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Cell Bio Phys Review 2 Lecture 10 SodiumPotassium Pump • Basolateral side • Generates negative sodium balance inside the cell • Allows for sodium to be pumped into cell from lumen • 3 Na for 2 K Nutrientcoupled Na+ Transport • JEJUNUM AND ILEUM POST-PRANDIAL STATE • activating Na+/glucose and Na+/amino acid cotransporters to get sodium into the cells • Again, sodium pumped into interstitium by Na-KATPase Na-H Exchanger • Duodenum + Jejunum • Alkalinity is high – postprandial state due to HCO3 • pH gradient pulls H out of epithelial cell, pushes Na in • HCO3 gets put into blood Interdigestive period • Distal Ileum and Colon • Na-H transporter • HCO3- and Cltransporter • CHLORIDE GETS ABSORBED • Both H and HCO3 come from H20 and CO2 POTASSIUM ABSORPTION • Jejunum and Ileum, K+ absorption occurs passively, likely from solvent drag • Active K+ absorption – DISTAL COLON • Use of K+-H+ pump Electrolyte Transport in Colon • ALDOSTERON STIMULATED • Na absorbed, K secreted • THIS IS HOW K IS SECRETED • Last line for Na absoprtion • Similar to late distal tubule and collecting ducts of the kidney • FLOW-RATE DEPENDENT • DIARRHEA • HYPOKALEMIA / tx hyperkalemia • Hyperchloremic metabolic acidosis with normal anion gap CHLORIDE SECRETION – drives secretion • Basolateral surface • ACh and VIP stimulate • Activate Adenyl Cyclase and cAMP • Open the Cl- channel in apical membrane • Na+ and H20 • Cholera toxin • A subunit • ADP ribosylation of Alpha-s subunit • Inhibits GTPase activity • Always on Summary Slide Diarrhea Osmotic • Cause – presence of nonabsorbable solutes in the lumen • Lactase deficiency • Lactose accumulates in lumen and retains water • Bacteria break it down and make it smaller molecules, increasing osmosis Secretion • Excessive secretion of fluid by crypt cells • Bacteria – cholera/E. Coli A 14 year old ballerina reports that she has chronic diarrhea. A detailed history reveals that she frequently drinks skim milk, that she does not use laxatives, and that she has noticed that her condition improves during times that she fasts for religious observances. In contrast to secretory diarrhea, which of the following is most likely seen with osmotic diarrhea? • A) It is characterized by an increase in the stool osmotic gap • B) Result of increased cell secretion • C) Result of decreased electroneural sodium absorption • D) Caused by bacterial toxins • E) Occurs only in the colon Lecture 11 Basic Liver anatomy • Blood Supply – 2 sources • • • • Hepatic artery proper – 25% and oxygenated Hepatic portal vein -75% and nutrient rich IVC drains it 10% of body’s total blood • Anatomical unit– liver lobule • Hexagonal cylindrical structure • At center – central vein • Functional unit – hepatocytes • Separated by sinusoidal capillaries – bathe hepatocytes • Fluid flow • High flow • High compliance • Low – resistance • Leaky endothelial cells – large fenestrations and large gaps between adjacent cells • Space of Disse - Gap between basolateral membranes of hepatocytes and sinusoidal wall Space of Disse Gap between basolateral membranes of hepatocytes and sinusoidal wall • Ito cells • Store fat/fat soluble • Inflammation myofibroblasts • FIBROSIS (Ito cell) Basolateral membrane Apical membrane KUPPFER CELLS • MAIN ROLE = REMOVE UNWANTED PARTICLES • EARLY EHTANOL-INDUCED LIVER INJURY • TNF-ALPHA AND ROS • TURNS ON THE STELLATE CELL MINOR ROLE – BREAK DOWN RBCS BILIRUBIN • REMOVE FROM BLOOD • CONJUGATE IT • UDP glucuronosultransferase (UGT1A1) • BABIES!!!! • Excreted into bile • Intestines • Deconjugate – urobilinogen • Reabsorb or oxidize to urobilin - urine • Urobilinogen – converted to stercobilin and gets feces Fasting Post-Prandial State • Glycogenolysis + gluconeogenesis (amino acids and fats) • Glycogen storage • Regulation • Convert fat to storage • • • Glucagon - stimulates B2 receptors - stimulates Insulin – inhibits Lipids • Acetyl-coa is converted to ketone bodies by b-oxidation • Ketone bodies (acetoacetate and bhydroxybutyrate) can be use by the body for energy • FYI: the liver can’t use ketone bodies for energy • Insulin stimulates glycogenesis Proteins • Liver doesn’t’ store AAs • Synthesize • Nonessential Aas • ALT and AST • Albumin and clotting factors • Catabolism • Generates 10% of body NH3 • Converts most of NH3 to urea • Neurotoxic. Lipids 101 Exogenous • Chylomicrons – small intestine • Lipoprotein lipase in blood – digests Triglycerides to muscle and adipose tissue • Liver takes up rest of chylomicrons and throws it in bile Endogenous • Synthesize lipoproteins • VLDLs – changed to IDL and LDLs in blood • Short half life • Returned to liver • High LDLS – good. • Produced cholesterol esters Acute Liver failure • ACETAMINOPHEN***** • NEW ONSET < 26 WEEKS DURATION • COAGULOPATHY • JAUNDICE • ENCEPHALOPATHY • NO FIBROSIS!!!!! CHRONIC LIVER FAILURE • ALCOHOL ABUSE****/VIRAL HEPATITIS • FIBROSIS • IRREVERSIBLE = CIRRHOSIS • PORTAL HTN • ASCITES – ALBUMIN AND FLUID LEAK INTO AB CAVITY • ENCEPHALOPATHY – WHY? NH3 • COAGULOPATHY LFTs • ALT and ALT – hepatocyte death • ALP – bile flow obstruction • GGT –damage to cholangiocytes Unconjugated • • Pre-hepatic • Increased production Hepatic • Decrease liver uptake • Decrease liver conjugation • Varying deficits in UGT1A1 activity • Neonatal jaundice • GilbertMeulengracht syndrome • Crigler-Najjar syndrome Conjugated • Decrease liver secretion • Dubin-Johnson syndrome • Decrease liver outflow • Cholestasis • Post-hepatic • Extrahepatic bile duct blockage • Gallstones