LIVER INTRODUCTION

 Liver & Biliary System:

Major Hepatic Functions:
• Nutrient Metabolism.
• Protein Metabolism.
• Carbohydrate Metabolism.
• Lipid Metabolism.
• Drug & Alcohol Metabolism.
• Cholesterol Metabolism.
 Protien Synthesis:
• Albumin, Coagulation Factors, Complement
Factors, Haptaglobin, Ceruloplasmin,
Transferrin, Protease Inhibitors.
 Storage:
• Iron, Vit. D & B12, Ferritin, Haemosiderrin,
Vit K, Folate & Copper.
 Excretion:
• Bilirubin
• Bile Salts
15% of the Liver Composes of Cells Other
Than Hepatocytes.
 Kupffer Cells:
• Removes Aged & Damaged RBC’s.
• Removes Bacteria, Viruses.
• IgG Complex Removal.
• Endotoxin Removal.
• Cytokine Production.
 Stellate Cells (ITO Cell’s):
• Uptake & Storage of VIT. A.
• Synthesis of Extracellular Matrix.
• Synth. & Release of Collagenase.
• Cytokine Synthesis & Release.
 Endothelial Cells, Line the Hepatic
Sinusoids:
• Functions: Hyaluron Uptake.
Lipoprotien Binding & Uptake
Cytokine Production
The functional Unit of The Liver is Acinus.
 AIMS of Investigation of Patient with Liver
Dis.:
• Detect Hepatic Abnormality.
• Measure the Severity of Liver Damage.
• Define the Structural Effects On Liver.
• Identify the Cause.
• Investigate the Complications.
 LFT’s (Liver Function Test):
• Do Not-Indicate a Specific Diagnosis.
• May Point To An Underlying Pathological
Process.
• Direct Further Investigation.
• S. Bilirubin assess Transport.
• Aminotransferases assess Hepato Cellular
Damage.
• Alkaline Phosphatase assess Biliary
Obstruction.
• GGT assess Enzyme Induction.
• S. Protiens assess Synthesis.
• Coagulation Tests assess Synthesis.
Aminotransferases:
• ALT & AST Transfers Amino Group From
Amino Acid to Keto Acid.
• Both ALT & AST Are Located in Cytoplasm of
Hepatocyte.
• Conc. Of ALT is Much Higher in Liver than in
any other Tissue. & is thus a Sensitive Index.
• 100-500 Times Rise in PCM Induced Injury
• 10-100 Times in - Viral Hepatitis
-Acute Drug Induced
Hepatitis
-Acute Circulatory Failure
-Exacerbation of CAH.
•2-10 Times Rise in CMV Infection &
Infectious
• <5 Fold Rise In:
-Acute Alcoholic Hepatitis.
- Obstructive Jaundice.
-Cirrhosis of Liver.
Alkaline Phosphatase:
• Widely Distributed.
• Significant Activity In Liver, GIT, Bone &
Placenta.
• Found in great Conc. In Membranes
Associated with Absorptive or Secretory
Functions.
• In Liver, Conc. In Sinusoidal & Biliary
Canalicular Memb.
• Normal Serum Level 3-13 KA units.
• In Hepatocellular Jaundice Rise is <21/2
 • Other Causes of Raised ALP.
• Paget’s Disease Hyper Parathyroidism
• Rickets Pregnancy
• Metastatic Bone Dis. Tumours of GIT
• Adolescence.
Gamma Glutamyl Transferase (GGT):
• GGT is a Microsomal Enzyme Found In Many
Cells & Tissues.
• Largest Conc. In Liver (Hepatocytes & Epith.
Of small Bile Ducts).
• Raised Levels in Biliary Obst. & Parenchymal
Damage.
 • Isolated Rise in Acute Alcoholism &
Microsomal Enzyme Inducing Drugs.
• Barbiturates Griseofulvin
• Carbamazepine INH.
• Ethonol Phenytoin
• Glucocorticoids Rifampicin

Plasma Protiens:
• Albumin- Synthesised in Liver (8-14gm)
day).
• Normal Value 3.5 – 5.5 gm%.
• In Chronic Liver Diseases,
CAH
CIRRHOSIS
[Link] is Low
 • Globulin level rises in Chronic Liver
Diseases.
-IgG increases in CAH & Cryptogenic
Cirrhosis
-IgA increases in Alc. Liver Disease
-IgM increases in Primary Biliary Cirrhosis
• Plasma Protien Electrophoresis.
Coagulation Factors:
• Liver Synthesises All Coagulation Factors.
• PT Depends on Factors I,II,V,VII, & X.
• If Plasma Conc. of any of these falls below
30% of normal PT is increased.
• Vit. K. Dependant Factors.
• PT Prolonged in.
-Severe Liver Damage (Acute Viral
Alfa-Feto Protien:
• Mainly Synthesised in Fetal Liver. &
production falls to low levels after Birth.
• Substantial Conc. In Chronic Liver Ds.
Suggests Hepatocellular Carcinoma.
• Measured by Electrophoresis & RIA.
• Conditions Ass. With Elevated α-Fetoprotien.
-HCC
-Carcinoma Stomach, GB
-CA Pancreas, Bile Duct
-Viral Hepatitis
-Chronic Active Hepatitis
-Cirrhosis.
α-1 Antitrypsin:
• It is α1-Globulin Produced by Liver .
• Comprises 90% of α1 Globulin Peak.
• α1 Antitrypsin Deficiency associated with
Liver Dis. (Cirrhosis) & Pulm Disease
(Emphysema).
Liver Biopsy:
• Using Trucut or Menghini’s Needle through
Intercostal space.
• Indications:
• In Cirrhosis:
-Clinical Suspicion But not LFT Proved
-Differentiate Between Various Forms
-Diagnose Fatty Liver
 • Diagnosis of Hepatic Malignancy.
• In Chronic Hepatitis.
• Diagnose Granulomatous Disease such as
TB, Sarcoid, Leprosy.
• Storage & Metabolic Disease.
• For Prognostic Purposes.
• For Staging of Lymphoma.
 C/I of Liver Biopsy:
• Coagulation Disorders Prolonged PT
• Gross Ascites Hydatid Cyst
• Severe Jaundice Hemangioma of Liver
• Hepato Biliary Infection Hepato Cellular
Failure
ERCP (Endoscopic Retrograde Cholangio
Pancreatography):
• Direct Visualisation & Manipulation of Papilla
of Vater.
• Manipulations within CBD.
• Radiological Imaging of Biliary Tree &
Pancreatic Duct.
Uses:
• Biopsy of Ampullary Carcinoma.
• Anatomical Study of Biliary Tree &
Pancreatic Duct.
• Remove Stones From CBD.
• Biliary Drainage in Malignant Strictures.
• Dilatation of Benign Strictures.
Complications:
PTC (Percutaneous Transhepatic
Cholangiography):
• Documentation & Localisation of Site of
Obstructions.
• Pre-Operative Planning of Surgery.
CT, USG,
MRI
 Major Manifestations of Liver Disease:
• Asymptomatic Abnormal LFT.
• Jaundice.
• Acute (Fulmimant) Hepatic Failure.
• Cirrhosis & Chronic Liver Disease
(Failure).
• PHT.
• Ascites.
• Hepatic Encephalopathy.
• Hepato Renal Failure.
 Jaundice:
• Yellow Discolouration of Skin, Mucous
Memb, Sclera.
• Usually Detectable when [Link] >
3mg/dl.
• Bilirubin does not cross BBB.
• 80-85% of Bilirubin derived from
catabolism of senescent RBC’s, 15-20%
is derived from BM from destruction of
maturing cells.
• Unconjugated Bilirubin is transported in
the Plasma bounded to albumin in a
reversible manner.
 Hepatic Metabolism:
• Three Phases : Hepatic Uptake
Conjugation
Excretion
 Hepatic Uptake: UB subjected to
Hepatocyte, Albumin Dissociates, UB enters
Liver Cell & binds to a Protein – “LIGANDIN”.
 Conjugation: In the Hepatocyte UB is
conjugated by Glucoronyl Transferase to
Bilirubin Monoglucoronide & Bilirubin
Diglucoronide.
 Excretion:
• Rate Limiting Step.
• This Step is more susceptible to
Impairment following Liver cell injury.
• As A Result: There is decreased excretion of
Bilirubin into Bile.
• Regurgitation of Conjugated Bilirubin into
Blood.
 Intestinal Phase of Bilirubin Metabolism:
• Conjugated Bilirubin reaches intestinal
lumen through Bile.
• Part of it is excreted in stool as such i.e,
Bilirubin Diglucoronide & Bilirubin
Monoglucoronide.
 • Rest is Metabolised to Urobilinogen. This
further Has 3 (three) fates:
a) Part of Urobilinogen is reabsorbed
from SI into
Portal Circulation reaching Liver.
b) Part is reabsorbed & excreted in
Urine as
Urobilinogen (upto 4 mg/day).
c) Part of Urobilinogen is excreted in
the stool as
Stercobilinogen which gives stool the
normal
Colour.
 Jaundice Classified in Two Ways:
 Based on Underlying Derangement
of Bil. Metabolism.
 Predominantly Unconjugated:
• Overproduction – Hemolysis, Ineffective
Erythropoesis.
• Decreased Up Take- Drugs, (Flavaspidic
Acid), Sepsis.
• Decreased Conjugation – Gilbert’s
Syndrome
Crigler – Najjar
Syndr.
Neonatal
Jaundice,
Acquired
 Predominantly Conjugated:
• Intrahepatic Causes:
-Familial/ Hereditary: Dubin – Johnson Synd., Rotor
Synd.,
Recurrent Benign Intra hepatic
Cholestasis,
Cholestatic Jaundice of Preg.
-Acquired Disorders: Hepatocellular diseases, Drug
Induced Cholestasis.
• Extrahepatic Causes:
- Stone In CBD, Tumours & Strictures of Bile Duct,
Periampullary Carcinoma, Ca-Head of Pancreas.
 Based on Pathological Mech. Giving
Rise to Jaundice:
• Hemolytic Jaundice
• Hepato cellular Jaundice
• Cholestatic Jaundice
 Hemolytic Jaundice:
• Results from increased destruction of
RBC’s & their Precursors.
• Unconjugated Bilirubin increased in
plasma.
Causes of Hemolysis:
 Intra Erythrocytic:
• Hereditary: Spherocytosis, sickle cell
disease, G-6 PD Def. & Thalasemia, P.K.
def.
• Acquired: B12 & folate deficiency, PNH.
 Extra Erythrocytic:
• Antibodies (Autoimmune & Isoimmune)
• Mechanical (Prosthetic Valves).
• Drugs (Dapsone, Sulphasalazine).
• Infections (Malaria).
• Neoplastic Disease.
 Clinical Features:
• Pallor
• Mild Jaundice
• No other signs of Liver Cell Failure
• Hepato Splenomegaly
• Urine turns dark yellow on standing
(Urobilinogen Urobilin).
 Investigations:
• [Link]. increased (<6mg%).
• No Bilirubin in Urine.
• Urinary Urobilinogen increased (>
4mg/day).
• Predominantly Unconjugated Serum
Bilirubin.
• SGOT/SGPT/SAP – WNL.
• Retic Count increased.
• Peripheral Smear – Helpful.
 Hepato Cellular Jaundice:
• Biliary Transport Impaired as a Result of
-Imparied Uptake of Unconjugaed
Bilirubin.
-Imparied Transport of Conjugated
Bilirubin Into
Biliary Canaliculi.
• In Hepato Cellular Jaundice concentration
of both Conjugated & Unconjugated
Bilirubin rises.
• Causes Hepatitis Cirrhosis
Viral
Alcoholic
Chr. Active
Drug Induced – (INH, R-Cin,
 Cholestatic Jaundice:
• Also Known as Surgical Jaundice
Intrahepatic Obstr’n Extra Hepatic
Obstr’n
Alcohol, Drugs Gall Stones In
CBD
Chr. Active Hepatitis Ca Head of
Pancreas
Viral Hepatitis Ca Ampulla of
Vater
Cirrhosis Stricture of Bile
Duct
Primary Biliary Cirrhosis Sclerosing
Cholangitis
 Clinical Features:
• Jaundice (Fluctuating / Progressive).
• Pruritis
• Clay Coloured Stools
• Fever With Chills
• Weight Loss
• Haemorrhagic Tendencies
• Bone Pains
Signs: Deep Jaundice, Scratch Marks,
Xanthomas, Xanthelasma, Palpable GB,
Hard Irregular Liver, Signs of Liver Cell
Failure (Late).
 Investigations:
• Bilirubin Present in Urine.
• Urobilinogen Absent in Urine
• [Link]. markedly increased
• Predominantly Conjugated
• SAP increased (3-4 Times)
• USG For Underlying Cause.
• Antimitochondrial Antibody. (PBC)
• ERCP.
• PTC
 Treatment: Depends on the underlying
cause of Cholestasis.
 Congenital Non-Hemolytic
Hyperbilirubinemia’s:
• Gilbert’s Syndrome.
• Crigler-Najjar Sydr. Type I&II.
• Dubin – Johnson Syndr.
• Rotor Syndr.
 Gilbert’s Syndr:
• Autosomal Dominant Inheretance.
• Minimal Def. of Glucoronyl Transferase
Enzyme leading to Unconjugated
Hyperbilirubinemia.
• More Common in Men.
• Usually Asymptomatic, & Jaundice
detected Incidentally.
 • Depth of Jaundice increased with
Infections, fatigue.
• Physical Exam’n normal except mild
jaundice.
• No Bilirubinuria.
• [Link]. Unconjugated.
• Normal-- PS, Retic. Count & Serum
Haptoglobin.
• Usually no Treatment is Necessary.
• Glucoronyl Transferase activity may be
increased by Phenobarbitone 60mg BD.
 Crigler-Najjar Syndr. – Type I:
• Autosomal Recessive
• Complete absence of Glucoronyl
 Crigler-Najjar Syndr. – Type II:
• Autosomal Dominant Inheritance.
• Partial Def. of Glucoronyl Transferase.
• Jaundice is mild but no Kernicterus.
• Phenobarbiturate, UV Light.
 Dubin – Johnson Syndrome:
• Autosomal Recessive Inheritance.
• Reduced ability to transport Bilirubin
Diglucoronide into Biliary canaliculi.
• Clinically presents with Jaundice.
• Conjugated hyperbilirubinemia &
Bilirubinuria.
• No treatment necessary.
 Rotor Syndrome:
• Autosomal dominant inheritance.
• Due to poor uptake & storage of Bilirubin by
liver cells.
• Clinically mild Jaundice.
• Conjugated Bilirubinemia.
• No treatment required.
Than
k
You