Jaundice and liver function tests

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Jaundice and liver function tests

• KVB

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Normal Liver

• The liver is the largest internal organ,measuring
  on an average 1500 g.
• The liver has a dual blood supply 2/3rd by the
  portal circulation 1/3rd of blood arriving from
  the hepatic artery.
• This dual blood supply accounts for the red
  colour of hepatic infarcts.

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The hepatic acinus
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The three zones of the acinus

• Zone 1 Bordering on the portal tract first to
  receive blood from the branches of the portal
  vein hepatic artery. Susceptible to
  toxin-mediated damage.
• Zone 3 Comprises hepatocytes around the
  THV,consequently the last to receive blood
  entering the acinus.This area is susceptible to
  ischemic injury during hypoperfusion of the
  liver.
• Zone 2 Located between Zones 1 3.

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FUNCTION OF THE LIVER

• The liver regulates most chemical levels in the
  blood and excretes bile, which helps carry away
  waste products from the liver.
• All the blood leaving the stomach and intestines
  passes through the liver.
• The liver processes this blood and breaks down
  the nutrients and drugs into forms that are
  easier to use for the rest of the body.
• More than 500 vital functions have been
  identified with the liver. Some of the more
  well-known functions include the following

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Glucose metabolism
Ammonia conversion
Protein metabolism
Fat metabolism
Vitamin and iron storage
Drug metabolism
Bile formation
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Main functions of the liver

• Metabolic functions
• Processing nutrients.
• Removal of impurities and neutralizing various
  toxins.
• Storage functions
• Storage of energy metabolites,predominantly in
  the form of lipids carbohydrates.
• Vitamins A B12,folate.
• Oligo-minerals like iron and copper.

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• Secretory functions
• Most of the plasma proteins,
• Lipids in the form of lipoproteins
• Carbohydrates that are being transported to other
  organs for metabolic conversion into energy.
• Excretory function
• Excretes bile into the intestine.

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Proteins secreted by the liver

• Albumin.
• Clotting factors.
• Acute-phase reactants C-RP,SAA protein.
• Binding carrier proteins, eg, transferrin,
  ceruloplasmin, thyroid-binding protein.
• Alpha-fetoprotein (AFP) is produced by fetal
  liver cells. Levels rise in patients with
  hepatocellular carcinoma.

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jaundice
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The main forms of jaundice

• Prehepatic hemolytic jaundice
• Bilirubin is predominantly in an unconjugated
  form. Seen in
• Autoimmune hemolytic anemia.
• Transfusion reaction.
• Malaria.
• Erythroblastosis fetalis.
• Resorption of bilirubin from internal hemorrhages
  ( massive hematoma, intestinal
  hemorrhage).
• Inefficient hematopoiesis (pernicious anemia,
  thalassemia).

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2) Hepatic jaundice

• Bilirubin is partially conjugated partially in
  an unconjugated form.
• Results from liver cell injury.

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The Hereditary Hyperbilirubinemias

• Inborn errors of bilirubin metabolism resulting
  in excessive amounts of bilirubin in the
  circulating blood, either because of increased
  bilirubin production or because of delayed
  clearance of bilirubin from the blood.

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• Hereditary hyperbilirubinemias can be divided
  into conjugated forms and unconjugated forms.

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Congenital hyperbilirubinemias
Unconjugated Conjugated
Gilberts syndrome Crigler-Najjar syndrome Rotor syndrome Dubin-Johnson syndrome

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• Both types of conjugated hyperbilirubinemias have
  a relatively benign course, but establishing the
  diagnosis is important to spare patients from
  undergoing multiple unnecessary procedures and to
  exclude other more serious causes of
  hyperbilirubinemia.

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Rotor syndrome

• Rotor syndrome is a rare, relatively benign
  autosomal recessive bilirubin disorder of unknown
  origin.
• It has many things in common with Dubin-Johnson
  syndrome except that in Rotor Syndrome, the liver
  cells are not pigmented. The main symptom is a
  non-itching jaundice.
• There is a rise in bilirubin in the patient's
  serum, mainly of the conjugated type.

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3) Post-hepatic obstructive jaundice

• Bilirubin is mostly in conjugated form.
• Results from the obstruction of major
  extrahepatic biliary ducts.

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Bilirubinuria

• Unconjugated bilirubin, typically found in
  hemolytic jaundice, circulates bound to albumin.
• Conjugated bilirubin typically found in the blood
  of patients suffering from hepatocellular or
  obstructive jaundice is water soluble will
  readily pass into the urine.

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Kernicterus

• The deposition of bilirubin in basal ganglia of
  the brain.
• Occurs typically in infants affected by the
  massive hemolysis of eryhthroblastosis fetalis.
• High levels of unconjugated bilirubin enable it
  to cross blood-brain barrier.
• Deposition of bilirubin causes brain injury.

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Causes of neo-natal jaundice

• sepsis
• hypoxia
• hypoglycemia
• hypothyroidism
• hypertrophic pyloric stenosis
• galactosemia
• fructosemia

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Evaluation of liver functionThe liver function
tests(LFTs)

• These tests monitor
• Liver cell integrity (known as necroinflammatory
  indices)
• AST,ALT,which can rise 50 times over normal
  values in massive liver necrosis.In viral
  hepatitis, levels of AST ALT are 4-6 times
  above the normal values.

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• Hepatic secretory function
• AlbuminNormal values are 3.5-5 g/dL.Reduced to lt
  3g/dL in chronic liver injury.
• Coagulation proteins Measure prothrombin
  time(PT).Prolonged PT is a very sensitive index
  of liver function loss.

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Serum protein electrophoresis

• This is an evaluation of the types of proteins
  that are present with in a patient's serum.
• By using an electrophoretic gel, major proteins
  can be separated out.
• This results in four major types of proteins.
  These are
• 1) Albumin,
• 2) Alpha globulins
• 3) Beta globulins
• 4) Gamma globulins

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Serum Electrophoresis
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• Serum protein electrophoresis is useful for
  evaluation of patients who have abnormal liver
  function tests since it allows a direct
  quantification of multiple different serum
  proteins.
• If the gamma globulin fraction is elevated,
  autoimmune hepatitis may be present.
• In addition a deficiency in the alpha globulin
  fraction can result in the diagnosis, or a
  clinical clue, to alpha-1 antitrypsin
  deficiency. This is a simple blood test that is
  commonly performed by hepatologists.

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Coagulation tests (e.g. INR)

• The liver is responsible for the production of
  coagulation factors.
• The international normalized ratio (INR) measures
  the speed of a particular pathway of coagulation,
  comparing it to normal.
• If the INR is increased, it means it is taking
  longer than usual for blood to clot.
• The INR will only be increased if the liver is so
  damaged that synthesis of vitamin K-dependent
  coagulation factors has been impaired it is not
  a sensitive measure of liver function.

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Serum glucose

• The liver's ability to produce glucose
  (gluconeogenesis) is usually the last function to
  be lost in the setting of fulminant liver failure.

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• Biliary excretory function
• BilirubinConjugated bilirubin that cannot be
  excreted into the intestine can be readily
  measured as direct bilirubin.
• Alkaline phosphatase Elevated levels are typical
  of obstructive jaundice.
• Gamma-glutamyl transferase(GGT) Primarily a
  hepatic enzyme and its rise is a reliable sign of
  biliary obstruction.Is also induced in liver
  cells in alcohol or phenobarbital injury to the
  p450 system.GGT is thus a marker of liver-cell
  injury,especially alcohol-induced injury.

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• Hepatic catabolic function include the
  detoxification of many metabolites.
• In practice,only the capacity of the liver to
  remove ammonia is measured.
• Elevation of blood ammonia is a good marker of
  severe liver injury.

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Other tests commonly requested alongside LFTs

• 5' nucleotidase (5'NTD)
• 5' nucleotidase is another test specific for
  cholestasis or damage to the intra or
  extrahepatic biliary system, and in some
  laboratories, is used as a substitute for GGT for
  ascertaining whether an elevated ALP is of
  biliary or extra-biliary origin.

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Lactate dehydrogenase (LDH)

• Lactate dehydrogenase is an enzyme found in many
  body tissues, including the liver.
• Elevated levels of LDH may indicate liver damage

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Why is it important to fractionate bilirubin in
the serum?

• Fractionation of bilirubin is important for
  elucidating the causes pathogenesis of
  jaundice.
• Normally,blood contains lt1.2 mg/dL of
  bilirubin,most of it being in an unconjugated
  (indirect) form-95.
• According to laboratory analysis,
  hyperbilirubinemia can be classified as the
  following
• Predominantly unconjugated(lt20).
• Mixed (CB 20-50).
• Predominantly conjugated (gt50).

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Thank you