Ganong’s Review of Medical Physiology, 24th Edition

SECTION IV: Gastrointestinal Physiology

For unicellular organisms that exist in a sea of nutrients, it is possible to satisfy nutritional requirements simply with the activity of membrane transport proteins that permit the uptake of specific molecules into the cytosol. However, for multicellular organisms, including humans, the challenges of delivering nutrients to appropriate sites in the body are significantly greater, particularly if the organisms are terrestrial. Further, most of the food we eat is in the form of macromolecules, and even when these are digested to their component monomers, most of the end products are water-soluble and do not readily cross cell membranes (a notable exception are the constituents of dietary lipids). Thus, the gastrointestinal system has evolved to permit nutrient acquisition and assimilation into the body, while prohibiting the uptake of undesirable substances (toxins and microbial products, as well as microbes themselves). The latter situation is complicated by the fact that the intestine maintains a lifelong relationship with a rich microbial ecosystem residing in its lumen, a relationship that is largely mutually beneficial if the microbes are excluded from the systemic compartment.

The intestine is a continuous tube that extends from mouth to anus and is formally contiguous with the external environment. A single cell layer of columnar epithelial cells comprises the semipermeable barrier across which controlled uptake of nutrients takes place. Various glandular structures empty into the intestinal lumen at points along its length, providing for digestion of food components, signaling to distal segments, and regulation of the microbiota. There are also important motility functions that move the intestinal contents and resulting waste products along the length of the gut, and a rich innervation that regulates motility, secretion and nutrient uptake, in many cases in a manner that is independent of the central nervous system. There is also a large number of endocrine cells that release hormones that work together with neurotransmitters to coordinate overall regulation of the GI system. In general, there is considerable redundancy of control systems as well as excess capacity for nutrient digestion and uptake. This served us well in ancient times when food sources were scarce, but may now contribute to the modern epidemic of obesity.

The liver, while playing important roles in whole body metabolism, is usually considered a part of the gastrointestinal system for two main reasons. First, it provides for excretion from the body of lipid-soluble waste products that cannot enter the urine. These are secreted into the bile and thence into the intestine to be excreted with the feces. Second, the blood flow draining the intestine is arranged such that substances that are absorbed pass first through the liver, allowing for the removal and metabolism of any toxins that have inadvertently been taken up, as well as clearance of particulates, such as small numbers of enteric bacteria.

In this section, the function of the gastrointestinal system and liver will be considered, and the ways in which the various segments communicate to provide an integrated response to a mixed meal (proteins, carbohydrates, and lipids). The relevance of gastrointestinal physiology for the development of digestive diseases will also be considered. While many are rarely life-threatening (with some notable exceptions, such as specific cancers) digestive diseases represent a substantial burden in terms of morbidity and lost productivity. A 2009 report of the U.S. National Institutes of Diabetes, Digestive and Kidney Diseases found that on an annual basis, for every 100 U.S. residents, there were 35 ambulatory care visits and nearly five overnight hospital stays that involved a gastrointestinal diagnosis. Digestive diseases also appear to be increasing in this population (although mortality, principally from cancers, is thankfully in decline). On the other hand, digestive diseases, and in particular infectious diarrhea, remain important causes of mortality in developing countries where clean sources of food and water cannot be assured. In any event, the burden of digestive diseases provides an important impetus for gaining a full understanding of gastrointestinal physiology, since it is a failure of such physiology that most often leads to disease. Conversely, an understanding of specific digestive conditions can often illuminate physiological principles, as will be stressed in this section.

CHAPTER 25 Overview of Gastrointestinal Function & Regulation

CHAPTER 26 Digestion, Absorption, & Nutritional Principles

CHAPTER 27 Gastrointestinal Motility

CHAPTER 28 Transport & Metabolic Functions of the Liver