MOD (liver stuff) Flashcards
Zones of the liver list
1 periportal (closest to vascular supply) 2 intermediate 3 centrilobular (closest to hepatic venule)
The diseases that first affect each liver zone?
Zone 1 periportal- viral hepatitis
Zone 2 intermediate- yellow fever
Zone 3 centrilobular- alcoholic hepatitis, ischemia, affected by toxins, contains cyto P450 sys
Kupffer cells and Ito cells
Kuppfer—liver macrophages that line sinusoids
Stellate (Ito) cells—in space of disse, store vitamin A at rest and produce ECM when active, produce fibrosis
Portal triad
HEPATIC artery
PORTAL vein
COMMON bile duct
When do ascites occur in liver
When there’s portal HTN and lymph fluid accum (liver is largest producer of lymph) in peritoneum, lymph is produced in space of disse and travels around and drains
Common metabolic causes of liver injury
- Hemochromatosis—genetics cause excessive iron absorption from intestines, which accum in liver
- A1AT deficiency—causes unopposed protease dmg
- Wilson’s disease—defect in copper secretion from liver causes it to accum (will be in urine too)
- GSDs and dev abnormalities like biliary atresia
Viral causes of liver injury
Hepatitis A (acute), B (chronic in Asians), C (most common cause of chronic and cirrhosis), herpes, adeno
Drug causes of liver injury
Adverse rxn to acetaminophen (Tylenol) causes half of liver injuries in US
Other causes of liver injury
-toxins like alc and vinyl chloride, vascular insults like thrombosis etc
Causes of acute vs chronic liver injury
Acute is hep A, whereas chronic (more common, can lead to fibr/cirr) is hep B/C (also autoimm, met/dev dis)
Which enzymes indicate liver injury vs biliary tree dmg?
ALT/AST is liver, GGTP and ALP are biliary tree (canaliculi enzymes)
Other test signs of liver damage vs biliary
- AMA elev is dx for Primary Biliary Cirrhosis (and other autoimm ab’s like ANA etc, for liver measure ferritin (dx hemochromatosis or secondary hemosiderosis), copper to dx wilson’s
- Liver dmage can involve coagulopathies (since liver cells make coag factors) and hypoalbuminemia (if chronic liver failure)
Hepatocellular histo changes in liver injury:
- dead hepatocyte necrosis/apoptosis which are acidophilic
- ballooning degen (enlarged liver cells) seen in NASH (non alc steat hep)
- mallory’s hyaline bodies—dmgd intermediate filaments in liver cells (chronic hepatitis)
- ground glass hepatocytes (HBV)
- atrophy (small liver cells)-vasc insuff or elderly
Intercell accum in liver injury
- A1AT globules
- lipid accum (steatosis)—large white round fat globules (macrovesicular steatosis pushes nuclei to periph)
- MPS, glycogen
- pigments: Iron (hemochrom/hemosiderin pigment), dubin-johnson syndrome (incr of conj bili in serum causes black liver, presents as jaundice), lipofuscin (wear and tear pigment), bile (cholestasis—bile can’t flow out of liver), copper (wilson’s disease)
acute vs chronic inflamm of liver
acute—short duration, hep A
chronic—fibrosing (instead of regen like in acute), Hep C mostly (also Hep B and Hep D), other
What can happen in fibrosis/ pathology?
From chronic injury, alc/NASH/ischemia, venous outflow obstruction (budd-bhiari syndrome is occlusion of hep veins), CHF, veno-occlusive disease, also from portal fibrosis (biliary or hepatitis)
- end stage fibrosis is cirrhosis (regen nodules encircled by fibrosis, can’t see central vein, parenchymal architecture disrupted)
- portal HTN
- decompensated cirrhosis can lead to ascites, hemorrhage, hep enceph, coagulopathy etc
Portal hypertension pathology
Involves ascites in peritoneum Portosys shunts (gut, but and caput)—esoph varices, caput medusa, hemorrhoids, splenomegaly, hepatic enceph from increased ammonia, coagulopathy from decr liver prod of clotting factors
Non-Alcoholic fatty lvier disease (NAFLD) Cause Dx Histo Stages
Cause: high cals + sedentary lifestyle, obesity, DM
Dx: neg alc history, fatty liver presence on liver biopsy (Gold std), imaging
Histo: hepatocell injury (ballooning/necro/apop/mallorys hyaline), inflame (neutros lymphos macros), fibrosis
Stages of lesions in NAFLD
normal, fatty change, steatohep/fibrosis, cirrohosis, hepatocellular carcinoma
Histo slides: Mallorys hyaline (alc liver dis) Hemochromatosis Councilman/acidiphilic/apoptotic bodies (in acute injury) Cholestasis Liver cirrhosis
Mallorys—pink stuff, usu in alc liver disease
Hemochrom—Accum of hemosiderin pigment in liver cells
Pink cytoplasm in cells
Cholestasis—greenish bile accum
Regen pink nodules (round circles) completely encircled by fibrous bands (blue)
6 types of cirrhosis/causes?
Alcoholic cirrhosis Cirr secondary to hemochromatosis Secondary to wilson’s disease Secondary to A1AT deficiency Biliary cirr Cirrhosis NOS (not otherwise specified)
Bile flow vs blood flow, and drainage of blood path
Blood flows from A/V into central vein (???), bile flows in opposite direction
Blood from spleen etc flow into portal vein to liver to sinusoids between liver cells to IVC to heart
Chronic heptatitis
Def
Staging
Dx
Diffuse necroinflammatory and fibrosing liver disease> 6 mo
Staging is amt of fibrosis—portal, 0 is no fibrosis and stage 4 is cirrhosis
Labs—prolonged INR (due to less clotting factors made so can’t clot as fast), elev bili (mainly conj or mix), low alb, thrombocytopenia (less than 150k platelets), thrombopoeitin, mild pancytopenia, high ferritin
Portal hypertension
- Increase in bp in portal venous system (veins that merge with portal vein and travel into liver), often due to scarring/remodeling (cirrhosis) increasing flow resistance
- increase pressure can cause collateral flow (reversal of flow from gastric to splenic v, causing splenomegaly), goes thru esoph and causes esoph varices, can also happen in rectum leading to hemorrhoids
Leading cause of death for chronic liver disease?
Rupture and hemorrhage of gastric and esoph varices
Ascites and how are they measured?
Increased lymp prod from liver
Serum ascities albumen gradient (SAAG) is serum albumin-ascites albumin), if it’s >1.1 this means portal HTN (an excess fluid would have lower alb than serum would), distends stomach
-low protein levels in ascites fluid occurs bc scarring causes fenestrations in endoth to become smaller so RBCs can cross but not prots