Physiology for MRCEM Primary

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Gastro-intestinal physiology

Small intestine

[box type=”download”]  Duodenally-mediated inhibition of gastric juice release and its hormonal components  Effects of addition of water, bicarbonate and bile upon duodenal chyme  Functional anatomy of the intestinal villus  Importance of the sodium pump in creating the osmotic gradient of the small intestine  Carbohydrate handling (brush border enzymes, cotransporters, diffusion)  Functional effects of proteases and carboxypeptidase  Calcium absorption via Ca-ATPase and Na-Ca antiporter mechanisms  Iron absorption via ascorbate complexes and carrier proteins  Fat handling (emulsification agents, micelles) and the handling of fatsoluble vitamins [/box]

The small intestine comprises the duodenum, jejunum and ileum.

When chyme first enters the duodenum, there is a continuation of gastric secretion thought to be due to the activation of G cells in the intestinal mucosa (the intestinal phase).
This is short lived as the duodenum becomes more distended with further gastric emptying.
Secretin is released in response to acid stimulation; it reaches the stomach via the bloodstream and inhibits the release of gastrin.
The presence of fatty acids, due to the breakdown of fats in the duodenum itself, releases gastric inhibitory peptide (GIP) and cholecystokinin (CCK), which inhibit the release of both gastrin and acid.
Both secretin and CCK stimulate the release of pepsinogen from the chief cells, thereby aiding protein digestion.

The chyme that first enters the duodenum is acidic, hypertonic and only partly digested; at this early stage, the nutrients formed cannot be absorbed.
There is an osmotic movement of water leading to the contents becoming isotonic.
The acidity is neutralized by the addition of both bicarbonate secreted by the pancreas and bile from the liver, and further digestion of the chyme is performed by the addition of enzymes from the pancreas, liver and intestine itself.

The lining of the small intestine is folded into villi.
Between the villi lie some small glands, called crypts, which can secrete up to 3 L of hypotonic fluid per day.
The villi have many small projections called microvilli (collectively called the brush border) that project towards the lumen of the intestine.
Each villus contains a single, blind-ended lymphatic vessel, called a lacteal, and also a capillary network.
Most nutrients are absorbed into the bloodstream via these vessels.
The venous drainage from the intestines, pancreas and part of the stomach passes via the hepatic portal vein into the liver; here, it passes through a second capillary bed to be processed before returning to the circulation.

Absorption of nutrients

As the contents of the intestine are isotonic with body fluids and mostly have the same concentration of the major electrolytes, their absorption is active.
Water cannot be moved directly, but follows osmotic gradients set up by the transport of ions.
The major contributor to this osmotic gradient is the sodium pump.
Na+–K+ ATPase is located on the blood side of the epithelial cell (basolateral membrane), and usage of 1 ATP results in expulsion of three Na+ ions from the cell in exchange for two K+ ions (against the respective concentration gradients), leading to a low concentration of Na+ and a high concentration of K+ within the cells.
The low intracellular concentration of Na+ ensures a movement of Na+ from the intestinal contents into the cell by both membrane channels and transported protein mechanisms.
Na+ is then rapidly transported out of the cell again by the basolateral Na+–K+ pump.
K+ leaves the cell, again via the basolateral membrane, down its concentration gradient.
This outward movement of K+ is linked to an outward movement of Cl−, against its concentration gradient, Cl− having entered down its concentration gradient like Na+ via the luminal membrane.

Carbohydrates are absorbed mostly in the form of monosaccharides (glucose, fructose and galactose).
They are broken down into monosaccharides by enzymes released from the brush border (maltases,
isomaltases, sucrase and lactase).
The monosaccharides are transported across the epithelium into the bloodstream by means of cotransporter molecules that link their inward movement with that of Na+ down its concentration gradient.
At the basolateral membrane, monosaccharides leave the cell either by simple diffusion or by facilitated diffusion down the concentration gradient.
The polypeptides produced in the stomach are broken down into oligopeptides in the small intestine by enzymes (proteases) secreted by the pancreas: trypsin and chymotrypsin.
These are further broken down into amino acids by another pancreatic enzyme, carboxypeptidase, and an enzyme located on the luminal membrane epithelial cells, aminopeptidase.
The free amino acids enter the epithelial cells by secondary active transport coupled to the movement of Na+ and a number of different cotransporter mechanisms.

Two very important minerals that are absorbed from the diet are calcium and iron.

Intracellular calcium concentrations are low and any free calcium in the diet can cross the luminal membrane down a steep concentration gradient through channels or by a carrier mechanism.
In the cell, it binds to a protein which carries it to the basolateral membrane, where it is actively transported against the concentration gradient by a Ca2+ ATPase, or by an Na+–Ca2+ antiporter linked with the movement
of Na+ down its concentration gradient into the cell and the removal of Ca2+ from it.

Most dietary iron is in the ferric (Fe3+) form which cannot be absorbed; however, in the ferrous (Fe2+)
form, it forms soluble complexes with ascorbate and other substances and can be readily absorbed.
These complexes are transported across the membrane by a carrier protein and, once in the cell, bind with a variety of substances including ferritin. A second carrier protein transports the iron across the basolateral membrane into the bloodstream.

Fats and lipids

Fat has to be emulsified (larger lipid droplets are broken down into smaller droplets) before pancreatic lipase breaks fat into monoglycerides and free fatty acids. The main emulsifying agents are the bile acids, cholic acid and chenodeoxycholic acid.
The free fatty acids and monoglycerides form tiny particles (4–5 nm in diameter) with the bile acids, called micelles.
The outer region of the micelle is hydrophilic and inner core is hydrophobic.
This arrangement allows the micelles to enter the aqueous layers surrounding the microvilli, and the monoglycerides, free fatty acids, cholesterol and fat-soluble vitamins can then diffuse passively into the duodenal cells.
Left over bile salts reach the ileum to get reabsorbed.
Once within the epithelial cells, the fatty acids and monoglycerides are reassembled into fats by a number of different metabolic pathways.
They then enter the lymphatic system via the lacteals and eventually reach the blood via the thoracic duct.
The fat-soluble vitamins, A, D, E and K, essentially follow the pathways for fat absorption.
The remaining water-soluble vitamins are mainly absorbed by diffusion or mediated transport.
The exception is vitamin B12, which must first bind with intrinsic factor (secreted from the parietal cells in the stomach wall).
When bound, vitamin B12 attaches to specific sites on the epithelial cells in the ileum where a process of endocytosis leads to absorption.