Repro/GI WK2 Liver
Terms
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copy deck
- 204
- 204
- How is the liver broken up
- 8 complete segments (instead of old lobes)
- What is the ligament in the center of the liver
- Falciform (w/ umbilical/paraumbilical channels)
- What is the name of the liver capsule & what is it made out of?
- Glisson's capsule – type 1 & 3 collagen
- What is the blood supply to the liver?
- Portal vein (from intestines) & hepatic artery
- What comes out of the liver
- Bile ducts & hepatic vein (R & L)
- Components of portal triad
- Hepatic artery, bile duct, portal Vein
- Lobular vs Acinar arrangement of liver
- Lobular – central vein in center. Acinar – portal triad in center (zone 1) vein in outside (zone 3)
- Where is most detox in liver?
- Near central vein (centrilobular)
- Zonal necrosis
- Ex = tylenol. Production of toxic by product results in necrosis of zone 3 cells.
- Protein malnutrition – hepatic signs
- Periportal fatty change in liver.
- Nutmeg liver
- CHF results in nutmeg appearance of liver.
-
Typical pattern of regeneration in liver:
Of neoplasm: -
Regen: Two cell thick sinusoids
Neoplasm >2 cells (i.e. 3-6) - One cause of hepatization of pancreas
- Deficinet copper diet.
- NonPerenchymal liver cells & function (3)
-
Kupffer – macrophages. Endothelial.
Stellate (ito) – Store Vit A and pathologically act as myofibroblasts. - Where do kupffer cells live?
- In the sinusoids of the liver.
- Causes of NASH
-
(nonalcoholic steatohepatitis) –
Obesity
Diabetes Mellitis
Metabolic disturbances (Fatty acids)
“Syndrome X†- Direct vs indirect bilirubin testing
-
Direct: Water soluble(unconjugated).
Indirect: Fat soluble (conjugated) - Prehepatic jaundice
- When more bilirubin is produced (from hemolysis) than the liver can conjugate.
- Bilirubin pathway
- Unconjugated Biliribin --> liver – conjugated --> portal blood --> systemmic circ --> kidney –conjugated out urine
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- 205
- Micro vs Macro nodular cirrhosis
- Micro is < 3mm
- Causes of macronodular cirrhosis
- HCV, HBV, Toxic chemicals.
- 4 common complications of cirrhosis
-
(PILE)
Portal hypertension,
infection
liver cell carcinoma,
Endocrine changes - Budd Chiari syndrome
- Hepatic vein thrombosis from any cause. Common causes – hypercoagulability, neoplasm, parasites. Clinical signs – Hepatomegaly, abdominal pain, ascites.
- Portal hypertension – anastamoses
- Gastroesophogeal (varices), Anorectal (hemorrhoids), periumbilical (spider angiomas)
- Endocrine problems w/ cirrhosis
- Peripheral conversion of testosterone and androstenedione into estrone and estradiol results in feminization. (Also, estrogen escapes the liver via anastomoses)
- What happens to male repro system in cirrhosis?
- Infertility due to loss of spermatogenic cells (don't know why)
- 206/207
- 206/207
- Which hepatitises can be chronic?
- B,C,D (also spread parenterally)
- Hep B is in which body fluids?
- Blood, semen, vaginal, saliva.
- Dane Particle
- Particle of HepB
- Three hep B antigens
-
HBsAg - envelope of virus, cytoplasm of hep.
HBcAg - Nucleocapsid of virus, nucleus
HBeAg - nucleocapsid of virus, nucleus. - Ground Glass Cell
- Hepatocyte with large glassy cytoplams. Indicative of HepB
- Which of the Hep B antigens does NOT confer long term immunity?
- HBeAg
- Def of chronic Hep B
- Persistance of HBsAg for more than 6 mos
- HDV dependent on?
- HBsAg from HepB
- Two types of HDV infections
- Coinfection (both at same time), Superinfection (serial infections)
- HBsAg antigen/antibody significance
- (as expected) Ag+Ab- = acute carrier, Ag-Ab+ = recovered
- HBcAg antigen/antibody significance
- Ag-Ab+ is EITHER carrier OR complete recovery
- What indicates active, infectious HBV
- HBeAg, or Dane particles.
- What makes HCV so likely to be chronic?
- Genome mutations (error prone viral polymerase)
- How are hepatitises removed from the body?
- Via destruction of affected hepatocytes (hence chronic causes liver damage)
- Councilman bodies
- Apoptic cells in the liver.
- Histo features of CAH
-
1. Piecemeal necrosis,
2. Fibrous bridges,
3. Liver cell rosettes,
4. Groundglass cells - HBV vs HCV
- See slide 73
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- 210
- Abnorm. Alkaline phosphatase is indicative of:
- Bile duct damage
- Murphy's sign
- Sensitivity to pressure on gall bladder area.
- Ampulla of Vater
- Sphincter in the common bile duct
- Sphincter of Oddi
- Spincteer b/t common bile duct and duodenum
- Primary Biliary Cirrhosis
- (unknown etiology). Slow progressing cholestatic liver disease. More common in women. Elevated Alk Phosph, GGT. Often AMA pos. Lymphocytes around bile duct.
- Functions (2) of bile salts
-
1. Detergent for fat dig/abs (and prevent bile stones).
2. Stim phosphatidylcholine change to bile. - Clin uses of Bile Salt therapy (ursodeoxycholic acid)
-
1. Treat cholestatic liver disease,
2. Treat pruritis ass. W/ cholestasis
3. Gallstone dissolution therapy - What enzyme conjugates bilirubin?
- Bilirubin UDP-Glucoronysyltransferase (bUDP-GT)
- Ntcp
- Transporter for bilirubin – Involved in Estrogen induced cholestasis, Jaundice of sepsis
- MRP2
- Transporter for bilirubin – Involvied in Dubin -Johnson and Jaundice of sepsis
- spgp/BSEP
- Trasporter for bilirubin. Involve in Estrogen & Sepsis induced jaundice, gall stones, PFIC2
- MDR3
- Bilirubin transporter. Involved in PFIC-3
- Fic1
- Ibilirubin transporter in the Ileum. Involved in BRIC, PFIC1
- Gilbert's disease
- Failure of bUDP-GT (extra TA in TATA box) results in jaundice when sick/stressed.
- Jaundice in newborns – cause, timeline
- Caused by hemolysis, hematoma. (inc RBC breakdown). UDP-GT is activated at birth, so jaundice peaks at ~day 4-5, regardless of expecting date.
- 4 causes of hyperbilirubinemia
-
1. Inc production (via RBC breakdown)(unconj)
2. Decrease uptake or transport (unconj)
3. Defect in conjugation (unconj)
4. Defect in excretion (conjugated) - Kernicterus
- Brain damage secondary to hyperbilirubinemia in newborn (unconj)
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- 211
- Sup Mesenteric Vein drains:
- Righ colon, small int.
- Inferior Mesenteric vein drains:
- Left colon
- Most common cause of portal hypertension
- Schistosomiasis
- Space of disse
- Area under endothilial cells in liver capillaries. (Home of ito cells)
- 4 collateral circulations in portal hypertension
- 1. Azygous. 2. Umbilical. 3. Retroperitoneal 4. Rectal
- Formula for surface tension
- T = press*rad/width
- Drugs to lower Portal inflow -
- 1. Beta Blockers 2. Vasopressin 3. Somatostatin
- Drugs to lower portal resistance
- Nitrates.
- 3 factors in ascites (cirrhotic)
-
1. Low albumin.
2. Hepatic outflow block
3. Portal hypertension - Hepatorenal syndrome
- Progressive renal failure w/ advance cirrhosis/ascites
- Hepatic encephalopathy
- Asterixis, Abnormal EEG, impaired cerebral function in advanced liver disease
- Asterixis
- Loss of of postural control of hands.
- 4 stages of Hep Encephalopathy
-
1. Confusion
2. Drowsiness
3. Somnolence
4. Coma. - Lactulose
- Initial treatment for hepatic encephalopathy (a non digestable disaccharide)
- Three theories of hepatic encephalopathy
- 1. Ammonia (block glutamine rec) 2. Tryptophan (block monoamine trans) 3. GABA benzodiazepine (Inc GABA)
- Underfill hypothesis of ascites
- Transudation of fluid in ascites causes increased sodium reabs
- Overfill hypothesis of ascites
- Retention of Na --> vol expansion --> ascites
- ALT
- Aminotransferase in liver. Increased in nonalcoholic disease, decreased in alcoholic
- AST
- Aminotransferase found in most tissues. Relatively constant concentration in blood.
- Normal ALT:AST
- 1
- Alkaline phosphatase
- Liver enzyme from plasma membrane. Marker of biliary tract disease
- GGT
- Liver enzyme, also sensitive for biliary tract.
- What 2 things favor zone 1 necrosis?
- Yellow phosphorous, and toxemia of pregnancy
- Liver growth enzymes
- HGF, TGF-a, EGF (require TNF, IL-6)
- TGF-B
- Negative regulator of hepatocyte growth.
- 2 death receptors on hepatocytes
- Fas and TNF-R1
- PPARa
- Combustion - oxidizes fatty acids
- PPARy
- Conservation - stores fatty acids
- Causes of micronodular cirrhosis
- Alcohol, nutritional.