LIVER

FUNCTION TEST

IKE DHIAH R
PREPARED FOR
CLINICAL ANALYSIS 2019
 PHYSIOLOGY OF LIVER

Metabolic Regulation

Hematological Regulation

Bile Production
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 METABOLIC REGULATION OF LIVER

• Carbohydrate metabolism
• Lipid metabolism
• Amino acid metabolism
• Waste removal
• Vitamin storage

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 HEMATOLOGICAL REGULATION OF
LIVER

• Phagocytosis and Antigen presentation

• Synthesis of plasma proteins
• Removal of circulating hormones
• Removal of antibodies
• Removal or Storage of Toxins

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 Liver Disease

Cholestasis Hepatocellular

Intrahepatic Extrahepatic
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 CLASSIFICATION OF LIVER DISEASE:
HEPATOCELLULAR

• Viral Hepatitis • Drugs induced

• Autoimmune hepatitis • Acetaminophen

• Impaired blood flow • ACEI

• Hypotension • Amiodarone

• Congestive heart failure • Antiepileptic

• Metabolic disease • Antimicrobial

• NAFLD • Statin
• NSAIDs

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 CLASSIFICATION OF LIVER DISEASE:
CHOLESTATIC

• Intrahepatic • Drugs induced

• Pregnancy • Antibiotics

• Infiltrative liver disease • Hormonal agents

• Inflammatory of bile ducts • NSAIDs

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 CLASSIFICATION OF LIVER TESTS

Hepatocellular
Protein Synthesis Cholestasis Detoxification
Injury

- Albumin - Bilirubin
- Prealbumin - ALP - Aminotransferase - Ammonia (NH3+)
- PT/INR (Clotting - 5’-nucleotidase (ALT & AST)
factors) - GGT 8
 ALKALIN PHOSPHATASE

• Liver, bone, small intestine, kidneys, • Hypothyroidism

placenta, and leukocytes • Hypophosphatemia
• Pernicious anemia
• Cholestatic • Zinc or Magnesium deficiency
• Bone disorders
• Pregnancy, Oral contraceptives
• Hyperthyroidism
• Small bowel obstruction
• Sepsis
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EVALUATION OF ELEVATED ALP

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 5’-NUCELOTIDASE

• Liver, brain, heart, and blood vessels

• Differentiating hepatocellular and

cholestatic liver disease

• Only elevated in Liver Disease

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 AMINOTRANSFERASE

• 24H from initiation of tissue damage to increasing of enzyme levels in plasma

• AST (Formerly SGOT: Serum Glutamic A Oxaloacetic Transaminase)
• ALT (Formerly SGPT: Serum Glutamic Pyruvic Transaminase)
• Elevation into thousands within 24-48 hours in bile duct obstruction which can
decline rapidly

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 AMINOTRANSFERASE

AST ALT

• Half life; 17 hours • Half life: 47 hours

• Cardiac muscle, skeletal muscle, kidneys, • More localized in liver
brain, lungs, intestines, and erythrocytes

• Musculoskeletal disease, Myocardial

infarction, Renal failure, Cerebral
infarction, Hemolysis

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 GAMMA GLUTAMYL TRANSPEPTIDASE

• Biliary excretory enzyme • Cholestatic disorders: Alcoholic

• Liver, kidneys, pancreas, spleen, Liver Disease
heart, brain, and seminal vesicles. • Pancreatic disease
• Myocardial infarction
• Severe COPD

• NOT elevated in Bone

disorders,Adolescence, Pregnancy

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 ASCITES

• Increased portal venous pressure

• Low plasma colloid oncotic pressure
• Sodium retention

• Serum albumin fall below30 g/L

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 BILIRUBIN

• ↑ Indirect Bilirubin:
• Hemolysis
• Reduced hepatic conversion to direct bilirubin
• Drugs: Probenecid, Rifampicin

• Direct Bilirubin
• Synthesized in hepatocytes by conjugating indirect
bilirubin, and secreted into bile
• Cleared by kidney

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 BILIRUBIN

• 300 mg bilirubin per day as a breakdown • 95% bilirubin serum: unconjugated

product of haem • Liver disease: conjugated

• 80% from RBC, remainder from

ineffective erytrhropoiesis
• Insoluble in water, carried in plasma
bound to albumin – not filtered at
glomerular unless glomerular proteinuria

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EVALUATION OF ELEVATED BILIRUBIN

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LABORATORY DIFFERENTIAL DIAGNOSIS
OF JAUNDICE

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CAUSES OF JAUNDICE

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 ALBUMIN

• Long half life (20 days) • Loss of albumin into extravascular

compartment
• Impaired albumin synthesis
• Ascites
• Complete cessation of albumin
• Poor nutritional status
production results in only 25% decrease
• Chronic synthetic dysfunction (cirrhosis)
in serum concentrations after 8 days)
• Systemic inflammation (severely ill)

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 CLOTTING FACTORS

Synthesis by Vitamin K Clotting

Liver (CoFactor) Factors

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 CLOTTING FACTORS

• Synthesis of prothrombin and other clotting factors are diminished – increased

PT
• Short half life prothrombin (<6h)

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 AMMONIA

• Acute liver failure

• Ammonia elevation correlates with severity of hepatic
encephalopathy (HE)
• Chronic liver failure
• Not well correlated
• HE: increase permeability of blood brain barrier to ammonia

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 HEPATIC
ENCELOPATHY

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DRUG INDUCED LIVER
INJURY

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 DEFINITIONS OF DRUG INDUCED LIVER
INJURY (DILI)

• INTRINSIC DILI
• Hepatotoxicity with potential to affect all individuals to varying
degrees. Reaction typically stereotypic and dose dependent
• IDIOSYNCRATIC DILI
• Hepatotoxicity affecting only rare susceptible individuals. Reaction
less dose dependent and more varied in latency, presentation, and
course
• CHRONIC DILI
• Failure of return of liver enzyme or bilirubin to pre-DILI baseline,
and/or other signs or symptoms of ongoing liver disease 6 months
after DILI onset

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 MOST COMMON DILI AGENT

DRUGS LATENCY TYPE OF INJURY

Short: <30 days

Moderate: 30-90 days 31

Long: >90 days

 MOST COMMON DILI AGENT

DRUGS LATENCY TYPE OF INJURY

Short: <30 days

Moderate: 30-90 days 32
Long: >90 days
 MOST COMMON DILI AGENT

DRUGS LATENCY TYPE OF INJURY

Short: <30 days

Moderate: 30-90 days
Long: >90 days
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 MOST COMMON DILI AGENT

DRUGS LATENCY TYPE OF INJURY

Short: <30 days

Moderate: 30-90 days
Long: >90 days
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 TREATMENT OF DILI

• Discontinue the drug (if possible) • N-acetylsisteine (NAC)

• Drug induced autoimmune like • Adults with early stage of ALF

hepatitis: (Acute Liver Failure)

• Drug withdrawal • Ursodeoxycholic acid

• Cholestatic DILI
• Corticosteroid (If laboratory
• Carnitine
abnormalities do not resolve after 6-
• Valproate induced liver injury
8 weeks)

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