liver tests Flashcards
- Recognize common liver chemistry tests and their clinical implications when abnormal, including AST and ALT, Alkaline phosphatase, and Bilirubin.
AST: hepatocellular damage. ALT: hepatocellular damage. Bilirubin: cholestasis, impaired conjugation or biliary obstruction. Alkaline phosphatase: cholestasis, infiltrative disease or biliary obstruction.
prothrombin time
•Assesses the extrinsic clotting pathway. When combined with serum albumin can assess synthetic function aka hepatic function.
Causes of Prothrombin time prolongation
hepatocellular dysfunction or Vitamin K deficiency
Non hepatic causes of low albumin levels
poor nutrition, nephrosis, malabsorption, severe illness with catabolism
Non hepatic causes of elevated prothrombin time
malabsorption, genetic causes
compare half lives of albumin and coagulation factors
albumin half life is 19-21 days. Coag factors half lives may be less than a day. These tests can be used to determine acute vs chronic components of hepatic function
Test to assess hepatic dysfunction vs Vit K deficiency with prolonged prothrombin time
Administer subcutaneous vitamin K and assess response. No correction indicates liver dysfunction. Normalization indicates vitamin K deficiency
- Characterize patterns of liver chemistry test abnormalities for hepatocellular and cholestatic liver diseases.
Hepatocellular injury or necrosis: predominantly AST and ALT elevation. Cholestatic pattern: predominantly alk phos elevation. Can also have a mixed pattern which indicates synthetic dysfunction
Function of AST and ALT
Both are aminotransferases which catalyze transfer of aa groups to form hepatic metabolites.
compare location in hepatocyte and organ expression of AST and ALT
AST: cytosol and mitochondria, liver, heart, muscle and blood. ALT: cytosol, liver only
AST:ALT ratio
normally 1 b/c impaired plasma clearance of AST by sinusoidal cells. Alcoholic liver disease is >2 b/c hepatic deficiency of B6 which is cofactor for ALT activity and alcohol induced injury to mitochondria enriched in AST.
hepatic causes of mild (< 5X) AST and ALT elevations
Chronic HBV and HCV, acute viral hepatitis (A-E, EBV, CMV), steatohepatitis, alcohol related liver injury, hemochromatosis, autoimmune hepatitis, alpha1- antitrypsin deficiency, Wilsons dz, celiac dz and cirrhosis
NON hepatic causes of mild (< 5X) AST and ALT elevations
hemolysis, myopathy, thyroid dz, strenous exercise
Causes of severe (>15X) AST and ALT elevations
acute viral hepatitis (A-E, herpes), meds/toxins, ischemic hepatitis, autoimmune hepatitis, Wilsons dz, acute Budd-Chiari syndrome, hepatic artery ligation or thrombosis
Alkaline phosphatase function
•Hydrolase enzyme responsible for removing phosphate groups from nucleotides, proteins and alkaloids
Tissue location of alk phos
Nearly all tissues: liver (microvilli of bile canaliculus), bone, placenta, intestine.
Causes of elevated alk phos
Cholestatic or infiltrative diseases of liver, Obstruction of biliary system, Bone disease, Pregnancy, renal failure, CHF
List infiltrative dz of liver that cause elevation in alkaline phosphatase
sarcoidosis, tuberculosis, fungal, granulomatous dz, amyloidosis, lymphoma, metastatic malignancy, hepatocellular carcinoma
How do you differentiate hepatobiliary vs nonhepatobiliary origin of elevated alk phos?
- 5’-nucleotidease: Significantly elevated only in liver disease, highest levels in cholestatic diseases. 2. gamma-glutamyltransferase (GGT): Not present in bone, Elevated after alcohol consumption and almost all types of liver disease
Bilirubin metabolism
Normal heme degradation product. Requires conjugation (glucuronidation) into water soluble forms before biliary excretion. Heme > heme oxygenase converts to biliverdin in kupffer cells of liver > biliverdin reductase converts to bilirubin > UDP glucuronyl transferase conjugates bilirubin into water soluble form in hepatocytes > bile canaliculus
Indirect vs direct bilirubin
indirect: measures unconjugated bilirubin before entering hepatocyte. Direct: measures conjugated bilirubin that has exited hepatocyte
hemolytic jaundice
overwhelmed conjugation: indirect bilirubin increases
Biliary obstruction- effect on direct and indirect bilirubin
obstruction leads to conjugated hyperbilirubinemia
Gilberts syndrome
dimished bilirubin-UGT (enzyme that conjugates bilirubin) leads to unconjugated hyperbilirubinemia with normal AST, ALT and alk phosph
Crigler-Najjar syndrome
rare autosomal recessive UDP-GT deficiency causes impaired bilirubin conjugation. Leads to unconjugated hyperbilirubinemia. Type I: severe jaundice, neuro impairment. Type 2: lower serum bilirubin, no neuro problems
Dubin-Johnson syndrome
defective secretion of conjugated bilirubin due to mutation of MRP-2 gene (responsible for transporting conjugated bilirubin from hepatocyte into bile canaliculus). Leads to conjugated hyperbilirubinemia
bilirubin levels in cirrhosis
conjugated hyperbilirubinemia- impairment of hepatocellular bilirubin secretion into bile, but bilirubin conjugation is preserved. Also, increased peripheral RBC destruction occurs
sites of cholestasis, detection method and examples
- lesion in canaliculus/ biliary ductules: detected by labs or liver biopsy. Includes cholestatic drugs, PBC and pregnancy. 2. intra/extra hepatic bile duct lesion: detected by imaging (US, ERCP, MRCP). Includes biliary atresia, PSC, gallstones, malignancy of pancreas or bile duct.
List diseases that cuase indirect hyperbilirubinemia
gilberts syndrome (nl LFTs), hemolysis (nl LFTs) , and crigler-Najjar syndrome
list diseases that cause direct hyperbilirubinemia
extrahepatic obstruction of bile flow, intrahepatic cholestasis, hepatitis, cirrhosis
Chronic Hepatitis B diagnosis
hepatitis B surface antigen (HBsAg) for >6 months
When is treatment considered in chronic hep B
1) HBsAg positive >6 months, 2) serum HBV DNA >10^5 copies/mL and 3) persistent or intermittent elevation in ALT and AST levels. OR if cirrhosis and positive HBV DNA (regardless of AST/ALT)
Benefits of chronic Hep B treatment
reduces the risk of progressive chronic liver disease and long-term complications of cirrhosis and hepatocellular carcinoma (HCC). prevent decompensation of liver disease (development of jaundice, ascites, variceal bleeding).
Hep B treatment results/goal
Although treatment can lead to viral suppression in HBeAg positive patients with normal ALT, the likelihood of HBeAg seroconversion (loss of HBeAg and developemend of HBeAb) is low. Goal is HBeAg seroconversion which is associated with negative HBV DNA when treatment is stopped. Goal is NOT to achieve loss of HBsAg
Chronic Hep B treatment
- Interferon (standard and pegylated): finite duration of treatment, absence of resistant mutants and more durable response. Interferon should not be used in patients with advanced liver disease. 2. nucleoside/tide analogs (lamivudine, adefovir, entecavir or tenofovir): less side effects
compare the Hep B antigens
HBsAg: surface antigen, marker of active infection. HBeAg: e antigen, surrogate marker of high viral load. HBcAg: core antibody, marker of active infection
Diagnosis of chronic Hep C
HCV RNA in the blood
Goal of HCV therapy
sustained virological response: eradicate HCV RNA and to remain HCV RNA negative 12 weeks after antiviral therapy is stopped
HCV standard of care
The current standard of care for treating HCV genotype 1 has been pegylated interferon, ribavirin and an NS3/4a protease inhibitor (boceprevir or telaprevir) for 24-48 weeks. Patients with other genotypes are currently treated with pegylated interferon and ribavirin
Unfavorable and favorable predictors of sustained virological response with HCV therapy
unfavorable: high baseline HCV RNA, genotype 1. black/hispanic, age, body weight, insulin resistance, more severe liver histology or steatosis. Favorable: low baseline HCV RNA, genotype 2/3, white
New Hep C treatments
target HCV encoded proteins vital to replication and life cycle of virus
Hereditary hemochromatosis benefits of treatment
prevent major causes of death in HH including decompensated cirrhosis, hepatocellular carcinoma, diabetes and cardiomyopathy. Survival is normal in patients in whom treatment is initiated before the development of cirrhosis or diabetes
Hereditary hemochromatosis treatment
Therapeutic phlebotomy (Each 500 mL of whole blood removed contains 200-250 mg of iron) once per week for one year then once every 2-4 months for maintenance. OR chelation with desferoxamine if anemic patient
Hereditary hemochromatosis treatment endpoint
serum ferritin of 50 ng/mL
Autoimmune hepatitis treatment
primary: Prednisone to suppress overactive immune system. Secondary: azathioprine, allows for lower doses of prednisone to be used. Stopping therapy results in a flair
Azathioprine side effects
reduction in the white blood cell count, nausea and rarely pancreatitis
corticosteroids side effects
weight gain, anxiety, osteoporosis, diabetes, high blood pressure and cataracts.
Primary biliary cirrhosis diagnosis
anti-mitochondrial antibody
Primary biliary cirrhosis treatment
Ursodiol (ursodeoxycholic acid)- a secondary bile acid which is a metabolic byproduct of intestinal bacteria. Improves bile acid transport/detox, cytoprotection and anti-apoptosis
Primary sclerosing cholangitis treatment
stent strictures with endoscopic retrograde cholangioscopy, treat cholangitis with antibiotics. Liver transplant is only long term treatment
Wilson disease treatment
general chelators that induce cupria (loss of copper in the urine) such as D-penicillamine and trientine, then zinc which interferes with uptake of copper from GI tract and induces enterocyte chelation of metals.
how do you monitor treatment of Wilson disease
24-hour urinary copper excretion. With chronic (maintenance) treatment, urinary copper excretion should run in the vicinity of 200-500 mcg per day on treatment. Values of urine copper excretion <200 mcg/day may indicate either non-adherence to theapy or overtreatment and excess copper removal
Non-alcoholic steatohepatitis treatment
Modifying risk factors for NASH: 1) Obesity, 2) Type II diabetes mellitus, and 3) Dyslipidemia. Investigational therapies have included use of diabetes drugs (even if not associated with diabetes) and vitamin E – an antioxidant.
what causes syphilis and what happens
treponema pallidum- causes demyelination of posterior columns in spinal cord and sclerosing of posterior roots. Results in decreased reflexes, decreased pain and proprioception.
microglia develop from what
monocytes- mesoderm derived
structures arising from surface ectoderm
lens of eye, epidermis and anterior pituitary
structures from neuroectoderm
CNS neurons, oligodendrocytes, astrocytes, ependymal cells,
internuclear ophthalmoplegia
seen in MS- demyelination of ipsilateral medial longitudinal fasciculus results innormal lateral rectus movement of eyes, but contralateral CN III does not stimulate medial rectus to fire. Abducting eye gets nystagmus
