (more common): URETHRAL FOLDS fail to close
*Ventral opening *UTI (down ~ dirty) Epispadias: Faulty positioning of the GENITAL TUBERCLE *Assoc. w/extrophy of bladder |
|
Klinefelter's Syndrome
|
XXY = The girly boy (1/850)
Tall w/long extremities, BUT... *Testicular atrophy w/dysgenesis of seminiferous tubules (low inhibin, high FSH) *Leydig dysfunction leading to low testosterone (high LH --> high E2) *High estrogen --> Gynecomastia, female hair/fat distribution |
|
Turner's Syndrome
|
XO (1/3000 --> 95% spontaneous abortion rate)
Short stature Ovarian dysgenesis (high FSH, LH) Webbing of the neck Preductal coarctation of the aorta Widely spaced nipples |
|
XYY males
|
XYY (1/1000)
NORMAL fertility Very tall Very severe acne 1-2% antisocial behavior |
|
Pseudohermaphroditism
|
Genetic gender clear
Phenotypic gender ambiguous or incorrect Female: CAH or exogenous androgens Male: Androgen insensitivity |
|
True hermaphroditism
|
2 X chromosomes necessary (XX or XXY only)
Testicular and ovary tissue present |
|
Androgen insensitivity
|
Androgen receptor defect
Rudimentary vagina only Testes usually in labia majora *Removed to prevent malignancy Since testosterone responses not observed (no feedback), high LH, testosterone, and ESTROGEN (via aromatase) |
|
Hydatiform mole
|
TREAT WITH METHOTREXATE (folate analog--chemo, mucositis, myelosuppression, macrovesicles in liver)
Cystic swelling of chorionic villi Proliferation of trophoblast --> HIGH B-HCG (syncytio in origin) Looks like "bunch of grapes" or "honeycombing" Complete = Empty egg + 2 sperm (XX) *COMPLETELY PATERNAL *No fetus *Commonly enlarged uterus Partial = Triploid or tetraploid Possible fetal parts |
|
Hydatiform mole treatment
|
Methotrexate
Dilatation and curettage |
|
Pregnancy-induced hypertension
|
Timespan = 20 weeks gestation to 6 weeks post-partum
Definition of pre-eclampsia = HEP Hypertension --> Headache, blurred vision, cerebral hemorrhage, mentation Edema --> Esp face and hands Proteinuria Eclampsia = HEP + Siezure Additional complications: *Placental ischemia due to poor spiral artery invasion *HELLP syndrome: Hemolysis, Elevated LFTs, Low Platelets) Pre-eclampsia: *Delivery as soon as possible *Bed rest and salt restriction Eclampsia treatment = Prevent seizures *IV magnesium sulfate *Diazepam (benzodiazepine) |
|
Abruptio placentae
|
Usually 3rd trimester
PAINFUL Premature detachment of placenta, possibly leading to DIC Increased risk w/blood pressure elevators (smoking, HTN, cocaine) |
|
Placenta Accreta
|
Defective decidual layer allows placenta to attach to myometrium
Possible massive bleeding post delivery Risk factors: 1. Prior C section 2. Inflammation |
|
Pre-eclampsia risk factors
|
1. Pre-existing hypertension
2. Trouble excreting fluid: chronic renal problems 3. Diabetes (causes hypertension AND renal problems) 4. Autoimmune disorders |
|
Placenta previa
|
Attachment of placenta to lower uterine segment
PAINLESS bleeding in any trimester (compare to Placenta Abuptio, which is painful and usually 3rd trimester) Risk factor: Prior C section |
|
Polyhydramnios
|
Causes:
1. Esophageal/dodenal atresia 2. Anencephaly Unswallowed fluid accumulates to >1.5-2 L |
|
Oligohydramnios
|
Causes: No pee
1. Bilateral renal agenesis, other renal problems 2. POSTERIOR URETHRAL VALVE (males) or other urinary obstruction Inability to excrete urine causes Potter's syndrome (compressed nose, pulmonary hypoplasia) |
|
Endometriosis
|
Endometrial glands/stroma outside the uterus (usually ovary, peritoneum)
*Endometriosis in myometrium = Adenomyosis *Relation to retrograde menstrual flow Any endometrial tissue (normal or pathologic) features CYCLIC BLEEDING --> Chocolate cysts *Severe menstrual pain Infertility |
|
Endometrial Hyperplasia
|
Causes: EXCESS ESTROGEN
1. Hormone replacement therapy 2. PCOS, other anovulatory cycles 3. Granulosa cell tumor Symptoms = Buildup to the point of hemorrhage --> Bleeding (repeat indefinitely) Increased risk for endometrial CA |
|
Mittelshmerz
|
When ovulation occurs, blood from ruptured follicle causes peritoneal inflammation
Mimics peritonitiz |
|
Leiomyoma
|
Most common tumor in women (more often black women)
Peak age = 20-40 Benign tumor of whorled smooth muscle bundles (rare transformation) ESTROGEN SENSITIVE (grows w/pregnancy, shrinks w/menopause) |
|
Leiomyosarcoma
|
Higher incidence in blacks
De novo appearance (NOT FROM FIBROIDS) Highly aggressive |
|
Gynecological tumor epidemiology
|
Incidence:
Endometrial > Ovarian >Cervical Worst Prognosis: Ovarian > Cervical > Endometrial |
|
PCOS
|
Obsesity --> Insulin resistance --> Increased GnRH pulses (LH >>FSH) --> Theca cell stimulation --> Androgen production (hirsutism), low estrogen (amenorrhea, decreased SHBG)
Treatment: 1. Weight loss (lose IR) 2. OCPs, gonadotropin analogs (inhibit GnRH) 3. Clomiphene (fertility drug) *Partial estrogen receptor agonist @pituitary (increases GnRH) 4. Surgery (cyst removal) Spironolactone, Ketoconazole for hirsutism |
|
Ovarian cysts
|
Follicular cyst: Unruptured graffian follicle
*Often secretes ESTROGEN Corpus luteum cyst: Persistent CL w/hemorrhage *Secretes PROGESTERONE Theca-lutein cyst: Bilateral, yellow *Caused by hCG (and other hormones) Chocolate cyst: Endometriosis *Varies w/menstrual cyle |
|
Germ cell tumors
|
Germ cell tumors:
*95% of testicular tumors *~30% ovarian tumors All malignant except female mature teratoma *Luckily, mature teratoma = 90% of ovarian germ cell tumors Discord among Young Things (DCYT) 1. Dysgerminoma/Seminoma *hCG *Fried eggs *Males: Painless enlargement, 15-35 2. Choriocarcinoma *hCG *Syncytioblast and trophpblast *Women: Theca-lutein cysts 3. Yolk sac *AFP *Primitive glomeruli w/Schiller-Duvals *Aggressive, children 4. Teratoma (2+ germ cell types) *Mature = benign in women *Immature = malignant *Struma ovari = thyroid tissue 5. Embryonal (no female equivalent) *Painful *Focal GLANDULAR differentiation in a sea of undifferentiated cells |
|
Ovarian non-germ cell tumors
|
~70% of ovarian tumors
1. Serous: BILATERAL, fallopian *Cystadenoma = 20% of ovarian tumors *Cystadenocarcinoma = 50% of ovarian tumors *PSAMMOMA BODIES! 2. Mucinous: Cervical *Cystadenoma = Multilocular *Cystadenocarcinoma = may cause PSEUDOMYXOMA PERITONEI from mucous leakage 3. Brenner: Benign, bladder 4. Fibroma: Spindle fibroblasts *MEIG'S: Pulling sensation in groin, ascites, hydrothorax 5. Granulosa: Granulosa cells *Estrogen secretion *Call-Exner bodies: Follicles w/no oocyte, eosinophilic fluid 6. Krukenberg: A met from the GI *Signet cells secreting mucin *P.P. = intraperitoneal accumulation of mucinous material |
|
Sarcoma botryoides
|
Rhabdomyosarcoma variant --> Spindle shaped tumor cells
Aggressive cancer affecting girls <4 Cells are DESMIN positive (muscle intermediate filaments) |
|
Benign Breast Tumors (3)
|
1. Fibroadenoma: Most common tumor if < age 25
*Small, well demarcated *Estrogen sensitive, but no CA risk 2. Intraductal papilloma *Serous or bloody nipple discharge 3. Phyllodes tumor (CT and cysts) *Large, bulky mass *Possible "leaf-like" projections |
|
Breast cancer facts
|
ER/PR positive = Tamoxifen
Erb-B2/Her-2 (EGF receptor) = Bad MOST IMPORTANT prognostic indicator = Axillary node involvement Risk factors: FH and ESTROGEN NOT INCREASED by fibroadenoma, non-hyperplastic cysts |
|
Most likely cause of breast "lumps" from age 25-menopause
|
Fibrocystic disease
Epithelial hyperplasia (>30, increased layers in terminal duct lobule) ~ increased cancer risk |
|
Most likely breast tumor <25
|
Fibroadenoma
Small, mobile, firm |
|
Malignant breast cancers
|
1. Invasive ductal (76%): Worst
2. Invasive loBular (8%): Often bilateral 3. Medullary (1-10%): Best prognosis 4. Comedocarcinoma: Ductal, caseous 5. Inflammatory: Orange peel 6. Paget's disease of the breast: Eczema, halo cells |
|
Fibrocystic disease of the breast
|
Most common cause of "breast lumps" age 25-menopause
Diffuse breast pain (multiple lesions) No CA risk except for epithelial type 1. Fibrosis: Stromal hyperplasia 2. Cystic: Fluid filled, "blue dome" 3. Sclerosing: Increased acini, fibrosis between lobules 4. Epithelial: Terminal duct layers increase *If ATYPICAL cells, increased CA risk *Women >30 |
|
Acute mastitis
|
Breast abscess usually caused by S. Aureus
Usually associated w/breast feeding |
|
Fat necrosis of the breast
|
Injury to breast tissue leaves a painless lump
|
|
Gynecomastia
|
Hyperestrogenism
(Cirrhosis, Testicular tumor, Puberty, Old age, XXY) Drugs: SOME DRUGS CREATE AWESOME KNOCKERS Spironolactone Digitalis Cimeditine Alcohol Ketoconazole |
|
Prostatitis
|
Symptoms = Dysuria, urgency/frequency, lower back pain
Acute: E. COLI Chronic: Abacterial > Bacterial |
|
Cryptoorchidism
|
Undescended testes --> More likely if premature
Low spermatogenesis (temperature) Increased risk of GERM CELL tumors |
|
Benign Prostatic Hyperplasia
|
Some features common to prostatits: dysuria, frequency/urgency
Add: difficulty starting and stopping stream Possible mechanisms: 1. Increased E2 with age 2. Increased prostate sensitivity to DHT PERI-URETHRAL nodular enlargement (middle and lateral lobes) Increased PSA |
|
Prostate cancer
|
Same pop as BPH: > 50
Usually in POSTERIOR lobe Labs: 1. Increased Prostatic Acid Phosphatase (PAP) 2. Increased PSA (decreased free PSA) 3. Bone met (common): High AP |
|
Testicular Non-Germ Cell Tumors (3
|
5% of testicular tumors
BENIGN Leydig cell: REINKE crystals and androgen production (also gynecomastia) Sertoli cell Testicular lymphoma: Most common testicular cancer in older men |
|
Tunica Vaginalis Lesions (3)
|
1. Varicocele ("bag of worms") --> Dilated vein in pampiniform plexus
*Infertility 2. Hydrocele: Incomplete fusion of PROCESSUS VAGINALIS (TUNICA VAGINALIS) allows fluid 3. Spermatocele: Dilated epididymis |
|
Peyronie's Disease
|
Fibrous tissue formation bends peni
|
|
CIN of the penis (3 types)
|
1. Bowen's: "Old, gray and single"
*Men in 5th decade *Single gray plaque on shaft or scrotum *10% SCC 2. Bowenoid papulosis: Papules on younger men *NOT invasive 3. Erythroplasia of Queyrat: Red, velvety plaques on the glans *Otherwise similar to Bowens Progression to SCC usually involves HPV and lack of circumcision |
|
Anti-androgen drugs
|
ALL ENCOURAGE GYNECOMASTIA
1. Finasteride: 5-a reductase inhibitor *BPH and Male pattern baldness *Possible gynecomastia 2. Flutamide: Competes w/androgens at receptor *Prostate CA--use w/leuprolide 3. Ketoconazole: Inhibits desmolase (steroid synthesis) *PCOS hirsutism *Also inhibits fungal steroid synthesis 4. Spironolactone: Competes for androgen receptor *PCOS hirsutism *Also competes for aldosterone receptor |
|
Leuprolide
|
GnRH analog (in "leu" of GnRH")
Pulsatile use: Increase fertility Continuous: Prostate CA, fibroids |
|
Mifepristone (RU-486)
|
Used w/misoprostol (PGE-1)
*Competes w/PGE-2, PGI-2 at prostaglandin receptor Competes at progesterone receptor Used for termination of pregnancy SE: Heavy bleeding GI (N/V) and abdominal pain *PGE-2 and PGI-2 are suppressors of Parietal cells--if blocked, STOMACH ACID |
|
Oral contraception effects
|
(+) ICE: (Infection, cancer, ectopic)
Decreased pelvic infection Decreased endometrial, ovarian CA Decreased ectopic pregnancy (-) COLD: Coagulation, Overweight, Lipids, Depression Hypercoagulable state Weight gain --> HTN Increased TGs Depression |
|
Anastrazole
|
Aromatase inhibitor
Used for breast cancer post-menopause |
|
Testosterone: Uses
|
Uses:
1. Hypogonadism, development 2. Burns 3. ER+ breast cancer SE/Tox: 1. Inhibition of Leydig cells --> gonadal atrophy 2. Premature epiphysial plate closure 3. Increased HDL, low LDL |
|
Estrogen: Uses
|
Uses:
1. Hypogonadism, development, HRT 2. Menstrual abnormalities 3. Androgen-dependent prostate CA Toxicity: 1. Endometrial hyperplasia, CA 2. Clear cell carcinoma (if DES) 3. Thrombi |
|
Progesterone: Uses
|
Stabilizes endometrium by increasing vascularization
Uses: 1.Oral contraceptives 2. Abnormal uterine bleeding 3. Endometrial cancer |
|
Tamoxifen
|
Used in ER/PR+ breast cancer
Estrogen antagonist on breast tissue Estrogen agonist on endometrium --> increased risk of endometrial CA |
|
Raloxifene
|
Estrogen agonist on bone
Estrogen antagonist on endometrium Treats Osteoporosis No increased risk of endometrial CA |
|
Trastuzumab
|
Monoclonal ab against HER-2 (erb-B2)
Uses: Metastatic breast cancer CARDIOTOXICITY |
|
Respiratory conducting zone
|
Warms, humidifies, filters air
NO GAS EXCHANGE Contain smooth muscle Pseudocolumnar cell lining Contain goblet cells (ex. TB's) Nose Pharynx Trachea--C rings Bronchi--O rings Bronchioles--loses cartilage Terminal bronchioles--loses goblets |
|
Alveolar cells
|
Type 1: SQUAMOUS diffusers
*97% of surface *Type 1 ~ 1 job (GAS exchange) Type 2: Surfactant + stem cells *Secrete dipalmitoyl phosphatidylcholine (SURFACTANT) *Lamellar bodies *CUBOIDAL and clustered *Source of reserve cells Clara cells: Surfactant + stem cells + toxin clearing *COLUMNAR cells w/secretory granules *Secrete component of surfactant *CLEAR TOXINS *Source of reserve cells |
|
Bronchi
|
Primary: Mainstem bronchi
Left and right Secondary: Lobar bronchi R: Superior, middle, inferior L: Superior, inferior Tertiary: egmental bronchi Several per lobe Each has 2 arteries running w/it: *Pulmonary *Bronchial Veins and lymphatics drain along BORDERS of bronchopulmonary segment |
|
Which bronchopulmonary segment is most likely to contain an aspiration?
|
R lower lobe --> Superior segment
This is the most posterior part of the lobe |
|
Where is the right pulmonary artery in relation to the bronchus?
|
Anterior to the bronchus (RALS)
|
|
Where can pain from the diaphragm be referred?
|
Pain can radiate to shoulder
|
|
Diaphragm perforations
|
T8 = 8 letters
VENA CAVA (IVC) T10 = 10 letters Esoph-vagus Esophagus + vagus nerve T12 = 12 letters Aortic Hiatus *Aorta (red) *Azygous vein (blue) --> Drains to SVC *Thoracic duct (white) |
|
Muscles of heavy/exercise breathing
|
Inspiration:
*External intercostal --> EXPAND ribcage *Scalene muscles --> Lift ribcage *Sternomastoids --> Lift ribcage Expiration *Internal intercostals --> Bring ribcage INWARD *Abdominal muscles |
|
Fetal lung maturity
|
Lecithin (dipalmitoyl phosphatidylcholine): Sphingomyelin ratio = > 2
|
|
Surfactant
|
Produced by type II pneumocytes
Decreases alveolar surface tension Increases compliance (reduces work of inspiration) |
|
What does the air pressure have to exceed to keep an alveolus open?
|
2 x surface tension
---------------------- radius |
|
Things that cause a RIGHT shift in the PO2 (x) vs. Hb saturation (y) curve
|
The CADET says its right to be "generous"
*Lower saturation than you'd expect --> more O2 given away CO2 Acid/Altitude DPG Exercise Temperature But people are BASICALLY stingy (Basic conditions cause left shift) |
|
Pulmonary HTN
|
Normal pulmonary artery P = 10-14 mm Hg
Pulmonary HTN = >25 mm Hg Primary = Unknown cause *Poor prognosis Secondary: #1 cause = COPD #2 cause = L --> R shunt |
|
Shunt
|
Physical changes in lung reduce ventilation
100% O2 does not help |
|
Alveolar gas equation
|
PAO2 = PIO2 - PACO2/R
PAO2 = Alveolar O2 PIO2 = Inspired O2 (usually 150) PACO2 = Alveolar CO2 R = Respiratory quotient (usually 0.8) Therefore, typical equation is; PAO2 = 150 - PACO2/0.8 |
|
A-a gradient
|
A-a gradient = PAO2 - PaO2
PAO2 = Alveolar O2 PaO2 = Capillary O2 Usually, artery misses out on 10-15 mm Hg of O2 |
|
V/Q
|
Ideally, V/Q = 1
Apex: V/Q = 3 (wasted ventilation) Base: V/Q =0.6 (wasted perfusion) *V and Q are greater at the base than the apex, but Q is disproportionately greater |
|
Pressures in the lung
|
Zone 1 (apex): Alveolar pressure #1
*PA > Pa > Pv Zone 2: Alveolar pressure #2 *Pa > PA > Pv Zone 3: Alveolar pressure #3 *Pa > Pv > PA |
|
Bohr effect
|
H+ in peripheral tissue shifts O2 dissociation curve to the right (CADET)
O2 is released |
|
Altitude changes
|
Ventilation: Increased acutely and chronically --> Alkalosis
*Renal excretion of bicarbonate Decreased pO2 causes pulmonary vasoconstriction --> RVH Erythropoietin --> Hct, Hb 2,3 DPG produced (binds to Hb to shift its behavior to the right) CELLULAR CHANGES *More mitochondria--more places to grab and use O2 |
|
4 types of COPD
|
1. Increased RV
2. Decreased FEV1 and FVC *FEV1 reduced more, so 3. FEV1/FVC also reduced 3. Decreased I/E ratio 4. Pulsus paradoxus Chronic bronchitis: GLAND hypertrophy (mucus) Emphysema: Destruction of alveolar walls, causing decreased recoil and enlarged air spaces Asthma: SMOOTH MUSCLE hypertrophy w/bronchial hyperresponsiveness and mucus plugs Bronchiectasis: Chronic necrotizing infection of bronchi |
|
Hilar mas arising from bronchus
Keratin pearls Intercellular bridge Think S. C.: *Sentral, Smoking *Cavitations, Keratin/bridges Releases parathyroid-like hormone |
Adenocarcinoma: Bronchial and bronchioalveolar
|
|
Small cell carcinoma
|
Aggressive tumor
*"Sentral" and "Smoking" *Undifferentiated neuroendocrine KULCHITSKY CELLS (small, blue) LAK's differentiation: L = Lambert-Eaton (autoAbs against Ca2+ channels) A= ACTH/ADH secretion (ectopic) K = Kulchitsky cells Responds to chemotherapy |
|
Large cell lung carcinoma
|
Aggressive tumor
*Peripheral *Undifferentiated tumor of pleomorphic giant cells w/LEUKOCYTE fragments in cytoplasm LESS responsive to chemo |
|
Bronchopneumonia
|
Intra-bronchiolar infiltrate leaks into alveoli
SKedooSH --> A staph and a strep S. Aureus Klebsiella S. Pyogenes H. Influenza |
|
Interstitial pneumonia
|
Runts may cough...legionella
Atypical pneumonia Inflammation of interstitial walls between alveoli Viruses (RSV, adenovirus) Mycoplasma Chlamydia Legionella |
|
Lung abscess
|
Aspiration (alcoholics, epileptics) or obstruction --> localized collection of pus
Staph AUREUS (gold/yellow), ANAEROBES |
|
Pleural effusion: Milky
|
Triglycerides
|
|
Asthma drugs
|
Nonspecific B2 agonists: Relaxes bronchial smooth muscle
Methylxanthines (Theophylline): Inhibits PDE to increase cAMP, which promotes bronchodilation Muscarinic antagonist (Ipratroprium): Competitively blocks muscarinic receptors to prevent bronchoconstriction Cromolyn: Prevents mast cell degranulation Corticosteroids: Inactivates NFKB (TF) to inhibit the synthesis of virtually all cytokines Zileuton: 5-Lipooygenase pathway inhibitor (blocks LT synthesis) Zafirlukast/Montelukast: Block LT receptors *Good for aspirin-induced asthma |
|
Effect of cAMP on bronchioles
|
Bronchodilation
When you go to CAMP, take in the fresh air B2 agonists (increases AC) Theophylline (inhibits PDE) |
|
H1 blockers
|
1st generation: Reversible inhibitors of H1 histamine receptors
Dimenhydrate --> DIMEN Diphenhydramine --> DIPHEN Chlorpheniramine --> CLORPHEN Uses: 1. Allergy --> Benadryl 2. Motion sickness --> Dramamine 3. Sleep aid Toxicity: 1. Sedation 2. Anti-muscarinic (Ach) 3. Anti-alpha adrenergic (NE) 2nd generation: Reversible inhibitors of H1 histamine receptors Loradatine, desloradatine Fexofenadine Cetirizine Uses: ALLERGY Toxicity: Less sedating due to decreased CNS entry |