Liver Function Flashcards
What are the functions of the liver?
- Excretion, plasma protein synthesis, blood clotting, metabolism and detoxication functions
- Assessed in clinical practice by a panel of lab tests
- Combination of lab tests known as liver function tests (LFTs); Liver chemistry tests; Liver tests
- LFTs indicate extent of anatomical and physiological damage
- No single test capable of indicating functional integrity of liver
What is the history facts you need to know of the liver?
• High risk behavior
– IV drug abuse, alcohol abuse, high risk sexual activity
• Systemic illness
– Diabetes, obesity, cancer
• Medications
– Acetaminophen, statins
• Family history of liver disease
– Hemochromatosis, Wilson disease, 1-antitrypsin deficiency
What should be observed in a physical exam of the liver?
• Jaundice
– Acute hepatitis, biliary obstruction or advanced chronic liver disease
• Abdominal pain and fever
– Cholecystitis, or inflammatory liver disease
• Stigmata of chronic cirrhosis
– Spider angioma, palmar erythema, gynecomastia, testicular atrophy
• Complications of liver disease
– Advanced liver disease
– Encephalopathy, ascites, GI bleeding (esophageal varices), coagulation disorders
What are the tests used for liver function?
Tests for excretory function
– Serum bilirubin (total, conjugated and unconjugated bilirubin)
• Enzyme levels in serum
– Enzymes that indicate hepatocellular damage
– Enzymes that indicate cholestasis
– Gamma glutamyl transferase (GGT)
• Tests for synthetic function
– Serum albumin
– Clotting factors (prothrombin time)
– Serum alpha feto protein (AFP)
• Tests for metabolic functions
– Serum ammonia (Hepatic encephalopathy)
– Plasma glucose
– Lipid metabolism
What is the significance of serum bilirubin?
- Conjugated bilirubin in hepatocyte → Biliary secretion → intestine
- Hepatocellular disease (acute and chronic): Elevated serum total, conjugated and unconjugated bilirubin (mixed)
– Elevated Unconjugated bilirubin: Lower capacity for uptake and conjugation
– Elevated Conjugated bilirubin: Inflammation causes intrahepatic cholestasis
– Conjugated bilirubin in urine
What is the significance of serum bilirubin in cholestatic disease?
In cholestatic disease (extrahepatic cholestasis)
– Serum conjugated bilirubin is elevated
– Conjugated bilirubin not excreted into bile; Regurgitates into blood and
appears in urine
– Urobilinogen and stercobilin not formed (clay/pale feces)
– Urobilinogen absent in urine
– Fecal stercobilin and urine urobilinogen depend on extent of cholestasis – Prolonged cholestasis, mild elevation of serum unconjugated bilirubin
(liver cell damage)
• Serum bilirubin difficult to distinguish hepatocellular from cholestatic disorder
Contrast intrahepatic and extrahepatic cholestasis
Intrahepatic-Hepatocyte inflammation compresses bile duct / Chronic cirrhosis
Extrahepatic- Gall stone in common bile duct/ Cancer head of pancreas
What might cause serum bilirubin to be elevated?
Serum conjugated bilirubin elevated in intra-hepatic or extra- hepatic cholestasis
– Intra-hepatic cholestasis observed in • Viral hepatitis and drug toxicity and
• Chronic cirrhosis
– Extra-hepatic cholestasis observed in
• Stone in common bile duct
• Tumors around common bile duct or head of pancreas
• Isolated hyperbilirubinemia (Conjugated or unconjugated)
- Inherited
– Normal enzyme levels (ALT/AST and ALP)
– Gilbert, Crigler-Najjar and Dubin-Johnson syndromes
Why are liver enzymes in serum important?
• Enzyme levels in serum differentiate between
– Hepatocellular damage
– Cholestasis
• Degree of rise indicates extent and severity of damage
What enzymes indicate hepatocellular injury?
• Aminotransferases (Transaminases)
– ALT (alanine aminotransferase): Cytosolic
– AST (aspartate aminotransferase): Mitochondrial
• Liver amino acid metabolism
• Elevated in acute viral hepatitis, drug induced hepatitis, and long-
standing liver disease (Acute and chronic)
• Acute liver disease=Highly Raised ALT levels; ALT levels»_space;>AST levels
• Long-standing chronic alcoholic cirrhosis, AST levels»_space;ALT levels
(AST: ALT ratio approx 2:1)
• Note: Enzyme levels normal in Gilbert syndrome
What enzymes indicate cholestasis?
• Cholestasis (intra-hepatic and extra-hepatic)
– Alkaline phosphatase (ALP)
– Gamma glutamyl transferase (GGT)
• Alkaline phosphatase (ALP)
– Secreted by biliary canaliculi
– Elevated in Intra-hepatic or extra-hepatic cholestasis (But much higher levels in extrahepatic cholestasis)
– Also elevated in pregnancy, normal growing children and bone diseases
How does GGT and ALP in cholestasis?
• Gamma glutamyl transferase (GGT) – Secreted by biliary ducts
– Induced by alcohol
– Marker of alcohol consumption (Isolated increase in GGT) – Differentiate hepatic and non-hepatic causes of raised ALP
• ALP and GGT elevated in biliary stasis
– Elevated ALP with jaundice (Signs of liver disease/cholestasis) – Extra-hepatic cholestasis – very high levels
– Intra-hepatic cholestasis
• Elevated ALP with normal GGT, indicates non-hepatic ALP (bone, placenta) • Isolated elevation in GGT and normal ALP, recent alcohol use or drugs that
induce GGT synthesis
What are the enzyme used to indicating cholestais?
Abdominal ultrasound assesses biliary tree
– Dilation of biliary tree = Extrahepatic cholestasis (Very high ALP and GGT)
– No biliary tree dilation= Intra-hepatic cholestasis (Slight increase ALP and GGT; Very High ALT and AST)
What are the functions of synthetic function of the liver?
• All plasma proteins, except -globulins synthesized by liver
• Serum albumin
– Only Liver synthesizes albumin
– Maintains colloidal osmotic pressure
– Long-standing (chronic) liver disease: Low serum
albumin
– Responsible for ascites and pedal edema in long-
standing liver disease
– Affects binding of hormones, calcium and drugs
(remember, albumin is major transport protein)
What are the indicators of acute hepatitis?
• In acute hepatitis, normal serum albumin levels • Decrease in serum albumin indicates long-
standing (chronic) liver disease, in conjunction
with other LFTs
• Serum y-globulins are elevated in cirrhosis (IgA)
resulting in B-y bridging in serum protein electrophoresis
What is the significance of clotting factors/prothrombin time?
- Liver synthesizes most clotting factors
- Post-translational gamma-carboxylation of glutamic acid of vitamin K dependent clotting factors (II, VII, IX, X)
• Increased prothrombin time
• Coagulopathy in liver disease (increased bleeding tendency) – Reduced clotting factors synthesis (hepatocellular damage)
– Impaired modification of vitamin-K dependent clotting factors
What is the significance of prothrombin (clotting factors) to cholestasis?
• Coagulopathy in cholestasis
– Reduced bile salt entry into intestine impairs fat-soluble vitamin absorption (vitamin K)
– Impairs post-translational -carboxylation of vitamin K dependent clotting factors (II, VII, IX and X)
• Monitor prothrombin time (INR) if liver biopsy or surgery planned
Why and how is plasma glucose tested in the liver?
Plasma glucose
– Liver functions as ‘glucostat’
– Liver stores glucose as glycogen when blood glucose level is high and releases glucose by glycogenolysis, when blood glucose level is low (in between meals)
– Chronic liver disease can alter plasma glucose level
– Hypoglycemia or hyperglycemia
How is ammonia measured for tests for liver function?
• Liver detoxifies Ammonia to urea
• Fulminant (Advanced) end-stage liver disease, impaired urea formation, blood ammonia levels rise
• Results in hepatic encephalopathy and altered consciousness (Coma)
• Causes: Neurotransmitter imbalance and TCA cycle depleted of -
ketoglutarate
• GI Bleeding (hematemesis) in long-standing liver disease precipitates hepatic encephalopathy
How can lipid metabolism be tested for in liver function?
- Liver secretes VLDL and transports TAG to peripheral tissues
- ‘Fatty liver’: Excessive TAG deposits in liver cells
• Contributory factors in alcoholism
– Decreased β-oxidation due to ↑NADH/NAD+ ratio
– Increased fatty acid and TAG synthesis
– Decreased VLDL secretion (hepatotoxic action of ethanol)
What are the special test for liver evaluation?
• Serum alpha fetoprotein (AFP): Tumor marker for liver cancer
• Serum iron, transferrin and ferritin
– Hemochromatosis
• Serum ceruloplasmin
– Wilson disease
• Serum α1-antitrypsin
– Inherited α1-antitrypsin deficiency
Why do we use LFTs?
- Assess intensity and type of jaundice (hepatic or obstructive)
- Assess extent of damage to hepatocytes by viruses, malignancy, drugs
- Differentiate between acute and chronic disorders (Serum albumin/ enzymes)
- Assess metabolic functions of liver
- Monitor drug therapy of hepatotoxic drugs
- Follow up and prognosis of liver diseases
