The document discusses the structure and functions of the liver. It is the heaviest organ, composed mainly of hepatocytes, and has a dual blood supply. The liver has important functions including protein synthesis, bile production, nutrient regulation, and metabolism of compounds for excretion. Liver function can be assessed through tests of detoxification/excretory function like bilirubin and enzymes, or biosynthetic function like albumin, coagulation factors, and prothrombin time. Jaundice results from elevated bilirubin and can be classified as hemolytic, hepatocellular, or cholestatic based on its underlying cause.

1. LIVER
 INTRODUCTION
 LIVER FUNCTION TEST
 JAUNDICE

2. INTRODUCTION

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.

6. BILIARY TRACT

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

16. Transaminases
 AST:ALT ratio
 Elevated in alcoholic disease
 2:1 - suggestive
 3:1 - diagnostic

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

18. Mild Transaminase elevation
 Hepatic: (AST predominant)
 Alcohol
 Steatosis
 Cirrhosis
 Non-hepatic:
 Hemolysis
 Myopathy
 Thyroid disease
 Strenuous exercise

19. Elevated AST &
ALT, <5X normal
Hx & physical; stop
hepatotoxic meds
LFTs, PT, albumin,
CBC, Hep A/B/C, Fe,
TIBC, Ferritin
Positive serology
Negative serology
Negative serology,
asymptomatic
Serologies:
HAV IgM
HBsAg
HBcIgM
HCV RNA

20. Stop alcohol & meds; wt
loss; glucose control
Repeat LFTs
Observation
Ultrasound, ANA, smooth
muscle Ab, ceruloplasmin,
antitrypsin, gliadin &
endomysial Ab
Negative Serology- Asymptomatic
Liver biopsy
Abnormal Normal
6 months

21. Consider ultrasound,
ANA, smooth muscle Ab,
ceruloplasmin, antitrypsin
Liver biopsy
Negative Serology- Clinical
Signs/Symptoms of Liver Disease
Abnormal
☺

22. Alkaline Phosphatase
 Produced by biliary epithelial cells
 Non-specific to liver: bone, intestine, placenta
 Elevations
 Biliary duct obstruction
 Primary biliary cirrhosis
 Primary sclerosing cholangitis
 Infiltrative liver disease- ie sarcoid, lymphoma
 Hepatitis/cirrhosis
 Medications

23. Medications
 Hormones- anabolic steroids, estrogen, methyltestosterone
 Antimicrobials- amox-clav, erythromycin, flucloxacillin,
TMP-SMX, HIV medication.
 Cardiovascular- captopril, diltiazem, quinidine.
 OHAs - chlorpropamide, tolbutamide.
 Psychiatric- fluphenazine, imipramine.
 Others- allopurinol, carbamazepine.

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)

33. Classification
Based on the pathological
mechanism giving rise to
jaundice
1. Hemolytic jaundice
2. Hepatocellular jaundice
3. Cholastatic jaundice

34. HEMOLYTIC JAUNDICE
Increased destruction of RBC’s
Unconjugated bilirubin increases
Causes
Intraerythrocytic
Hereditary- spherocytosis,
sickle cell disease.
Acquired – B12 & folate def.
Extraerythrocytic
Antibodies, malaria, drugs.

35. Hepatocellular
jaundice
 Liver cell damage &
impaired transport of
bilirubin across the cell
 Mixed
hyperbilirubinemia
 Causes:
 Viral hepatitis
 Alcoholic hepatitis
 Drug induced hepatitis
 Cirrhosis

36. CHOLASTATIC JAUNDICE
 Failure of bile flow anywhere
between hepatocytes &
duodenum
 Conjugated predominantly.
 Causes:
Canalicular- alcohol, viral,
cirrhosis, sepsis.
Biliary – gall stones, ca
pancreas, strictures.

37. Conjugated bili;
Abnormal alk phos,
ALT, AST
Unconjugated bili;
Normal alk phos, ALT,
AST
RUQ u/s to assess ductal
dilatation
Hemolysis studies,
review meds

ALT eval,
review meds,
AMA, ERCP or
MRCP, liver bx
ERCP or
MRCP
Elevated Bilirubin
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