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The Human Gastrointestinal (GI) Tract

The Strategy

Humans (and most animals) digest all their food extracellularly; that is, outside of cells.

The Topology

The diagram shows the major topological relationships in the body. The linings of all are all continuous with the surface of the body. Anything placed within their lumen is, strictly speaking, outside the body. This includes


Food placed in the mouth is

The Stomach

The wall of the stomach is lined with millions of gastric glands, which together secrete 400–800 ml of gastric juice at each meal. Several kinds of cells are found in the gastric glands

Parietal cells

Parietal cells secrete

Hydrochloric acid (HCl)

Parietal cells contain a H+/K+ ATPase. This transmembrane protein secretes H+ ions (protons) by active transport, using the energy of ATP. The concentration of H+ in the gastric juice can be as high as 0.15 M, giving gastric juice a pH somewhat less than 1. With a concentration of H+ within these cells of only about 4 x 10-8 M, this example of active transport produces more than a million-fold increase in concentration. No wonder that these cells are stuffed with mitochondria and are extravagant consumers of energy.

Intrinsic factor

Intrinsic factor is a protein that binds ingested vitamin B12 and enables it to be absorbed by the intestine. A deficiency of intrinsic factor — as a result of an autoimmune attack against parietal cells — causes pernicious anemia.

Chief cells

The chief cells synthesize and secrete pepsinogen, the precursor to the proteolytic enzyme pepsin.

Pepsin cleaves peptide bonds, favoring those on the C-terminal side of tyrosine, phenylalanine, and tryptophan residues. Its action breaks long polypeptide chains into shorter lengths.

Secretion by the gastric glands is stimulated by the hormone gastrin. Gastrin is released by endocrine cells in the stomach in response to the arrival of food.

Absorption in the stomach

Very little occurs. However, some water, certain ions, and such drugs as aspirin and ethanol are absorbed from the stomach into the blood (accounting for the quick relief of a headache after swallowing aspirin and the rapid appearance of ethanol in the blood after drinking alcohol).

As the contents of the stomach become thoroughly liquefied, they pass into the duodenum, the first segment (about 10 inches [25 cm] long) of the small intestine. Most of our ingested vitamins and minerals are absorbed here.

Two ducts enter the duodenum:

The Liver

The liver secretes bile. Between meals it accumulates in the gall bladder. When food, especially when it contains fat, enters the duodenum, the release of the hormone cholecystokinin (CCK) stimulates the gall bladder to contract and discharge its bile into the duodenum.

Bile contains:

The Hepatic Portal System

The capillary beds of most tissues drain into veins that lead directly back to the heart. But blood draining the intestines is an exception. The veins draining the intestine lead to a second set of capillary beds in the liver. Here the liver removes many of the materials that were absorbed by the intestine:

The liver serves as a gatekeeper between the intestines and the general circulation. It screens blood reaching it in the hepatic portal system so that its composition when it leaves will be close to normal for the body.

Furthermore, this homeostatic mechanism works both ways. When, for example, the concentration of glucose in the blood drops between meals, the liver releases more to the blood by

The Pancreas

The pancreas consists of clusters of endocrine cells (the islets of Langerhans) and exocrine cells whose secretions drain into the duodenum.

Pancreatic fluid contains: The secretion of pancreatic fluid is controlled by two hormones:

The Small Intestine

Digestion within the small intestine produces a mixture of disaccharides, peptides, fatty acids, and monoglycerides. The final digestion and absorption of these substances occurs in the villi, which line the inner surface of the small intestine.

This scanning electron micrograph (courtesy of Keith R. Porter) shows the villi carpeting the inner surface of the small intestine.

The crypts at the base of the villi contain stem cells that continuously divide by mitosis producing
  • more stem cells
  • Paneth cells, which secrete antimicrobial peptides [Link to discussion] that suppress the concentration of bacteria in the small intestine.
  • cells that migrate up the surface of the villus while differentiating into
    1. columnar epithelial cells (the majority). They are responsible for digestion and absorption.
    2. goblet cells, which secrete mucus;
    3. endocrine cells, which secrete a variety of hormones;
      Link to Gut Hormones.

The continuous production of new epithelial cells replace older cells that after about 5 days die by apoptosis.

The villi increase the surface area of the small intestine to many times what it would be if it were simply a tube with smooth walls. In addition, the apical (exposed) surface of the epithelial cells of each villus is covered with microvilli (also known as a "brush border"). Thanks largely to these, the total surface area of the intestine is approximately 40 square meters, some 20 times the surface area of the exterior of the body (~2 m2).

The electron micrograph (courtesy of Dr. Sam L. Clark) shows the microvilli of a mouse intestinal cell.

Incorporated in the plasma membrane of the microvilli are a number of enzymes that complete digestion:

Humans with a rare genetic inability to form microvilli die of starvation.

The Large Intestine (colon)

The large intestine receives the liquid residue after digestion and absorption are complete. This residue consists mostly of water as well as any materials that were not digested.

The colon contains an enormous (~413) population of microorganisms. (Our bodies consist of about the same number (~313) of cells)

Most of the species live there perfectly harmlessly; that is, they are commensals. Some are actually beneficial, e.g.,

Most of the bacteria belong to the Firmicutes and Bacteroidetes (although used as an indicator of water pollution by feces, E. coli is actually a minor component). In both obese mice (ob/ob) and humans, the relative proportion of Bacteroidetes declines and, in mice at least, the efficiency with which residual food is absorbed increases. Putting humans on a diet causes them to regain the normal proportion of Bacteroidetes. Why this relationships exists remains to be discovered.

How one member of the Bacteroidetes avoids attack by its host's immune system.

Bacteria flourish to such an extent that as much as 50% of the dry weight of the feces may consist of bacterial cells.

Reabsorption of water is the chief function of the large intestine. The large amounts of water secreted into the stomach and small intestine by the various digestive glands must be reclaimed to avoid dehydration. If the large intestine becomes irritated, it may discharge its contents before water reabsorption is complete causing diarrhea. On the other hand, if the colon retains its contents too long, the fecal matter becomes dried out and compressed into hard masses causing constipation.

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30 October 2018