Lecture 13 Liver Disease 1 Flashcards
What is acute vs chronic liver disease?
acute is sx less than 6 vs chronic > 6 months
acute is self-limiting hepatocyte inflammation or damage vs chronic is permanent structural changes that occur due to damage
acute is less common than chronic
Causes for acute: acetaminophen overdose (most common), drugs, viral hepatitis, viral infections, acute fatty liver of pregnancy, poisonous plants, etc
Causes for chronic: alcohol, viral infection including viral hepatitis, NAFLD, drugs, genetic disorders, immunological disorders, malignancy
What is steatosis, findings?
aka ‘fatty liver’
accumulation of fat on liver generally due to increased fatty acids to liver, increased lipogenesis, reduced clearance of lipids by liver
often early stage of chronic liver disease,, can be reversible
can progress into hepatitis
Findings: sx range from none to fatigue, mild ab discomfort
visible on ultrasound, mild elevations in liver enzymes (AST/ALT)
What is hepatitis, findings/presentation?
continuous inflammation secondary to damage often caused by accumulation of fat on liver
usually damage leads to inflammation and can result in necrosis of hepatocytes, Kupffer cells activated by inflammation release cytokines and cause hepatocyte necrosis, neutrophils accumulate around hepatocytes leading to further inflammatory cells, liver tries to repair itself but inflammation continues if underlying source stays
can be reversible to a degree
Findings: none to severe sx ⇒ nausea, fatigue, jaundice, tenderness, enlarged liver visible on imaging, elevated liver enzymes may be seen
What is steatohepatitis?
when both fatty liver and inflammation are present concurrently
reversible if cause of liver injury is removed
What is the mechanism of liver fibrosis?
deposition of EC matrix and proteins including collagen in response to chronic liver injury
MOA: activation of hepatic stellate cells (HSC) due to ongoing injury primarily responsible
these cells are surrounded by hepatocytes and endothelial cells and ⇒ store Vit A, dormant in healthy liver, activated by Kupffer cells
when activated they act as proliferative myofibroblast (cell that tries to repair injured tissue by laying down collagen)
persistent activation results in accumulation of HSCs and EC matrix = scar tissue disrupting function of liver
What is cirrhosis, types?
parenchymal tissue disrupted by fibrosis and reduced mass = loss of fx, irregular nodules form due to regeneration attempt of hepatocytes and replace otherwise smooth liver tissue = loss of elasticity
reorganization of hepatic vasculature occurs ⇒ due to fibrosis blood flow is impeded = increased resistance to portal blood flow = elevated portal BP
risk of hepatic cell carcinoma
Types: Compensated - despite scarring and damage liver able to carry out its fx, many pt have few or no sx
Decompensated - liver unable to carry out fx resulting in range of sx and complications
What are S&S of decompensated cirrhosis?
encephalopathy, asterixis
scleral icterus, bad breath
SOB, dyspnea
hypotension, edema
portal hypotension
testicular atrophy, gyno
jaundice, angiomas, erythema of palms, loss of body hair, pruritis
fatigue, weight loss, malaise
What are causes of chronic liver disease?
alcohol use, metabolic syndrome (non-alcoholic liver disease)
hepatitis viruses and others
drugs
autoimmune disease: primary sclerosing cholangitis, primary biliary cholangitis
chronic bile duct obstruction, biliary cirrhosis
Budd-Chiari syndrome (blockage of liver blood flow)
inherited disorders: Wilson’s disease, Alpha 1-trypsin deficiency, CF
What is alcoholic liver disease (ALD) and its stages?
excessive alcohol intake can cause this
majority of pt are men but women more susceptible to alcohol induced liver injury
lipid droplets accumulate in hepatocytes after moderate alcohol consumption
Stages: Steatosis - metabolism of alcohol = increases lipogenesis, also induces catabolism of peripheral fat increasing lipids in circulation (reversible with abstinence)
Hepatitis - mech unknown, increased acetaldehyde (disrupts cell fx), induction of hepatic enzymes that generate reactive oxygen species that damage cellular protein, membranes, mitochondria ⇒ promote apoptosis
Hepatitis + Fibrosis - abstinence can reverse damage to a degree, if hospitalized can manage with prednisolone 40 mg QD F28D (d/c if no response at 7 days)
Cirrhosis
What is considered low risk of alcohol intake according to Health Canada and how does it work with liver disease?
for Women: 0-2 drinks/day and no more than 10 per week
for Men: 0-3 drinks/day and no more than 15/week
in pt with liver disease continued drinking will increase rate of damage to liver and risk of cirrhosis, excess consumption (>2/day for men and 1 for women) may contribute to abnormal liver tests
What is non-alcoholic liver disease (NAFLD), MOA, risk fx, and management?
aka metabolic dysfunction-associated fatty liver disease (MAFLD)
90-95% is NAFL, 5-10 NASH/MASH
MOA: liver damage due to accumulation of fat (TG) within hepatocytes
Risk Fx: metabolic syndrome - obesity, elevated lipids, DM, HTN
environmental fx - high calorie diet, sedentary lifestyle
genetics
Management: vast majority won’t develop severe disease (80% managed with lifestyle), if cirrhosis develops its managed similarly to ALD cirrhosis
What is FIB-4?
non-invasive method of assessing extent of hepatic scarring in pt suspected to have NAFLD
is = (age x AST (U/L)) / (platelet count (10^9/L) x square root of ALT (U/L))
if >1.3 pt should be referred to hepatologist,, used to stratify pt into high, intermediate, and low risk of developing cirrhosis over next 10 years
can be used in AUD and HCV as well but NOT ALD
What is the Child-Pugh-Turcotte score, and what components are involved?
is used to assess severity of liver disease, can be used to guide drug dosing
Components: encephalopathy, ascites (none ⇒ mild to moderate, bilirubin (mg/dL), albumin (g/dL), prothrombin time seconds prolonged, INR
What are different manifestations of end-stage liver disease?
jaundice, cholestasis, hepatomegaly, portal hypertension, ascites, hepatic encephalopathy, coagulopathy, liver failure, malignancy
What is hepatic cholestasis?
is the reduction or stoppage of bile flow, occurs when flow impaired from hepatocytes ⇒ duodenum (impaired secretion/obstruction)
bile accumulates in liver ⇒ absorbed by blood and circulates ⇒ has bilirubin so we can see S&S like: yellowing of skin and eyes, pruritis (due to bile salts in PNS), dark urine, light-coloured stool
What is cholestatic pruritis and how is it managed?
Presentation: itch typically not accompanied by rash, intensity not associated with severity of liver disease, usually worse at night
Management: Cholestyramine 4 g PO up to QID ⇒ exchanges Cl- for bile acids in small intestine resulting in bile acid excretion in stool,, space other drugs by 4 hours
AE: constipation, diarrhea, bloating, rarely hyperchloremic metabolic acidosis,, if pt doesn’t respond to cholestyramine can try naltrexone, rifampin, sertraline
What is portal hypertension, types, moa in end-stage liver disease, and what does it cause?
abnormally high BP in portal venous system, diagnosed as hepatic venous pressure gradient > 5 mmHg
Types: prehepatic, intrahepatic, posthepatic
MOA: increased resistance to blood flow in liver due to fibrosis, imbalance of vasoconstrictors and dilators (reduced production of albumin by hepatocytes)
Results in: collateral blood vessel formation = portosystemic shunts ⇒ caput medusae (umbilical veins to ab wall), rectal hemorrhoids (collaterals formed to rectal veins), varices (collaterals to esophagus and stomach) - high risk if HVPG >/= 10 mmHg
ascites, hepatic encephalopathy - portosystemic shunts, splenomegaly due to increased blood volume
What is caput medusae?
appearance of large and swollen veins on the surface of abdomen that occurs due to collateral vessel formation from portal hypertension in end-stage liver disease/cirrhosis
as blood flows through the vessels cannot stand the pressure of increased blood flow so they become distorted
