jaundice master ppt

Approach to the Patients with JaundiceApproach to the Patients with Jaundice

Dr Suresh Kubavat

MD (Internal Medicine)

Consultant Physician

Shradha Arogyamandir - Junagadh

9427257977

Dr Suresh Kubavat

MD (Internal Medicine)

Consultant Physician

Shradha Arogyamandir - Junagadh

9427257977

Gross Hepatic AnatomyGross Hepatic Anatomy

Gross Hepatic AnatomyGross Hepatic AnatomyGross Hepatic AnatomyGross Hepatic Anatomy

Liver Histological StructureLiver Histological Structure

Liver Histological StructureLiver Histological StructureLiver Histological StructureLiver Histological Structure

Functions of the LiverFunctions of the Liver1.Metabolism • Fats ,Proteins,Carbohydrates,Hormones

2.Storage (as Glycogen)

3.Interconversion=Glucose-Fat-Amino acids

4.Production:Fatty acids,Triglycerides,Phos --pholipids,ketones,Cholesterol,Albumin, Fibrinogen

5.Exocrine:Bile-Bilirubin-Helps digestion

6.Detoxification of ciculating toxins.

7. Drug metabolism and excretion.

8. Removal of particulate matters-Kupffer cells

Normal Bile PhysiologyNormal Bile PhysiologyNormal Bile PhysiologyNormal Bile Physiology• 300mg bile/day

2 roles: 1. excretion

2. emulsification of fat

• Water (98%)

• Bile Salts

• Bile pigments (Bilirubin)

• Fatty Acids

• Lecithin (Fat emulsifier,Cell protector)

• Cholesterol

• Na,K,Ca,Cl,Hco3

• 300mg bile/day

2 roles: 1. excretion

2. emulsification of fat

• Water (98%)

• Bile Salts

• Bile pigments (Bilirubin)

• Fatty Acids

• Lecithin (Fat emulsifier,Cell protector)

• Cholesterol

• Na,K,Ca,Cl,Hco3

Normal Bilirubin MetabolismNormal Bilirubin MetabolismNormal Bilirubin MetabolismNormal Bilirubin Metabolism

• Bile:300mg/Day-80% from aged dying RBCs

-20% from premature destruction in BM

HemoglobinHeme + Globin

HemeBiliverdin+CO+Iron

Biliverdin(Water insoluble)Binds with Albumin(becomes

water soluble)Liver:unconj bil taken up by hepatocytes

conjugates to glucuronic acidBileexcr to intestine goes to terminal ilium+colonbecomes unconjugated

converted to urobilinogen80-90% excreted in faeces

as urobilins+10-20% absorbed thru intestineportal v.

LiverReexcreted

A small fraction escapes hepatic uptake excr in urine

• Bile:300mg/Day-80% from aged dying RBCs

-20% from premature destruction in BM

HemoglobinHeme + Globin

HemeBiliverdin+CO+Iron

Biliverdin(Water insoluble)Binds with Albumin(becomes

water soluble)Liver:unconj bil taken up by hepatocytes

conjugates to glucuronic acidBileexcr to intestine goes to terminal ilium+colonbecomes unconjugated

converted to urobilinogen80-90% excreted in faeces

as urobilins+10-20% absorbed thru intestineportal v.

LiverReexcreted

A small fraction escapes hepatic uptake excr in urine

PathophysiologyPathophysiology• Jaundice = Bilirubin staining of tissue @ level

greater than 3

• Mechanisms:

– ↑ production of bilirubin (Hemolysis)

– ↓ hepatocyte transport

– ↓ conjugation

– Impaired excretion of bilirubin(Hepatitis,drugs,sepsis,

Dubin-Johnson )

– Impaired delivery of bilirubin into intestine

• “surgically relevant jaundice” or obstructive jaundice

– “Cholestasis” refers to the latter two,

impaired excretion and obstructive jaundice

• Jaundice = Bilirubin staining of tissue @ level greater than 3

• Mechanisms:

– ↑ production of bilirubin (Hemolysis)

– ↓ hepatocyte transport

– ↓ conjugation

– Impaired excretion of bilirubin(Hepatitis,drugs,sepsis,

Dubin-Johnson )

– Impaired delivery of bilirubin into intestine

• “surgically relevant jaundice” or obstructive jaundice

– “Cholestasis” refers to the latter two,

impaired excretion and obstructive jaundice

Definition of JaundiceDefinition of Jaundice

• Jaundice is yellow discoloration of the sclera, skin and mucous membranes resulting from accumulation of bilirubin.

• Normal bilirubin levels are 0.4+0.2 mg per dl, with > 95% unconjugated.

• Hyperbilirubinemia is separated into two classes : unconjugated (> 80% of total bilirubin) and conjugated (>30 % of total bilirubin)

• Jaundice is yellow discoloration of the sclera, skin and mucous membranes resulting from accumulation of bilirubin.

• Normal bilirubin levels are 0.4+0.2 mg per dl, with > 95% unconjugated.

• Hyperbilirubinemia is separated into two classes : unconjugated (> 80% of total bilirubin) and conjugated (>30 % of total bilirubin)

Algorithm for PT with jaundice.Algorithm for PT with jaundice.History+Physical exam+Lab tests

Isolated elevation of the Bilirubin

Bilirubin & other liver tests elevated

Direct hyperbilirubinemia

Inherited disorders1.Dubin – Johnson Syndrome2.Rotor’s Syndrome

Indirect hyperbilirubinemia

DrugsRifampicin

Hemolytic Disorders-Sphero,Ellipto,G6PD,Sickle,immuneIneffective erythropoiesis-Iron,Folate,B12 def,Thallesemia.

Inherited Disorders1. Gilbert’s Syndrome2. Crigler–Najjar Syndromes

ALGORITHM CONTINUEDALGORITHM CONTINUEDBilirubin & other liver tests elevated

Hepatocellular Pattern Cholestatic Pattern

SGPT/OT elevated out of proportion to

Alkaline phosphatase

Alkaline phosphatase elevated out of proportion to

SGPT/OT

Hepatocellular PatternHepatocellular Pattern

1. Viral SerologiesHepatitis A IgMHepatitis B Surface Antigen

& core antibody (IgM)Hepatitis C RNA2. Toxicology screenAcetaminophen level3. Ceruloplasmin (If Pt < 40)4. ANA, SMA, LKM(Liver

Kidney Microsomal Antibody), SPEP( Serum protein electrophoresis)

Additional Virologic Testing

CMV DNA, EBV capsid antigen

Hepatitis D antibody(If indicated)

Hepatitis E IgM(If indicated)

If negative

If negative Liver Biopsy

Cholestatic PatternCholestatic Pattern

UltrasoundDilated DuctsExtra hepatic cholestasis

CT/ERCP

Ducts not DilatedIntra hepatic cholestasis

Serologic testingAMAHepatitis SerologiesHepatitis ACMV, EBVReview Drugs

MRCP/Liver Biopsy

Liver Biopsy

Negative

AMA +ve

PrehepaticPrehepatic• Unconguated Bil ↑

• LFT’s N

• ↓ Haptoglobins (a protein in blood that combines with hb to form a complex that is removed from @ by the liver)

• Reticulocytes ↑

• Coombs test +ve

• Urine urobilinogen +

• Unconguated Bil ↑

• LFT’s N

• ↓ Haptoglobins (a protein in blood that combines with hb to form a complex that is removed from @ by the liver)

• Reticulocytes ↑

• Coombs test +ve

• Urine urobilinogen +

HepaticHepatic• ALT(SGPT) ↑ ↑ ↑

• ALP N or ↑

• Bil ↑

• Albumin ↓

• INR ↑

• Hepatitis serology

• Autoantibodies• Anti-mitochondrial PBC

• Anti-nuclear & antimicrosomal, Autoimmune hepatitis

• Caeruloplasmin ↑ • Wilson’s

• γ-Globulins ↑• Cirrhosis esp autoimmune

• Transferrin ↑ ↑• Haemochromatosis

• α-foetoprotein, αFP ↑• HCC(Hepato cellula Carcinoma) in cirrhosis

• ALT(SGPT) ↑ ↑ ↑

• ALP N or ↑

• Bil ↑

• Albumin ↓

• INR ↑

• Hepatitis serology

• Autoantibodies• Anti-mitochondrial PBC

• Anti-nuclear & antimicrosomal, Autoimmune hepatitis

• Caeruloplasmin ↑ • Wilson’s

• γ-Globulins ↑• Cirrhosis esp autoimmune

• Transferrin ↑ ↑• Haemochromatosis

• α-foetoprotein, αFP ↑• HCC(Hepato cellula Carcinoma) in cirrhosis

Hepatic CausesHepatic Causes• Viral Hepatitis : A,B,C,D,E / EBV / CMV /Herpes Simplex.

• Alcohol

• Drug toxicity : Predictable: Paracetamol

Unpredictable:INH

• Environmental toxins : Vinyl chloride (PVC)Ca

Jamaica Bush Tea

Kava Kava

Wild mushrooms

• Wilson’s disease

• Autoimmune hepatitis.

• Viral Hepatitis : A,B,C,D,E / EBV / CMV /Herpes Simplex.

• Alcohol

• Drug toxicity : Predictable: Paracetamol

Unpredictable:INH

• Environmental toxins : Vinyl chloride (PVC)Ca

Jamaica Bush Tea

Kava Kava

Wild mushrooms

• Wilson’s disease

• Autoimmune hepatitis.

Alcoholic Liver DiseaseAlcoholic Liver Disease• The history is the key – 60 grams-aprox 60ml/day

• Gynecomastia, parotids, Dupuytren’s

• Lab clues: SGOT/SGPT > 2, SGOT < 300

• Alcoholic hepatitis:Anorexia, fever, jaundice, hepatomegaly

• Treatment: Abstinence,Nutrition

• Prednisolone (Antiinflamatory)

• Pentoxifylline (Decreases the risk of developing hepatorenal syndrome and thus diminishes mortality.

• The history is the key – 60 grams-aprox 60ml/day

• Gynecomastia, parotids, Dupuytren’s

• Lab clues: SGOT/SGPT > 2, SGOT < 300

• Alcoholic hepatitis:Anorexia, fever, jaundice, hepatomegaly

• Treatment: Abstinence,Nutrition

• Prednisolone (Antiinflamatory)

• Pentoxifylline (Decreases the risk of developing hepatorenal syndrome and thus diminishes mortality.

Alcoholic Liver DiseaseAlcoholic Liver DiseaseDiscriminant Function Formula:

DF =[4.6 x (Pt PT – control PT)] + T.Bili

Consider treatment for DF > 32

• Prednisolone 40 mg/day x 28 days

– contraindications: infection, renal failure, GIB

• Pentoxifylline 400 mg PO tid x 28 days

Discriminant Function Formula:

DF =[4.6 x (Pt PT – control PT)] + T.Bili

Consider treatment for DF > 32

• Prednisolone 40 mg/day x 28 days

– contraindications: infection, renal failure, GIB

• Pentoxifylline 400 mg PO tid x 28 days

Autoimmune HepatitisAutoimmune Hepatitis• Widely variable clinical presentations

– Asymptomatic LFT abnormality (ALT and AST)

– Severe hepatitis with jaundice

– Cirrhosis and complications of portal HTN

• Often associated with other autoimmune dz

• Diagnosis:

– Compatible clinical presentation

– ANA or ASMA with titer 1:80 or greater

– IgG > 1.5 upper limits of normal

– Liver biopsy: portal lymphocytes + plasma cells

• Widely variable clinical presentations

– Asymptomatic LFT abnormality (ALT and AST)

– Severe hepatitis with jaundice

– Cirrhosis and complications of portal HTN

• Often associated with other autoimmune dz

• Diagnosis:

– Compatible clinical presentation

– ANA or ASMA with titer 1:80 or greater

– IgG > 1.5 upper limits of normal

– Liver biopsy: portal lymphocytes + plasma cells

Acetaminophen ToxicityAcetaminophen Toxicity• Safe Dose is < 4 gms/Day for an adult.

• Danger dosages (70 kg patient)

– Toxicity possible > 10 gm

– Severe toxicity certain > 25 gm

– Lower doses potentially hepatotoxic in:

• Chronic alcoholics

• Malnutrition or fasting

• Dilantin, Tegretol, phenobarbital, INH, rifampin

-Antidote – N acetyl cysteine within 16 Hrs

• Safe Dose is < 4 gms/Day for an adult.

• Danger dosages (70 kg patient)

– Toxicity possible > 10 gm

– Severe toxicity certain > 25 gm

– Lower doses potentially hepatotoxic in:

• Chronic alcoholics

• Malnutrition or fasting

• Dilantin, Tegretol, phenobarbital, INH, rifampin

-Antidote – N acetyl cysteine within 16 Hrs

Post - hepaticPost - hepaticPost - hepaticPost - hepatic

• ALT(SGPT) N or ↑

• ALP(Alk PO4) ↑ ↑ ↑

• Bil ↑

• INR ↑

• CEA, Ca19.9 ↑

• Pancreatic & cholangio Ca

• ALT(SGPT) N or ↑

• ALP(Alk PO4) ↑ ↑ ↑

• Bil ↑

• INR ↑

• CEA, Ca19.9 ↑

• Pancreatic & cholangio Ca

Cholestatic Jaundice-IntrahepaticCholestatic Jaundice-Intrahepatic

• Viral : B & C

Fibrosing cholestatic

HepA,EBV,CMV

• Alcoholic hepatitis

• Drug Toxicity :

Pure cholestasis-Anabolic Steroids

Contraceptives

Cholestatic Hepatitis

Chlorpromazine

Erythromycin

• Viral : B & C

Fibrosing cholestatic

HepA,EBV,CMV

• Alcoholic hepatitis

• Drug Toxicity :

Pure cholestasis-Anabolic Steroids

Contraceptives

Cholestatic Hepatitis

Chlorpromazine

Erythromycin

Chronic cholestasis

Chlorpromazine,

Prochlorperzine.

• Primary Biliary Cirrhosis

• Prim Scler Cholangitis

• Vanishing Bile duct Syn

• Inherited – progr familial intrahepatic cholestasis

Benign recur cholestas

• Cholestasis of Preg

• TPN

• Non hepatobil sepsis

Chronic cholestasis

Chlorpromazine,

Prochlorperzine.

• Primary Biliary Cirrhosis

• Prim Scler Cholangitis

• Vanishing Bile duct Syn

• Inherited – progr familial intrahepatic cholestasis

Benign recur cholestas

• Cholestasis of Preg

• TPN

• Non hepatobil sepsis

Cholestatic Jaundice-Intrahepatic- contCholestatic Jaundice-Intrahepatic- cont• Benign Post op cholest

• Paraneoplastic Syndr

• Venoocclusive Dis

• Infiltrative diseases

TB,Lymphoma,sarcoid

• Benign Post op cholest

• Paraneoplastic Syndr

• Venoocclusive Dis

• Infiltrative diseases

TB,Lymphoma,sarcoid

Cholestatic Jaundice-ExtrahepaticCholestatic Jaundice-Extrahepatic• A. Malignant

Cholangiocarcinoma,Pancreatic ca, Ca-GB,

Ampulla Ca, Malig involvement of porta hepatis

lymph nodes.

• B. Benign

Choledocolithiasis,Post op biliary stricture,

Primary sclerosing cholangitis, Chronic

pancreatitis, AIDS Cholangiopathy,

Mirizzi Syndrome:stricture of common hepatic duct

Parasitic disease- Ascariasis.

• A. Malignant

Cholangiocarcinoma,Pancreatic ca, Ca-GB,

Ampulla Ca, Malig involvement of porta hepatis

lymph nodes.

• B. Benign

Choledocolithiasis,Post op biliary stricture,

Primary sclerosing cholangitis, Chronic

pancreatitis, AIDS Cholangiopathy,

Mirizzi Syndrome:stricture of common hepatic duct

Parasitic disease- Ascariasis.

Obstructive JaundiceObstructive JaundiceCBD stones (choledocholithiasis) vs. tumor

• Clinical features favoring CBD stones:

– Age < 45

– Biliary colic

– Fever

– Transient spike in AST or amylase

• Clinical features favoring cancer:

– Painless jaundice

– Weight loss

– Palpable gallbladder

– Bilirubin > 10

CBD stones (choledocholithiasis) vs. tumor

• Clinical features favoring CBD stones:

– Age < 45

– Biliary colic

– Fever

– Transient spike in AST or amylase

• Clinical features favoring cancer:

– Painless jaundice

– Weight loss

– Palpable gallbladder

– Bilirubin > 10

Ascending CholangitisAscending Cholangitis• Pus under pressure

• Charcot’s triad: fever, jaundice, RUQ pain

– All 3 present in 70% of patients, but fever > 95%

– May also present as confusion or hypotension

• Most frequent causative organisms:

– E. Coli, Klebsiella, Enterobacter, Enterococcus

– anaerobes are rare and usually post-surgical

• Treatment:

– Antibiotics: Levaquin, Zosyn, meropenem

– ERCP with biliary drainage

• Pus under pressure

• Charcot’s triad: fever, jaundice, RUQ pain

– All 3 present in 70% of patients, but fever > 95%

– May also present as confusion or hypotension

• Most frequent causative organisms:

– E. Coli, Klebsiella, Enterobacter, Enterococcus

– anaerobes are rare and usually post-surgical

• Treatment:

– Antibiotics: Levaquin, Zosyn, meropenem

– ERCP with biliary drainage

Ascending CholangitisIndications for Urgent ERCP

Ascending CholangitisIndications for Urgent ERCP

• Persistent abdominal pain

• Hypotension despite adequate IVF

• Fever > 102

• Mental confusion

• Failure to improve after 12 hours of antibiotics and supportive care

• Persistent abdominal pain

• Hypotension despite adequate IVF

• Fever > 102

• Mental confusion

• Failure to improve after 12 hours of antibiotics and supportive care

Obstructive JaundiceMalignant Causes

Obstructive JaundiceMalignant Causes

• Cancer of the Pancreas

• Cancer of the Bile Ducts (Cholangiocarcinoma)

• Ampullary Tumors

• Portal Lymphadenopathy

• Cancer of the Pancreas

• Cancer of the Bile Ducts (Cholangiocarcinoma)

• Ampullary Tumors

• Portal Lymphadenopathy

Primary Biliary CirrhosisPrimary Biliary Cirrhosis• Cholestatic liver disease (ALP)

– Most common symptoms: pruritus and fatigue

– Many patients asx, and dx by abnormal LFT

• Female:male ratio 9:1

• Diagnosis:

– Compatible clinical presentation

– AMA titer 1:80 or greater (95% sens/spec)

– IgM > 1.5 upper limits of normal

– Liver biopsy: bile duct destruction

• Treatment: Ursodeoxycholic acid 15 mg/kg

• Cholestatic liver disease (ALP)

– Most common symptoms: pruritus and fatigue

– Many patients asx, and dx by abnormal LFT

• Female:male ratio 9:1

• Diagnosis:

– Compatible clinical presentation

– AMA titer 1:80 or greater (95% sens/spec)

– IgM > 1.5 upper limits of normal

– Liver biopsy: bile duct destruction

• Treatment: Ursodeoxycholic acid 15 mg/kg

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis• Cholestatic liver disease (ALP)

• Inflammation of large bile ducts

• 90% associated with IBD

– but only 5% of IBD patients get PSC

• Diagnosis: ERCP (now MRCP)

– No autoantibodies, no elevated globulins

– Biopsy: concentric fibrosis around bile ducts

• Cholangiocarcinoma: 10-15% lifetime risk

• Treatment: Liver Transplantation

• Cholestatic liver disease (ALP)

• Inflammation of large bile ducts

• 90% associated with IBD

– but only 5% of IBD patients get PSC

• Diagnosis: ERCP (now MRCP)

– No autoantibodies, no elevated globulins

– Biopsy: concentric fibrosis around bile ducts

• Cholangiocarcinoma: 10-15% lifetime risk

• Treatment: Liver Transplantation

Diagnosis of Immune-Mediated Liver Disease

Diagnosis of Immune-Mediated Liver Disease

LFT Serology Quantitative Immunoglobulins

Biopsy

AIH SGPT ANA

ASMA

IgG Portal inflammation

Plasmacytes

Piecemeal necrosis

PBC ALP AMA IgM Bile duct destruction

granulomas

PSC ALP none normal Periductal concentric

fibrosis

Common causes of JaundiceCommon causes of Jaundice

• Hepatitis

• Obstructive jaundice

• Primary liver cancer

• Liver secondaries

• Cirrhosis

• Haemolysis

• Gilbert’s syndrome

• Septicaemia

• Hepatitis

• Obstructive jaundice

• Primary liver cancer

• Liver secondaries

• Cirrhosis

• Haemolysis

• Gilbert’s syndrome

• Septicaemia

Unusual Causes of JaundiceUnusual Causes of Jaundice

• Ischemic hepatitis

• Congestive hepatopathy

• Wilson’s disease

• AIDS cholangiopathy

• Amanita phalloides (mushrooms)

• Jamaican bush tea

• Infiltrative diseases of the liver

– Amyloidosis

– Sarcoidosis

– Malignancy: lymphoma, metastatic dz

• Ischemic hepatitis

• Congestive hepatopathy

• Wilson’s disease

• AIDS cholangiopathy

• Amanita phalloides (mushrooms)

• Jamaican bush tea

• Infiltrative diseases of the liver

– Amyloidosis

– Sarcoidosis

– Malignancy: lymphoma, metastatic dz

Wilson’s DiseaseWilson’s Disease• Autosomal recessive – copper metabolism

• Chronic hepatitis or fulminant hepatitis

• Associated clinical features:

– Neuropsychiatric disease

– Hemolytic anemia

• Physical exam: Kayser-Fleischer rings

• Diagnosis: ceruloplasmin, urinary Cu

• Treatment: d-penicillamine

• Autosomal recessive – copper metabolism

• Chronic hepatitis or fulminant hepatitis

• Associated clinical features:

– Neuropsychiatric disease

– Hemolytic anemia

• Physical exam: Kayser-Fleischer rings

• Diagnosis: ceruloplasmin, urinary Cu

• Treatment: d-penicillamine

LFTs and urine summaryLFTs and urine summaryLFTs and urine summaryLFTs and urine summary

BloodBlood UrineUrine

SGPTSGPT ALPALP BilBil UrobilinogenUrobilinogen BilirubinBilirubin

Pre- Pre- hepatichepatic

N N ↑↑ Present absent

HepaticHepatic ↑↑↑ N or ↑ ↑↑ N Present

Post-Post-

hepatichepaticN or ↑ ↑↑↑ ↑↑ absent Present

Broad Differential DiagnosisBroad Differential Diagnosis↑production ↓transport or

↓conjugationImpaired excretion

Biliary obstruction

↑ Unconjugate ↑ Unconjugate ↑ Conjugated ↑ Conjugated

Hemolysis Gilbert’s Rotor’s CH/CBD stone

Transfusions Crigler-Najarr DubinJohnson Stricture

Txfusion rxn Neonatal Cancer Cancer

Sepsis Cirrhosis Cirrhosis Chronic pancreatitis

Burns Hepatitis Hepatitis PSC

Hgb-opathies Drug inhibition Amyloidosis

Pregnancy

Causes of JaundiceCauses of JaundiceUnconjugated hyperbilirubinemia•Hemolysis

– Glucose-6-phosphate deficiency– Medications

•Bilirubin overproduction– Ineffective erythropoiesis– Large hematoma– Pulmonary embolism with infarction

•Neonatal causes– Physiologic jaundice– Breast milk jaundice

•Uridine diphosphate glucuronosyltransferase deficiencies– Gillbert’s syndrome– Crigler-Najjar syndrome ( I and II)

•Miscellaneous causes– Hypothyroidism– Thyrotoxicosis– Fasting

Unconjugated hyperbilirubinemia•Hemolysis

– Glucose-6-phosphate deficiency– Medications

•Bilirubin overproduction– Ineffective erythropoiesis– Large hematoma– Pulmonary embolism with infarction

•Neonatal causes– Physiologic jaundice– Breast milk jaundice

•Uridine diphosphate glucuronosyltransferase deficiencies– Gillbert’s syndrome– Crigler-Najjar syndrome ( I and II)

•Miscellaneous causes– Hypothyroidism– Thyrotoxicosis– Fasting

Causes of JaundiceCauses of JaundiceConjugated hyperbilirubinemia• Congenital causes

– Rotor’s syndrome– Dubin-Johnson syndrome– Choledochal cysts

• Familial disorders– Benign recurrent intrahepatic cholestasis– Cholestasis of pregnancy

• Hepatocellular defects– Ethanol abuse– Viral infection

• Cholestatic syndromes– Primary billiary cirrhosis– Primary sclerosing cholangitis– Billiary obstruction– Pancreatic disease

• Systemic disease

• Infiltrative disorders

• Postoperative complications

• Renal disease

• Sepsis

• Medications

Conjugated hyperbilirubinemia• Congenital causes

– Rotor’s syndrome– Dubin-Johnson syndrome– Choledochal cysts

• Familial disorders– Benign recurrent intrahepatic cholestasis– Cholestasis of pregnancy

• Hepatocellular defects– Ethanol abuse– Viral infection

• Cholestatic syndromes– Primary billiary cirrhosis– Primary sclerosing cholangitis– Billiary obstruction– Pancreatic disease

• Systemic disease

• Infiltrative disorders

• Postoperative complications

• Renal disease

• Sepsis

• Medications

HistoryHistory• Oral Exposure:Alcohol,Chemicals,Rx Med,OTC Med,

Complementary med,Alternative Med,Contamin food.

• Parenteral Exposure:IV inj,Transfusions, Tattoo(Hep C), Intranasal drugs(Hep C)

• Sexual exposure(Hep B).

• Exposure to Endemic area-Travel history(Hep A).

• Professional Exposure:Drs,Paramedics(Hep B+C).

• Occupational exposure to Hepatotoxins.

• Oral Exposure:Alcohol,Chemicals,Rx Med,OTC Med, Complementary med,Alternative Med,Contamin food.

• Parenteral Exposure:IV inj,Transfusions, Tattoo(Hep C), Intranasal drugs(Hep C)

• Sexual exposure(Hep B).

• Exposure to Endemic area-Travel history(Hep A).

• Professional Exposure:Drs,Paramedics(Hep B+C).

• Occupational exposure to Hepatotoxins.

HepatotoxinsHepatotoxins• Molibdinum

• Nickel.

• Phosphorus.

• Selenium.

• Thallium.

• Tin.

• Molibdinum

• Nickel.

• Phosphorus.

• Selenium.

• Thallium.

• Tin.

• Antimony

• Arsenic

• Barium

• Bismuth.

• Cadmium.

• Chromium.

• Copper.

• Iron.

• Lead.

• Manganese.

• Antimony

• Arsenic

• Barium

• Bismuth.

• Cadmium.

• Chromium.

• Copper.

• Iron.

• Lead.

• Manganese.

Occupational ExposureOccupational ExposureOccupation Maker Worker User

Artificial pearls

Air Pilots, Hanger workers

Cement,Rubber,Plastic,Leather

Chemical,Pharma industry

Color,Dye,Insecticides

Glass,Ink,Paint,Perfumes

Dry cleaners,Varnish,Waterproofer

Metal polish

Refrigeration,Printers

Soap,Thermometer,Wax

Tobacco denicotisers.

History for the Jaundice PatientsHistory for the Jaundice Patients• Related to viral hepatitis – Preceding arthralgia/myalgia

• Blood transfusions – B

• Intravenous drug use – B

• Needle stick exposure – B

• Sexual practices – HIV hepatitis

• Contact with jaundiced persons – B

• Work in renal dialysis units – B

• Surgeons in trauma units - B

• exposed to IV drug users - B

• Shared razors/tooth brushes - B

• Body piercing (ears,nose) -B

• Tattoos -B

• Related to viral hepatitis – Preceding arthralgia/myalgia

• Blood transfusions – B

• Intravenous drug use – B

• Needle stick exposure – B

• Sexual practices – HIV hepatitis

• Contact with jaundiced persons – B

• Work in renal dialysis units – B

• Surgeons in trauma units - B

• exposed to IV drug users - B

• Shared razors/tooth brushes - B

• Body piercing (ears,nose) -B

• Tattoos -B

SYMPTOMSSYMPTOMS

• Fever- Low gr to High grade

• Low gr-hepatits

• High gr + RUQ abd pain-Choledocolithiasis,Ascending colangitis.

• Arthralgia,Myalgia

• Rash

• Anorexia, Wt loss

• Avulsion to tobacco • Abd Pain-Mild/Severe, Acute/Chronic• Pruritus• Change in urine,stool colour

• Fever- Low gr to High grade

• Low gr-hepatits

• High gr + RUQ abd pain-Choledocolithiasis,Ascending colangitis.

• Arthralgia,Myalgia

• Rash

• Anorexia, Wt loss

• Avulsion to tobacco • Abd Pain-Mild/Severe, Acute/Chronic• Pruritus• Change in urine,stool colour

Physical Examination

Ascites+Jaundice.

Laennec’s(Alcoholic)+other cirrhosis

CirrhosisMalignancy

Abd.Malignancy

Murphy’s sign :Severe RUQ tenderness with resp arrest in inspiration.

Enlarged tender liver,

Jugular venous distention, edema, Enlarged tender liver.

Enl supracl node(Virchow’s node),Periumbilical

node(sister marry joseph’s node),Nodular hard liver.

Spider nevi,palmar erythema,gynecomastia,caput medusae,Dupuytren’s contracture,Enlaged parotids,testicular

atrophy,R.pl effusion,Enlarged L.lobe of liver,Ascites,Enl spleen.

CholecystitisAcute Cholangitis

Viral Hepatitis,Amyloidosis,

R.Heart failure.

R.Sided Heart failure

Spider Nevi

Palmar Erythema

Gynecomastia

Caput Medusae

Dupuytren’s contracture

Virchow’s Node

Sister Marry Joseph’s Nodule.

Gross specimen of cirrhosis of the liver

Gross specimen of cirrhosis of the liver

Evaluation of the Jaundiced PatientPHYSICAL EXAM

Evaluation of the Jaundiced PatientPHYSICAL EXAM

• BP/HR/Temp

• Mental status

• Asterixis

• Abd tenderness

• Liver size

• Splenomegaly

• Ascites

• Edema

• BP/HR/Temp

• Mental status

• Asterixis

• Abd tenderness

• Liver size

• Splenomegaly

• Ascites

• Edema

• Spider angiomata

• Hyperpigmentation

• Kayser-Fleischer rings

• Xanthomas

• Gynecomastia

• Left supraclavicular adenopathy (Virchow’s node)

• Spider angiomata

• Hyperpigmentation

• Kayser-Fleischer rings

• Xanthomas

• Gynecomastia

• Left supraclavicular adenopathy (Virchow’s node)

Common causes of Jaundice and relevant investigations

Common causes of Jaundice and relevant investigations

• Acute hepatitis

– Hepatitis serology

– HBsAg, IgM anti-HBc, HBeAg, Anti-HBe

– IgM anti HAV, Anti Delta antibody

– Anti HCV

– Ig M anti HEV

– IgM EBV, IgM CMV, IgM Lepto antibody

• Pancreatic/biliary disease

– Ultrasonography

– Endoscopic retrograde cholangio-pancreatography

– Percutaneous transhepatic cholangiography

– CT Scanning

– MRI-MRCP

• Acute hepatitis

– Hepatitis serology

– HBsAg, IgM anti-HBc, HBeAg, Anti-HBe

– IgM anti HAV, Anti Delta antibody

– Anti HCV

– Ig M anti HEV

– IgM EBV, IgM CMV, IgM Lepto antibody

• Pancreatic/biliary disease

– Ultrasonography

– Endoscopic retrograde cholangio-pancreatography

– Percutaneous transhepatic cholangiography

– CT Scanning

– MRI-MRCP

Common causes of Jaundice and relevant investigations - contd

Common causes of Jaundice and relevant investigations - contd

• Malignancy

– Liver biopsy

– Alpha fetoprotein

• Cirrhosis

– Liver biopsy

– Immunoglobulins

– Auto antibodies

– Iron studies

– Serum, urine and liver copper; serum ceruloplasmin

– Alpha 1 antitrypsin

• Malignancy

– Liver biopsy

– Alpha fetoprotein

• Cirrhosis

– Liver biopsy

– Immunoglobulins

– Auto antibodies

– Iron studies

– Serum, urine and liver copper; serum ceruloplasmin

– Alpha 1 antitrypsin

Common causes of Jaundice and relevant investigations - contd

Common causes of Jaundice and relevant investigations - contd

• Haemolysis

– Reticulocyte count

– Haptoglobin

– Direct and indirect Coombs’ Test

– G-6-P-D level

• Gilbert’s Syndrome

– Increase in unconjugated bilirubin following 2-3 days on 1 400 calorie diet

• Haemolysis

– Reticulocyte count

– Haptoglobin

– Direct and indirect Coombs’ Test

– G-6-P-D level

• Gilbert’s Syndrome

– Increase in unconjugated bilirubin following 2-3 days on 1 400 calorie diet

Tips on Interpretation of Lab TestsTips on Interpretation of Lab Tests• SGPT?OT > ALP Hepatocellular Process

• ALP > SGPT/ OT Cholestatic Process

• Bilirubin : Increased in both but if

D>I : Cholestatic

I>D : Prehepatic.

D=I : Hepatocellular

.Albumin – if normal Acute cause like

Hepatits,Choledocolithiasis.

Prothrombin time: chronic cause + Signific hepatocell dysfunction.

If PT improves after inj Vit K Good liver functions.

If PT doesn’t improve after KSev hepatocellular injury.

• SGPT?OT > ALP Hepatocellular Process

• ALP > SGPT/ OT Cholestatic Process

• Bilirubin : Increased in both but if

D>I : Cholestatic

I>D : Prehepatic.

D=I : Hepatocellular

.Albumin – if normal Acute cause like

Hepatits,Choledocolithiasis.

Prothrombin time: chronic cause + Signific hepatocell dysfunction.

If PT improves after inj Vit K Good liver functions.

If PT doesn’t improve after KSev hepatocellular injury.

Haemolytic anaemiaHaemolytic anaemia

Mechanism Examples

Abnormal red cell Hereditary spherocytosismembrane Drug e.g. Sulphonamides

sulphonylureas, alpha-methyldopa, levodopa Primary immune deficiency

Rigid red cell membrane Sickle cell , Thalassaemia

Trauma to red cells Cardiac haemolysis (prostheticvalves) Microangiopathic

haemolysis

Mechanism Examples

Abnormal red cell Hereditary spherocytosismembrane Drug e.g. Sulphonamides

sulphonylureas, alpha-methyldopa, levodopa Primary immune deficiency

Rigid red cell membrane Sickle cell , Thalassaemia

Trauma to red cells Cardiac haemolysis (prostheticvalves) Microangiopathic

haemolysis

Commonly used drugs causing jaundiceCommonly used drugs causing jaundice

• Drugs causing hepatitis– Amitriptyline– Isoniazid– Erythromycin (estolate)– Nitrofurantoin– Paracetamol (more than 4g a

day)– Ferrous sulphate overdose– Halothane

• Drugs causing cholestasis– Oral contraceptives– Chlorpromazine– Haloperidol– Chlorpropamide

• Drugs causing hepatitis– Amitriptyline– Isoniazid– Erythromycin (estolate)– Nitrofurantoin– Paracetamol (more than 4g a

day)– Ferrous sulphate overdose– Halothane

• Drugs causing cholestasis– Oral contraceptives– Chlorpromazine– Haloperidol– Chlorpropamide

Causes of postoperative jaundiceCauses of postoperative jaundice• Hypertension/cardiac failure

• Post-transfusion hepatitis

• Drugs including anaesthetics, particularly halothane on second exposure

• Unmasked chronic liver disease

• Unmasked biliary tract disease

• Pulmonary embolism

• Acalculus/acute cholecystitis

• Transfusion load/haemolysis post cardiopulmonary bypass pump

• Cholestasis following major abdominal surgery & TPN

• Sepsis (pneumonia,urinary tract infection)

• Hypertension/cardiac failure

• Post-transfusion hepatitis

• Drugs including anaesthetics, particularly halothane on second exposure

• Unmasked chronic liver disease

• Unmasked biliary tract disease

• Pulmonary embolism

• Acalculus/acute cholecystitis

• Transfusion load/haemolysis post cardiopulmonary bypass pump

• Cholestasis following major abdominal surgery & TPN

• Sepsis (pneumonia,urinary tract infection)

Liver biopsy- indicationsLiver biopsy- indications• Assessment of abnormal liver function tests

• Diagnosis and prognosis of chronic hepatitis and/or cirrhosis

• Confirmation and prognosis of alcoholic liver disease

• Detection of systemic disorders involving the liver, including fever of unknown origin

• Assessment and severity of drug inducted liver injury

• Confirmation of suspected hepatic malignancy, primary or metastatic

• Confirmation of multisystem infiltrative disorders

• Screening of relatives of patients with familial disease

• Tissue of culture

• Evaluation of response to therapies for liver disease (e.g. Wilson’s disease, hemochromatosis, autoimmune hepatitis, chronic viral hepatitis)

• Exclusion of graft rejection, reinfection, or ischemia after liver transplant

• Assessment of abnormal liver function tests

• Diagnosis and prognosis of chronic hepatitis and/or cirrhosis

• Confirmation and prognosis of alcoholic liver disease

• Detection of systemic disorders involving the liver, including fever of unknown origin

• Assessment and severity of drug inducted liver injury

• Confirmation of suspected hepatic malignancy, primary or metastatic

• Confirmation of multisystem infiltrative disorders

• Screening of relatives of patients with familial disease

• Tissue of culture

• Evaluation of response to therapies for liver disease (e.g. Wilson’s disease, hemochromatosis, autoimmune hepatitis, chronic viral hepatitis)

• Exclusion of graft rejection, reinfection, or ischemia after liver transplant

Liver biopsy- contra-indicationsLiver biopsy- contra-indications

Absolute Relative

Severe coagulopathy Ascites

PT > 3 seconds prolonged

Platelets < 60 000/mm

Abnormal bleeding time

Suspected echinococcal disease

Presumed hemangioma

Uncooperative patient

Absolute Relative

Severe coagulopathy Ascites

PT > 3 seconds prolonged

Platelets < 60 000/mm

Abnormal bleeding time

Suspected echinococcal disease

Presumed hemangioma

Uncooperative patient

Critical Questions in the Evaluation of the Jaundiced Patient

Critical Questions in the Evaluation of the Jaundiced Patient

• Acute vs. Chronic Liver Disease

• Hepatocellular vs. Cholestatic

– Biliary Obstruction vs. Intrahepatic Cholestasis

• Fever

– Could the patient have ascending cholangitis?

• Encephalopathy

– Could the patient have fulminant hepatic failure?

• Acute vs. Chronic Liver Disease

• Hepatocellular vs. Cholestatic

– Biliary Obstruction vs. Intrahepatic Cholestasis

• Fever

– Could the patient have ascending cholangitis?

• Encephalopathy

– Could the patient have fulminant hepatic failure?

Evaluation of the Jaundiced PatientLAB EVALUATION

Evaluation of the Jaundiced PatientLAB EVALUATION

• AST-ALT-ALP

• Bilirubin – total/indirect

• Albumin

• INR

• Glucose

• Na-K-PO4, acid-base

• Acetaminophen level

• CBC/plt

• AST-ALT-ALP

• Bilirubin – total/indirect

• Albumin

• INR

• Glucose

• Na-K-PO4, acid-base

• Acetaminophen level

• CBC/plt

• Ammonia

• Viral serologies

• ANA-ASMA-AMA

• Quantitative Ig

• Ceruloplasmin

• Iron profile

• Blood cultures

• Ammonia

• Viral serologies

• ANA-ASMA-AMA

• Quantitative Ig

• Ceruloplasmin

• Iron profile

• Blood cultures

Drugs causing high SGPT/OTDrugs causing high SGPT/OT

• Aspirin,PCM

• Brufen,Naproxen

• Phenytoin,Sod valproate

• Carbamazepine

• Tetra,Sulpha,TMP

• INH,NFT,Fluconaz

• Aspirin,PCM

• Brufen,Naproxen

• Phenytoin,Sod valproate

• Carbamazepine

• Tetra,Sulpha,TMP

• INH,NFT,Fluconaz

• Statins

• Niacin

• Amiodarone

• Hydralazine

• Quinidine

• Tricyclic Antidep

• Statins

• Niacin

• Amiodarone

• Hydralazine

• Quinidine

• Tricyclic Antidep

Other disease causing abn OT/PTOther disease causing abn OT/PT

• Hemachromatosis

• Wilson’s disease

• Alpha 1 antitrypsin def(with emphysema)

• Celiac sprue

• Crohn’s disease

• Ulcerative colitis

• Hemachromatosis

• Wilson’s disease

• Alpha 1 antitrypsin def(with emphysema)

• Celiac sprue

• Crohn’s disease

• Ulcerative colitis

Evaluation of the Jaundiced PatientEvaluation of the Jaundiced Patient• Ultrasound:

– More sensitive than CT for gallbladder stones

– Equally sensitive for dilated ducts

– Portable, cheap, no radiation, no IV contrast

• CT:

– Better imaging of the pancreas and abdomen

• MRCP:

– Imaging of biliary tree comparable to ERCP

• ERCP:

– Therapeutic intervention for stones

– Brushing and biopsy for malignancy

• Ultrasound:

– More sensitive than CT for gallbladder stones

– Equally sensitive for dilated ducts

– Portable, cheap, no radiation, no IV contrast

• CT:

– Better imaging of the pancreas and abdomen

• MRCP:

– Imaging of biliary tree comparable to ERCP

• ERCP:

– Therapeutic intervention for stones

– Brushing and biopsy for malignancy

Utility of Liver Function TestUtility of Liver Function Test

• Sensitive and non invasive method of screening for the presence of liver dysfunction

• The pattern of test abnormalities may allow to recognize type of liver disorder

• To assess the severity of liver disorder

• To follow the course of disease

• Sensitive and non invasive method of screening for the presence of liver dysfunction

• The pattern of test abnormalities may allow to recognize type of liver disorder

• To assess the severity of liver disorder

• To follow the course of disease

THANK YOU ALL !THANK YOU ALL !

Thanks to my son Vishwas

for helping me in preparing this PPT

presentation !