Physiology of the Colon and Its Measurement

Gross Anatomy

In adult cadavers the colon is approximately 1.5 m long. The musculature in the colonic wall is composed of outer longitudinal and inner circular layers. From the cecum to the rectosigmoid junction, the longitudinal layer is organized in three thick bands, the taeniae, with a thin layer of longitudinal muscle in between these bands. At the rectosigmoid junction, the three taeniae broaden to form a uniformly thick layer throughout the rectum. In the anal canal, the longitudinal muscle layer extends into a plane between the external anal sphincter and the circular muscle layer that thickens to become the internal anal sphincter to insert on the perianal skin as the corrugator cutis ani muscle. Other than humans, only primates, horses, guinea pigs, and rabbits have taeniae coli ; the taeniae coli are thought to function as suspension cables upon which the circular muscle arcs are suspended, facilitating efficient contraction of the circular muscle. Thus a 17% contraction of circular muscle reduces the luminal diameter of the colon by two-thirds. If the longitudinal muscles were arranged concentrically, an identical contraction of circular muscle would reduce luminal diameter by only one-third. Whether or not longitudinal and circular muscles contract synchronously during peristalsis is controversial.

The colon is suspended from the posterior abdominal wall by a mesentery. The mesentery is relatively narrow, restricting mobility of the cecum and ascending and descending colon. Around the transverse and sigmoid colon, the mesentery is broader, permitting considerable movement and contributing to the tendency in some individuals to have a pendulous transverse colon or a floppy sigmoid colon. This contributes to the looping of the colonoscope during examination.

Enteric Nervous System

Colonic neurons, interstitial cells of Cajal (ICC), and smooth muscle work in concert to effectuate colonic contraction. The enteric nervous system possesses afferent neurons, interneurons, and motor neurons that can initiate physiologic motor activity in the absence of extrinsic input. The ICC form extensive networks in the myenteric plexus (ICC _MY ), which is situated between longitudinal and circular muscle layers, and the submucosal plexus (ICC _SM ) deep to the circular muscle layer (see Fig. 144.5 ), from where it regulates mucosal absorption. A separate layer—the intramuscular ICC (ICC _IM )—is found in the septa that separate bundles of circular muscle cells. ICC _MY and ICC _SM form extensive networks along the colon and are electrically coupled to one another, the smooth muscle cells, and enteric motor neurons. ICC regulate colonic motility via several mechanisms. They generate electrical slow waves, which then propagate through smooth muscle cells via gap junctions and influence the smooth muscle membrane potential and membrane potential gradient, and they partly mediate mechanosensitivity in smooth muscle. They may also mediate neurotransmission from axons of enteric motor neurons to the smooth muscle, although this has recently been questioned.

Cellular Basis for Motility

Contraction of smooth muscle results from interactions between smooth muscle, the ICC, the intrinsic or enteric nervous system, and the extrinsic nervous system. ICC are the pacemaker cells, responsible for generating slow wave activity that drives smooth muscle contraction. ICC also amplify neuronal input, act as mechanotransducers, and regulate smooth muscle membrane potential. The three basic electrical events recorded from human colonic circular smooth muscle in vitro are : (1) slow wave activity with a frequency of two to four contractions/minute, originating along the submucosal plexus border of the circular muscle layer; (2) membrane potential oscillations (MPOs), with a frequency of approximately 18 contractions/minute, originating in the myenteric plexus border of circular muscle; and (3) action potentials superimposed upon slow waves and MPOs.

Slow waves and MPOs summate in the central region of circular muscle producing a complex pattern of activity that regulates contractile amplitude and frequency. The predominant contractile rhythm recorded from the human colon in vitro and in vivo corresponds to the slow wave frequency of two to four/minute. Repolarization of membrane potential during slow waves results in opening of L-type calcium channels and, when a firing threshold is reached, action potentials. The result is Ca ²⁺ influx through voltage-dependent dihydropyridine-sensitive L-type Ca ²⁺ channels. Calcium phosphorylates the myosin light chains in the contractile apparatus to trigger cross-bridge cycling and smooth muscle contraction. Action potentials superimposed upon slow waves greatly augment Ca ²⁺ entry. Between slow waves, the open probability for Ca ²⁺ channels is low, so action potentials and powerful muscle contractions do not occur. Colonic slow waves may also trigger sufficient Ca ²⁺ influx to activate the contractile apparatus. Strain gauge transducers used in older studies were too insensitive to detect small contractile events. L-type Ca ²⁺ channels are blocked by nifedipine. In the presence of nifedipine, smooth muscle contraction is inhibited and action potentials are absent. Tonic contractions are generated by continuous action potentials. In contrast to regular cyclical contractile activity in the stomach and small intestine, colonic motility is markedly irregular. This irregularity is partly attributable to the variable frequency and duration of action potentials but is not well understood.

Extrinsic Nerve Supply to the Colon

The extrinsic innervation includes sympathetic and parasympathetic components. The vagus (parasympathetic) innervates the proximal colon. The parasympathetic input to the distal colon is derived from the sacral (S2-S4) segments of the spinal cord via the pelvic plexus. After entering the colon, these fibers form the ascending colonic nerves, traveling orad in the plane of the myenteric plexus to supply a variable portion of the left colon. The sympathetic fibers originate in the paravertebral “chain” ganglion, segments from the T12 to L4 levels of the spinal cord, and are conveyed to the colon via arterial arcades of the superior and inferior mesenteric vessels. The sympathetic nervous system provides excitatory input to the sphincters and a tonic inhibitory input to nonsphincteric muscle. Norepinephrine is the major neurotransmitter released by sympathetic nerves throughout the small and large intestine. The extrinsic nerves modulate the intrinsic neural activity. For example, sympathetic nervous system exerts a tonic inhibitory input on colonic motor function, primarily via stimulation of α ₂ -adrenergic receptors, which hyperpolarize cholinergic neurons in the myenteric plexus. Thus the α ₂ agonist clonidine decreases colonic tone, whereas the α ₂ antagonist yohimbine increases colonic tone in humans ; clonidine also enhances mucosal absorption of fluid and salt.

Regional Heterogeneity in Colonic Function

The right colon functions primarily as a reservoir for mixing and storage processes, the left colon as a conduit, and the rectum and anal canal enable defecation and continence. The ileocolonic sphincter regulates the intermittent aborad transfer of ileal contents into the colon, mainly after meals, and prevents reflux of bacteria into the ileum. The rate of delivery of liquids into the proximal colon can influence colonic transit. Thus a liquid marker injected directly into the proximal colon is emptied more rapidly than after oral ingestion of the same marker. There is evidence for adaptation in these regional functions. Within 6 months after a right hemicolectomy, isotope movement from the small to large bowel normalizes in response to the augmented storage capacity in the residual transverse and descending colon. In humans the ileocolonic sphincter plays only a minor role in regulating ileocolonic transit.

Colonic Fluid and Electrolyte Transport

Under basal conditions, the healthy colon receives approximately 1500 mL of chyme over 24 hours, absorbing all but 100 mL of fluid and 1 mEq of sodium and chloride, which are lost in the feces. Colonic absorptive capacity can increase to 5 to 6 L and 800 to 1000 mEq of sodium and chloride daily when challenged by larger fluid loads entering the cecum, as long as there is a slow infusion rate (i.e., 1 to 2 mL/minute). In addition to the ascending and transverse colon, the rectosigmoid may also participate in this compensatory absorptive response. Absorptive mechanisms are constitutively expressed in crypt epithelial cells; secretion is regulated by one or more neurohumoral agonists released from lamina propria cells, including myofibroblasts.

When the colon is perfused with a plasma-like solution, water, sodium, and chloride are absorbed, and potassium and bicarbonate are secreted into the colon. Absorption of sodium and secretion of bicarbonate in the colon are active processes occurring against an electrochemical gradient. There are several different active (transcellular) processes for absorbing sodium, and these show considerable segmental heterogeneity in the human colon. The regional differentiation of colonic mucosal absorption is also demonstrated by regional effects of glucocorticoids and mineralocorticoids on sodium and water fluxes. For example, in the distal colon, epithelial Na ⁺ , K ⁺ , and ATPase are activated by mineralocorticoids. On the other hand, the Na ⁺ /H ⁺ exchange is activated in proximal colonic epithelium by the mineralocorticoid, aldosterone. Specific channels are involved in water transport across surfaces and epithelia. These water channels, or aquaporins (AQPs), are a diverse family of proteins, of which AQP8 is expressed preferentially in colonic epithelium and small intestinal villus tip cells.

Potassium is absorbed and secreted by active processes; it is unclear if chloride is absorbed by an active process. In contrast to the small intestine, glucose and amino acids are not absorbed in the colon.

Colonic conservation of sodium is vital to fluid and electrolyte balance, particularly during dehydration, when it is enhanced by aldosterone. Patients with ileostomies are susceptible to dehydration, particularly when placed on a low sodium diet or during an intercurrent illness. In addition to glucocorticoids and mineralocorticoids (aldosterone), other factors enhancing active sodium transport include somatostatin, α ₂ -adrenergic agents, and short-chain fatty acids (SCFAs). Clonidine mimics the effects of adrenergic innervation by stimulating α ₂ receptors on colonocytes. In contrast, stimulation of mucosal muscarinic cholinergic receptors inhibits active NaCl absorption and stimulates active chloride secretion. Somatostatin, a peptide released by submucosal and myenteric nerves, also has potent antisecretory effects.

Colonic Metabolism

In the proximal colon, bacteria ferment organic carbohydrates to SCFAs, predominantly acetate, propionate, and butyrate. There is a low, normal rate of SCFA production from malabsorbed (up to 10% of ingested) carbohydrates; diets high in fiber, beans, resistant starches, and complex carbohydrates increase the production of SCFA. SCFA are rapidly absorbed from the colon, augment sodium, chloride, and water absorption and constitute the preferred metabolic fuel for colonocytes. SCFA may also serve to regulate proliferation, differentiation, gene expression, immune function, and wound healing in the colon.

Colonic Microflora

The human intestinal tract contains a large variety of microorganisms, of which bacteria are the most dominant and diverse. Contrary to earlier estimates that suggested that the number of bacteria exceeded human cells by a factor of 100, a revised estimate suggests that the number of bacteria and cells in humans is similar (i.e., approximately 39 trillion). Three bacterial divisions, the Firmicutes (gram positive), Bacteroidetes (gram negative), and Actinobacteria (gram positive), dominate the adult human gut microbiota. Among other multifaceted effects, microflora can affect gastrointestinal (GI) motility by releasing bacterial substances or end products of bacterial fermentation (e.g., SCFA), affecting intestinal neuroendocrine factors, and by modulating immunity. The composition of microbiota is associated with stool consistency. Moreover, the profile of the colonic mucosal microbiota differed between constipated patients and healthy people, independent of colonic transit, and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. In contrast, the fecal microbiota were associated with colonic transit and were not different between constipation and health. Genera from Firmicutes ( Faecalibacterium , Lactococcus , and Roseburia ) were correlated with faster colonic transit. Perhaps this association is mediated by cholic acid, which increases the relative abundance of Firmicutes over Bacteroidetes and accelerates colonic transit, particularly in irritable bowel syndrome (IBS). Alternatively, it is conceivable that faster transit is associated with lesser production of secondary bile acids, which may alter the microbiota.

Small intestinal bacterial overgrowth is a recognized complication of intestinal motility disorders (e.g., intestinal pseudoobstruction, scleroderma, radiation enteropathy). During a lactulose-hydrogen breath test, some patients with IBS have increased breath hydrogen excretion. This has erroneously been attributed to small intestinal bacterial overgrowth. Rather, in many patients the increased breath hydrogen excretion is explained by rapid small intestinal transit, hence colon delivery, and bacterial metabolism of lactulose. Thus lactulose and glucose hydrogen breath tests are not recommended for identifying small intestinal bacterial overgrowth.

Colonic Motility