The Large Intestine PDF

THE LARGE INTESTINE (Dr. Hızır Kurtel)  Although the large intestine is generally perceived as a simple storage depot for fecal material, it is now recognized as a digestive and abrorptive organ of significant import.  One of the most important functions of the large intestine is to a...

THE LARGE INTESTINE (Dr. Hızır Kurtel)  Although the large intestine is generally perceived as a simple storage depot for fecal material, it is now recognized as a digestive and abrorptive organ of significant import.  One of the most important functions of the large intestine is to absorb most of the water and electrolytes which escape form absorption in the small bowel each day. In addition large number of bacteria in the colon transform food residues and dietary fiber into substances of caloric value, which are subsequently absorbed.  The mixing and propulsive activities of the colonic smooth muscle are designed to fascilitate absorption by continuously re-exposing chyme to the absorptive cells. When “chyme” has been sufficiently dehdyrated and residual material reaches the rectum, the urge to defecate is felt. The process of defecation is complex and involves both voluntary and involuntary reflexes. Medical Physiology A Cellular and Molecular Approach, Updated 2nd Ed. INTESTINAL FLUID AND ELECTROLYTE MOVEMENT Henry J. Binder Microscopic view of the anatomy of small and large intestine Medical Physiology A Cellular and Molecular Approach, Updated 2nd Ed. INTESTINAL FLUID AND ELECTROLYTE MOVEMENT Henry J. Binder After completing this lecture students should be able to; 1-define the major functions of the large intestine 2-describe the characteristics of colon movements 3-describe the defecation reflex and its control 4-characterize the clinical correlations of the large intestine  The large intestine consists of cecum (which plays no significant role in humans), colon, rectum, and anal canal. Its main functions are; 1- store food residues 2- secrete mucus 3- absorb remaining water and electrolytes Approximately 2 liters of water is ingested each day and 7 liters of various secretions enters the GI tract. Of this total of 9 liters, about 8.5 liters is absorbed in the small intestine. Approximately 500 ml is passed on to the colon which normally absorbs 80% to 90% of the water presented to it The important physiologic aspect of water fluxes in the small intestine that net movement of water is in the direction which maintains isotonicity of the intestinal contents with plasma. Major route of absorption of sodium in the colon is electogenic transport (secondary active transport process). Because of the «tight» nature of the tight junctions that connect cells in colon, a relatively large potential difference exists between the mucosal (negative) and serosal (positive) sufaces of the absorptive cells. This electical difference favors the net secrretion of K+ into lumen. Secretion of HCO3- occurs in exchange for absorption of Cl-. Cellular mechanisms of K+ secretion and absorption. A, In the small intestine, K+ absorption occurs via solvent drag. B, Throughout the colon, passive K+ secretion occurs via tight junctions, driven by a lumen- negative transepithelial voltage. C, Throughout the colon, active K+ secretion is transcellular. D, In the distal colon, active K+ absorption is transcellular. The thickness of the arrows in the insets indicates the relative magnitude of K+ flux in different segments.  The colon absorbs 400-1000 ml of fluid each day. Sodium is actively transported from the lumen to the blood. Chloride moves in exchange for bicarbonate, and water moves passively. 500-1500 The anal canal which is about 3 cm long and lies entirely outside the abdominal cavity, has internal and external sphincters which remain closed except during defecation.  The large intestine receives both parasympathetic and sympathetic innervation.  Vagal fibers supply the cecum and the colon as far as the distal third of the transverse region.  Parasympathetic fibers supplying the rest of the colon, rectum, and anal canal are from the pelvic nerves from the sacral spinal cord (nervi erigentes).  The sympathetic input is from the celiac and superior mesenteric ganglia (cecum and colon) and from sympathetic nerves from the lumbar spinal cord and the superior hypogastric plexus (rectum and anal canal)  The external anal sphincter receives branches of somatic nerves arising from the sacral region of the spinal cord. The Intestinal Flora:  The microflora of the human colon consists of both aerobic and anaerobic bacteria. The exremely large number of bacteria in the colon is exemplified by the fact that nearly one third the dry weight of feces consists of bacteria.  A major factor contributing to the abundant flora in the colon is the low peristaltic activity. Normal peristalsis in the small bowel is sufficient to prevent bacterial overgrowth. The intestinal flora perform a number of functions: 1- fermentation of indigestible carbohydrates (notably cellulose) and lipids. As a result of carbohydrate fermentation short chain fatty acids are produced along with a number of gases which form about 500 ml of flatus each day (more if diet is rich in indigestible carbohydrates).  While nutritional importance of short-chain fatty acid absorption remains uncertain a potentially important physiologic effect of short chain fatty acids in the human colon is augmentation of sodium, potassium and water absorption.  Luminal bicarbonate neutralizes a significant fraction of the acid load generated by those volatile short chain fatty acids, resulting in production of carbon dioxide and water. Short chain fatty acids (SCFA) are absorbed in the large bowel and are defined as 1-6 carbon volatile fatty acids (containing fewer than six carbons) which can present straight or branched- chain conformation. Acetic acid (C2), Propionic acid (C3), Butyric acid (C4) are the most abundant, representing 90–95% of the SCFA present in the colon Lactate, although is not a SCFA, is also produced by some members of the microbiota, under normal physiological conditions it does not accumulate in the colon due to the presence of some bacteria, that can convert lactate into different SCFA  SCFA, utilized in the enterocytes through different ways: passive diffusion; carrier-mediated transportation by Slc5a8 and Slc16a1; and binding GPR41, GPR43 and GPR109a. After being absorbed SCFAs are transported into portal vein via superior mesenteric vein and inferior mesenteric vein depending on the absorption sites, and dispersed to peripheral tissues such as skeletal muscle, liver and adipose tissue to take effects Journal of Gastroenterology January 2017, Volume 52, Issue 1, pp 1–8 SCFA regulate intestinal barrier integrity by inducing intestinal epithelial cell secretion of IL-18, antimicrobial peptides, mucin, and upregulating the expression of tight junction. SCFA induce neutrophils migration to inflammatory site and enhance their phagocytosis. SCFA regulate the T cell function not only through the protein–coupled receptor (GPCR) pathway but also inhibition of histone deacetylase (HDAC). The differentiation of T cells is mediated both by SCFA regulation of DCs and the direct act of SCFA on T cells. SCFA regulate the generation of Th1, Th17 and Treg in different cytokine milieus. SCFA also inhibit intestinal macrophage production of proinflamamtory cytokines through inhibition of HDAC, and possibly induce intestinal IgA production of B cells. Moreover, SCFAs inhibit the carcinogenesis through promoting apoptosis and suppressing proliferation of tumor cells  The intestinal flora perform a number of functions: 2- Bile acids which are not absorbed in the ileum enter the colon, where they are extensively metabolized by the microflora and passively absorbed. Bile acid diarrhea (BAD) is a condition in which bile acids are not properly processed within the digestive system, resulting in symptoms of chronic diarrhea (This leads to increased fluid secretion, resulting in watery stools and a speeding up of intestinal motility) This condition can also be known as bile acid malabsorption (BAM). However research suggests that the condition may not always be due to malabsorption The intestinal flora perform a number of functions: 3-conversion of bilirubin to urobilinogens. The intestinal flora perform a number of functions: 4- bacteria are able to synthesize certain vitamins e.g.: vitamin K, vitamin B12, thiamine, riboflavin.  Excessive use of laxatives together with a nonabsorbale antibiotic, can produce vitamin K deficiency. There are four major sources of gastrointestinal gas; 1- swallowed air 2- carbon dioxide liberated from the reaction of hydrogen and bicarbonate ions in the gut lumen 3- volatile metabolites produced by intestinal bacteria 4- diffusion of gas from blood to lumen. The Movements of the Colon  Characteristically material travels along the colon at 5-10 cm/hr and typically remains within the colon for 16-20 hours.  The colon exhibits mixing movements (haustrations) and sluggish propulsive movements.  Several times a day usually after meals, a more vigorous propulsive movement of the colon occurs in which a portion of the colon remains contracted for rather longer than during a peristaltic wave. This is called mass movement and results in the emptying of a large portion of the proximal colon. When they force a mass of fecal material into rectum, the desire for defecation is experienced.  Mass movements are initiated in part, by intrinsic reflex pathways resulting from distention of the stomach and duodenum.  These are termed the gastro-colic and duodeno-colic reflexes. These intrinsic motor patterns are modified by autonomic nerves and by hormones. The Rectum and Defecation:  The rectum is a muscular tube about 12-15 cm long. It is normally empty but when a mass movement forces feces into the rectum the urge to defecate is initiated.  The internal anal sphincter is not under voluntary control. It is supplied by both sympathetic and parasympathetic neurons.  Contraction of the smooth muscle of the internal anal sphincter is initiated by sympathetic stimulation and relaxation by parasympathetic stimulation.  The external anal sphincter is composed of skeletal muscle. It is supply by the pudental nerve and is under voluntary control from the age of about 18 months. Both anal sphincters maintain in a tonic state of contraction.  About 100-150 g of feces are normal eliminated each day consisting of 30-50 g of solids and 70-100 g of water.  The solid portion consists largely of cellulose, epithelial cells, shed from the lining of the GI tract, bacteria, some salts and the bwo pigment stercobilin.  It is possible to inhibit reflex consciously if the circumstances are not convenient under such conditions the urge to defecate will often subside until reinitiation by the arrival of further fecal material in the rectum.  Under influence of the parasympathetic system the walls of the Sigmoid colon and the rectum contract to move feces towards the anus. The anal sphincters relax to allow feces to move through the anal canal. Expulsion of the fecal materials is aided by voluntary contractions of the diaphragm and the muscles of the abdominal wall as well as closure to glottis Colonic Pain:  As in the small intestine, colonic pain arises from distention and stretching of the bowel wall. Clinical Correlations  The colon is prone to many diseases, such as carcinoma and ulcerative colitis, a chronic inflammatory disease of unknown cause.  In addition, a huge number of patients consult their doctors regarding symptoms such as colonic pain, constipation, and diarrhea; in some instances, these may reflect some serious organic disease but, in others, they result from dysfunction of a colon which is structurally normal.  The osmotic action of certain luminal constituents opposes normal water and electrolyte absorption from the bowel lumen.  Osmotic laxatives such as magnesium sulfate act in this way in both small intestine and colon.  Unabsorbed lactose in subjects who are deficient in the brush border enzyme lactase holds water in the lumen of the small intestine. However, in the colon, bacteria metabolize the lactose to C02, H2, and water.  When fat is malabsorbed in the small intestine, fatty acids enter the colon and bacteria hydroxylate them to compounds, such as 10-hvdroxystearic acid, which are powerful secretagogues in the colon; thus steatorrhea is accompanied by increased stool water.  Bile acids are normally conserved in the enterohepatic circulation. Approximately 10 per cent of the bile acid pool ~ 300 mg) passes daily into the colon. Bacteria modify these bile acids.  A major stool bile acid is deoxycholic acid, produced by dehydroxylation and deconjugation of glyco- or taurocholic acid. This bile acid, like the hydroxy-fatty acids, is a secretagogue in the colon.  The term “cholerrheic enteropathy” has been applied to the situation in which excessive amounts of bile acids enter the colon and cause diarrhea as the result of terminal ileal disease or resection.  In ulcerative colitis involving a large area of the colon, diarrhea is the result of extensive mucosal inflammation and edema. In this situation, protein-rich fluid exudes from the mucosa. Frank bleeding from the irnIcosa is also common.  If the diet is poor in nonabsorbable residue, as Western Hemisphere diets tend to be, there is comparatively little solid matter in the ileal effluent. Water absorption by the colon produces small, hard, pellety stools. Colonic smooth muscle has difficulty in propelling the material, and constipation is likely to result.  Like other hollow organs with smooth muscle in the wall, the colon responds to distention with high residue material by contraction.  In some patients, constipation is the result of a generalized depression of smooth muscle activity in the body. A good example of this generalized depression is the constipation of pregnancy where high circulating levels of progesterone depress the tone of viseral smooth muscle.