The small intestine Medical Assignment Help

STRUCTURE

The small intestine extends from the duodenum to the ileum. Its surface area is enormously increased by mucosal folds. In addition, the mucosa has numerous finger-like projections called villi and the surface area is further increased by microvilli . Each villus consists of a core containing blood vessels, lacteals (lymphatics) and cells, e.g. plasma cells and lymphocytes, and is covered by epithelial columnar cells that are absorptive. Opening into the lumen between the villi are the crypts of Lieberkiihn. The epithelial cells are formed at the bottom of these crypts and migrate to the tops of the villi, from where they are shed. This process takes 3-4 days. On its luminal side the epithelial cell has a brush border of microvilli that is covered by the glycocalyx. The lamina propria contains plasma cells, lymphocytes, macrophages, eosinophils and mast cells. Scattered throughout the gut are peptidesecreting cells.
Most of the blood supply to the small intestine is via branches of the superior mesenteric artery. The terminal branches are end arteries, i.e. there are no local anastomotic connections.
Histochemically there are three types of nerves in the gut:
• Cholinergic parasympathetic (with muscarinic or nicotinic receptors)

• Adrenergic sympathetic (with both a and f3 receptors)

• Non-cholinergic, non-adrenergic. The transmittershere are thought to be either cyclic nucleotides and A TP (the purinergic system) or intestinal hormones, e.g. vasoactive intestinal peptide (VIP) (peptidergic system) or nitric oxide which is now thought to act as a neurotransmitter.

he structure of the small intestine.

he structure of the small intestine.

FUNCTION

The small intestine is concerned with the digestion and absorption of nutrients, salt and water. It produces many enzymes and hormones in order to carry out these processes. Nutrients can be absorbed throughout the small intestine with the exception of vitamin BJ2 and bile salts, which have specific receptors in the terminal ileum. The small intestine also has local defence mechanisms to prevent antigens from entering the body.

Functions of the small intestine.

Functions of the small intestine.

General principles of absorption

SIMPLE DIFFUSION. This process requires no energyand takes place if there is a concentration gradient from he intestinal lumen (high concentration) to the bloodstream (low concentration).
ACTIVE TRANSPORT. This requires energy and can work against a concentration gradient. A carrier protein is required and the process is sodium dependent. For example, glucose enters the enterocyte on the luminal side via a sodium-dependent carrier molecule and leaves on the serosal side via a sodium-independent carrier that is found in the basolateral membrane. A gradient is maintained across the membrane by an energy-dependent sodium pump (Na”, K+ATPase) that keeps the intracellular sodium concentration low.
FACILITATED DIFFUSION. This is an energy-independent carrier-mediated transport system that allows a faster absorption rate than simple diffusion, e.g. fructose absorption.

Absorption in the small intestine

CARBOHYDRATE. Dietary carbohydrate consists mainly of starch with some sucrose and a small amount of lactose. Starch is a polysaccharide made up of numerous glucose units. Its hydrolysis begins in the mouth by salivary amylase. The majority of hydrolysis takes place in the upper intestinal lumen by pancreatic amylase. This hydrolysis is limited by the fact that amylases have no specificity for some glucose/glucose branching links.

The small intestine

The small intestine

These breakdown products, together with sucrose and lactose, are hydrolysed on the brush border membrane by their appropriate oligo- and di-saccharidases to form the monosaccharides glucose, galactose and fructose. These monosaccharides are transported into the cells, largely by sodium-dependent active transport systems.
PROTEIN. Dietary and endogenous proteins (desquamated cells, intestinal secretions) are mainly digested by pancreatic enzymes prior to absorption. These proteolytic enzymes are secreted as proenzymes and transformed to active enzymes in the lumen. The presence of protein in the lumen stimulates the release of enterokinase, which activates trypsinogen to trypsin, and this in turn activates the other proenzymes, chymotrypsin and elastase. These enzymes break down protein into oligopeptides. Some diand tri-peptides are absorbed intact by a carrier-mediated process, while the remainder are broken down into free amino acids by peptidases on the microvillus membranes of the cell, prior to absorption in a similar way to disaccharides. These amino acids are transported into the cell by a number of different carrier systems.

Diagrammatic representation of solute transport across the apical membrane showing glucose/galactose sodium-linked transport. The Na+, K+ ATPase pump is located in the basolateral membrane.

Diagrammatic representation
of solute transport across the apical
membrane showing glucose/galactose
sodium-linked transport. The Na+, K+
ATPase pump is located in the
basolateral membrane.

Dietary fat mainly consists oftriglycerides with some cholesterol and fat-soluble vitamins. Emulsification of fat occurs in the stomach and is followed by hydrolysis of triglycerides in the duodenum by pancreatic lipase to yield fatty acids and monoglycerides. Bile enters the duodenum following gallbladder contraction. Bile contains phospholipids and bile salts, both of which are partially water soluble and act as detergents. They aggregate together to form micelles with their hydrophilic ends on the outside. Trapped in the hydrophobic centre of this micelle are the monoglycerides, fatty acids and cholesterol; these are then transported to the intestinal cell membrane. At the cell membrane the lipid contents of the micelle are absorbed, while the bile salts remain in the lumen. Inside the cell the monoglycerides and fatty acids are re-esterified to triglycerides. The triglycerides and other fat-soluble molecules (e.g. cholesterol, phospholipids) are then incorporated into chylomicrons to be transported into the lymph.

(a) The pathophysiology of fat absorption. (b) Diagram showing the formation of mixed micelles

(a) The pathophysiology of fat absorption.
(b) Diagram showing the formation of mixed micelles

The pathophysiology of fat absorption is shown . Interference with absorption can occur at all stages, as indicated, giving rise to steatorrhoea.
WATER AND ELECTROLYTES. A large amount of water and electrolytes, partly dietary, but mainly from intestinal secretions, are absorbed coupled with monosaccharides and amino acids in the upper jejunum. Some water and electrolytes are absorbed in the ileum and right side of the colon, where active sodium transport occurs but which is not coupled to solute absorption. Intestinal secretion also takes place and abnormalities of this mechanism cause secretory diarrhoea.

WATER-SOLUBLE VITAMINS, ESSENTIAL METALS

AND TRACE ELEMENTS. These all have to be absorbed in the small intestine. It must be remembered that vitamin B\2 (see p. 304) is the only substance other than bile salts that is specifically absorbed in the terminal ileum alone and malabsorption of both these substances will always occur following ileal resection.

CALCIUM

IRON.

Defence against antigens.

The normal intestinal mucosa forms an intrinsic barrier to the absorption of many antigens such as bacteria, viruses or dietary proteins. The mucosa contains scattered lymphoid cells as well as lymphoid aggregates, e.g. the tonsils and Peyer’s patches, to form the gut-associated lymphoid tissue (GALT).
Antigenic priming of the GALT can give rise to specific secretory immunity, not only in the gut but also in other mucosal-associated lymphoid tissue (MALT), e.g. respiratory tract, lacrimal, salivary and mammary glands. This is because of the migration of specifically primed T and B cells from the GALT via the local mesenteric lymph nodes, and the thoracic duct and peripheral circulation back to the lamina propria (of gut or other mucosal tissue) where they become immunoglobulin (Igj-producing plasma cells.

Small intestinal mucosa with a Peyer's patch ing the gut-associated lymphoid tissue.

Small intestinal mucosa with a Peyer’s patch
showing the gut-associated lymphoid tissue.

Local mucosal immunity is provided by the secretory immunoglobulin (sIg) system. There are approximately 1010 Ig-producing immunocytes (plasma cells and plasmoblasts) per metre of human small bowel of which 70-90% are IgA immunocytes. Dimeric and polymeric IgA (pIgA) and IgM, containing a disulphide-Iinked polypeptide called T (or ‘joining’) chain, are transported through the glandular epithelium via the transmembrane pIg receptor called ‘secretory component’ (SC) into the gut lumen. These antibodies are the first line of defence against antigens in the lumen and may take part in the immunological homeostasis within the mucosa, e.g  dampening T-cell-rnediated hypersensitivity responses against harmless absorbed luminal antigens. sc expression can be up-regulated by lymphokines, e.g. interferon-y (IFN-I’) and tumour necrosis factor-a (TNF-a) secreted by activated T cells and macro phages respectively, thus promoting the transport of IgA and IgM into the lumen.
A specialized epithelial cell above the Pey r’s patches, called the ‘M’ or ‘membrane’ cell, lacks Sc and HLA-DR expression; these cells allow non-selective inward transport of luminal antigens. Antigens may also be taken up by other epithelial cells (expressing HLA-DR) on a genetically restricted basis and may subsequently be presented directly by antigen-presenting cells (macro phages) to primed (memory) T lymphocytes. Intraepithelial lymphocytes (IEL) are mainly T cells with a predominance of TS (CDS+) cells, whereas the lamina propria contains mainly T4 (CD4+) subsets. Most human IELs express the T cell receptor a/{3 (TCRa/{3) which, along with considerable CD45RO expression, suggest that they are traditional memory T cells. Few cells express TCRy/8.

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Gastroenterology

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