Week 7 - Disorders of the Liver Flashcards
what is nonalcoholic fatty liver disease (NAFLD)
- spectrum of disease that ranges from simply fatty liver (steatosis) that causes no hepatic inflammation
- to severe liver scarring (nonalcoholic steatohepatisis)
what causes NAFLD
- fat deposition (hepatic steatosis) in the liver from causes that aren’t alcohol, viral hepatitis, or autoimmune disease
who is at an increased risk of NAFLD (3)
- metabolic syndrome
- obesity
- type 2 DM
what does NAFLD cause an increased risk of
- CVS risk
how does type 2 DM increase the risk of NAFLD
- due to insulin resistance
- insulin resistance causes the hepatocytes to increase fat storage & decrease fatty acid oxidation
- in other words, decreased secretion of fatty acids into the bloodstream, and increased synthesis & uptake of free FA
what is steatosis
- the accumulation of fat in the liver
what can steatosis lead to? how?
- fat in hepatocytes becomes vulnerable to degradation
- cell death & inflammation = steatohepatitis
what is NASH
- nonalcoholic steatohepatitis
- when both steatosis & inflammation occur in the absence of alcohol
what can NASH lead to
- inflammation –> fibrosis and then cirrhosis
list causes of toxic & drug induced hepatitis (3)
- systemic poisons
- those converted in the liver to toxic metabolites
- alcohol
what are 2 examples of systemic poisons that cause toxic
- carbon tetrachlroide
- gold compounds
what is an example of an agent that is converted in the liver to toxic metabolites
- tyenol
what increases the risk of toxic & drug induced hepatitis
- polypharmacy
how long does it take for liver necrosis to occur after acute exposure to a toxic substance
- 2-3 days
what is chronic hepatitis
- liver inflammation peristing for more than 6 months
what are the 3 most common causes of chronic hepatitis
- HBV
- HCV
- alcoholism
what can chronic hepatitis cause
- continued hepatocyte destruction which leads to
- irreversible scarring & fibrous alteration in the liver architecture which leads to
- cirrhosis (“cirrhosis is fibrosis”)
what is cirrhosis
- an irreversible distortion in liver architecture
- resulting in extensive fibrosis & hepatocyte dysfunction
what is the leading cause of cirrhosis
- alcohol abuse
the major manifestations of cirrhosis is a result of.. (3)
- hepatocyte failure
- portal hypertension
- or both
what is portal hypertension
- high pressure in the portal vein
what causes portal hypertension
- the extensive fibrosis that occurs during cirrhosis results in increased resistance to blood flow
- which has profound consequences on the low pressure portal blood flow & leads to portal hypertension
what does fibrosis of the bilary system cause?
- cholestasis = impaired flow of bile from the liver
list the effects of portal hypertension (4)
- edema & ascites
- varicosities
- splenomegaly
- gastropathy
list the effects of liver cell failure (10)
- ascites & edema
- jaundice
- coma
- fetor hepaticus
- spider nevi
- gynecomastia
- loss of sexual hair
- testicular atrophy
- liver “flap”
- bleeding tendencies –> anemia
what is ascites
- accumulation of fluid in the peritoneal cavities
when does ascites occur in cirrhosis
- in the later stages
list 3 reasons why ascites & edema occur during cirrhosis
- portal hypertension
- hepatocyte failure
- hepatorenal syndrome
how does portal hypertension cause ascites & edema?
- the high pressure in the portal vein causes fluid to be pushed out into the tissues (increased hydrostatic pressure) & across tissues (such as into the peritoneal cavity)
how does hepatocyte failure cause ascites
- hepatocytes are responsible for albumin
- hepatocyte failure = decreased albumin = decreased plasma osmotic pressure (which typically keeps fluid in)
describe how hepatorenal syndrome can cause ascites (3 main things)
- the liver is responsible for breaking down aldo
- hepatocyte failure = impaired breakdown of aldo
- also, there is reduced inactivation of ADP
- also, there is diminished secretion of ANP (which increases the excretion of water & Na)
= retention of water & Na
what are 3 consequences of ascites
- upward pressure on diaphragm impairs respiration
- peritonitis
- impaired digestion & absorption
how does portal hypertension cause splenomegaly
- the high pressure can cause blood to back up into the spleen (remember that the portal vein carries blood from the spleen & GI)
what are 3 consequences of splenmegaly
- causes the spleen to trap blood elements =
- thrombocytopenia (which leads to bleeding disorders)
- anemia
- leukocytopenia
what are varicosities
enlarged veins
list 3 places where portal hypertension causes varicosities
- esophagus
- rectal
- abdomin
how does portal hypertension cause varicosities`
- the hypertension causes blood to back up into the systemic veins
= formation of bypass channels called anastomosis
what do esophageal varices cause
- since these veins are fragile. they can rupture and cause upper GI bleeds
= hematemesis & melena
what do rectal varices cause
- hemorrhoids
what can rectal varices cause
- bleeding
what is the upper GI bleed caused by esophageal varices complicated by
- thrombocytopenia
- coagulopathy
what do abdominal varices cause
- caput medusae (causes the abdomin to look like the head of medusa)
how does hepatocyte failure cause bleeding tendencies & anemia
- causes impaired clotting factor synthesis, vit K deficiency, and/or thrombocytopenia (due to splenomegaly from portal HTN)
= bleeding disorders & blood loss anemia
how does hepatocyte failure cause jaundice
- causes hepatic jaundice
- also thru intrahepatic cholestasis
how does hepatocyte failure effect hormones
- causes impaire breakdown of steroid hormones such as estrogen, testosterone, and aldo
what does impaired steroid hormone breakdown cause (6)
- water/Na+ retention
- testicular atrophy
- gynecomastia
- amenorrhea
- spider nervi
- abnormal hair growth
what is testicular atrophy?
- shrinkage of the testicles
what is gynecomastia? what causes it?
- swelling of breast tissues in men
- due to increased estrogen
what is amenorrhea
- absence of menstruation
how does hepatocyte dysfunction effect CNS function & cause risk of coma
- due to impairment of urea production causing ammonia accumulation
- ammonia can cross the blood-brain barrier causing hepatic encephalopathy
what can cause worsened hepatic encephalopathy
- large meal high in protein
- GI bleeds
- constipation
- anything that causes decreased blood vol, K+
- renal dysfunction
how can hepatic encephalopathy by treated
- with lactulose
what are 2 other conseuuences of increased ammonia
- fetor hepaticus (foul breath)
- liver “flap” (coarse hand tremor)
how does impaired hepatocyte function effect drug metabolism
- can cause impaired clearance of drugs = drug toxicity
- due to diminished conjugation or cytochrome P450 activity
what does impaired drug clearance cause
- elevated levels of drugs or metabolites in the blood & toxic effects
see table 46-13 for all factors that precipitate hepatic encephalopathy, too long for flashcards
…
what is a way to remember the conseuqneces of portal hypertension
Ascites Bleeding tendencies (due to varices & thrombocytopenia due to splenomegaly) Caput medusae & varices Diminished liver function Enlarged spleen
