Flashcards in Medical Physiology Block 6 Week 2 Deck (76):
Describe differences in the anatomy of the small intestine and large intestine.
the colon does not have villi; colon does not participate in nutrient absorption; small intestine does not actively secrete potassium; small intestine has paneth cells (anti-microbial function)
What characteristics are similar in both the small intestine and large intestine
both have folds (folds of Kerkring in SI and semilunar folds in LI); both contain crypts (or glands); both contain microvilli (LI does not contain macrovilli); both actively absorb sodium
What is the benefit of increased luminal surface area?
Increasing the space available for intestinal absorption (similar to alveolar structure in maximizing diffusion)
What is the basic structure of the intestine?
The basic structure of the intestine is a hollow cylinder with columnar epithelial cells lining the lumen, with circular and longitudinal layers of smooth muscle in the wall, and with endocrine and neural elements
Where are progenitor or undifferentiated cells found in the intestine?
in the crypts
Is secretion of electrolytes a basal process of the intestine?
No; induced by different chemicals and metabolites
How is sodium absorbed in the intestine? where?
sodium/glucose and sodium/AA transporters become activated postprandially (electrogenic; insensitive to intracellular signaling molecules; jejunum and ileum); Electroneutral Na-H exchange, in the absence of Cl-HCO 3 exchange, is stimulated by the high pH of the HCO 3−-rich luminal contents (sensitive to amiloride and intracellular signaling molecules; another sodium/proton exchanger on basolateral membrane; duodenum and jejunum); Na-H and Cl-HCO 3 exchange is coupled by a change in intracellular pH that results in electroneutral NaCl absorption, which is the primary mechanism for interdigestive Na + absorption (sensitive to aldosterone and intracellular signaling molecules; primarily active during interdigestive period; ileum and proximal colon); Distal colon absorbs sodium through ENaCs (electrogenic; sensitive to aldosterone and amiloride)
What is the effect of aldosterone on enterocytes?
increases activity of sodium/potassium pump, ENaCs, and apical potassium channels
Which part of the small intestine participates least in active absorption of nutrients and electrolytes?
The absorption of sodium in the small intestine is similar to its absorption in what other organ? which segment?
kidney; proximal tubule
How is chloride absorbed in the intestine? where?
passive (both paracellular and transcellular; postprandial; lumen negative transepithelial voltage whenever sodium is electrogenically absorbed; jejunum, ileum, and distal colon); electroneutral Cl-HCO 3 exchange (basolateral sodium/proton exchanger; ileum, proximal and distal colon); Electroneutral NaCl absorption can mediate Cl − absorption in the interdigestive period (pH i couples the two exchangers; ileum and proximal colon)
How is bicarbonate produced in the cell to later be secreted into the lumen?
water and carbon dioxide enter the cell through the basolateral membrane; following hydrolysis of water, hydroxyl anion reacts with carbonic anhydrase to form bicarbonate
How is chloride secreted in the lumen by crypt cells?
driven by NKCC1 at basolateral membrane (transporter of sodium, potassium, and chloride); electrogenic; Different types of apical chloride channels exist (CFTR and others; sensitive to intracellular signaling molecules)
What are the secretagogues? What is the historic rationale for increasing secretion in response to these stimuli? what intracellular signaling molecules are downstream of these stimuli? what other action do these stimuli cause?
bacterial endotoxins (body sequesters toxins by diluting them); hormones and neurotransmitters (transient; VIP, Ach, immune: bradykinin, histamine, serotonin, prostaglandins); laxatives (bile acids); calcium and cyclic AMP; increase GI motility
How is potassium absorbed in the intestine? where?
passive absorption in SI: solvent drag; Active transcellular absorption of potassium in the distal colon is the result of the activity of a potassium/proton exchanger in the apical membrane
How is potassium secreted in the intestine? where?
passive excretion in the proximal and distal colon due to lumen negative transepithelial voltage; basolateral uptake of K + through the Na-K pump and the Na/K/Cl cotransporter, followed by the efflux of K + through apical K + channels (also in proximal and distal colon)
Do intracellular signaling molecules (calcium and cyclic AMP) increase potassium secretion?
What molecules are absorptagogues?
Mineralocorticoids, glucocorticoids, somatostatin, enkephalins, and norepinephrine (decrease intracellular calcium?)
Describe starch (amylose and amylopectin) digestion in the lumen.
salivary and pancreatic amylase are endoenzymes that hydrolyze alpha 1,4 internal linkages; products of amylose digestion are maltotriose and maltose; product of amylopectin is maltotriose, maltose, and alpha-limit dextrins (alpha 1,6)
Describe digestion of carbohydrates at the brush border.
lactase splits lactose into galactose and glucose; maltose splits maltotriose and maltose to glucose molecules; sucrase splits maltotriose, maltose, and sucrose (fructose + glucose); isomaltase (in complex with sucrase) splits maltotriose, maltose, and alpha-limit dextrins
Can enterocytes absorb disaccharides and polysacchardies?
Describe absorption of monosaccharides by enterocytes. How are they secreted in to the blood?
galactose and glucose enter the cell through sodium-dependent secondary active transport (SGLT); fructose enters the cell passively through GLUT5; all passively through GLUT2
Which organs are involved in protein digestion?
stomach and intestine (pancreas)
How is fructose different from glucose?
glucose is an aldose; fructose is a ketose; both have D isomerization
How is galactose different from glucose?
d-galactose is identical, except the H and OH on C-4 are inverted
What is sucrose?
fructose + glucose
What is lactose?
galactose + glucose
How is amylopectin different from amylose? what is amylose?
has alpha 1,6 linkages (branched); polysaccharide of glucose
What is glycogen similar to?
amylopectin (alpha 1,6 linkages); branches
Why can't cellulose be digested?
Cellulose has a beta-glycosidic linkage and humans do not have a beta-glycosidase
Can oligopeptides be absorbed by enterocytes?
Yes; proton-driven cotransport with sodium/proton exchanger at the apical membrane (amino acid transport may be sodium dependent)
What is the difference between an endopeptidase and exopeptidase? what are examples and where are they located?
cleave inner peptide bonds (leaving small oligopeptides; pepsin, trypsin, and elastace in the lumen); hydrolyze peptide bonds near carboxyl terminal, thereby resulting in the release of individual amino acids (aminopeptidases and carboxypeptides at the brush border)
Are amylases proenzymes? are proteases?
No; yes (cleaved by enterokinase in intestine)
Can proteins be digested intracellularly?
How are proteins absorbed during the neonatal period? does this mechanism absorb proteins in adults?
pinocytosis; yes, M cells package antigens in clathrin-coated vesicles for mucosal immunity (most degraded by lysosomes)
How do amino acids exit the enterocyte? oligopeptides? can amino acids enter the enterocyte through basolateral membrane?
sodium-independent transporter; same mechanism since they are broken down into amino acids by intracellular proteases; yes, sodium-dependent transporters
How are lipids digested?
Dietary lipids are disrupted mechanically in the mouth and stomach, and the resulting lipid particles are stabilized as an emulsion
What is an ester?
combination of carboxylic acid and hydrocarbon
What are examples of emulsion stabilizers? why is this important?
Phospholipids and cholesterol are well suited as emulsion stabilizers because they dissolve neither in oil nor in water, but they have excellent interfacial solubilities at oil-water interfaces; Prevent coalescence of the emulsion particle
What are the components of the core of a lipid droplet (or emulsion)
The core of the emulsion particle is composed of triacylglycerides, cholesteryl esters, and other nonpolar or weakly polar lipids
What does digestion of lipids occur?
stomach (swallowed salivary lipase and gastric lipase) and small intestine (bile secretions from liver and gallbladder; pancreatic lipases secreted by acinar cells)
What is the function of gastric lipases?
serine hydroylases (strip individual fatty acids from triacylglycerol)
What signaling molecules are release following arrival of fatty acids to duodenum?
GIP (increases insulin secretion; incretin) and CCK (stimulates the flow of bile into the duodenum by causing the gallbladder to contract and the sphincter of Oddi to relax; also stimulates the secretion of pancreatic enzymes)
What is pancreatic lipase? can it digest lipids alone? what is the product?
esterase; no, cofactor is colipase (can penetrate the phospholipid coating of the TAG emulsion); fatty acids and sn2 monoacylglycerol
What is the product of carboxyl ester hydrolase? phospholipase A?
cholesterol and glycerol; lysophosphatidlycholine (release sn2 fatty acid)
What happens to lipids that are not digested by the small intestine?
In the human colon, both TAGs and phospholipids are totally hydrolyzed by bacteria
How are fatty acids that become freed transported in the lumen?
solubilized in micelles by bile acids
How are emulsions broken down into mixed micelles?
Pieces of the multilamellar liquid-crystalline layer of surface lipids buds off as a multilamellar vesicle; The addition of more bile salts to the vesicle thins out the lipid coating (unilamellar vesicle); Further addition of bile salts leads to formation of a mixed micelle, in which hydrophobic lipid tails face inward and polar head groups face outward
What are lipases inhibited by?
what lipids form micelles in water?
fatty acids, bile acids, and lysophosphatidylcholine
How do lipids diffuse across the unstirred water layer into the enterocyte? how does solubility change with size of the fatty acid chain?
Mixed micelles carry lipids through, first the mucous gel layer, and then the acidic unstirred layer to the surface of the enterocyte; monoacylglycerols, fatty acids, lysophosphatidylcholine, and cholesterol leave the mixed micelle and enter an acidic environment created by an apical sodium/proton exchanger; fatty acids are protonated by acidic environment; Lipids enter the enterocyte by nonionic diffusion or incorporation into the enterocyte membrane (collision), or carrier-mediated transport; As fatty acid chain length increases, the monomer's solubility in water decreases, whereas its partitioning increases
How does the enterocyte modify fatty acids and lipids?
The enterocyte takes up short- and medium-chain fatty acids and glycerol and passes them unchanged into the blood capillaries; the enterocyte also takes up long-chain fatty acids and monoacylglycerols (fatty acid-binding protein) and resynthesizes them into triacylglycerols in the smooth endoplasmic reticulum (packaged in to chylomicrons)
How are lipids transported to the circulation?
Lymph lacteals originate in the tips of the villi and discharge their contents into the cisternae chyli; Lymph flow from the cisternae chyli to the thoracic duct
Which vitamins are fat-soluble? water-soluble?
A, D, E, and K; C
How are vitamins ingested? what changes in the stomach?
conjugated to proteins; acidity of gastric juice free the vitamins
How are vitamins transported in the lumen of the small intestine?
In the proximal small intestine, fat-soluble vitamins incorporate with other lipid products into emulsion droplets, vesicles, and mixed micelles, which ferry them to the enterocyte surface for uptake (simple diffusion or through transporters)
Describe digestion and absorption of folate.
The absorption of dietary folate (folate polyglutamate) requires deconjugation by a brush border peptidase to monoglutamate (which can enter the enterocyte through transporter- folate/hydroxl exchange); The enzyme difolate reductase acts on PteGlu1 to first form dihydrofolate (DHF) and then the biologically active derivative THF
What is the importance of folate? what is another name for folate?
Folate is essential for the synthesis of thymine and purines (critical components of DNA); can produce methionine; vitamin B9
What is importance of cobalamin? what is it also called?
Coenzyme for homocysteine : methionine methyltransferase; vitamin B12
Describe digestion and absorption of cobalamin.
Cobalamin reaches the stomach bound to protein in ingested food; pepsin and low gastric pH release it from the proteins (binds to heptocorrin, a glycoprotein); upon reaching the duodenum, haptocorrin is degraded (binds to intrinsic factor, secreted by parietal cells in stomach); cobalamin-intrinsic factor complex bind receptors on apical membrane in the ileum; complex dissociates within the cell; transcobalamin II transports it out of the cell and into the circulation (to the liver)
Describe calcium absorption. what is the role of vitamin D?
occurs by active transport in the duodenum and by diffusion through the small intestine; binds calbindin (cytoplasmic carrier) are is secreted in circulation by calcium pump (sodium/calcium exchanger on the basolateral membrane); vitamin D activates calbindin and is later absorbed in jejunum
Where does magnesium get actively absorbed?
ileum; passively in small intestine (solvent drag?)
Which form of iron is soluble?
ferrous (+2); ferric iron forms salt complexes
Describe iron absorption. how is heme-bound iron absorption different?
none-heme: absorption restricted to duodenum (DMT1 receptor: iron/proton cotransporter); iron binds to mobilferrin and exits cell through ferroportin transporter; ferroxidase hephaestin oxidizes ferrous iron to ferric, which binds to transferrin for carriage in blood; heme oxygenase splits the heme iron releasing free ferric iron, CO, and biliverdin (cell reduces biliverdin to bilirubin which is excreted in bile)
How can ferric iron be reduced to ferrous iron?
complexing with ascorbic acid or by Dcytb brush border enzyme
How can iron be stored?
Iron can be stored complexed to apoferritin (ferritin) or as insoluble hemosiderin
Describe bicarbonate rich fluid secretion by cholangiocytes.
chloride recycling to power chloride/bicarbonate exchanger (similar to pancreatic duct cells); paracellular movement of sodium and water
Describe isotonic reabsorption of solutes by the gallbladder.
Leaky gallbladder epithelium isotonically reabsorbs sodium chloride and to a less extent sodium bicarbonate (apical sodium/proton and chloride/bicarbonate exchanger; electroneutral); remaining gallbladder bile has a higher concentration of bile salts, potassium, and calcium; net secretion of proton ions into the lumen (neutralizes secrete bicarbonate and even acidifies the bile); regulated by VIP and serotonin (which block reabsorption)
What is the source of bile pigments?
Synthesized from cholesterol and conjugated with glycine or taurine
Describe the metabolism of bile pigments.
Bacteria can convert the bilirubin glucoronide back to bilirubin (and further converted to urobilogen, which can be converted in to stercoblin in the colon, or urobilin in the kidney)
Describe the enterohepatic circulation.
The enterohepatic circulation of bile acids is a loop consisting of secretion by the liver, reabsorption by the intestine, and return to the liver in portal blood for repeat secretion into bile
What is the role of peptide YY? what is it's stimulus?
inhibits meal-stimulated GI functions; release in response to fat in ileum and colon
What peptides are release during fasting? hormones?
ghrelin (stimulates appetite) and motilin; glucagon
Describe the control of appetite.
insulin and leptin stimulate the hypothalamus producing satiety and increases energy expenditure by activating sympathetic pathways; also suppress neurons involved in stimulation of eating behavior
What is the key molecule regulating gastric emptying and pancreatic and biliary secretions?