Chapter 14d and 14e – Digestive System

1. Stomach and Intestinesa. Small intestine

i. First part of small intestine is duodenum, then jejunum, then ileumb. Duodenum has four parts

i. 1st part or superior part (transverse)1. Has

ii. 2nd part of descending part (descending)1. Has common opening for common bile duct and main pancreatic duct

iii. 3rd part is Horizontaliv. 4th part is Ascending

c. 2nd part of duodenum has two openingsi. Main pancreatic and common bile duct which join and open into sphincter of Oddiii. Ampulla of Vater is tissue which surrounds sphincter of Oddi

d. Function of duodenumi. Regulates stomach and gallbladder emptying in response to acid chymeii. Secretes secretin in response to high acid and fatty acids in lumen

1. Inhibits gastric acid secretioniii. Secretes CCK in response to fatty chyme

1. This induces gallbladder contractioniv. Secretes enterogastrone inhibits stomach peristalsis

e. Function of small intestinei. Digest and absorption of food by breakdown of nutrients into absorbable componentsii. Wall of small intestine looks like finger like structure called villi.

iii. Inside villi we have capillary blood vessels absorption occurs between wall of villi and capillary

iv. 80-90% of absorption occurs in epithelial cells in small intestinev. 90% of fluid in fecal material is absorbed in large intestine

vi. Before having peristalsis, we have two types of contractions1. Slow wave without having stimulus and without action potential

a. Very weak contraction which is in Cajal cells2. Slow wave converted into segmental contraction every 1 cm in small intestine

a. Necessary for mixing of chimed with gastric juice and digestion and absorption by villi and then capillary

b. BER – basic electrical rhythmi. Slow waves set basic electrical rhythm (12/min)

3. After segmental we have peristalsis (propulsive contractions) spike wavea. Means movement of remnants of chyme to next part of GIb. At end it reaches ileocecal junction

i. Transit time from pylorus to ileocecal junction is 3-5 hoursii. Relaxation of this junction is by gastrin

iii. It relaxes and cecum receives fecal material – called semisolid and not called chyme anymore.

iv. Fecal material is released into cecum which is first part of large intestine

1. Any infection, irritation to ileocecal junction leads to diarrhea2. Any inflammation or infection in small intestine increases

abdominal cavity pressure a. Leads to opening of pyloric sphincter and lower

esophageal sphincter which leads to vomitingb. Vomiting center is in medulla oblongata which is part

of brain stemvii. Every 90 minutes we have strong contraction which clears residual food from GI tract

viii. Gastroileal reflex1. Mediated by ANS and gastrin2. Presence of food in stomach triggers increased peristalsis in ileum and relaxation of

ileocecal sphincter

2. Functions of Ileocecal valvea. Prevent backflow of fecal contentsb. Normally closed c. After a meal, gastroileal reflex allows relaxation (gastrin) and increases terminal ileal peristalsisd. About 1500ml of chyme passes to cecum each daye. Irritation of cecum delays emptyingf. Clinical note about appendicitis

i. Appendix is cecal vestige and appendicitis gives massive signal to ileocecal sphincter causing spasm and paralysis which completely blocks flow

3. Peristalsisa. Peristaltic rush

i. Triggered by irritation such as infection diarrheaii. Peristalsis action becomes more powerful and rapid

b. Peristalsis during fastingi. During long duration of eating of fasting, migrating motor complex (MMC) occurs every 1.5

to 2 hours to clear buildup of excessive (potentially harmful) digestive secretions in upper GIc. Actions of folds and villi

i. Muscularis can cause folding on wall and cause folds to move along wallii. Purpose is to increase contact with chyme by churning and increasing surface area

4. Vomitinga. Center is medulla oblongatab. Stimulation of receptors in fourth ventricle in brain by radiation can causes vomiting as well

5. Structure of large intestine

a. Innervation is by ANS which controls enteric – Meissner and Auerbachb. Blood supply of duodenum and small and large intestine is by superior and inferior mesenteric

arteriesc. 90% of fluid from fecal material is absorbed by large intestined. Slow wave, segmental contraction, spike wave (peristalsis)e. Defecation

i. Called Valsalva maneuver1. When rectum is filled with fecal material which is close to anal canal, this increases

intra-abdominal pressure which leads to defecation of fecal material.

6. Pancreasa. Located between second part of duodenum and spleenb. Head of pancreas toward duodenum, tail is toward spleenc. Has two parts

i. Endocrine and exocrine part1. Exocrine part

a. Secretes 3 enzymesi. Lipase for fat digestionii. Amylase for carbs

iii. Protease for proteinsii. Pancreas secretes bicarbonate

1. Neutralizes acidic chyme that reaches duodenumd. Composition of pancreatic secretions (always isotonic)

i. At low flow rates isotonic fluid which is mainly Na+ and Cl-ii. At high flow rates isotonic fluid which is mainly Na+ and HCO3

-

e. Formation of pancreatic secretioni. Acinar cells

1. Produce a small volume of initial pancreatic secretionii. Ductal cells

1. Modify initial pancreatic secretion by secreting bicarbonate iii. Pancreatic enzymes and bicarbonate are produced by acinar cellsiv. This is released into main pancreatic duct opens into 2nd part of duodenum which is called

ampulla of Vaterf. 3 factors increase pancreatic enzyme secretion

i. Secretin by S cells1. Increase ductal cells bicarbonate secretion2. Bicarbonate is secreted into duodenum to neutralize H+

ii. CCK by I cells1. Respond to small peptides, amino acids, and fatty acids duodenal lumen2. Acts on pancreatic acinar cells increases enzyme (amylase, lipase, and proteases)

and bicarbonate secretioniii. Vagus nerve accelerates pancreatic enzyme secretion

1. Responds to small peptides, amino acids, and fatty acids in duodenal lumen

2. Stimulates secretion by acinar cells

7. Bilea. Composition

i. Formed of bile salt, phospholipid, cholesterol, and bilirubin (bile pigments)ii. 50% has bile salt, 2% is bilirubin, 4% cholesterol, 40% phospholipids

iii. Bilirubin is product of dead red blood cells. b. Produced continuously by hepatocyte which is cell of liverc. Drains into hepatic ducts and stored in gallbladderd. Formation of bile

i. Hepatocytes uptake cholesterol and convert into primary bile acid1. Primary bile acids are cholic acid and chenodeoxycholic acid

ii. Bloodstream carries primary bile acid to intestine1. Bacteria from intestine converts primary into secondary bile acid

a. Secondary bile acids are deoxycholic acid and lithocholic acidiii. Bloodstream carries secondary to liver againiv. Bile acids are conjugated with amino acids glycine and taurine to form bile salt

1. Bile salt is importantv. Bile itself has bilirubin, water, and some ions

e. Bile salt has two surfacesi. Hydrophilicii. Lipophilic

iii. Called amphipathic means two surfaces with one side hydrophilic and other hydrophobic (lipophilic)

iv. Bile salts accelerates digestion and absorption of lipids in watery environment of small intestine

v. Has important function1. Depends on their amphipathic properties2. Without bile salt, lipids would be insoluble (cannot dissolve) in watery environment

of small intestinea. This leads to less digestion and absorption of lipids.

3. Bile salts emulsify (act as detergent) directly on lipids in second part of duodenum.a. Emulsification means it breaks down the lipid and converts it into lipids

droplets (small pieces)4. Having bile salt is bile increases rate of digestion and absorption of lipids by

pancreatic enzymes in duodenum because the pH in duodenum ranges between 3-5. 5. Bile acids pH ranges close to 7 but bile salt ranges between 1-4.

a. Bile salt accelerates digestion of lipids by pancreatic enzymes in watery environment of duodenum.

6. Bile salt surrounds the lipids droplets and together they form micelle. Bile salt surrounds lipid droplets.

vi. Deficiency of bile salt1. Deficiency of lipid absorption and digestion by small intestine

a. Causes excretion of fat tissue by fecal material which is called blobs. Yellowish tissue that exists in feces which is sign for deficiency of bile salt so it couldn’t absorb fats and liver by small intestines

8. Contraction of Gallbladdera. CCK informs gallbladder that bile is needed to emulsify and absorb lipids

i. Causes contraction of gallbladder and relaxation of sphincter of Oddib. Ach contracts gallbladder

9. Lipid a. Digestion of lipid in small intestine epithelial cell

i. Triglyceride converts into two molecules of fatty acids and monoglyceride. 1. Enzyme is pancreatic lipases

ii. Conversion of cholesterol ester into cholesterol and fatty acid1. Enzyme is cholesterol ester hydrolase enzyme

iii. Phospholipid converts into lysolecithin and fatty acid1. Enzyme is phospholipase A2

iv. Digestion of lipids 1. 1st step occurs in oral cavity by lingual lipase2. 2nd step maybe 10% of digestion of lipids occurs in stomach by gastric lipase.

3. 3rd step 90% of digestion of lipids are completed in small intestine with the action of pancreatic enzymes (pancreatic lipases, cholesterol ester hydrolase, and phospholipase A2)

b. Absorption of lipidsi. Lumen, epithelia cell of small intestine, and bloodii. BS stands for bile salt, FFA is free fatty acids

iii. Has 5 steps1. After emulsification of lipid by bile salt, then the bile salt converts lipid into lipid

droplets which are cholesterol monoglyceride lysolecithin and free fatty acids.

2. Bile salt and lipid droplets form micelle3. Micelle diffuse from lumen to the apical membrane of intestinal epithelial cell.

a. This means micelles enter to cell of small intestine lumen and bile salt are left behind and reabsorbed in ileum which is last part of small intestine.

b. From ileum, the bile salt is reabsorbed by enterohepatic circulation which carries bile salt to liver again

4. Inside the intestinal epithelial cell, the lipid products are re-esterified.a. This means lipid products combine with 3 fatty acids which forms cholesterol

ester, triglyceride and phospholipid5. Re-esterified lipids combine with a protein called APO protein.

a. This protein is produced by intestinal epithelial cells which is necessary for absorption of chylomicron.

b. This means chylomicron can’t be absorbed without apo protein. 6. Exocytosis of chylomicron to lymphatic system (lymph) and from this system which

opens into thoracic duct and this opens and releases into venous system

iv. Disorders1. Abetalipoproteinemia

a. Cause i. Is due to deficiency or lack of APO protein beta

b. Signs and symptomsi. Without apo protein chymomicron can’t be reabsorbedii. Steatorrhea Means having fat (yellowish tissue) in fecal material

iii. Mental retardationiv. Muscle weaknessv. Retinitis pigmentosa inflammation of retina

vi. Hypocholesterolemia1. Cholesterol is precursor for and 6 hormones

a. Vitamin D Deficiency osteoporosis – fracture of bone

10. Carbohydrate digestion a. Steps

i. Starch is converted into alpha dextrins, maltose, maltoriose (by alpha amylase from saliva)ii. Conversion of alpha dextrin into glucose by alpha dextrinase

iii. Conversion of maltose into glucose by maltaseiv. Conversion of maltoriose into glucose by sucrase

b. Disaccharides into monosaccharidesi. Converted into trehaloase, lactose, and sucroseii. Conversion of trehalose into glucose by trehalase enzyme

iii. Conversion of lactose into glucose and galactose by lactase enzymeiv. Conversion of sucrose into glucose and fructose by sucrase enzyme

11. Absorption of carbohydrates by epithelial cells of small intestinea. Lumen, epithelial cell of small intestine, bloodb. SGLT1, SGLT1, GLUT5 in lumen. In blood we have GLUT2, GLUT2, GLUT2c. SGLT1 is sodium glucose transport protein, GLUT5 is fructose transporter, GLUT2 is glucose

transporter. d. Steps

i. Sodium symports glucose, galactose.ii. Fructose enters by GLUT5. All from lumen into epitheliai cell of small intestine.

iii. From epithelial cell moved to blood stream by GLUT2 which is glucose transporter. Glucose, galactose, and fructose.

e. Other absorptioni. Absorption of sodium chloride

1. Passive diffusion of sodium which symports chloride in small intestine.2. Sodium itself can symport glucose, and antiports hydrogen ion.

ii. Absorption of potassium1. By small intestine2. Deficiency of potassium is result of diarrhea or vomiting which leads to hypokalemia. 3. This means no repolarization phase

iii. Water absorption1. Depends on solute absorption2. More solute absorption means more fluid absorption

iv. Fat soluble vitamins such as A, D, E, and K1. Absorbed by micelles which are absorbed by epithelial cell of small intestine

v. Water soluble vitamins1. Are absorbed by sodium cotransport (symport)

vi. Vitamin B121. Is absorbed in ileum

vii. Calcium absorption 1. Occurs in small intestine and distal tubule in nephron which is under control of PTH-

parathyroid hormone2. Deficiency of calcium in bone could be due to deficiency of vitamin D3. Deficiency of vitamin D in children is called rickets, in adults is osteomalacia

12. Protein digestion and absorptiona. Activation of GI protease

i. We have inactive forms of some enzymes then they become active formii. These active enzymes digest the proteins

iii. Activation of GI proteases1. 1 - Stomach

a. In stomach, we have pepsinogen converted into pepsin by HCl.2. 2 – small intestine

a. We have trypsinogen conversion into trypsin by enzyme enterokinase (comes from brush border of intestine)

3. 3- we have 5 pancreatic enzymes in inactive form but later become active. 5 enzymes are

a. Trypsinogen into trypsinb. Chymotrypsinogen into chymotrypsinc. Proelastase into elastased. Procarboxy-peptidase type A into carboxypeptidase type Ae. Procarboxy-peptidase type B into carboxypeptidase type Bf. Trypsin converts all inactive forms into active for all these proteins

iv. Digestion of proteins in GI1. Stomach

a. Protein converted into amino acids and oligopeptides by pepsin (comes from stomach)

2. Small intestinea. Protein converted into amino acids, dipeptides, and tripeptides by the 5

pancreatic enzymes. b. All released into main pancreatic duct into duodenum

v. Absorption of proteins in GI1. Lumen, epithelial cells of small intestine, and blood (capillary)2. Sodium symports amino acids, dipeptides, and tripeptides from lumen into epithelial

cells of small intestine. 3. All these are also absorbed into blood from epithelial cell all by sodium as well.

13. Iron absorptiona. As free iron, or iron bound to hemoglobin or myoglobinb. In intestine, heme iron is digested by lysosomal enzyme (hydrolases) and releases free iron. c. Free iron binds to apoferritin which is carried in blood d. Then iron is bound to beta globulin which is called transferrin. e. Transferrin transports iron from small intestine to the liver for storage of iron. f. From liver, is transported to bone marrow for production of red blood cells.

14. Bilirubin a. Is result of damaged red blood cells

b. Damaged red blood cells release hemoglobin which is made into iron and globin. Globin in spleen is converted into biliverdin by biliverdin reductase enzyme

c. Biliverdin is made into bilirubin which combines with albumin in system circulation (in blood). d. Billirbuin is carried by albumin and gets to liver. e. In liver, bilirubin is conjugated with glucuronic acid which together form bilirubin glucuronide. This

conjugation into bilirubin glucuronide is by glucouronyl transferasef. This enzyme deficiency in premature newborn or newborn

i. Leads to Newborn jaundiceg. Conjuaged bilirubin gets to small intestineh. Small intestine bacteria convert glucuronate into billirubinogen which goes to urobilinogen. This

comes in two forms. One is urobilin which is released into urine which gives it yellow color. Other form is sterocobilin which gives greenish and brownish color in fecal matter.

15. Micelle is combination of a. Goal is emulsification. It converts into lipid product and is ready for digestion by pancreatic lipases

16. Jaundicea. Is due to high level of bilirubin which is product of dead red blood cellsb. Is yellowish color of skinc. Three types

i. Hemolytic – destruction of red blood cells1. Sickle cell disease is example

ii. Obstructive (hepatic)1. Is obstruction or closure of bile duct2. Tumor3. Stone4. Infection5. Any liver disorder gives jaundice or hepatitis which is viral infection of liver

a. Alcoholic people have risk for damaged liverb. This may give them jaundice

6. This leads to retro flow of bile into systemic circulation (blood)7. Conjugated bilirubin ends up in blood

iii. Post hepatic obstruction of common bile duct that carries bile to duodenum

17. Gall stone cholelithiasisa. Cause

i. Imbalance in concentration of cholesterol and bile salt ii. Sometimes is due to high level of bilirubin

iii. We can have different types1. High cholesterol is yellowish color2. High bilirubin in greenish

18. Acute cholecystitis – means inflammation of gall bladder

a. Inflammation of gall bladder that is for storage of bileb. Signs and symptoms

i. Immediately after eating, 1 to 2 hours later patient has pain in abdominal cavity especially in right upper quadrant of abdominal cavity.

ii. Murphy sign positive is when you touch is upper right quadrant and patient has pain. During deep inspiration, touch in upper right quadrant and patient feels pain, something is wrong in liver or gall bladder

iii. Pain, nausea, abdominal painiv. Treatment

1. Cholecystostomy – remove gall bladder

19. Livera. Liver is formed of hepatocytes and some blood vessels.

i. We have hepatic artery branch of celiac artery branch of abdominal aorta. ii. Function of left and right hepatitis arteries gives blood to cells of liver hepatocytes

iii. We have hepatic veins, left and right, which release into inferior vena cava which collect deoxygenated blood from liver tissue and release into inferior vena cava

iv. We have bile ducts1. Left and right lobes (really made of four lobes)

a. Left lobes and right each have a hepatic duct, left and right hepatitis duct which come together to form common hepatitis duct which joins to cystic duct which comes from gall bladder.

b. Cystic and common hepatitis duct form common bile duct and forms main Pancreatic duct which together form ampulla of Vater which joins sphincter of Oddi

c. Relaxation of Oddi is by CCKd. Contraction of gall bladder by CCK

v. Ilium is connected to large intestine. Then we have sigmoid and rectum. vi. Left gastric vein, splenic vein, inferior mesenteric vein, superior mesenteric vein, and portal

veins which all carry good things to liver and contain bacteria from large and small intestineb. Blood flow into liver

i. Liver receives 1459 ml/min and portal vein carries 1100 ml/min of blood. ii. Portal vein carries absorbed vitamins, proteins, glucose, ions, medicines, and bacteria to

liver. iii. Hepatic artery carries 350 ml/min.

c. Metabolic functions of the liveri. Anabolic/catabolic functions of liver are…

1. Storage of glycogen2. Gluconeogenesis formation of glucose from certain amino acids, lactate, or

glycerol3. Glycogenolysis4. Glycogenesis formation of glycogen from glucose5. Breakdown of insulin and other hormones

d. Other metabolic activitiesi. Storage of ironii. Removal or excretion of drugs, hormones

1. Liver can detoxify and excrete many drugs 2. Hormones or metabolites are reduced and excreted3. Excess plasma Ca is excreted via bile

iii. Liver damage can cause a build up of these agents and lead to toxicity or hyperactivitye. Liver is for filtration by Kupffer cellsf. Liver is main place for carbs and storage vitamins

20. Pathology of livera. Hepatitis inflammation of liver

i. Viral infection of liverii. Sometimes due to poisons, autoimmunity, or hereditary conditions

iii. Anything that leads to damage of liver tissue gives patient jaundiceb. Hemochromatosis

i. Genetic disorder that leads to accumulation of iron in bodyii. Over storage of iron leads to destruction of liver

c. Cancer of the liver i. Having tumor in liver by spreading of tumor cells from colon cancer. Colon cancer, tumor

cells can spread liverd. Wilson disease

i. Hereditary disease which causes accumulation of copper

21. Crohn’s diseasea. Form of inflammatory bowel disease (IBD)b. Cause is an overactive immune response which leads to chronic inflammation autoimmune

disorderc. Inflammation causes intestinal wall to become thickd. Autoimmune diseases

i. Antibody can irritate any part of GI tractii. Is completely different from Conns which is hyperaldosteronism

iii. Signs and symptoms of Crohn’s1. Patient has severe diarrhea2. Pain with passing stool (tenesmus)3. Dehydration4. Malabsorption5. Maldigestion6. Vitamin deficiency 7. Anemia8. Lose weight9. Abdominal pain10. Fever

11. Risk for bacterial infectioniv. Treatment

1. Eat small amount of food throughout day2. Drink lots of water3. Avoid high-fiber foods accelerate peristalsis4. Avoid fatty, greasy, or fried foods5. Avoid or limit alcohol and caffeine consumption6. Replace vitamin D, calcium, and vitamin B12 to prevent anemia

v. Medications1. Antidiarrheal drugs Loperamide (Imodium)2. Corticosteroids prednisone and methylprednisolone3. Immunomodulators Azathioprine

a. Quiet immune system’s reaction4. Antibiotics for abscesses or fistulas

22. Cirrhosisa. Scaring of liver and poor liver functions as result of chronic liver diseaseb. Causes

i. Could be post hepatitis inflammation of liver1. Due to Hepatitis C or B

ii. Could be alcoholic personiii. Could be fibrosis of liver which is based on genetic disorder. iv. Autoimmune inflammation of liverv. Disorders of drainage of liver system (biliary system)

1. Primary biliary cirrhosisvi. Metabolic disorders of iron and copper

1. (hemochromatosis and Wilson’s disease)c. Signs and symptoms

i. Vomiting Contains fresh bloodii. Nausea

iii. Weaknessiv. Lose weightv. Jaundice

vi. Ascites accumulation of fluids in abdomenvii. Ascites is accumulation of fluid in peritoneal cavity which covers internal organs in ab cavity

1. Liver cannot receive large amount of blood, so we have retro flow of blood into venial system

2. Over time we have elimination of water into peritoneal cavity ascites which is accumulation of water into peritoneal cavity

viii. Treatment1. Go for liver transplant

23. Gallstone

a. Imbalance of bile salt, bilirubin, or cholesterol leads to this.b. You have jaundice as wellc. Two main types

i. Stones made out of cholesterol1. Most common

ii. Stones made from too much bilirubin in bile1. These stones are called pigment stones

d. Causes could bei. Conditions that cause liver to make too much bilirubin

1. Hemolytic anemia, sickle cell anemiaii. Liver cirrhosis and biliary tract infections

e. Signs and symptomsi. Pain right upper or middle upper abdomenii. Occurs within minutes of eating a meal

iii. Feveriv. Jaundicev. Nausea and vomiting

24. Spleena. Main organ which recollects dead red blood cellsb. Forms biliverdin and unconjugated bilirubin

25. Exam questionsa. 35 year old may surgery and doctor removed fundus of stomach. What types of symptoms may the

patient have after surgery. i. Anemiaii. Jaundice

iii. Infection in abiv. Protein disorder

v. No intrinsic factor, person will have anemia and protein disorder from deficiency of HCl so no conversion of pepsinogen into pepsin

b. 25 year old female has ab pain, diarrhea, vomiting, dehydration, low blood pressure, vitamin deficiency, protein deficiency, risk for anemia. What disorder?

i. Crohn’s disease is answer

c. 65 year old male had severe pain on right upper quadrant in ab cavity and radiation of pain right side of back. Pain is worse after eating and skin becomes yellow from jaundice

i. Answer is Cholelithiasis which is stone that blocks common bile duct for release of bile.