3. STRUCTURE
Heaviest organ in the body
(weighs 1.0—1.5 kg.)
Majority of cells are hepatocytes.
(2/3rd of liver mass.)
Remaining — Kupffer cells, Ito cells,
Endothelial cells, Bile ductular cells
Blood supply :dual blood supply- 20%
hepatic artery & 80% from the portal vein.
4. STRUCTURE
Organised in lobules with portal areas at
periphery and central veins in centre.
Functionally organised into acini
Zone 1 - portal area
Zone 2 - hepatocytes
Zone 3 - central veins.
Blood flows from Zone 1 to Zone 3.
8. Synthesis of proteins (albumin, coagulation
factors, hormonal and growth factors)
Production of bile and its carriers (bile acids,
cholesterol, lecithin, phospholipids)
Regulation of nutrients (glucose, glycogen, lipids,
cholesterol, amino acids)
Metabolism and conjugation of lipophilic
compounds (bilirubin, drugs, ammonia) for
excretion in the bile or urine.
9. LIVER FUNCTION TESTS
2 types –
Based on
Detoxification and
Excretory Functions
Tests that Measure
Biosynthetic Function
of the Liver
10. Based on Excretory Functions :
Serum Bilirubin :
Breakdown product of heme-containing
proteins found in the blood
Two fractions — conjugated (direct, soluble) –
increases in liver & biliary disease
Unconjugated (indirect, bound to albumin) –
increases in hemolysis
Normal value – 0.3 to 1 mg/dl.
11. Serum Enzymes
Two categories:
(1) Reflect damage to hepatocytes: AST &
ALT
(2) Reflects cholestasis : alkaline
Phosphatase (ALP) & 5’ nucleotidase
12. AST & ALT
Released into the blood in greater amounts during
damage to the liver cell membrane.
ALT is found primarily in the liver.
Normal value 5-40mg/dl.
Pattern of elevation is helpful diagnostically. In
acute hepatocellular disorders, ALT > AST. An
AST:ALT ratio > 2:1 is suggestive while a ratio > 3:1
is highly suggestive of ALD.
13. Alkaline phosphatase (ALP)
Distinct isoenzymes found in the liver, bone,
placenta
Normal value 80-140mg/dl.
During obstruction to biliary tract ALP is
produced excessively
GGT
Raised in biliary obstruction
More specific for liver
14. Transaminases
May not be elevated in chronic liver disease
Cirrhosis
Minimal ALT elevations (<1.5 X normal)
Race/Gender
Obesity
Muscle injury
15. Transaminases
Mild elevations – more to come
Marked elevations
Acute toxic injury- i.e. Paracetamol, ischemia
Acute viral disease
Alcoholic hepatitis
17. Mild Transaminase elevation
AST or ALT < 5 times upper limit of normal
Etiologies
Hepatic: (ALT-predominant)
Chronic Hep C ▪Hemochromatosis
Chronic Hep B ▪Medications/Toxins
Acute viral hep ▪Autoimmune Hep
Steatosis ▪Alpha1 Antitrypsin Def
Wilson’s Disease ▪Celiac Disease
24. Tests that Measure Biosynthetic Function
of the Liver
Serum Albumin
Synthesized exclusively by hepatocytes
Hypoalbuminemia is more common in chronic
liver disorders such as cirrhosis
Normal value 3.5 – 5mg/dl
Serum Globulins
Increase in specific isotypes of globulins occurs
in chronic liver diseases
25. Coagulation Factors
Made exclusively in hepatocytes
Due to rapid turnover, single best acute measure of
hepatic synthetic function
Serum prothrombin time - collectively measures
factors II, V, VII, IX and X.
Normal value 11-12.5sec.
26. PROTHROMBIN TIME
The prothrombin time (PT) does not become
abnormal until more than 80 percent of liver
synthetic capacity is lost.
Factor VII has a short half-life of only about six
hours.
Single best acute measure of hepatic synthetic
function.
27. PROTHROMBIN TIME
Factors II, VII, IX and X requires vitamin K for
biosynthesis.
PT can be prolonged in hepatitis, cirrhosis or in
Vit K deficiency.
Trial of vit K injections (e.g., 5 mg/day s for three
days) is the most practical way to exclude vitamin
K deficiency.
Prolongation of PT > 5 sec above control and not
corrected by vit K is a poor prognostic sign.
28. SERUM ALBUMIN
Synthesised exclusively by the liver.
Half life—15-20 days.
Not a good indicator of acute hepatic dysfunction.
Sign of chronic liver disease.
29. SERUM GLOBULINS
Gamma globulin fraction synthesised by B cells.
Alpha and beta fractions by liver.
Gamma globulins increase in chronic liver
disease.
30. Jaundice or icterus, is yellowish
discoloration of tissue resulting from the
deposition of bilirubin.
Clinical jaundice – S Bilirubin >2.5mg%
JAUNDICE
31. NORMAL BILIRUBIN
METABOLISM haem (from RBCs) is oxidised to Bili verdin by
an enzyme - heme oxygenase
Biliverdin is reduced to Bili rubin by Bili verdin
reductase
Uptake of bilirubin by the liver is mediated by
a carrier protein (receptor)
On the smooth ER, bilirubin is conjugated with
glucoronic acid catalyzed by UDP glucuronyl
tranferase
“Conjugated” bilirubin is water soluble and is
secreted by the hepatocytes into the biliary
canaliculi
Converted to stercobilinogen (urobilinogen)
(colorless) by bacteria in the gut
Oxidized to stercobilin which is colored
(excreted in feces)
32.
33. Classification
Based on the pathological
mechanism giving rise to
jaundice
1. Hemolytic jaundice
2. Hepatocellular jaundice
3. Cholastatic jaundice