Week 1/2 - D(2) - Physiology 4,5,7 - Digestion/absorption (carbs, proteins, lipids, iron, vit B12, water), Bile/gallstones

Question 1

What is digestion defined as? Where do most digestion processes occur?

Answer 1

Digestion is the enzymatic conversion of complex dietary substances to a form that can be absorbed Most digestive processes occur in the small intestine

Question 2

What is the enzyme that breaks down complex carbohydrates into oligosaccharides? Where is the enzyme released from? What breaks these down into smaller absorbale carbohydrates? give examples of these smaller final products of carbohydrate digestion

Answer 2

Amylsase released from salivary glands and pancreatic acinar cells breaks down comlex carbohydrates such as starch into oligosacchardies (eg lactose and sucrose)

Question 3

What breaks these down the oligosaccharides (eg lactose and sucrose) into smaller absorbale carbohydrates? give examples of these smaller final products of carbohydrate digestion

Answer 3

Oligosaccharidases (lactase, maltase, sucrase-isomaltase) then break these down into monosacchardies - smaller absorbale carbohydrates eg * Glucose * Fructose * Galactose

Question 4

What is the intolerance that can build up from an inability to breakdown lactose? - one of the main carbohydrates ind dairy products Symptoms? What is due to a deficiency of?

Answer 4

Lactose intolerance is a digestive disorder caused by the inability to digest lactose, the main carbohydrate in dairy products. It can cause various symptoms, including bloating, diarrhea and abdominal cramps. People with lactose intolerance have a brush border enzyme deficiency where enough of the enzyme lactase is not made, which is needed to digest lactose

Question 5

Where are the final products of carbohydrate digestion (glucose, galactose and fructose) absorbed?

Answer 5

Final product of carbohydrate digestion is absorbed in the duodenum and jejunum

Question 6

What is the transporter that mediates the absorption of glucose/galactose and fructose into the enterocye at the apical membrane? What is the transport that mediates the exit of glucose/galactose/fructose at the basolateral membrane of the enterocyte into the bloodstream?

Answer 6

Glucose/galactose are absorbed by secondary active transport mediated by SGLT1 (sodium dependent glucose transporter 1) Fructose is absorbed by facilitated diffusion mediated by GLUT5 (glucose transporter 5) Exit for all monosaccharides is mediated by facilitated diffusion by GLUT2 (glucose transporter 5)

Question 7

Proteins Protein must (after the first six months of life) be digested to oligopeptides and amino acids for efficient absorption Where are the digestive enzymes for proteins released from?

Answer 7

The digestive enzymes for proteins are released from both the stomach and pancreas

Question 8

What is released from the stomach and how does it start digestion of the protien? What is released from the pancreas and how does it get converted to its active form to digest the protein?

Answer 8

Digestion in stomach * HCl (released from gastric parietal cells) begins to denature the proteins. It also converts pepsinogen (released from chief cells) to pepsin * Pepsin is autocatalytic and therefore has a positive feedback converting more pepsinogen to pepsin * It cleaves proteins into peptides Digestion in duodenum * Pancrease release proteases as proenzymes which are converted to there active form by enteropeptidases (enterokinases) in the duodenum

Question 9

Where are additional proteases present? (ie not the gastric or pancreatic proteases)

Answer 9

Additional proteases are present * At the brush border (microvilli of small intestine) * Within the cytoplasm of enterocytes

Question 10

What are the different types of lipids?

Answer 10

Fats/oils - triaceyglycerols (triglycerides) Phospholipids Cholesterols and cholesterol esters Fatty acids

Question 11

Ingested lipids must be converted from solid fat and oils into an emulsion of small oil droplets suspended in water How does emulsification of fats occur?

Answer 11

Emulsification occurs by * Mouth - chewing * Stomach - gastric churning and squeezing through the narrow pylorus - content mixed with digestive enzymes from mouth and stomach * Small intestine - segmentation (mixing of chyme with digestive juices) and peristalsis mix the luminal content with pancreatic and biliary secretions

Question 12

What are the biliary secretions that emulsify fats? What does failure to secrete bile salts result?

Answer 12

Bile salts released into the duodenum from the gall bladder in response to cholecystokinin act to help emulsify large lipid droplets to smaller lipid droplets Failure to secrete bile salts results in Lipid malabsorption - steatorrhea (fatty faeces) Secondary vitamin deficiencies due to failure to absorb fat soluble vitamins- vitamin A, D, E and K

Question 13

After the emulsification of the fats (bile salts mainly) How is fat digested?

Answer 13

1. fat goes to stomach where there is little digestion 2. fat goes to small intestine 3. bile (made by liver and stored in gallbladder) is released into small intestine 4. bile emulsifies the fats 5. fat-digesting enzymes - lipases from pancreas (and gastric lipases) breaks the fats down 6. fats pass to the digestive tract with help of bile 7. fats enter the cells and they extract the lipids

Question 14

What are the breakdown products of triacylglycerolds that can be absorbed? Where are they absorbed?

Answer 14

Free fatty acids and monoacylglycerides are absorbed mainly in the duodenum and jejunum of small intestine (same as carbs and proteins) via different transport processes

Question 15

What is the transport process that is thought to mediate the absorption of cholesterol into the enterocytes of the small intestine?

Answer 15

This transport process is the Neimann-Pick C1-like 1 (NPC1L1) protien

Question 16

Which drug can be given as first and second line for hypercholesterolaemia?

Answer 16

First line - statins - they are HMG CoA reductase inhibtors (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) HMG CoA reducatse is the rate limiting step in cholesterol synthesis Second line - ezetemibe - inhibits NPC1L1 protein (Neimann-Pick C1-Like 1 protein) preventing absorption of cholesterol

Question 17

Iron is: * one of the most abundant elements on the earth * an important constituent of haemoglobin and myoglobin and acts as co-factor for numerous enzyme-mediated processes * crucially important in carriage of oxygen by haemoglobin What is the form of dietary iron? What is the form of iron that is aborbale in the dudoenum?

Answer 17

Dietary iron mainly comes in the oxidised form Fe3+ However it is Fe2+ that is absorbed across the apical membrane of the dudoendal entercoytes (iron supplements given as the ferrous Fe2+)

Question 18

What is the reduction of iron from Fe3+ to Fe2+ promoted by? What does iron bind to and where is it produced from? What does it prevent?

Answer 18

The oxidised ferric state , Fe3+ of iron is reduced to the reduced ferrous state, Fe2+ by Fe3+ accepting an electron This is promoted by HCl within the stomach and vitamin C amongst other thing Gastroferrin secreted by the gastric parietal cells binds to Fe2+ to prevent the formation of insoluble anion salts

Question 19

Absorption of vitamin B12 is important for healthy red blood cells and for the nervous system Where is vitamin B12 found in the diet? therefore who is susceptible to a deficiency What is needed for its absorption and where is it abosrbed?

Answer 19

Vitamin B12 is found in meats and fish but not in vegetables - therefore vegans are susceptible to a deficiency The stomach parietal cells release intrinsic factor which binds to vitamin B12 in the small intestine The vitamin B12-intrinsic factor complex is absorbed in the terminal ileum by endocytosis

Question 20

Where is bile produced? Which cells? What is its function?

Answer 20

Bile is produced in the liver from hepatocytes and bile duct cells (cholangiocytes) Its function is to particpate in the digestion and absorption of fats and the excreetion of products of metabolism

Question 21

Where is bile during meals? What stimulates its release during a meal? Where is it released into?

Answer 21

Between meals, bile is stored and concentrated in the gall bladder - sphincter of oddi closed During a meal, chyme in duodenum stimulates gall bladder smooth muscle to contract (via cholecystoknin (released from I cells) and vagal impulses) Sphincter of oddi opens via cholecystokinin Bile spurts into the duodenum via the major duodenal papilla

Question 22

What are the primary bile acids? Where are they synthesised? How are secondary bile acids formed and what are they?

Answer 22

Primary bile acids are those synthesised by the liver - secreted by the hepatocytes are mainly cholic and chenodeoxycholic acid Secondary bile acids result from bacterial actions in the colon - primary bile acids are dehydroxaylated by bacteria in the small intestine Deoxycholic acid and lithocholic acid are the types

Question 23

What is the most common pathology of the biliary tract? Why may it occur?

Answer 23

Most common pathology of the biliary tract is cholelithiasis (chole - bile) (lithiasis - stony secretions) (gallstones) Excess cholesterol relative to bile acids may precipitate into microcrystals that aggregate into gallstones

Question 24

What is the most common treatment of symptomatic gallstones? What is a medication that can sometimes be suitable for patients with very small asymptomatic stones? - what is the most frequent adverse effect

Answer 24

Laproscopic cholecystectomy is the best treatment for symptomatic stones eg causing cholangitis or pancreatitis Medication that can be given for small asymptomatic stones - ursodeoxycholic acid (secondary bile acid) which can dissolve cholesterol stones Most frequent adverse effect of urseodeoxycholic acid is diarrhoea

Question 25

Absorption of water is a passive process driven by the transport of solutes from the lumen of the intestines into the bloodstream What is the particular solute that water mainly follows? Approximately 9.3 litres of water enter the GI tract per day (combination of ingestion of liquid and GI digestive juices (saliva, gastric, bile, pancreatic, intestinal) * Where is the water absorbed? * State the amounts if possible?

Answer 25

Water follows the reasborption of sodium (Na+) Approx 9.3 litres of water enters the GI tract per day Approx 8.3 litres is reaborbed in the small intestine Approx 1 litre enters the large intestine of which 90% is reaborbed 100 ml of water is normally contained within the faeces

Question 26

Faeces normally contains approximately 100ml of water (along with 50ml cellulose, bilirubin and bacteria) What amount of loss of fluid is diarrhoea defined as?

Answer 26

Diarrhoea is defined as loss of fluid and solutes from the GI tract in excess of 500ml per day

Question 27

There are 5 main principle mechanisms of Na+ reabsorption in the GI tract What is the mechanism that is exploited when giving rehydration therapy to treat diarrhoea?

Answer 27

Rehydration therapy exploits the sodium glucose co-transporter - SGLT1 (sodium dependent glucose transporter 1)

Question 28

What does oral rehydration solution at home contain?

Answer 28

6 level teaspoons of Sugar. Half level teaspoon of Salt. One Litre of water

Question 29

How does oral rehydration therapy exploit the sodium dependent glucose transporter?

Answer 29

2 Na+ bind to SGLT1 -> Affinity for glucose increases, glucose binds -> Na+ & glucose translocate from extracellular to intracellular -> 2 Na+ dissociate, affinity for glucose falls and glucose dissociates ->repeat Absorption of Na+ and glucose by SGLT1 cause accompanying absorption of H2O