Liver disorders

Question 1

liver

general

Answer 1

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

Question 2

Hepatocytes

remove, synthesize, produce

Answer 2

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

Question 3

Hepatocyte

produce, excrete, store, process

Answer 3

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

Question 4

Bilirubin

general

Answer 4

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.

watch video in canvas

Question 5

Biliary Obstruction

Answer 5

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.

Question 6

Answer 6

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3 types of jaundice

Question 7

Hyperbilirubinemia

general

Answer 7

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.

Question 8

Hepatocellular vs. Cholestasis

Answer 8

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

Question 9

Question 10

Acute Liver Conditions

Question 10

Chronic Liver Conditions

Question 11

Question 12

Question 13

video slide 20

Question 14

NAFLD (Nonalcoholic fatty liver disease)

general

Answer 14

~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

Question 15

NAFLD

PE findings

Answer 15

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)

Question 16

NAFLD

Lab Findings

Answer 16

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.

Question 17

cirrhosis

etiology

Answer 17

Most common:
Chronic alcoholism
Chronic viral hepatitis (B/C)
Hemochromatosis
NAFLD/NASH

Question 18

NAFLD

Diagnosis (4)

Answer 18

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.

Question 19

cirrhosis

clin man

Answer 19

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%.

Question 20

Complications of Portal Hypertension

Hepatic encephalopathy
Precipitation factors

Answer 20

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)

Question 21

Treatment of Hepatic Encephalopathy: Lactulose

Answer 21

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

Question 22

Acute Liver Failure

general and causes

Answer 22

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

Question 23

acute liver failre

Sx (3)

Answer 23

Confusion, jaundice, ascites
High mortality

Question 24

acute liver failure

Dx

Answer 24

History = hepatic encephalopathy
Blood work: elevated transaminases (often with abnormal bilirubin and alk phos); prolonged prothrombin time (INR ≥ 1.5)
CT head

Question 25

acute liver failure

Tx

Answer 25

ICU monitoring
Supportive treatment: fluid balance, mechanical ventilation, treatment of underlying cause
Liver transplant if no improvement

Question 26

Liver cirrhosis

liver biopsy

Answer 26

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

Question 27

Alcohol Liver Disease

general and RF

Answer 27

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

Question 28

alcohol liver disease

S/Sx and Dx

Answer 28

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

Question 29

alcohol liver disease

Tx

Answer 29

Treatment
Abstinence and counseling
Steroid taper in acute alcoholic hepatitis?