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122 Cards in this Set
- Front
- Back
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What are the 5 functions of the liver?
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1. Storage, metabolism, and release of nutrients and some vitamins
2. Detoxification and elimination of toxins, drugs, and metabolites 3. Sythesis of biologically important proteins such as albumin, clotting factors, apolipoproteins 4. Synthesis and secretion of bile important for lipid digestion and absorption 5. Role in immune function and clearance of intestinally absorbed bacteria |
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What are the 7 components of bile?
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water
bile acids - major organic constituents phospholipids cholesterol bile pigments - bilirubin metabolites of hormones, drugs inorganic ions - HCO3 from duct cells |
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What is the function of OATP?
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Organic Anion Transport Protein
transports bilirubin and Sodium from sinusoid to hepatocyte |
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What is the function of NTCP?
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Na Tauricholate Cotransporter Protein
transports bile salts and sodium from sinusoid to hepatocyte |
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What is the function of BSEP?
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Bile Salt Export Pump
belongs to MDR family transports bile salts from hepatocyte to bile canaliculus requires ATP |
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What is the function of ABC?
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ATP Binding Cassette Protein
transorts cholesterol form hepatocyte to bile canaliculus |
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What is the function of MRP2?
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Multi-Drug Resistance Protein 2
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What is the difference between a bile salt and a bile acid?
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a bile salt is a bile acid plus sodium
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What is the FXR receptor?
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nuclear receptor that allows bile salts to regulate the transcription of transporter genes
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What types of cells line bile ducts?
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cholangiocytes - columnar epithelial cells specialized to modify bile
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What are the functions of bile ducts?
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1. Ductules are freely permeable to water so bile becomes isotonic
2. Ductules scavenge solutes such as glucose and amino acids that entered leaky canaliculus and absorbs them using cotransporters 3. Cholangiocytes secrete HCO3 in response to secretin in a manner similar to pancreatic duct cells 4. Ductules secrete IgA molecules into bile. |
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What is the response of bile ducts to secretin?
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cholangiocytes secrete HCO3
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What is the precursor molecule to bile?
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cholesterol
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What is another name for bile acid?
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cholic acid
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What is the rate-limiting step in bile formation?
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7alpha hydroxylase
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How much bile acid is synthesized in humans each day?
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200-400 mg/day
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Where are bile acids synthesized?
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liver
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What is the alternative pathway to bile acid synthesis?
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starts with initial formation of oxysterols and leads to chenodeoxycholic acid
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What are the primary bile acids? Where are they synthesized?
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cholic acid (3 OH)
chenodeoxycholic acid (2 OH) synthesized in liver |
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What are the secondary bile acids? Where are they synthesized?
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deoxycholic acid (2 OH)
lithocholic acid (1 OH) synthesized by gut bacteria |
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What is ursodeoxycholic acid?
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bile acid that was first discovered in bear bile
also present in humans to a small extent very good at solubilizing gallstones - used therapeutically |
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What two amino acids are bile acids conjugated to?
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glycine
taurine |
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Why are bile acids conjugated to amino acids?
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lowers the pKa
increases water solubility |
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What other molecules do bile acids combine with to form mixed micelles?
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cholesterol
phospholipids fatty acids lipophilic products of digestion |
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What stimulates the gallbladder to contract? Where is is secreted from? What is another effect on the gallbladder?
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cholecystokinin (CCK)
secreted from the duodenum relaxation of the Sphincter of Oddi |
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What is the enterohepatic circulation of bile salts?
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90% of bile salts are reabsorbed in the small intestine and returned to the liver via the portal vein
50% is absorbed passively and 50% by a Na coupled cotransporter in the distal ileum |
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What can cause fat malabsorption?
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interruption of enteropathic bile circulation b/c of ileal disease or ingestion of bile acid binding agents
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What comprises bilirubin?
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breakdown of heme pigments - particularly from hemoglobin
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How does bilirubin get to the liver?
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hemoglobin is broken down to bilirubin in the spleen
bilirubin is insoluble, so it is conjugated to albumin and passes through the systemic circulation to the liver |
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What is bilirubin conjugated with in the liver?
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UDP-Glucuronic acid
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What is bilirubin converted to in the small intestine?
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urobilinogen - excreted in urine, responsible for the color
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What is bilirubin converted to in the colon?
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stercobilin - responsible for the color of stool
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What are high levels of bilirubin in the blood known as?
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jaundice
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Which prohormone is produced in the liver?
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angiotensinogen
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How does the liver metabolize foreign molecules?
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most often involves oxidation or conjugation
most hydroxylation is by the cytochrome P450 family of enzymes |
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What are the 4 functions of the small intestine?
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1. digestion
2. absorption 3. secretion 4. motility |
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What is the lifespan of small intestine epithelial cells?
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3-6 days
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What s a Paneth cell?
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cell in small intestinal mucosa which secretes antimicrobial peptides called defensins, a part of the innate host defense system
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What are the two phases of small intestinal digestion?
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1. Intraluminal phase - by secreted enzymes
2. Epithelial phase - by brush border hydrolases or within enterocyte |
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What are 4 polysaccharides?
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1. starch
2. amylose 3. amylopectin 4. glycogen |
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What are 2 disaccharides?
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1. sucrose
2. lactose |
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What are 2 monosaccharides?
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1. fructose
2. glucose |
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What types of carbohydrates can we absorb?
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monosaccharides
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How much of the typical American diet is from carbohydrates?
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50%
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What is acarbose?
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an amylase inhibitor used to delay glucose absorption
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What are the products of amylopectin breakdown by amylase?
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maltriose
maltose alpha-limit dextrin (amylase cannot cleave 1-6 bonds) |
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What is the optimum pH for amylase?
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7.0
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What are some features of sucrase-isomaltase?
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synthesized as one polypeptisde
pancreatic proteases cleave protein into 2 subunits which remain attached by noncovalent interactions |
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What are some intestinal brush border enzymes?
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maltase
sucrase lactase isomaltase |
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What is SGLT1?
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a sodium-glucose/galactose transporter
transports monosaccharides from lumen into cell |
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What is the role of GLUT2?
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low-affinity, high-capacity transporter
transports glucose/galactose and fructose down concentration gradient from cell into blood |
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What is GLUT5?
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brush border fructose transporter
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How does lactase deficiency lead to diarrhea?
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lactose accumulation in bowel lumen leads to lactic acid production by bacteria, which leads to increased luminal osmolality and water accumulation in the lumen
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How many essential amino acids are there?
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9
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What types of protein are absorbed?
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amino acids
dipeptides tripeptides |
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Where does protein digestion begin?
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in the stomach with pepsin
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What is enterokinase?
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cleaves trypsinogen to trypsin
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What enzyme cleaves many zymogens, includin chymotrypsinogen?
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trypsin
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What is the difference between an endopeptidase and an exopeptidase?
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endopeptidases cleave in the middle of a protein
exopeptidases cleave a terminal amino acid from a protein |
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Where does trypsin cleave?
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next to basic redidues, like arginine and lysine
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Where does chymotrypsin cleave?
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aromatics
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Where does elastase cleave?
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aliphatic residues
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What are the products of intraluminal hydrolysis of proteins?
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40% amino acids and 60% small peptides
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How many different peptidases are there at the brush border?
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20
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How many amino acid transporters are present in the brush border?
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at least 7
some are Na dependent some are H dependent |
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What is the specific carrier for small peptides in the luminal brush border?
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PepT1
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What ion is linked to PepT1?
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H+
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What does PepT1 transport?
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every possible di- and tri-peptide
including drugs like beta-lactam antibiotics and ACE inhibitors |
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What is cystinuria?
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autosomal recessive disease characterized by increased excretion of cationic amino acids and cystine
primary clinical problem is kidney stones enriched in cystine |
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What is Hartnup disease?
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autosomal recessive disease of impaired absorption of neutral amino acids
major symptoms are those of niacin deficiency since niacin is synthesized from the neutral amino acid tryptophan |
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What is the optimal pH for lipase enzymes?
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6-7
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What is the optimal pH for gastric lipase?
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4
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What are the four steps in lipid digestion?
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1. Emulsification: physical process takes place in stomach
2. Digestion: stomach and duodenum 3. Solubilization: requires bile salts and mixed micelles 4. Absorption: normally fairly complete |
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What do we call excess lipid secretion in the stool?
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steatorrhea
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What are the products of pancreatic lipase?
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triglyceride -> 2 monoglycerides + 2 free fatty acids
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What is the product of cholesterolester hydrolase?
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cholesterol
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What is the product of phospholipase A2?
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lecithin -> lysolecithin
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Where does intestinal lipid digestion occur?
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lumen
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What is the purpose of bile salts in the intestinal lumen?
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to organize free fatty acids that have been digested into mixed micelles
this allows them to be transported at a much higher rate over to the brush border for absorption |
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What is colipase?
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anchors pancreatic lipase to the fat droplet preventing its displacement by bile salts
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How does Orlistat/Xenical/Alli work?
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covalent lipase inhibitor - goal is to inhibit about 1/3 of fat absorption
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What happens in the unstirred layer?
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monomeric fatty acids are in equilibrium with micelles b/c of slightly acidic pH of unstirred layer
fatty acid transport protein on enterocyte brush border absorbs fatty acids, cholesterol, and monoglycerides |
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What is a chylomicron?
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packages of resynthesized triglycerides in enterocytes that are released by exocytosis into lacteals
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What are lacteals?
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terminal lymph vessels in the intestine
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What is necessary for transport of chylomicrons?
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apolipoprotein coat
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Where does cholesterol come from?
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diet and bile, mostly
small amount from shed mucosal cells |
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How much of luminal cholesterol is typically absorbed?
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50%
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What is sitosterolemia?
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a disease in which plant sterols accumulate in the blood and body tissues
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What is Zetia (ezetimibe)?
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a cholesterol absorption blocker that blocks the permease mechanism by which sterols enter the enterocyte
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What happens to cholesterol after it enters the enterocyte?
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moves to the ER and is esterified by ACAT
incorporated into chylomicrons exported to lymphatic circulation chylomicron remnants taken up by liver and cholesterol is either secreted into bile or plasma |
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Where is calcium absorption most active?
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duodenum
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What regulates calcium absorption?
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active form of Vitamin D that has been hydroxylated once in the liver and once in the kidney
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What mediates calcium transport across the apical brush border?
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calcium entry channel - CaT1
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What binds calcium within the enterocyte?
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calbindin
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How does calcium exit the enterocyte?
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calcium ATPase PMCA1 transports it across basolateral membrane
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How does Vitamin D regulate calcium absorption?
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it binds to a nuclear Vitamin D receptor to modify gene transcription of calbindin gene
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What two things can be absorbed in the stomach?
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lipophilic molecules like ethanol
weak acids like aspirin |
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What is absorbed in the distal portion of the small intestine?
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bile
Vitamin B12 |
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How does the small intestine isotonically absorb fluid?
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water flows in to the space between epithelial cells to dilute locally hypertonic solution, but by the time it exits the lateral space the solution is isotonic
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What are two important modes of intestinal sodium absorption?
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Na/H CL/HCO3 countertransport
cotransport with organic solutes |
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What is the mechanism of cholera toxin?
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covalently modifies and activates adenylyl cyclase, which promotes activation of cAMP
this stimulates the apical CFTR chloride channel in crypt cells to secrete chloride into the lumen |
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What are some inducers of colonic and small intestinal secretion?
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cholera
unsaturated fatty acids like castor oil bile acids certain hormones like VIP |
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What is the frequency of slow wave occurrence in the small intestine?
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12/min in duodenum decreasing to 9/min in ileum
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What modulates slow wave amplitude in the small intestine?
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excitatory and inhibitory neurotransmitters
when slow wave amplitude reaches electrical threshold, a series of action potentials is initiated |
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What are ICC cells?
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interstitial cells of cajal
are the origin of slow waves in the stomach, intestine, and colon form a meshwork that is coupled to smooth muscle by gap junctions bear cKit receptor |
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What is the absorptive state and how long does it last?
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the time that food is in the lumen of the small intestine
usually lasts 4-6 hours with each meal |
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What types of contraction occur in the absorptive state?
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segmental contractions of circular smooth muscle
contraction of muscularis mucosa that leads to rhythmic villar contractions - mix the unstirred layer and compress lacteals |
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What is Starling's Law of the Intestine?
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a distension in the small intestine leads to ascending contraction and descending relaxation
contraction mediated by Ach and Substance P relaxation mediated by VIP |
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What is the migrating motility complex?
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the predominant intestinal motor pattern in the postabsorptive state
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How long does it take for the MMC to move from the antrum of the stomach to the ileocecal junction?
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about 90 minutes
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What hormone seems to regulate the MMC?
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motilin
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What inhibits the MMC?
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food entering the small intestine
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What is different about the outer muscle layers of the rectum as compared to the colon?
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the rectum has a complete outer longitudinal layer that surrounds the entire rectum
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What regulates the contraction and relaxation of the ileocecal sphincter?
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local myenteric reflexes
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What is the frequency of slow waves in the colon?
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variable but highest in the transverse colon and rectum (11/min)
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What is the gastro-colic reflex?
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mass contractions of the colon increase after a meal, especially in children
this is why babies often poop right after a meal |
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What happens to the muscle in the rectum when distended?
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inner smooth muscle relaxes - involuntary
outer skeletal muscle contracts - voluntary |
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What is Hirschprung's disease and what is the treatment?
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a.k.a. congenital megacolon
myenteric plexus in colon normally exerts a net inhibitory influence when neurons are absent in the rectum, the aganglionic segment is contracted, resulting in a large distended colon treatment is to remove the rectal aganglionic segment |
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What is the effect of fiber on the transit time of material through the colon?
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can reduce transit time from 3 days to 24-40 hours
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What is the role of the cecum?
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fermentation of carbohydrate to gases and short chain fatty acids, which are partially reabsorbed
metabolization of bile acids synthesis of Vitamin K |
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What happens to the bacterial population of the gut as you travel from stomach to colon?
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changes from primarily aerobic to anaerobic
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How is sodium absorbed in the colon?
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proximal - Na/H exchange coupled to Cl/HCO3 exchange resulting in a net absorption of NaCl
distal - electrogenic absorption using an aldosterone-regulated channel at the apical membrane and a Na/K ATPase at the basolateral membrane |
