The Small Intestine:

Your Small Intestine:

The small intestine is the portal for absorption of virtually all nutrients into blood. Accomplishing this transport entails breaking down large supramolecular aggregates into small molecules that can be transported across the epithelium. An exception to this statement is seen in herbivores, where large amounts of short chain fatty acids are absorbed at other sites.

By the time ingesta reaches the small intestine, foodstuffs have been mechanically broken down and reduced to a liquid by mastication and grinding in the stomach. Once within the small intestine, these macromolecular aggregates are exposed to pancreatic enzymes and bile, which enables digestion to molecules capable or almost capable of being absorbed. The final stages of digestion occur on the surface of the small intestinal epithelium.

The net effect of passage through the small intestine is absorption of most of the water and electrolytes (sodium, chloride, potassium) and essentially all dietary organic molecules (including glucose, amino acids and fatty acids). Through these activities, the small intestine not only provides nutrients to the body, but plays a critical role in water and acid-base balance.

You might be surprised to find out the solution for SIBO is very similar to many other digestive disorders. Watch YouTube click here on SIBO ; Small Intestinal Bacterial Overgrowth (SIBO)

Core concepts in small intestinal physiology are presented as the following topics:

•Gross and Microscopic Anatomy of the Small Intestine

•Villi, Crypts and the Life Cycle of Small Intestinal Enterocytes

•Small Intestinal Motility

•Overview of Transport Across the Intestinal Epithelium

•Secretion in the Small Intestine

•Absorption in the Small Intestine: General Mechanisms

•Absorption of Water and Electrolytes

•Absorption of Monosaccharides

•Absorption of Amino Acids and Peptides

•Absorption of Lipids

Advanced and supplemental topics related to physiology of the small intestine:

•Small Intestinal Brush Border Enzymes

•Absorption of Minerals and Metals

•Absorption of Vitamins

•Paneth Cells

•M Cells (Microfold Cells)

•Tuft Cells

•Ontogeny of Small Intestinal Digestive and Absorptive Function

•Gastrointestinal Transit: How Long Does It Take?

Pathophysiology and diseases affecting the small intestine:

•The Gastrointestinal Barrier

•Pathophysiology of Diarrhea

•Lactose Intolerance (Lactase Non-Persistence)

•Allergic Reactions to Red Meat

Digestive Physiology of Herbivores

Roughly 50% of the organic carbon on earth is tied up in cellulose. This represents an enormous source of energy, yet vertebrate cells do not produce the cellulases necessary to break down this abundant material.

Fortunately, many microbes produce cellulases which allow them to utilize dietary cellulose and other plant wall materials. Cellulolytic microbes inhabit the digestive tract of all animals, allowing the animal to siphon off and assimilate the end products of fermentation, particularly short chain or volatile fatty acids.

The relative value of fermentation to an animal's nutrition pretty much depends on the size of its fermentation vat. Fermentation occurs in the colon of dogs and humans, but their large bowel is rather small and the benefit they gain from fermentation is trivial. In contrast, herbivores make a living on cellulose by possessing massive fermentation vats as part of their digestive tract.

Exocrine Secretions of the Pancreas

Pancreatic juice is composed of two secretory products critical to proper digestion: digestive enzymes and bicarbonate. The enzymes are synthesized and secreted from the exocrine acinar cells, whereas bicarbonate is secreted from the epithelial cells lining small pancreatic ducts.

Digestive Enzymes

The pancreas secretes a magnificent battery of enzymes that collectively have the capacity to reduce virtually all digestible macromolecules into forms that are capable of, or nearly capable of being absorbed. Three major groups of enzymes are critical to efficient digestion:

1. Proteases

Digestion of proteins is initiated by pepsin in the stomach, but the bulk of protein digestion is due to the pancreatic proteases. Several proteases are synthesized in the pancreas and secreted into the lumen of the small intestine. The two major pancreatic proteases are trypsin and chymotrypsin, which are synthesized and packaged into secretory vesicles as the inactive proenzymes trypsinogen and chymotrypsinogen.

As you might anticipate, proteases are rather dangerous enzymes to have in cells, and packaging of an inactive precursor is a way for the cells to safely handle these enzymes. The secretory vesicles also contain a trypsin inhibitor which serves as an additional safeguard should some of the trypsinogen be activated to trypsin; following exocytosis this inhibitor is diluted out and becomes ineffective - the pin is out of the grenade.

Once trypsinogen and chymotrypsinogen are released into the lumen of the small intestine, they must be converted into their active forms in order to digest proteins. Trypsinogen is activated by the enzyme enterokinase, which is embedded in the intestinal mucosa.

Once trypsin is formed it activates chymotrypsinogen, as well as additional molecules of trypsinogen. The net result is a rather explosive appearance of active protease once the pancreatic secretions reach the small intestine.

Trypsin and chymotrypsin digest proteins into peptides and peptides into smaller peptides, but they cannot digest proteins and peptides to single amino acids. Some of the other proteases from the pancreas, for instance carboxypeptidase, have that ability, but the final digestion of peptides into amino acids is largely the effect of peptidases on the surface of small intestinal epithelial cells. More on this later.

2. Pancreatic Lipase

A major component of dietary fat is triglyceride, or neutral lipid. A triglyceride molecule cannot be directly absorbed across the intestinal mucosa. Rather, it must first be digested into a 2-monoglyceride and two free fatty acids. The enzyme that performs this hydrolysis is pancreatic lipase, which is delivered into the lumen of the gut as a constituent of pancreatic juice.

Sufficient quantities of bile salts must also be present in the lumen of the intestine in order for lipase to efficiently digest dietary triglyceride and for the resulting fatty acids and monoglyceride to be absorbed. This means that normal digestion and absorption of dietary fat is critically dependent on secretions from both the pancreas and liver.

Pancreatic lipase has recently been in the limelight as a target for management of obesity. The drug orlistat (Xenical) is a pancreatic lipase inhibitor that interferes with digestion of triglyceride and thereby reduces absorption of dietary fat. Clinical trials support the contention that inhibiting lipase can lead to significant reductions in body weight in some patients.

3. Amylase

The major dietary carbohydrate for many species is starch, a storage form of glucose in plants. Amylase (technically alpha-amylase) is the enzyme that hydrolyses starch to maltose (a glucose-glucose disaccharide), as well as the trisaccharide maltotriose and small branchpoints fragments called limit dextrins. The major source of amylase in all species is pancreatic secretions, although amylase is also present in saliva of some animals, including humans.

Other Pancreatic Enzymes

In addition to the proteases, lipase and amylase, the pancreas produces a host of other digestive enzymes, including ribonuclease, deoxyribonuclease, gelatinase and elastase.

Bicarbonate and Water

Epithelial cells in pancreatic ducts are the source of the bicarbonate and water secreted by the pancreas. Bicarbonate is a base and critical to neutralizing the acid coming into the small intestine from the stomach. The mechanism underlying bicarbonate secretion is essentially the same as for acid secretion by parietal cells in the stomach and is dependent on the enzyme carbonic anhydrase. In pancreatic duct cells, the bicarbonate is secreted into the lumen of the duct and hence into pancreatic juice.

Secretion of Bile and the Role of Bile Acids In Digestion

Bile is a complex fluid containing water, electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin that flows through the biliary tract into the small intestine. There are two fundamentally important functions of bile in all species:

•Bile contains bile acids, which are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine.

•Many waste products, including bilirubin, are eliminated from the body by secretion into bile and elimination in feces.

Adult humans produce 400 to 800 ml of bile daily, and other animals proportionately similar amounts. The secretion of bile can be considered to occur in two stages:

•Initially, hepatocytes secrete bile into canaliculi, from which it flows into bile ducts. This hepatic bile contains large quantities of bile acids, cholesterol and other organic molecules.

•As bile flows through the bile ducts it is modified by addition of a watery, bicarbonate-rich secretion from ductal epithelial cells.

In species with a gallbladder (man and most domestic animals except horses and rats), further modification of bile occurs in that organ. The gall bladder stores and concentrates bile during the fasting state. Typically, bile is concentrated five-fold in the gall bladder by absorption of water and small electrolytes - virtually all of the organic molecules are retained.

Secretion into bile is a major route for eliminating cholesterol. Free cholesterol is virtually insoluble in aqueous solutions, but in bile, it is made soluble by bile acids and lipids like lecithin. Gallstones, most of which are composed predominantly of cholesterol, result from processes that allow cholesterol to precipitate from solution in bile.

Role of Bile Acids in Fat Digestion and Absorption

Bile acids are derivatives of cholesterol synthesized in the hepatocyte. Cholesterol, ingested as part of the diet or derived from hepatic synthesis is converted into the bile acids cholic and chenodeoxycholic acids, which are then conjugated to an amino acid (glycine or taurine) to yield the conjugated form that is actively secreted into cannaliculi.

Bile acids are facial amphipathic, that is, they contain both hydrophobic (lipid soluble) and polar (hydrophilic) faces. The cholesterol-derived portion of a bile acid has one face that is hydrophobic (that with methyl groups) and one that is hydrophilic (that with the hydroxyl groups); the amino acid conjugate is polar and hydrophilic.

Their amphipathic nature enables bile acids to carry out two important functions:

• Emulsification of lipid aggregates: Bile acids have detergent action on particles of dietary fat which causes fat globules to break down or be emulsified into minute, microscopic droplets. Emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplets.

• Solubilization and transport of lipids in an aqueous environment: Bile acids are lipid carriers and are able to solubilize many lipids by forming micelles - aggregates of lipids such as fatty acids, cholesterol and monoglycerides - that remain suspended in water. Bile acids are also critical for transport and absorption of the fat-soluble vitamins.

Role of Bile Acids in Cholesterol Homeostasis

Hepatic synthesis of bile acids accounts for the majority of cholesterol breakdown in the body. In humans, roughly 500 mg of cholesterol are converted to bile acids and eliminated in bile every day. This route for elimination of excess cholesterol is probably important in all animals, but particularly in situations of massive cholesterol ingestion.

Interestingly, it has recently been demonstrated that bile acids participate in cholesterol metabolism by functioning as hormones that alter the transcription of the rate-limiting enzyme in cholesterol biosynthesis.

Enterohepatic Recirculation

Large amounts of bile acids are secreted into the intestine every day, but only relatively small quantities are lost from the body. This is because approximately 95% of the bile acids delivered to the duodenum are absorbed back into blood within the ileum.

Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic circulation. Bile acids are then transported across the hepatocytes to be resecreted into canaliculi. The net effect of this enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a single digestive phase.

It should be noted that liver disease can dramatically alter this pattern of recirculation - for instance, sick hepatocytes have decreased ability to extract bile acids from portal blood and damage to the canalicular system can result in escape of bile acids into the systemic circulation. Assay of systemic levels of bile acids is used clinically as a sensitive indicator of hepatic disease.

Pattern and Control of Bile Secretion

The flow of bile is lowest during fasting, and a majority of that is diverted into the gallbladder for concentration. When chyme from an ingested meal enters the small intestine, acid and partially digested fats and proteins stimulate secretion of cholecystokinin and secretin. As discussed previously, these enteric hormones have important effects on pancreatic exocrine secretion. They are both also important for secretion and flow of bile:

• Cholecystokinin: The name of this hormone describes its effect on the biliary system - cholecysto = gallbladder and kinin = movement. The most potent stimulus for release of cholecystokinin is the presence of fat in the duodenum. Once released, it stimulates contractions of the gallbladder and common bile duct, resulting in delivery of bile into the gut.

• Secretin: This hormone is secreted in response to acid in the duodenum. Its effect on the biliary system is very similar to what was seen in the pancreas - it stimulates biliary duct cells to secrete bicarbonate and water, which expands the volume of bile and increases its flow out into the intestine.

NOTE :-

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