jaundice master ppt
TRANSCRIPT
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 !