The Digestive System

In general, what happens Inside of the gastrointestinal (GI) tract?

Food is broken down by hydrolysis into molecular monomers.

Where does the absorption of monomers occur?

Inside the small intestine.

What are the 4 means of motility through the GI tract?

Ingestion, Mastication, Deglutition, Peristalsis

What is ingestion?

taking food into mouth

What is mastication?

chewing food and mixing it with saliva

What is deglutition?

swallowing food

What is peristalsis?

rhythmic wave-like contractions that move food through GI tract

What are the common functions of the GI tract? (5)

Secretion, Digestion, Absorption, Storage and Elimination, Immune Barrier

Common Exocrine secretions

HCl, H2O, HCO3-, bile, lipase, pepsin, amylase, trypsin, elastase, and histamine

Common Endocrine secretions

gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP, and somatostatin

What is digestion?

The breakdown of food molecules into smaller subunits

What is absorption?

The passage of digested end products into blood or lymph.

What are the beginning and endpoints of the GI tract?

The mouth and the anus

What are the organs in the digestive system?

oral cavity, pharynx, esophagus, stomach, and small and large intestine

What are the accessory organs in the digestive system?

The teeth, tongue, salivary glands, liver, gallbladder, and pancreas

What are tunics? Name all 4 of them.

Tunics are the layers of the GI tract. The 4 tunics are the mucosa, submucosa, muscularis, and serosa.

This is the absorptive and secretory layer lining lumen of GI tract. In places it is highly folded with villi to increase absorptive area. It contains lymph nodules, mucus-secreting goblet cells, and thin layer of muscle.

The mucosa tunic of the GI tract.

This is a thick, highly vascular layer of connective tissue where absorbed molecules enter blood and lymphatic vessels. It contains glands and nerve plexuses (submucosal plexus) that carry ANS activity to muscularis mucosae of small and large intestines.

The submucosa tunic of the GI tract

This tunic in the GI tract is responsible for segmental contractions and peristaltic movement through the GI tract. It has an inner circular and outer longitudinal layer of smooth muscle. Activity of these layers moves food through tract while pulverizing and mixing it.

The muscularis tunic of the GI tract

This is a major nerve supply located in between the layers of smooth muscle in the muscularis tunic of the GI tract. It includes fibers and ganglia from both the Sympathetic and Parasympathetic systems.

Myenteric plexus

This is the outermost layer of the GI tract. It serves to bind and protect. It consists of areolar connective tissue covered with layer a of simple squamous epithelium.

Serosa

How is the GI tract regulated?

Parasympathetic effects, arising from vagus and spinal nerves, stimulate motility and secretions of GI tract.

Sympathetic activity reduces peristalsis and secretory activity.

This is an intrinsic system that controls the movements of the GI tract.

the enteric nervous system

What influences motility in the GI tract?

paracrine and hormonal signals

Mastication

More commonly referred to as chewing, this involves mixing food with saliva, which contains an enzyme called salivary amylase which partially digests the food.

Describe the voluntary and involuntary phases of deglutition.

Deglutition, also known as swalling, begins in a voluntary oral phase and forms a food bolus. The subsequent pharyngeal and esophageal phases are involuntary and cannot be stopped. To swallow, the larynx is raised so that an epiglottis covers entrance to respiratory tract. A swallowing center in the medulla orchestrates the complex pattern of contractions required for swallowing.

What does the esophagus connect?

The esophagus connects the pharynx to the stomach.

Describe the different muscular makeup of the different parts of the esophagus.

Upper third contains skeletal muscle.
Middle third contains mixture of skeletal and smooth.
Terminal portion contains only smooth.

These are wave-like muscular contractions that propel food through the GI tract.

Peristalsis

After food passes into the stomach, what prevents reflux?

constriction of the gastroesophageal sphincter

What is the most distensible part of the GI tract?

the stomach

What does the stomach empty into?

the duodenum

What are the functions of the stomach?

-storage of food
-initial digestion of proteins
-killing bacteria with high acidity
-moving soupy food mixture (chyme) into intestine

What are the names of the sphincters that enclose the top and bottom of the stomach?

gastroesophageal sphincter on top and pyloric sphincter on bottom

What are the 3 regions of the stomach?

Fundus
Body
Antrum

These result from the foldoing of the inner surface of the stomach

rugae

What happens in the stomach that leads to food eventually propelling into the small intestine?

Churning of chime (soupy food mixture) due to contractions which mixes it with gastric secretions.

Describe the components of the gastric mucosa.

Gastric mucosa has gastric pits in its folds. Cells that line folds deeper in the mucosa, are exocrine gastric glands

Goblet cells, parietal cells, chief cells, Enterochromaffin-like cells, G cells, D cells. Where are they located and what do each secrete?

They are various cells contained in gastric glands, that each secrete different products to form gastric juice.

Goblet cells secrete mucus.
Parietal cells secrete HCl and intrinsic factor (necessary for B12 absorption in intestine).
Chief cells secrete pepsinogen (precursor for pepsin)
Enterochromaffin-like cells secrete histamine and serotonin
G cells secrete gastrin
D cells secrete somatostatin

How is HCl- in the stomach produced?

Parietal cells pump H+ into lumen via an H+/ K+ pump (pH ~1). Cl- is secreted by facilitated diffusion. H+ comes from dissociation of H2CO3. Cl- comes from blood side of cell in exchange for HCO3-.

What causes the stomach to secrete HCl-?

HCl- is indirectly secreted in response to the hormone gastrin; and ACh from the vagus. These are indirect effects since both stimulate release of histamine which causes the parietal cells to secrete HCl.

What does HCl in the stomach do? (2 things)

1)Makes gastric juice which denatures proteins to make them more digestible.
2)Converts pepsinogen into pepsin

How is the Stomach protected Against HCL and Pepsin? (3 ways)

1st line of defense is the adherent layer of mucus ( a stable gel of mucus coating the gastric epithelium), which contains bicarbonate for neutralizing HCL, and serves as a barrier to the actions of pepsin.

Gastric epithelial cells contain tight junctions to prevent HCL and pepsin from penetrating the surface.

These gastric epithelial cells are replaced every 3 days.

What partially digests proteins in the stomach?

pepsin

What happens to carbohydrate digestion due to salivary amylase once it reaches the stomach?

It is inactivity by the acidity of the stomach.

What are the only 2 commonly ingested substances that get absorbed in the stomach?

alcohol and aspirin

Erosions of mucous membranes of stomach or duodenum caused by action of HCl

Peptic ulcers

What is the name of the syndrome in which duodenal ulcers result from excessive gastric acid in response to high levels of gastrin.

Zollinger-Ellison syndrome

infection associated with ulcers

Helicobacter pylori

2 ways to treat ulcers?

antibiotics

proton pump inhibitors such as Prilosec

an inflammation that results in acid damage due to histamine released by inflammation

acute gastritis

how do you treat gastritis?

histamine receptor blockers

the longest part of the GI tract

the small intestine

from top to bottom, what are the 3 parts of the small intestine?

(pyloric sphincter) -->1.Duodenum -->2.Jejunum -->3.Ileum -->(large intestine)

what facilitates absorption of digested food occurs in small intestine?

its long length and large surface area

what are the scientific names of the Large folds in the small intestine? Microscopic finger-like projections? Apical hair-like projections?

plicae circulares

villi

microvilli

what is found on the top of each villus in the small intestine? what is found in each villus?

columnar epithelial cells interspersed with goblet cells. these epthelial cells are replaced via osmosis in crypts of Lieberkuhn.

Inside each villus are lymphocytes, capillaries, and central lacteal

A carpet of hair-like microvilli project from apical surface of each epithelial cell

brush border

intestinal enzymes attached to microvilli that are not secreted into the lumen

brush border enzymes

what are the 2 types of contractions that occur in the small intestine?

which one is the major contraction of the SI

Peristalsis, Segmentation (major)

weak and slow contraction in the SI that occurs mostly because pressure at pyloric end is greater than at distal end
Segmentation

Peristalsis

small intestine contraction of circular smooth muscle to mix chyme

Segmentation

what drives contractions?

graded depolarizations called slow waves

interstitial cells of Cajal (ICC)

long, interconnected, non-neuronal/non-muscular cells which produce slow waves and spread depolarization from cell to cell via gap junctions

What happens when slow waves exceed their threshold?

Action potentials are triggered. in smooth muscle by opening V-gated Ca2+ channels.This influx of Ca2+ produces the depolarization phase of the AP and stimulates contraction. Repolarization follows via a K+ efflux.

What modifies contractions?

ANS activity modifies contractions.
Specifically, ACh from Parasymp increases amplitude and duration of slow waves.

Norepi and Epi from Symp decrease activity of intestines.

What does the Large Intestine digest?

nothing

What does the large intestine do?

absorbs H2O, electrolytes, B and K vitamins, and folic acid

Describe the internal surface of the large intestine.

no villi or crypts and is not very elaborate

What are the microfluora in the LI, and what do they do?

Microfuluora are commensal bacteria of 400 species
which produce folic acid and vitamin K and ferment indigestible food to produce fatty acids. They also reduce the ability of pathogenic bacteria to infect the LI.

What are the beginning and endpoints of the large intestine connected to?

the small intestine and the anus

What path would chyme take throughout the large intestine, starting with the cecum?

(small intestine) --> Cecum --> ascending colon -> transverse colon --> descending colon --> sigmoid colon --> rectum --> anal canal --> (anus)

Which intestine absorbs more water?

small intestine

how much of the water in the large intestine is absorbed?

90%

how is water absorbed in the LI? what stimulates reabsorption?

osmotic gradient setup by Na+/K+ pumps

aldosterone stimulates it

describe defecation reflex

1. begins with relaxation of the external anal sphincter allowing feces to enter anal canal
2. Longitudinal rectal muscles contract to increase rectal pressure; internal anal sphincter relaxes
3. Excretion is aided by contractions of abdominal and pelvic muscles which push feces from rectum

What is the largest internal organ?

the liver

Describe the structure of the liver

Hepatocytes form hepatic plates that are 1–2 cells thick. Plates are separated by sinusoids which are fenestrated and permeable even to proteins. They contain phagocytic Kupffer cells.

How can a damaged liver regenerate itself? In which cases is the liver incapable of regeneration?

Mitosis of its hepatocytes.

In some cases, such as alcohol abuse or viral hepatitis, regeneration does not occur. This can lead to liver fibrosis and ultimately cirrhosis

Describe the hepatic portal system

Food absorbed in SI is delivered 1st to liver
Capillaries in digestive tract drain into the hepatic portal vein which carries blood to liver
Hepatic vein drains liver
Liver also receives blood from the hepatic artery

functional units formed by hepatic plates
In middle of each is central vein
At edge of each are branches of hepatic portal vein and artery which open into sinusoids

liver lobules

recirculation of compounds between liver and intestine

enterohepatic circulation

What are the 5 major categories of liver function?

1. Detoxification of the blood
2. Carbohydrate Metabolism
3. Lipid Metabolism
4. Protein Synthesis
5. Secretion of Bile

What actions does the liver take to detoxify blood? (4)

1. Phagocytosis by Kupffer cells.
2. Chemical alteration of biologically active molecules.
3. Production of urea, uric acid, and other molecules that are less toxic than parent molecules.
4. Excretion of molecules in bile.

What actions does the liver take to metabolize carbohydrates? (3)

1. It converts blood glucose to glycogen and fat.
2. It produces glucose from glycogen and other molecules via glyconeogenesis.
3. It secretes glucose into the blood.

What actions does the liver take to metabolize lipids? (3)

1. It synthesizes lipids and cholesterol.
2. It excretes cholesterol in bile.
3. It produces ketone bodies from fatty acids.

What actions does the liver take to synthesize proteins? (3)

1. It produces albumin.
2. It produces plasma transport proteins.
3. It produces clotting factors such as fibrinogen and prothrombin.

What actions does the liver take to secrete bile? (2)

1. It synthesizes bile salts
2. It conjugates and excretes bile pigment (bilirubin).

Other than the liver, where else is bilirubin produced?

The spleen and the bone marrow.

What is bilirubin a derivative of?

The heme group in Hb, but without the iron group.

What stimulates the detoxification of xenobiotics and steroid hormones in the liver?

activation of nuclear receptors =SXR (steroid and xenobiotic receptor)

Describe the detoxification of xenobiotics and steroid hormones.

xenobiotics and steroid hormones are made anionic via conjugation by the liver. this product is then transported by multispecific organic anion transport carriers to bile or urine then excreted.

what makes up 70% of total plasma protein and contributes most of the colloid osmotic pressure of blood

albumin

sac-like organ attached to inferior surface of liver

gallbladder

what is the function of the gallbladder?

Stores and concentrates bile continuously produced by liver
When SI is empty, sphincterof Oddi in common bile duct closes and bile is forced into gallbladder
Expands as it fills with bile
When food is in SI, sphincter of Oddi opens, gall bladder contracts, and bile is ejected thru cystic duct into common bile duct then to duodenum

where is the pancreas located?

behind the stomach

differentiate between the endocrine and exocrine functions of the pancreas

Endocrine function performed by islets of Langerhans. this involves secretion of insulin and glucagon.

Exocrine secretions include bicarbonate solution and digestive enzymes which pass in the pancreatic duct to SI. Exocrine secretory units are acini.

where are pancreatic juice and bile from the pancreas secreted into?

the duodenum of the small intestine

what does pancreatic juice consist of and what does it digest?

Contains water, bicarbonate, and digestive enzymes including amylase for starch, trypsin for proteins, and lipase for fats.

(Brush border enzymes are also required for complete digestion)

zymogens

the inactive form of pancreatic enzymes.. the form in which they are normally produced

what activates zymogens?

trypsin

What role does the vagus nerve play in neural and endocrine regulation?

regulating and coordinating digestive activities

From where is the hormone, gastrin secreted, and what roles does it lay in neural and endocrine regulation? (3)

Secreted by the stomach

1. Stimulates parietal cells to secrete HCl
2. Stimulates chief cells to secrete pepsinogen.
3. Maintains the structure of gastric mucosa.

From where is the hormone, secretin secreted, and what roles does it lay in neural and endocrine regulation? (2)

Secreted by the small intestine

1. Stimulates water and bicarbonate secretion in pancreatic juice.
2. Potentiates actions of choleycytokinin on pancreas.

From where is the hormone, choleycytoinin, secreted, and what roles does it lay in neural and endocrine regulation? (4)

Secreted by the small intestine

1. Stimulates contraction of the gallbladder
2. Stimulates secretion of pancreatic juice enzymes
3. Inhibits gastric motility and secretion.
4. Maintains structure of exocrine pancreas (acini).

From where is the hormone, gastric inhibitory peptide (GIP), secreted, and what roles does it lay in neural and endocrine regulation? (2)

Secreted by the small intestine

1. Inhibits gastric motility and secretion.
2. Stimulates secretion of insulin from pancreatic islets.

From where is the hormone, glucogen-like peptide I (GLP-I), secreted, and what roles does it lay in neural and endocrine regulation? (3)

Secreted by the ileum and colon

1. Inhibits gastric motility and secretion
2. Stimulates secretion of insulin from pancreatic islets.
3. Stimulates intestinal secretion of Cl-, causing elimation of NaCl and water in the feces.

How is gastric function regulated?

Automatically.

Waves of contraction are initiated spontaneously by pacesetter cells and secretion occurs in absence of hormonal and neural input
ANS and hormonal effects are superimposed on automatic activity

What are the 3 phases of extrinsic control of gastric function?

cephalic, gastric, and intestinal phases

What stimulates vagus activity in the cephalic phase of the extrinsic control of gastric function?

sight, smell, and taste of food

What does the activation of the vagus during the cephalic phase of the extrinsic control of gastric function lead to?

Stimulates chief cells to secrete pepsinogen
Directly stimulates G cells to secrete gastrin
Directly stimulates ECL cells to secrete histamine
Indirectly stimulates parietal cells to secrete HCl

What does the gastric phase of the extrinsic control of gastric function involve?

Distension of the stomach stimulates the vagus nerve. The vagus nerve then stimulates acid secretion. Gastrin secretion occurs until it is inhibited at a pH below 2.5.

Short polypeptides and amino acids stimulate G cells to secrete gastrin and chief cells to secrete pepsinogen
Gastrin stimulates ECL cells to secrete histamine which stimulates parietal cell secretion of HCl
This is a positive feedback mechanism: As more HCl and pepsinogen are secreted, more polypeptides and amino acids are released

Secretion of HCl is also regulated by a negative feedback mechanism:
HCl secretion decreases if pH < 2.5; at pH 1 gastrin secretion stops
D cells stimulate secretion of somatostatin which inhibits gastrin secretion

What signifies the beginning of the intestinal phase of the extrinsic control of gastric function?

when chyme enters the SI and inhibits gastric activity

enterogasterones

hormones that inhibit gastric motility and secretion

what does the enteric nervous system consist of?

ENS organized into ganglia interconnected by 2 plexuses:
Outer myenteric (Auerbach’s) plexus found along entire length of GI tract
Inner submucosal (meissner’s plexus) located only in small and large intestine

what stimulates smooth muscle contraction in peristalsis?

ACh and substance P stimulate smooth muscle contraction above bolus
NO, VIP, and ATP stimulate smooth muscle relaxation below bolus

what are some paracrine regulators in the intestine?

ECL cells release serotonin and motilin in response to pressure and chemical stimuli in SI
Serotonin stimulates intrinsic afferents which activate motor neurons in intrinsic NS
Motilin stimulates contraction in duodenum and stomach antrum
Guanylin, from ileum and colon, stimulates production of cGMP which inhibits absorption of Na+and causes secretion of Cl- and H2O
Uroguanylin found in urine---appears to be prod. by intestines and may function as hormone that stim. kidneys to excrete salt in urine

how are intestinal mediated and regulated?

Can be mediated by enteric NS and paracrines; and regulated by ANS and hormones

Gastroileal reflex refers to increased motility of ileum and movement of chyme thru ileocecal sphincter in response to increased gastric activity
Ileogastric reflex decreases gastric motility in response to distension of ileum
Intestino-intestinal reflex causes relaxation of rest of intestine when any part is overdistended

what stimulates the secretion of pancreatic juice?

Secretion of pancreatic juice is stimulated by secretin and CCK (cholecystokinin)

what stimulates the secretion of secretin and CCK?

Secretin is secreted in response to duodenal pH < 4.5
Stimulates release of HCO3- into SI by pancreas
CCK is secreted in response to fat and protein content of chyme in duodenum
Stimulates production of pancreatic enzymes
Enhances secretin
Stimulates contraction of sphincter of Oddi

Describe The Action of Pancreatic Amylase

Most carbohydrates are ingested as starch--a polymer of glucose
Salivary amylase begins starch digestion
Pancreatic amylase converts starch to oligosaccharides
Oligosaccharides hydrolyzed by SI brush border enzymes

Describe the Mechanism of the Digestion and Absorption of Protein

Begins in stomach when pepsin digests proteins to form polypeptides
In SI, the pancreatic juice enzymes endopeptidases (trypsin, chymotrypsin, elastase) cleave peptide bonds in interior of polypeptides
SI exopeptidases (carboxypeptidase -pancreatic juice and aminopeptidase- brush border enzyme) cleave peptide bonds from ends of polypeptides
Results in free amino acids, dipeptides, and tripeptides
Free amino acids absorbed by cotransport with Na+ into epith. cells and secreted into blood caps.
Di- and tripeptides carried into epith. cell where hydrolyzed into free amino acids then secreted

Describe the general mechanism for the digestion and absorption of lipids

Occurs in SI
Arrival of lipids in duodenum causes secretion of bile
Fat is emulsified by bile salt micelles
Forms tiny droplets of fat dissolved in bile salt micelles
Greatly increases surface area for fat digestion