question

What do abnormal liver function tests indicate?

answer

Can be first indication of underlying liver disease but normal results do not rule out liver disease

question

What is jaundice?

answer

AKA Icterus, yellowing of the eyes, skin, mucous membranes, body fluid from increased bilirubin

question

What condition can be confused with jaundice?

answer

Carotenemia - excess carotene in the blood, usually from diet high in carrots and other foods with beta-carotene

question

Describe the process to make bilirubin

answer

old or damaged RBC circulates through the reticuloendothelial system, the fragile membrane eventually ruptures and the contents of the cell are expelled into the bloodstream. One of the cellular components released when this happens is hemoglobin, which is ingested by phagocytic cells called macrophages. This phagocytosis splits the hemoglobin into its constituent heme and globin portions. The heme undergoes an oxidation reaction catalyzed by the enzyme oxygenase, to give biliverdin, iron and carbon monoxide. The biliverdin is a green-colored pigment which then undergoes a reduction reaction to yield a yellow pigment called bilirubin. This reaction is catalyzed by the cytosolic enzyme biliverdin reductase.

question

What is the difference between conjugated and unconjugated bilirubin?

answer

Unconjugated is insoluble and referred to as free, or indirect bilirubin, is in the blood stream, and is bound to albumin. Conjugated bilirubin has been processed in the liver and is water soluble, moves to the biliary tree and cystic ducts to be excreted by the intestines through feces or by the kidneys through urine.

question

What causes an increase in unconjugated bilirubin?

answer

Increased hemolysis, also possibly sickle cell disease

question

What causes an increase in conjugated bilirubin?

answer

caused by disease in the liver including liver cirrhosis and Gilbert's syndrome.

question

What is kernicterus?

answer

Usually in infants, bilirubin encephalopathy - deposits of bilirubin in the brain. Babies with bilirubin encephalopathy are lethargic, hypotonic or hypertonic, and have a high pitched cry, opisthotonus, seizures, and may die if bilirubin is not lowered. Can cause severe permanent neurologic symptoms (choreoathetosis, spasticity, hearing loss, ataxia, mental retardation). Less severe injury is associated with mild neurological abnormalities including hearing loss

question

What is physiologic jaundice?

answer

In neonates, breakdown of red blood cells (which release bilirubin into the blood) and to the immaturity of the newborn's liver which cannot effectively metabolize the bilirubin and prepare it for excretion into the urine. Typically appears between the 2nd and 5th days of life

question

In adolescents, jaundice is caused by this syndrome?

answer

Gilbert's syndrome

question

What are some causes of jaundice in young adults?

answer

viral hepatitis, alcohol, and biliary tract disease

question

What is the mostly likely cause for jaundice in elderly?

answer

Greater than 50% are related to malignancy in the liver

question

What are the normal values for total bilirubin?

answer

0.2 to 1.3 mg/dl

question

At what bilirubin level is jaundice clinically apparent?

answer

greater than 3 mg/dl

question

When evaluating the patient with jaundice, first determine ......?

answer

If it is unconjugated or conjugated.

question

What type of bilirubin is tested for in the the urine?

answer

Conjugated - cheap test

question

What are some causes of conjugated hyperbilirubinemia?

answer

Cholelithiasis, cholangiocarcinoma, sclerosing cholangitis, AIDS cholangiopathy, pancreatitis, strictures, parasitic infections, viral hepatitis, alcoholic hepatitis, NASH, primary biliary cirrhosis, medications, sepsis, infiltrative diseases, TPN, pregnancy, ESLD

question

What are some causes of unconjugated hyperbilirubinemia?

answer

Gilbert's syndrome, heart failure, medications, Crigler-Najjar syndrome, hemolysis, hyperthyroidism, cirrhosis, Wilson's disease

question

History should include .......?

answer

Symptoms, duration of LFT abnormalities, risk factors of ETOH abuse, drug use, medications, chemical exposures, blood transfusions, sexual history, travel, medical, surgical history, family history

question

Symptoms of liver disease

answer

fatigue, anorexia, malaise, weight loss or gain, fever, pruritis, RUQ pain, GI bleeding OR NONE

question

Mechanisms that cause unconjugated hyperbilirubinemia

answer

Over production of bilirubin, reduced bilirubin uptake, impaired bilirubin conjugation

question

Gilbert's Syndrome

answer

Common genetic disorder affecting 3-7% of population and males more than females. Impaired conjugation of bilirubin. Usually less than 3mg/dl, indirect unconjugated. Higher with fasting or illness

question

Signs of chronic liver disease

answer

Ascites, caput medusa (visible blood vessels on abdomen), coagulopathies, edema, gynecomastia, jugular venous distention, palmar erythema, portal hypertension, right plural effusion, right sided heart failure, spider angioma, splenomegaly, testicular atrophy, varices

question

Risk factors for liver disease

answer

Healthcare worker, exposure to toxins, chemicals, wild mushrooms, alcohol, hepatic toxic medications; institutionalized (nursing home, psych institutions, jail), blood transfusions, transplantation, hemodialysis, IV drug use, tattoos, piercings, risky sexual activity

question

Tests usually included for hepatic panel

answer

bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transpeptidase (GGTP), alkaline phosphatase, lactate dehydrogenase (LDH)

question

Initial evaluation of abnormal LFTs

answer

Repeat the test to confirm the result; 5% of normal patients have result outside normal, LFTs correlate with BMI

question

What normal physiologic changes can cause elevated alkaline phosphatase?

answer

third trimester pregnancy

question

Markers of liver injury

answer

Elevated AST, ALT, alkaline phosphatase

question

Markers of liver function

answer

albumin, bilirubin, prothrombin time

question

Factors that can affect hepatic function

answer

nutrition, hemolysis, antibiotic use, systemic illness

question

AST test

answer

Aspect of liver assessed: hepatocyte injury; Origins: liver, heart, skeletal muscle, kidney, brain, RBC Aspirin, Statins, Tequila

question

ALT test

answer

Aspect of liver assessed: hepatocyte injury. Origins: LIVER ONLY A LIVER T

question

Alkaline phosphatase

answer

Aspect of liver assessed: cholestasis Origins: Liver, bone, intestine, placenta

question

GGT

answer

Aspect of liver assessed: When elevated with alk phosphotase, indicated liver origin of alk phos. Origins: LIVER

question

Serum albumin

answer

Aspect of liver assessed: Reflects synthetic capacity of liver. Origins: Liver or diet

question

Nonhepatic Sources of Abnormalities for laboratory tests

answer

bilirubin: red blood cells (hemolysis, hematoma) AST: Skeletal muscle, cardiac muscle, red blood cells ALT: skeletal muscle, cardiac muscle, kidneys LDH: heart, red blood cells, (hemolysis) Alk phos: Bone, first trimester placenta, kidneys, intestines

question

Hepatocellular pattern of abnormal LFTs

answer

Transaminase elevation greater than alkaline phosphatase elevation

question

Cholestatic pattern of abnormal LFTS

answer

Alkaline phosphatase > transaminase

question

Further tests after elevated LFTs

answer

Ultrasound, CT, MRCP

question

Biliary ducts dilated on scan - obstruction

answer

Extrahepatic obstruction: Stones, polyp, stricture, pancreatic cancer, cholangiocarcinoma, ampullary cancer, primary sclerosing cholangitis, adenopathy

question

Biliary ducts normal on scan (impaired excretion)

answer

Intrahepatic cholestasis: hepatitis, cirrhosis, drugs, toxins, sepsis, TPN, post-op primary biliary cirrhosis, primary sclerosing cholangitis, infiltration

question

Marked transaminase elevation >1000

answer

Acute viral hepatitis, ischemic hepatitis, medication or toxin induced hepatitis, autoimmune hepatitis, acute bile duct obstruction, acute budd-chiari syndrome

question

Mild transaminase elevations 175-200

answer

Alcoholic liver disease, medications/toxins, chonic hep B or C, Nonalcoholic fatty liver disease (NAFLD), Autoimmune hepatitis, hemochromatosis, Wilson disease (in pts <40 years old), Alpha 1 antitrypsin deficiency

question

Most useful measure of liver cell injury

answer

ALT. AST is less specific

question

Common conditions causing elevations in AST and ALT

answer

MI, Rhabdo

question

Causes of mild increase in AST/ALT levels

answer

NAFLD, Hep C, Alcholic fatty liver disease, medication effects - statins

question

Causes of increase in Alk phosphotase levels

answer

Bile duct obstruction, primary sclerosing cholangitis, primary biliary cirrhosis

question

Evaluation of elevated Alk phos levels

answer

GGT: elevated = liver disease Normal = bone disease Blood type O and B may increase after fatty meal Placental source during pregnancy

question

Follow up tests for cholestatic liver disease

answer

MRCP, ERCP, liver biopsy

question

Alcoholic liver disease

answer

AST > ALT ratio >2; ratios >3 more specific. May see macrocytosis but not specific

question

Alcoholic liver disease risk factors

answer

Female, AA and hispanic, obesity, genetic factors

question

Questions to ask r/t alcohol use

answer

CAGE Cut down- been told by friends/family to reduce ETOH Anyone annoy or criticize you about drinking Guilty - feel guilty about drinking Eye opener - need drink first thing in the morning

question

Findings in alcoholic hepatitis

answer

Bili>4.5, AST<500, ALT 2.5. Rule out acute viral, autoimmune, obs or malignant liver disease. Imaging with US or CT. Liver biopsy gold standard

question

Typical transaminase elevations in hepatocellular disease - Alcoholic hepatitis

answer

Alcoholic hepatitis: AST 160 ALT 80

question

Typical transaminase elevations in hepatocellular disease - Autoimmune hepatitis

answer

Autoimmune hep: AST 130 ALT 180

question

Typical transaminase elevations in hepatocellular disease - Chronic Hepatitis C

answer

Chron Hep C: AST 46 ALT 78

question

Typical transaminase elevations in hepatocellular disease - Acute Hepatitis C

answer

Acute Hep C: AST 400 ALT 800

question

Typical transaminase elevations in hepatocellular disease - ETOH and tylenol toxicity

answer

ETOH and Tylenol tox: AST 19,000 ALT 16,000

question

Typical transaminase elevations in hepatocellular disease - Acute Hepatitis A

answer

Acute Hep A: AST 2,000 ALT: 2000

question

aminotransferase levels <300

answer

alcoholic hepatitis, non-alcoholic fatty liver, chronic viral hepatitis B and C

question

aminotransferase levels 500-5000

answer

acute viral hepatitis, autoimmune hepatitis, drug reaction

question

aminotransferase levels greater than 5000

answer

acetaminophen related liver failure, ischemia, or herpes simplex hepatitis

question

Symptoms of pancreatic cancer

answer

vague abdominal pain for weeks or > 2 months, weight loss, abrupt onset of painless jaundice.

question

Risk factors for pancreatic cancer

answer

smoking, family history of pancreatic cancer, history of chronic pancreatitis, older age, male, african american, diabetes, obesity, Non-O blood group, high fat diet, or high meat low vegetable diet, occupational exposure to chlorinated hydrocarbon solvents and nickel

question

Top clinical presentation of pancreatic cancer

answer

Asthenia, weight loss, anorexia, abdominal pain, jaundice

question

Sensitivity of Ultrasound for diagnosis of Pancreatic CA

answer

90% , lower sensitivity for tumors < 3 cm

question

What is the most common cause of abnormal LFTs in the US primary care population?

answer

Fatty liver

question

What are other common causes of elevated LFTs in US?

answer

Fatty liver prevalence about 30%, Nonalcoholic steatohepatitis (NASH), alcoholic liver disease, viral hepatitis (chronic HBV and HCV)

question

Nonalcoholic fatty liver disease

answer

fatty infiltration of the liver with our without inflammation. Assoc with obesity, hyperlipidemia, DM. Risk factor for developing cirrhosis. Liver biopsy - no serologic tests for this disease

question

Hepatitis A

answer

3500 new infections in 2013, oral fecal route, sexual contact, ingestion of contaminated food or drink. Low potential for chronic infection, most with acute disease recover with no lasting liver damage, rarely fatal. Supportive care. Vaccine available

question

Antibody tests for Hep A

answer

Gold standard - Serum IgM anti-HAV detects acute illness before onset of symptoms and 4-6 months after Serum IgG anti-HAV remains positive after recovery

question

Risk factors for Hep A

answer

travel to regions with high rates of Hep A, sex contacts of infected persons, household members of infected persons, men who have sex with men, IV drug use, clotting disorders

question

Incubation period for Hep A

answer

15-50 days (average 28 days)

question

Hepatitis B

answer

19,800 new infections in 2013, 1.2 million chronic HBV infections contact with infectious blood, semen, and other body fluids through birth to an infected mother, sexual contact, sharing needles, needle stick injuries. chronic infection >90% in infants, 25-50% of children age 1-5, 6-10% in older children and adults. 15-25% of chronically ill develop cirrhosis, liver failure, or liver cancer . Supportive care. Vaccine available

question

Hepatitis B antibody tests - susceptible

answer

HBsAg (hep B surface Antigen) - Negative Anti-HBc (Total hepatitis B core antibody): Negative Anti-HBs (Hepatitis B surface antibody): Negative

question

Hepatitis B antibody tests - immune due to natural infection

answer

HBsAg: negative anti-HBc: positive anti-HBs: positive

question

Hepatitis B antibody tests - Immune due to hepatitis B vaccination

answer

HBsAg: negative anti-HBc: negative anti-HBs: positive

question

Hepatitis B antibody tests - Acutely infected

answer

HBsAg: positive anti-HBc: positive IgM anti-HBc: positive anti-HBs: negative

question

Hepatitis B antibody tests - Chronically infected

answer

HBsAg: positive anti-HBc: positive IgM anti-HBc: negative anti-HBs: negative

question

Hepatitis B antibody tests - Interpretation unclear

answer

1. Resolved infection (most common) anti-HBs negative 2. False-positive anti-HBc, thus susceptible 3. "Low level" chronic infection 4. Resolving acute infection

question

Persons at risk for Hep B

answer

Infants born to infected mothers, persons with multiple sex partners, persons with STDs, men who have sex with men, IV drug users, household contacts of infected persons, healthcare workers, hemodialysis patients, residents and staff of institutions, travelers to regions with intermediate or high rates of infection

question

Incubation period for Hep B

answer

45-160 days (average 120 days)

question

Hepatitis C

answer

29,700 new infections in 2013, 3.2 million chronic infections. Spread by contact with blood of an infected person contaminated needles and drug equipment. Less commonly spread through sexual contact, birth to an infected mother, needlestick or other sharp injury. 75-80% develop chronic illness, 15-25% clear virus. 60-70% of those with chronic illness develop chronic liver disease, 5-20% develop cirrhosis. Risk of liver cancer. Treated with antivirals. No vaccine

question

Persons at risk for Hep C

answer

Current of former IV drug users, recipients of clotting factors prior to 1987, recipients of blood transfusions or organ donations before 1992, long term hemodialysis patients, HIV infected patients, infants born to infected mothers

question

Incubation period for Hep C

answer

14-180 days (average 45 days)

question

Symptoms of all forms of Hepatitis

answer

loss of appetite, nausea, vomiting, abdominal pain, gray colored stool, joint pain, jaundice

question

What is important regarding Hep C and alcohol?

answer

Greatest risk for cirrhosis in those with Hep C is alcohol use. Patients with Hep C should be counseled to avoid alcohol

question

Hepatitis C test - HCV antibody nonreactive

answer

No HCV antibody detected. Sample can be reported as nonreactive for HCV antibody. No further action required. If recent exposure in person tested is suspected, test for HCV RNA.

question

Hepatitis C test - HCV antibody reactive

answer

Presumptive HCV infection. A repeatedly reactive result is consistent with current HCV infection, or past HCV infection that has resolved, or biologic false positivity for HCV antibody. Test for HCV RNA to identify current infection.

question

Hepatitis C test - HCV antibody reactive, HCV RNA detected

answer

Current HCV infection. Provide person tested with appropriate counseling and link person tested to care and treatment.

question

Hepatitis C test - HCV antibody reactive, HCV RNA not detected

answer

No current HCV infection. No further action required in most cases. If distinction between true positivity and biologic false positivity for HCV antibody is desired, and if sample is repeatedly reactive in the initial test, test with another HCV antibody assay.

question

Acute onset of jaundice in a patient older than 50

answer

Consider malignancy, especially pancreas

question

What is important regarding pregnant women and Hep B?

answer

All pregnant women should be tested and if positive, newborn should be treated with Hep B immunoglobulin and vaccination to reduce the risk of vertical transmission

question

How many abnormal LFTs are normal on repeat?

answer

Up to 30%. Cut off values need to be adjusted for gender and BMI

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