2.1 Function

The colon contributes to three important functions in the body: (1) concentration of fecal effluent through water and electrolyte absorption, (2) storage and controlled evacuation of fecal material and (3) digestion and absorption of undigested food. Although the colon is not essential for survival, its functions contribute significantly to the overall well-being of humans. The colon can be functionally divided through the transverse colon into two parts, the right and left colon. The right colon (cecum and ascending colon) plays a major role in water and electrolyte absorption and fermentation of undigested sugars, and the left colon (descending colon, sigmoid colon and rectum) is predominantly involved in storage and evacuation of stool.

The human colon is a muscular organ measuring approximately 125 cm in length in vivo. Its wall consists of the four basic layers found in other GI hollow visceral organs -the mucosa, submucosa, circular muscle and longitudinal muscle - but several important differences exist. The mucosa lacks the villous projections found in the small intestine and presents a relatively smooth surface, but numerous crypts extend from its surface. Cell types lining the surface and the crypts resemble those in the small intestine but are composed of significantly greater numbers of goblet cells. These cells secrete mucus into the lumen, and mucus strands can often be identified in association with stool. This observation is misconstrued by some patients as a response to underlying colonic pathology. The haustral folds, which help define the colon on barium x-ray, are not a static anatomical feature of the colon but rather result from circular muscle contractions that remain constant for several hours at a time. The outer or longitudinal muscle is organized in three bands, called taeniae coli, which run from the cecum to the rectum where they fuse together to form a uniform outer muscular layer. These muscular bands and elongated serosal fat saccules, called appendices epiploicae, aid in the identification of the colon in the peritoneal cavity.

The colon is innervated by the complex interaction of intrinsic (enteric nervous system) and extrinsic (autonomic nervous system) nerves (Figure 1). The cell bodies of neurons in the enteric nervous system are organized into ganglia with interconnecting fiber tracts, which form the submucosal and myenteric plexi. These nerves are organized into local neural reflex circuits, which modulate motility (myenteric), secretion, blood flow and probably immune function (submucosal). Release of excitatory neurotransmitters such as acetylcholine, substance P and serotonin (5-HT) serves to activate local circuits such as those innervating muscle contractions. Their receptor subtypes provide pharmacological targets for the development of drugs designed to alter colonic functions such as motility. The major inhibitory neurotransmitter is nitric oxide. The importance of the enteric nervous system is exemplified by Hirschsprung's disease, where there is a congenital absence of nitric oxide -containing inhibitory neurons over variable lengths of the rectum and colon. This results in an inability of the colon to relax in the affected region. Infants typically present with bowel obstruction or severe constipation. Barium x-rays identify the affected region as a constricted segment because the excitatory effects of the neurotransmitter acetylcholine are unopposed as a result of the absence of inhibitory neurotransmitter.

The autonomic nervous system comprises sensory nerves, whose cell bodies are found in the dorsal root ganglia, and motor nerves, the sympathetic and parasympathetic nerves. Parasympathetic nerves innervating the right colon travel in the vagus nerve, and those innervating the left colon originate from the pelvic sacral nerves. Parasympathetic nerves are predominantly excitatory, and sympathetic nerves inhibitory. Autonomic nerves modulate the enteric neural circuits within the colon and participate in neural reflexes at the level of the autonomic ganglia, spinal cord and brain. Brain-gut connections are important both for perception of visceral stimuli (sensory) and in modifying colonic function (motor) in response to central stimuli. An example of a central stimulus that can evoke significant changes in colonic activity through this connection is acute stress. This stimulus provokes release of central hormones, such as corticotropin releasing factor. These hormones activate parasympathetic pathways that stimulate motility patterns in the colon and can result in diarrhea.

The colon is highly efficient at absorbing water. Under normal physiological conditions, approximately 1.5 L of fluid enters the colon each day, but only about 100-200 mL is excreted in the stool. The maximal absorptive capacity of the colon is up to about 4.5 L per day, so that diarrhea (increased water in stools) will not occur unless the ileocecal flow rate exceeds the absorptive capacity and/or the colonic mucosa itself is secreting. The fundamental feature of colonic electrolyte transport that enables this efficient water absorption is the ability of the colonic mucosa to generate a large osmotic gradient between the lumen and the intercellular space. This osmotic gradient is created by electrogenic sodium transport. This depends upon the energy-dependent Na⁺/K⁺-ATPase pump on the basolateral membrane, which pumps sodium from inside the cell against a large concentration gradient into the intercellular space (see Figure 5 in Chapter 7, "The Small Intestine"). Luminal sodium in turn enters the apical membrane of the cell through sodium channels, flowing down the concentration gradient created by the pump. In contrast to the small intestine, where sodium in the intercellular space can diffuse back into the lumen and become iso-osmotic, hypertonic solutions are maintained in the intercellular space because the tight junctions are much less permeable to sodium diffusion. The net result is that the hypertonic fluid within the intercellular space draws water passively into the mucosa from the lumen. It also results in highly efficient absorption of sodium. Of the 150 mEq of sodium that enters the colon each day, less than 5 mEq is lost in the stool. The tight junctions are highly permeable to potassium, in contrast to sodium, allowing potassium to move from plasma to the lumen. Potassium pumped into the cell by the Na⁺/K⁺-ATPase pump can also be secreted into the lumen. Potassium is normally secreted into the lumen unless intraluminal potassium rises above 15 mEq/L. This handling of potassium may account for hypokalemia seen with colonic diarrhea and may play a role in maintaining potassium balance in the late stages of renal failure. Other transport mechanisms, similar to those found in the small intestine (see Chapter 7, Section 5), are also found on colonic enterocytes, which maintain electrical neutrality, intracellular pH and secretion. Nutrient cotransporters, however, are not found in the colon.

The regulation of water and electrolyte transport in the colon also involves the complex interplay between humoral, paracrine and neural regulatory pathways (see Chapter 7). One important difference is the effect of aldosterone, which is absent in the small intestine. This hormone is secreted in response to total body sodium depletion or potassium loading and stimulates sodium absorption and potassium secretion in the colon.

Much less is known about the motility of the colon compared to other regions of the GI tract. The movement of fecal material from cecum to rectum is a slow process, occurring over days. Functionally, the contraction patterns in the right colon (cecum and ascending colon) cause significant mixing, which facilitates the absorption of water, whereas in the left colon (sigmoid and rectum) they slow the movement of formed stool, forming a reservoir until reflexes activate contractions to advance and evacuate stool.

Several fundamental contractile patterns exist within the colon. Ring contractions are due to circular muscle contraction and can be tonic or rhythmic. Tonic contractions are sustained over hours and form the haustral markings evident on barium x-rays; they appear to play a role in mixing. Rhythmic ring contractions can be intermittent or regular. Regular contractions are non-occlusive, occur over a few seconds, and migrate cephalad (right colon) and caudad (left colon). Presumably, they too play a role in mixing. Intermittent ring contractions occur every few hours, occlude the lumen, and migrate caudad. They result in the mass movement of stool, particularly in the sigmoid colon and rectum. Contractions of the longitudinal muscle appear to produce bulging of the colonic wall between the taeniae coli, but the importance of this action remains poorly understood. The origin of these contractions is also poorly understood but appears to depend on slow-wave properties of the smooth muscle (regular rhythmic contractions) in some cases, and predominantly neural factors (intermittent rhythmic contractions) in others. These in turn are modulated by the interaction of paracrine, humoral and other neural pathways.

The nature of the contractile patterns within the colon depends upon the fed state. This is best exemplified during eating when the "gastrocolic reflex" is activated. Food in the duodenum, particularly fatty foods, evokes reflex intermittment rhythmic contractions within the colon and corresponding mass movement of stool. This action, which is mediated by neural and humoral mechanisms, accounts for the observation by many individuals that eating stimulates the urge to defecate.

Greater numbers of bacteria (more anaerobes than aerobes) are found within the colonic lumen than elsewhere in the GI tract. These bacteria digest a number of undigested food products normally found in the effluent delivered to the colon, such as complex sugars contained in dietary fiber.

Complex sugars are fermented by the bacteria, forming the short-chain fatty acids (SCFAs) butyrate, propionate and acetate. These SCFAs are essential nutrient sources for colonic epithelium, and in addition can provide up to 500 cal/day of overall nutritional needs. They are passively and actively transported into the cell where they become an important energy source for the cell through the ß-oxidation pathway. The importance of this role is illustrated by the effects of a "defunctioning" colostomy, which diverts the fecal stream from the distal colon. Examination of this area typically reveals signs of inflammation, termed diversion colitis. This inflammation can be successfully treated with the installation of mixtures of short-chain fatty acids into the rectum.

Fermentation of sugars by colonic bacteria is also an important source of colonic gases such as hydrogen, methane and carbon dioxide. These gases, particularly methane, largely account for the tendency of some stools to float in the toilet. Nitrogen gas, which diffuses into the colon from the plasma, is the predominant gas. However, the ingestion of large quantities of undigested complex sugars such as found in beans or the maldigestion of simple sugars such as lactose can result in large increases in production of colonic gas. This can lead to patients' complaints of abdominal bloating and increased flatus.

When bile salts in long-chain fatty acids are malabsorbed in sufficient quantities, their digestion by colonic bacteria generates potent secretagogues. Bile salt malabsorption causing "choleraic diarrhea" typically occurs following terminal ileum resection, usually for management of Crohn's disease. When the resection involves segments greater than 100 cm this problem is further complicated by depletion of the bile salt pool, because bile salt production cannot compensate for the increased fecal loss. In these circumstances diarrhea also results from fat malabsorption. The proposed mechanisms by which multiple metabolites of bile salts and hydroxylated metabolites of long-chain fatty acids act as secretagogues provide an example of how multiple regulatory systems can interact to control colonic function. These mechanisms include disruption of mucosal permeability, stimulation of Cl^- and water secretion by activating enteric secretomotor neurons, enhancement of the paracrine actions of prostaglandins by increasing production, and direct effects on the enterocyte that increase intracelluar calcium.