Liver disorders Flashcards
liver
general
Largest organ in the body
Weighs 1-1.5 kg
Size and shape generally match overall body appearance
Dual blood supply
Hepatic artery: 20% of blood supply, oxygenated blood
Portal vein: 80% of blood supply, nutrient-rich, some oxygen
Hepatocytes
remove, synthesize, produce
Remove/excrete waste, hormones, drugs, toxins
Enzymes alter substances to help urinary excretion
Synthesize plasma proteins including clotting factors
Albumin, fibrinogen, globulins
Produce immune factors
Phagocytes in liver produce acute phase reactants in response to microbes
Hepatocyte
produce, excrete, store, process
produce, excrete, store, process
Excrete bilirubin
Byproduct of hemoglobin breakdown conjugated by hepatocytes
Excreted in the bile
Store vitamins, minerals, sugars
Glycogen, iron, copper, vitamins A, D, E, K, B12
Process nutrients absorbed from digestive tract
Bilirubin
general
Catabolism of Hgb releases heme → biliverdin → unconjugated bilirubin → bound to albumin or unbound.
Unconjugated bilirubin is lipid-soluble, renal system does not eliminate it.
Unbound bilirubin taken up by hepatocytes → conjugated bilirubin, water-soluble → becomes part of bile.
Bile flows into common hepatic duct. 50% flows into the cystic duct and stored in gallbladder. Remainder through common bile duct, converging with pancreatic duct to empty into duodenum through sphincter of Oddi.
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Biliary Obstruction
Blockage of bile flow into small intestine.
Inability of bilirubin to reach intestinal tract gives pale color to stools.
Can occur anywhere along path from liver to intestinal tract. Gallstones are most prevalent cause - dilation of common bile duct and jaundice.
Jaundice is consequence of bile stasis and buildup of conjugated bilirubin in blood.
Normal total serum bilirubin = 0.2to 1.2 mg/dL. Jaundice is evident clinically at 3 mg/dl.
Normal urine contains no bilirubin; with obstructive jaundice, conjugated bilirubin is excreted in urine, giving it dark color.
3 types of jaundice
Hyperbilirubinemia
general
Evaluation of isolated hyperbilirubinemia begins with determining conjugated (direct) or unconjugated (indirect).
Increase in unconjugated bilirubin results from overproduction, impairment of uptake, or impaired conjugation.
Evaluation of unconjugated hyperbilirubinemia = evaluation for hemolytic anemia.
Hepatocellular vs. Cholestasis
Hepatocellular injury
Hallmark is elevated AST/ALT
Marker of injury, inflammation, necrosis of hepatic parenchyma
Cholestasis
Hallmark is elevated Alkaline phosphatase +/- increased total bilirubin
Marker of obstruction and inhibition of bile flow
Mixed Pattern
Presence of both hepatocellular and cholestatic injury
Acute Liver Conditions
Chronic Liver Conditions
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NAFLD (Nonalcoholic fatty liver disease)
general
~25% of US population
Obesity epidemic: ↑ incidence and prevalence
Main contributing factors
Obesity
Diabetes mellitus
Hypertriglyceridemia
Risk 4 to 11 x higher in those with metabolic syndrome/insulin resistance
Physical activity may be protective
NAFLD
PE findings
Asymptomatic or mild RUQ discomfort
Hepatomegaly ~75%
May or may not be stigmata of chronic liver disease
Signs of portal hypertension if advanced fibrosis/cirrhosis
NAFLD Fibrosis Score (http://nafldscore.com)
NAFLD
Lab Findings
May be mild or moderate elevations in AST and ALT.
Degree of aminotransferase elevation does not predict degree of hepatic inflammation or fibrosis
Normal levels do not exclude NAFLD.
When elevated, AST and ALT typically 2x to 5x upper limit of normal, with AST/ALT ratio of < 1 (unlike alcoholic fatty liver disease, which typically has AST/ALT ratio >2).
Alkaline phosphatase may be elevated to 2x to 3x upper limit of normal.
Serum albumin and bilirubin levels are typically within the normal range.
May be elevated serum ferritin or transferrin saturation.
cirrhosis
etiology
Most common:
Chronic alcoholism
Chronic viral hepatitis (B/C)
Hemochromatosis
NAFLD/NASH
NAFLD
Diagnosis (4)
Requires all of these:
1. Hepatic steatosis by imaging or bx
2. Exclusion of significant alcohol consumption
3. Exclusion of other causes of hepatic steatosis
4. Absence of coexisting chronic liver disease
Radiologic findings can make diagnosis if other causes of hepatic steatosis have been excluded.
Liver biopsy if diagnosis not clear or to assess degree of hepatic injury.
Bx is only method to differentiate NAFLD from NASH.
cirrhosis
clin man
May have no symptoms for long periods.
Symptom onset usually insidious.
Fatigue, disturbed sleep, muscle cramps, weight loss are common.
Advanced cirrhosis:, anorexia may be extreme, with associated N/V, reduced muscle strength/exercise capacity.
May be abdominal pain.
Menstrual abnormalities (amenorrhea), erectile dysfunction, loss of libido, gynecomastia
Hematemesis is presenting symptom in 15–25%.
Complications of Portal Hypertension
Hepatic encephalopathy
Precipitation factors
Accumulation of serum ammonia in the brain due to lack of excretion by liver
Precipitating Factors: infection, GI bleeding, hyponatremia, hypovolemia, sedating drugs
Clinical Findings: decreased mental function, poor concentration, Asterixis, stupor
Diagnosis: no gold standard
Clinical findings/psychometric testing
Serum ammonia levels not useful
Management:
Non-absorbable disaccharides: Lactulose
Non- absorbable antibiotics: Rifaxamin (suppresses bowel flora, decreasing ammonia production)
Treatment of Hepatic Encephalopathy: Lactulose
Non-absorbable disaccharide syrup
Digested by colonic bacteria
Acidifies colon contents
Favors formation of non-absorbable ammonium ion (NH4+)
Favors change in bowel flora: fewer ammonia-forming organisms
Continued use after acute episode may reduce frequency of recurrences
Acute Liver Failure
general and causes
Rapid development of hepatocellular dysfunction with associated coagulopathy and mental status changes in patient without known prior liver disease
Causes
Medications: most common in US is acetaminophen
Alcohol
Viral Hepatitis
Acute fatty liver of pregnancy
Wilson disease
Autoimmune hepatitis
acute liver failre
Sx (3)
Confusion, jaundice, ascites
High mortality
acute liver failure
Dx
History = hepatic encephalopathy
Blood work: elevated transaminases (often with abnormal bilirubin and alk phos); prolonged prothrombin time (INR ≥ 1.5)
CT head
acute liver failure
Tx
ICU monitoring
Supportive treatment: fluid balance, mechanical ventilation, treatment of underlying cause
Liver transplant if no improvement
Liver cirrhosis
liver biopsy
Gold standard for diagnosis
FibroTest (FibroSure in the US): biomarker test that uses six blood serum tests to generate a score correlated with degree of liver damage.
May eventually have same prognostic value as liver biopsy
Alcohol Liver Disease
general and RF
Major cause of liver disease in United States
15-20% chronic heavy drinkers develop hepatitis or cirrhosis
Defined as 60-80 g/day for men and 20g/day for women
Risk Factors
FHx, Hx substance abuse, underlying depression or anxiety disorder
alcohol liver disease
S/Sx and Dx
Acute hepatitis can present with signs of liver failure: jaundice, ascites, etc.
Diagnosis
History, history, history
2:1 ratio of AST/ALT
Serum alcohol level, ethyl gluconuride
Iron Studies ( ferritin, iron, TIBC), Folate, Vitamin B12
Liver biopsy not warranted
alcohol liver disease
Tx
Treatment
Abstinence and counseling
Steroid taper in acute alcoholic hepatitis?
