What are the three sections of the small intestine?
Duodenum
Mesentery
Jejunum
Length of duodenum
25cm approx
Which is the longest section of the small intestine?
Ileum
Which section does most of the absorption take place in?
Jejunum
Which layer are the major blood supplies and nerves found?
Submucosal layer
What are the invaginations in the small intestine called?
The Crypts of Leiberkuhn
What cell types are found in the mucosal layer of the small intestine?
Enterocytes (mainly)
Goblet cells
Enteroendocrine cells
What cell types are found in the crypts of leiberkuhn?
Paneth Cells
Stem cells to make new epithelial cells
What are enterocytes for? How long to they live?
Absorption and transport cells
1-6 days lifespan
What structures do enterocytes have?
Microvilli that make up the “brush border” and increase surface area and covered in glycocalyx. There are several thousand microvilli per cell
What are glycocalyx?
- a rich carbohydrate layer on apical membrane that serves as protection from the digestional lumen but allows for absorption
- It also traps a layer of water known as the unstirred layer that regulates the rate of absorption from intestinal lumen
What are goblet cells
Mucous containing granules that accumulate at the apical end of a cell causing a goblet shape. There is a greater abundance of goblet cells the further along the bowel you get as more water is absorbed so the food bolus gets drier and needs more mucus to lubricate transport
What is mucous?
Large glycoprotein that facilitates passage of material through the bowel
What are enteroendocrine cells
Columnar epithelial cells that are scattered among the absorptive cells. In the intestines they are often found in the lower part of the crypts and are hormone secreting (eg to influence gut motility)
What are the qualities of villi?
- They only occur in the small intestine
- They are motile and have a rich blood supply and lymph drainage for absorption of digested nutrients
- they have good innervation from the submucosal plexus
- have simple epithelium (1 cell thick) like the rest of the intestine and dominated by enterocytes
What are Paneth cells?
They are only found in the bases of crypts and contain large acidophilic grandules containing:
-lysozyme
-glycoproteins and zinc
and also engulf some bacteria and protozoa. They also may have a role in regulating intestinal flora
Why is zinc required in paneth cells?
It is an essential trace metal for a number of enzymes
What are the stem cells in the GI tract for?
Replenish surface epithelium by dividing by mitosis and migrating up to the tip of the villus and replacing older cells that die by apoptosis. They differentiate into various cell types - pluripotent
What are the steps of stem cells replacing epithelial cells in villus?
An ‘escalator’ of epithelial migration -
dividing stem cells in the crypts move to surface and tips of villi.
At the villus tips, cells become senescent, sloughed into the lumen of the intestine and digested and reabsorbed.
Why is there such a rapid turnover of enterocytes?
Because they are suceptible to toxins/damage/bacteria due to their job of absorbing stuff taken in, a rapid turnover of cells makes the effect of the toxins/bacteria minimal and any lesions are short lived. EXAMPLE CHOLERA
How does cholera cause disease and death?
Cholera enterotoxin results in prolonged opening of chloride channels in small intestine allowing uncontrolled secretion of water. This means bodily fluids move freely into lumen and out through intestine leading to rapid and massive dehydration and death.
What is the treatment for cholera?
Treatment is rehydration and if kept alive for 3 days the patient normally gets better as cholera bacterium removed and epithelium replaced however it is hard to get clean non cholera infected water in areas where cholera is prevalent eg natural disaster zones or developing countries
What differs the duodenum in the small intestine?
Presence of Brunner’s glands
What are Brunner’s glands?
Submucosal coiled tubular mucous glands secreting alkaline fluid that open into the base of crypts. The alkaline secretions of brunner’s glands neutralise acidic chyme from the stomach and protect the proximal small intestine and also help optimise the pH for pancreatic digestive enzymes
What differs in jejunum in the small intestine?
Presence of numerous large folds in the submuosa called pilae cirulares or valves of Kerckring. They are also present in other parts of small intestine but here they tend to be taller, thinner and more frequent
What differs in the ileum?
Lots of Peyer’s patches which are large clusters of lymph nodules in the submucosa. They are prime immune system against intestinal bacteria and are well positioned to prevent bacteria from colon migrating up into small intestine
What are the immune system mechanisms against intestinal bacteria?
Peyer’s patches
Bactericidal Paneth cells
Rapid cell turnover
What are the functions of small intestine motility?
- Mix ingested food with digestive secretions and enzymes
- Facilitate contact between contents of intestine and the intestinal mucosa
- Propel intestinal contents along alimentary tract
How does segmentation work in the small intestine?
MIXES contents of the lumen by stational contraction of circular muscles at intervals. More contractions in duodenum than ilium so pancreatic enzymes and bile can mix with chyme, net movement toward colon
How does peristalsis work in the small intestine?
Sequential contraction of adjacent rings of smooth muscle propels chyme towards the colon - most waves only about 10cm so short.
This and segmentation lead to chyme propelled toward colon
What is the migrating motor complex
Cycles of smooth muscle contractions of adjacent segments of small intestine IN FASTING beginning in stomach toward colon. Prevents migration of colonic bacteria into ileum and may clean the intestine of residual food. Also occur in fed state- less ordered and less frequent
Is the small intestine an acidic or alkaline environment?
Alkaline
How do digestive enzymes and bile enter the duodenum?
Pancreatic duct and bile duct. The duodenal epithelium also produes it’s own digestive enzymes.
What enzyme begins carbohydrate digestion in the mouth?
Salivary alpha amylase
What enzyme does the duodenum secrete for carb digestion? What does it do? What conditions does it need?
Pancreatic alpha amylase continues digestion of starch and glycogen that started in the mouth
Needs Cl- for optimum activity and a neutral or slightly alkaline pH
How is an alkaline pH maintained in the small intestine?
Brunner’s glands in duodenum
Where does pancreatic alpha amylase act? Where are products digested?
Mainly in the lumen and also adsorbs to the brush border. Digestion of amylase products and simple carbs occurs at membrane
How is glucose and galactose absorbed in the small intestine?
Secondary active transport - chemical protein and electrochemical gradient. Carrier protein SGLT-1 on apial membrane.
How is fructose absorbed in the small intestine?
Facillitated diffusion using carrier protein GLUT-5 on apical membrane
What does GLUT-2 do?
Facillitates exit at the basolateral membrane
What does trypsin do and how is it activated?
It activates other proteases as pepsin is inactivated by the alkaline environment
Trypsin is activated by enterokinases, an enzyme on the duodenal brush border
How are amino acids absorbed in the small intestine?
Facillitated diffusion and secondary active transport
What happens to peptidases before they are absorbed in the small intestine?
Brush border peptidases break them down
What are the 4 stage processes in the small intestine for digestion of lipids?
- secretion of bile and lipases
- emulsificaiton
- enzymatic hydrolysis of ester linkages
- solubilizaiton of lipolytic products in bile salt micelles
What makes lipids more complicated to digest?
They are poorly soluble in water
What do bile salts do
Facilitate the emulsification of fat into a suspension of lipid droplets, increasing SA for digestion and allows pancreatic lipase to split triglycerides
What is a triglyceride broken down into?
2 Fatty acids and a monoglyceride at fat/water interface
What is the process of lipid digestion?
Lipase breaks down triglycerides into monoglycerides and free fatty acids. Pancreatic lipase complexes with colipase prevents bile salts from displacing lipase from the fat droplet
What are 2 other important lipid enzymes
Phospholipase A2
Pancreatic cholesterol esterase
What does phospholipase A2 do?
Hydrolyses fatty acids at the 2 position in many phospholipids resulting in lysopohospholipids and free fatty acids
What does pancreatic cholesterol esterase do?
Hydrolyses cholesterol ester to free cholesterol and fatty acid
What is the structure of a bile salt molecule?
Steroid nucleus, planar - two faces, amphipathic.
The hydrophobic face dissolves in fat (nucleus and methyl) and the hydrophillic face (hydroxyl and carboxyl) dissolves in water
What are bile salt micelles
hydrophilli head region in contat with solvent, hydrophobic tail regions in the micelle centre
What are mixed micelles?
water insoluble monoglycerides from lipolysis that are solubilised by forming a core and stabilised by bile salts
How are micelles absorbed?
Bile salts are absorbed in the ileum but the lipid absorption is in the middle of the jejunum
Where do the bile salts go after micelles absorbed?
Back to liver for recyling - enterohepatic circulation
Why are micelles used in lipid absorption?
They are absorbed so much quicker than emulsion, they allow transport across the unstirred layer and present the fatty acids and monoglycerides to the brush border
When in the enterocytes, how are lipids metabolised?
They resynthesize into triglycerides by 2 pathways - monoglyceride acylation (major) and phosphatidic acid pathway (minor)
What happens in monoglyceride acylation?
Fatty acid binds to apical membrane
Fatty acid binding proteins (FABP) facilliate transfor of fatty acids from apical membrane to the smooth ER
In SER, fatty acids esterified into diglycerides and triglyerides
What happens in the phosphatidic acid pathway?
Triglycerides are synthesised from CoA fatty acid and alpha glycerophosphate
What are chylomicrons?
Lipoprotein particles synthesised in enteroytes as an emulsion of 80-90% triglyeride, 8-9% phospholipid, 2% cholesterol and 2% protein with trace carbs
What happens to chylomicrons made in enterocytes?
Transported to golgi and secreted across the basement membrane by exocytosis. Too big to enter the blood capillaries of villi so instead enter lacteals
What are lacteals
Lymph channels
How is the ileum seperated from the colon?
Ileocaecal sphincter
What does relaxation and contraction do in the ileum?
Controls passage of material into colon
Prevents backflow of bacteria into the ileum