Flashcards in AS Lecture 3 - Small Intestine Deck (64):
What is the structure of the digestive epithelium/SI?
External wall has longitudinal and circular muscles
How is the internal mucosa arranged?
Arranged in circular folds and covered in villi - has invaginations
What is the name for the intestinal invaginations?
Crypts of Lieberkuhn
What are the function of villi?
Increase SA in the si to allow for maximum absorption of nutrients
Motile and have a rich blood supply/lymph drainage for absorption of digested nutrients
Good innervation from submucosal plexus
What are the cell types of the SI?
Mucosa lined with: enterocytes (primarily), goblet cells (scattered), enteroendocrine
Paneth and stem cells - crypts
What are enterocytes?
Tall columnar with micro villi and basal nucleus
Short lifespan of 1-6 days
What are microvilli?
Make up brush border, several 1000 per cell
Surface covered in glycocalyx
How is surface area increased with villi and microvilli?
Villi and Microvilli increase SA from 0.4m^2 to 200m^2
What is the function of goblet cells?
Secrete mucus, 2nd most abundant cell in SI
Mucus secretion granules accumulate at apical end
What is mucus and what does it do?
Large glycoprotein that facilitates passage of material through the bowel
What are enteroendocrine cells and what is their function?
Columnar epithelial cells, scattered among absorptive cells in lower parts of the crypt
Hormone secreting to influence gut motility
What is the function of Paneth cells?
Contain large acidophilic granules (lysozyme and glycoproteins and zinc) which help to protect against bacteria - may be protecting stem cells
Engulf bacteria and Protozoa so may have roles in regulating intestinal flora
What is the epithelial lifespan?
Cell proliferation, differentiation and death is a continuous cycle in gut
Stem cells in crypts replace the other cells
Enterocytes and goblet cells have a lifespan of 36hrs
What are stem cells and how does this relate to the epithelial life span?
Pluripotent/undifferentiated cells, cells move up from crypts to replace dead cells (by apoptosis) from the surface of the epithelium. They continually divide by mitosis
Why is there such a rapid turnover in the small intestine as it takes up so much energy?
Enterocytes are first line of defence against pathogens and toxins, so anything that disturbs the cell function/metabolic rate/causes lesions will be short lived, as they will be rapidly displaced and replaced
Severe intestinal dysfunction can occur if it doesn't have a rapid turnover
How does the cholera enterotoxin cause cholera?
Symptoms: Extreme diarrhoea, massive dehydration and death
Cause: Results in opening of Cl- channels in SI allowing uncontrolled secretion of water
Treatment: rehydration until cholera bacteria will clear and epithelium will be replaced
What are some histological features of the Duodenum?
Have Brunner's glands, which open into base of crypts
What are some histological features of the Jejunum?
Plicae circulares/valves of Kerckring - numerous, large folds in submucosa
Also present in duodenum/ileum but tend to be taller, thinner and more frequent in JJM
What are some histological features of the Ileum?
Lots of Peyer's patches - helps prime immune system against intestinal bacteria. ALSO, have bactericidal Paneth cells and rapid cell turnover to defend the SI - prevent colon bacteria from moving up the gut
List 3 functions of SI motility
Mix ingested food w/digestive secretions and enzymes
Facilitate contact between intestine and intestinal mucosa
Propel intestinal contents along alimentary tract
What is Segmentation
Mixes contents of lumen, causing stationary contraction of circular muscles at intervals
More frequent in duodenum which allows pancreatic enzymes and bile to mix with chyme
Chyme moves in both directions but net movement is towards colon
Not very organised
What is Peristalsis in SI?
Sequential contraction of adjacent rings of smooth muscle
Propels chyme towards colon - waves travel about 10cm
Segmentation and peristalsis result in chyme being segmented, mixed and propelled towards colon
What is the Migrating motor complex?
Cycles of SM contractions (when fasting), cycle of contractions of adjacent segments of small intestine - sweeping to colon, and once it reaches ileum, it begins in duodenum again
Can occur during fed state but less ordered/frequent
How does digestion occur in duodenum?
SI digestion occurs in alkaline env - digestive enzymes and bile enter duodenum from pancreatic duct/bile duct (hepatopancreatic sphincter)
Duodenal epithelium also produces its own digestive enzymes
Which mechanisms of absorption are used in the SI?
Primary/secondary active transport (require energy from ATP hydrolysis/electrochemical gradient respectively)
All need carrier proteins apart from passive diffusion
How does digestion of carbohydrates occur?
Begins in mouth by salivary alpha-amylase, which is destroyed in stomach
Most occurs in small intestine
What are the types of carbohydrate structures?
Simple - monosaccharides/disaccharides
Complex - polysaccharides
How does pancreatic alpha amylase function?
Secreted into duodenum in response to meal
Continues starch and glycogen digestion in SI
Need Cl- for optimum activity and neutral/alkaline pH (Brunner's gland secrete alkaline)
Where does pancreatic alpha amylase act?
Mainly in lumen - some adsorbed onto brush border
Digestion of complex carbs (starch/glycogen) into simpler sugars in lumen, then disaccharides digested on membrane into glucose
How does carbohydrate absorption occur?
2ry active transport for glucose and galactose using SGLT-1 (on apical membrane)
Facilitated diffusion for fructose using GLUT-5 (on apical membrane)
GLUT-2 helps exit in basolateral membrane
Why isn't fructose absorption very high?
Isn't absorbed as much as by facilitated diffusion, but it isn't needed as much
How does digestion of proteins occur?
Begins in stomach by pepsin, but inactivated in alkaline SI
Pancreatic proteases secreted as precursors
Trypsin activated by enterokinase (enzyme on duodenal brush border) and then activates other proteases
How are amino acids digested?
Absorbed by facilitated diffusion and 2ry active transport
Brush border peptidases break down larger peptides before absorption
Di/tri-peptides are absorbed using carrier proteins distinct from single a.a. - mostly broken down by cytoplasmic peptidases before they cross the basolateral membrane
How does lipid digestion occur - 4 stage process?
Poorly soluble in water, 4 stage process: secretion of bile/lipases, emulsification, enzymatic hydrolysis of ester linkages, solubilisation of lipolytic products in bile salts micelles
How does emulsification of lipids occur?
Bile salts facilitate fat emulsification into suspension of lipid droplets to increase SA
Allows pancreatic lipases to split triglycerides - which is then broken down into 2 FA and a monoglyceride at fat/water interface
What is the composition of bile salts?
Amphipathic - steroid nucleus planar w/2 faces: hydrophilic (hydroxyl/carboxyl) face dissolves in water and hydrophobic (nucleus and methyl) face dissolves in fat
How do micelles work and what do they look like?
Bile salts surrounding a lipid core. Hydrophilic head in contact with surroundings, sequestering hydrophobic tail regions in micelle centre
How does digestion of lipids occur?
Lipase breaks dome triglycerides into monoglycerides and FA
Pancreatic lipases complex with colipase which prevents bile salts from displacing lipase from the fat droplet
What other lipid enzymes exist?
Phosphlipase A2 - hydrolyses FA at 2 position, resulting in lyso-phospholipids and free FA
Pancreatic cholesterol esterase - hydrolyses cholesterol ester to free cholesterol and FA
How do Micelle's facilitate lipid absorption?
Absorbed quicker than emulsified lipids - allow transport across unstirred layer and present FA and monoglycerides to brush border - not absorbed together (bile salts absorbed in ileum, lipid in jejunum)
How are monoglycerides and free FA resynthesised into TG?
Monoglyceride acylation and phosphatidic acid pathway
How does the SI transition between each part?
No sudden transition between duodenum, jejunum as all have same basic histological organisation
What is the function of the small intestine?
To absorb nutrients, salt and water
How long is the small intestine and each of its parts?
SI: 6m long, 3.5cm in diameter
What is the mesentery?
Throws the SI into folds, supports the blood supply
What is the structure of villi and where are they normally found?
Mainly in SI, and they have simple epithelium, dominated by enterocytes (columnar absorptive cells)
What is the function of enterocytes?
Absorption and transport of substances
What do tight junctions do?
They prevent proteins moving between surfaces of cells
What is glycocalyx and what is it made of?
Rich carbohydrate layer on apical membrane which serves as protection from digestional lumen but allows for absorption
How does glycocalyx work?
It traps a layer of water and mucus (unstirred layer) which regulates rate of absorption from intestinal lumen
Why does the abundance of goblet cells increase as you travel down the GI tract?
Because mucus helps move the material through the bowel and when it gets to the large intestine, it becomes much more difficult to move, so it needs the mucus to provide lubrication
Where are Paneth cells found?
Bases of crypts
How does the escalator of epithelial migration work?
Programmed cell death in the villus tips - cells are then digested and reabsorbed, stem cells in crypts divide by mitosis to replace the suface and tips of villi
What are Brunner's glands and what is their function?
Submucosal coiled tubular mucous glands secreting alkaline fluid which neutralize the acidic chyme from stomach protecting the proximal SI and help optimise pH for action of pancreatic digestive enzymes
What is the function of the migrating motor complex?
Prevents migration of colonic bacteria into ileum, may clean intestine of residual food
Where in the duodenum does digestion occur?
Both in the lumen and in contact with the membrane
How are the mixed micelles in the small intestine made/work?
Water insoluble monoglycerides from lipolysis are solubilised by forming a core, stabilised by bile salts
What happens to the bile salts in the micelle once the lipid has been reabsorbed?
Bile salts are transported back to the liver for recycling (enterohepatic circulation)
How does monoglyceride acylation occur?
FA binds to apical membrane and FABP facilitate transfer into SER, where they are esterified into diglycerides and triglycerides
How does Phosphatidic acid pathway work?
TG are synthesised from CoA fatty acid and alpha-glycerophosphate
What are chylomicrons?
Lipoprotein particles synthesised in enterocytes as emulsion - 80-90% TG, 8-9% phospholipids, 2% cholesterol, 2% protein, with trace carbohydrates
How are chylomicrons transported?
To the Golgi and secreted across basement membrane by exocytosis - too big to enter capillaries so enter lacteals instead
How is the ileum separated from the colon?
By the ileocaecal sphincter, where relaxation and contraction controls the passage of material into the colon, preventing back flow of bacteria