Exam 3: Liver Pathophysiology Flashcards
Bile flows from the liver into the duodenum when:
Eating - otherwise into the gallbladder
Bile is composed of:
Bile acids
Bile salts
Bicarb
Wastes from the liver
Liver produces ___% of the body’s daily lymph:
50%
Liver lymph differs from the rest of the body’s in this way:
High in protein
The liver is “mushy” because:
Very little structural tissue/basement membrane
Proteins synthesized by the liver:
Albumin
Fibrinogen
Prothrombin
Lipoproteins
Bile is positively/negatively charged and hydrophilic/hydrophobic:
Negatively
Hydrophobic
25% of the body’s cholesterol is in this organ:
Brain
Bridging fibrosis is:
A reversible (early on) linking of regions of the liver by fibrous strands; caused by inflammation
This occurs in the liver when fibrosis continues to develop along with parenchymal injury:
Liver divides into nodules of regenerating hepatocytes surrounded by scar tissue
Role of stellate cells in liver injury:
With inflammation, stellate cells lay down dense extracellular collagen matrix (causing fibrosis)
Activated stellate cells in the liver are called:
Myofibroblasts
Lab tests for hepatocyte integrity:
Serum aspartate aminotransferase (AST)
Serum alanine aminotransferase (ALT)
(Old names SGOT, SGPT)
Typical AST/ALT values:
< 50
Lab tests for biliary tract integrity:
Serum alkaline phophatase (AP/ALP/ALKP)
Serum ɣ-glutamyltransferase (GGT)
Alk phophatase not a reliable indicator for biliary disease by itself because:
Also found in bone cells
Lab tests for serum bilirubin:
Direct (conjugated)
Total (conjugated + unconjugated)
Lab tests for hepatocyte functioning:
Serum albumin
Prothrombin time
Serum ammonia
Using serum albumin as an indicator of liver functioning:
If serum albumin is ↓ and total protein is too, liver is not working well
If serum albumin is ↓ but total protein is okay, liver is okay - it only makes enough albumin to bring oncotic pressure up to normal
Ammonia builds up during liver failure due to:
Inability to metabolize/digest nitrogenous byproducts from gut bacteria via the urea cycle
Estrogen-related abnormalities in liver disease:
Hypogonadism
Gynecomastia
Palmar erythema
Spider angiomas
Blood sugar abnormality in liver disease:
Hypoglycemia; liver no longer making/breaking down glucose
Normal liver venous pressure:
10mmHg
S/s of hepatic portal hypertension:
Ascites Esophageal varices Hemorrhoids Caput medusae Splenomegaly
Coagulopathy seen in liver failure:
Impaired clotting and clot breakdown; liver makes both clotting factors and plasminogen
Life threatening complications of liver failure:
Multiple organ failure Coagulopathy Hepatic encephalopathy Hepatorenal syndrome Varices rupture Hepatocellular carcinoma
Normal bilirubin production amount and sources:
0.2 - 0.3 g/day
Primary source: breakdown of senescent erythrocytes
Minor source: degradation of tissue heme-containing proteins
Extrahepatic bilirubin binds to:
Serum albumin, for delivery to the liver and hepatocellular uptake
Liver processing of bilirubin:
Glucoronidation into bilirubin monoglucuronides/diglucuronides (conjugated bilirubin), which are excreted into bile
Gut processing of conjugated bilirubin:
Gut bacteria deconjugate bilirubin and degrade it to urobilinogens + pigment residues
Most excreted into feces, some reabsorption/re-excretion into bile
Three causes of jaundice related to ↑ unconjugated bilirubin:
Excess bilirubin production
Reduced hepatic uptake
Impaired conjugation
Two causes of jaundice related to ↑ conjugated bilirubin:
Decreased hepatocellular excretion
Impaired bile flow
Pathogenesis of unconjugated bilirubin jaundice:
Fraction tightly bound to albumin is insoluble, so not excreted by kidney
Unbound fraction diffuses into tissues (esp. brain) and produces toxic injury
Pathogenesis of conjugated bilirubin jaundice:
Soluble in water, weak albumin binding, so excreted by kidney
Mild jaundice without tissue injury
Jaundice tx for hemolytic disease of the newborn:
UV light; skin can conjugate bilirubin under UV
Changes seen in parenchyma d/t cholestasis:
Enlargement of bile canaliculi
Apoptosis of hepatocytes
Bile uptake by Kupffer cells
Changes seen in portal tracts d/t cholestasis:
Bile duct proliferation Edema Bile pigment retention Neutrophilic inflammation Toxic degeneration of neighboring hepatocytes
% of liver function that must be lost for hepatic failure to occur:
80-90%
Special problems r/t hepatic failure:
Hepatic encephalopathy
Hepatorenal syndrome
Cirrosis causes hepatic portal hypertension by:
Impairing blood flow through liver via fibrosis/scarring
Downstream effects of hepatic portal hypertension:
Ascites
Portosystemic shunts
Splenomegaly
Three clinical states of hepatitis:
Carrier/asymptomatic
Acute viral hepatitis
Chronic viral hepatitis
Common characteristics of HAV/HEV:
Self-limiting 2-8 week incubation Acute only - no carrier or chronic states Do not cause cancer Fecal-oral transmission Not common in US
HAV-specific characteristics:
Common childhood disease in developing countries; more dangerous in adults
Sporadic infections - associated with oysters and warm-water seafood
HEV-specific characteristics:
Endemic and seen in travellers; sporadic infections rare
20% mortality rate in pregnant women
Characteristics of HBV, HCV, and HDV:
Can cause carrier state, chronic hepatitis, and cancer
Parenteral transmission
Present in the US
HDV-specific trait:
Only survives along with coexisting HBV infection
ETOH effect on hepatocytes:
Can no longer incorporate fatty acids into lipoproteins for export –> hepatic steatosis (fatty liver)
Relationship between hepatic steatosis and alcoholic hepatitis:
Steatosis can turn into hepatisis with severe exposure; abstinence can have hepatitis revert to steatosis
Incidence of alcoholic liver diseases:
Hepatic steatosis: 90-100%
Alcoholic hepatitis: 10-35%
Cirrhosis: 8-20%
Physical characteristics of cirrhotic liver and causes:
Nodularity from fibrous scarring
Greenish tint from bile
Yellowish tint from bilirubin
The body’s only way of eliminating iron is:
Bleeding
Hemochromatosis is:
The uncontrolled uptake of iron
Demographics and genetic basis of hemochromatosis:
Mostly males (5-7:1) in their 50s or older
Autosomal recessive, affecting 0.5% of people
10% are heterozygous carriers
Sequelae of hemochromatosis:
Cirrhosis (100%)
DM (75-80%)
Skin pigmentation (75-80%)
Bantu siderosis is:
Another primary iron overload condition
Three secondary iron overload causes:
- Transfusion (0.25 gm/unit)
- β-thalassemia
- Sideroblastic anemia
Describe primary biliary cirrhosis:
Destruction (often fatal) of intrahepatic bile ducts, most commonly with antimitochondrial antibodies present
Lab abnormalities seen in primary biliary cirrhosis:
Elevated alk phos & cholesterola
Hyperbilirubinemia late in disease
Describe secondary biliary cirrhosis:
Obstruction of the extrahepatic biliary tract due to: Gallstones Biliary atresia Malignancy (biliary tree/pancreas) Surgical strictures
Describe primary sclerosing cholangitis:
Destruction of intra- and extrahepatic bile ducts
Associated with ulcerative colitis (develops 2nd) but no antimitochondrial antibodies
Elevated alk phos
Manifestations of hepatic vein outflow obstruction:
Ascites Hepatomegaly Abdominal pain Elevated transaminases Jaundice
Manifestations of impaired intrahepatic blood flow:
Ascites (cirrhosis)
Esophageal varices
Elevated transaminases
Manifestations of impaired portal vein inflow:
Ascites
Esophageal varices
Splenomegaly
Intestinal congestion
Manifestations of impaired hepatic artery inflow:
Ischemia to bile ducts/parenchyma
Loss of graft in transplant
Causes of hepatocellular carcinoma:
HBV Chronic liver disease (HCV, ETOH) Aflatoxin (from peanuts) Tyrosinemia Cirrhosis
Relationship between HBV and HCC:
Early infection with HBV gives increased risk of HCC
Prognosis for HCC:
Mean survival 7 months
Risk factors for cholesterol gallstones:
Fair (or Native American) Forty (older) Female Fertile Fat Gallbladder stasis Hyperlipidemia
Risk factors for pigment gallstones:
Chronic hemolytic syndrome
Biliary infection
GI disorders (Crohn’s)
Asian descent
Choledocholithiasis is:
Presence of stones in the biliary tree, not the gallbladder
Sequelae of choledocholithiasis:
Biliary obstruction Pancreatitis Cholangitis Hepatic abscess Chronic liver disease/biliary cirrhosis Acute calculous cholecystitis
Major causes of acute pancreatitis:
IGETS Idiopathic (most common) Gallstones (2nd most common) Ethanol Trauma Steroids
