38257492 Jaundice Master PPT

8/4/2019 38257492 Jaundice Master PPT

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Approach to the Patients with Jaundice

Dr Suresh Kubavat

MD (Internal Medicine)

Consultant Physician

Shradha Arogyamandir - Junagadh

9427257977


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Gross Hepatic Anatomy


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Gross Hepatic Anatomy


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Liver Histological Structure


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Liver Histological Structure


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Functions 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


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Normal 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


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Normal Bilirubin Metabolism

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

-20% from premature destruction in BM

HemoglobinHeme + GlobinHemeBiliverdin+CO+IronBiliverdin(Water insoluble)Binds with Albumin(becomes

water soluble)Liver:unconj bil taken up by hepatocytesconjugates to glucuronic acidBileexcr to intestinegoes to terminal ilium+colonbecomes unconjugatedconverted to urobilinogen80-90% excreted in faeces

as urobilins+10-20% absorbed thru intestineportal v.LiverReexcreted A small fraction esca es he atic u take excr in urine


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Pathophysiology 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 orobstructive jaundice

Cholestasis refers to the latter two,

impaired excretion and obstructive jaundice


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Definition of Jaundice

Jaundice is yellow discoloration of the sclera,skin and mucous membranes resulting fromaccumulation 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)


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

Isolated elevation ofthe Bilirubin

Bilirubin & otherliver tests elevated

Directhyperbilirubinemia

Inherited disorders1. Dubin Johnson Syndrome2. Rotors Syndrome

Indirecthyperbilirubinemia

DrugsRifampicin

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

Inherited Disorders1. Gilberts Syndrome2. CriglerNajjar Syndromes


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ALGORITHM CONTINUED

Bilirubin & other liver tests elevated

Hepatocellular Pattern Cholestatic Pattern

SGPT/OT elevated out ofproportion to

Alkaline phosphatase

Alkaline phosphataseelevated out of proportion to

SGPT/OT


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Hepatocellular 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 MicrosomalAntibody), SPEP( Serumprotein electrophoresis)

Additional VirologicTesting

CMV DNA, EBV capsidantigen

Hepatitis D antibody(Ifindicated)

Hepatitis E IgM(Ifindicated)

If negative

If negative LiverBiopsy


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Cholestatic Pattern

UltrasoundDilated DuctsExtra hepaticcholestasis

CT/ERCP

Ducts not DilatedIntra hepaticcholestasis

Serologic testingAMAHepatitis SerologiesHepatitis ACMV, EBVReview Drugs

MRCP/Liver Biopsy

Liver Biopsy

Negative

AMA +ve


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Prehepatic

Unconguated Bil

LFTs N

Haptoglobins (aprotein in bloodthat combines withhb to form acomplex that isremoved from @ bythe liver)

Reticulocytes

Coombs test +ve

Urine urobilinogen +


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Hepatic ALT(SGPT)

ALP N or

Bil

Albumin

INR

Hepatitis serology

Autoantibodies

Anti-mitochondrial PBC

Anti-nuclear & antimicrosomal, Autoimmune

hepatitis

Caeruloplasmin

Wilsons

-Globulins

Cirrhosis esp autoimmune

Transferrin

Haemochromatosis

-foetoprotein, FP

HCC(Hepato cellula Carcinoma) in cirrhosis

H ti C


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

Alcohol

Drug toxicity : Predictable: Paracetamol

Unpredictable:INH

Environmental toxins : Vinyl chloride (PVC)CaJamaica Bush Tea

Kava Kava

Wild mushrooms Wilsons disease

Autoimmune hepatitis.


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

Gynecomastia, parotids, Dupuytrens

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

Alcoholic hepatitis:Anorexia, fever, jaundice,hepatomegaly

Treatment: Abstinence,Nutrition

Prednisolone (Antiinflamatory)

Pentoxifylline (Decreases the risk ofdeveloping hepatorenal syndrome andthus diminishes mortality.


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Alcoholic Liver Disease

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 28days


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Autoimmune 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


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Acetaminophen 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


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Post - hepatic

ALT(SGPT) N or

ALP(Alk PO4)

Bil INR

CEA, Ca19.9

Pancreatic &cholangio Ca

Ch l t ti J di I t h ti


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Cholestatic Jaundice-Intrahepatic

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 familialintrahepatic cholestasis

Benign recur cholestas

Cholestasis of Preg

TPN

Non hepatobil sepsis


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Cholestatic Jaundice-Intrahepatic- cont

Benign Post op cholest

Paraneoplastic Syndr

Venoocclusive Dis

Infiltrative diseases

TB,Lymphoma,sarcoid

Ch l t ti J di E t h ti


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Cholestatic 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.


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Obstructive 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


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Ascending Cholangitis

Pus under pressure Charcots 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


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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


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Obstructive JaundiceMalignant Causes

Cancer of the Pancreas

Cancer of the Bile Ducts(Cholangiocarcinoma)

Ampullary Tumors

Portal Lymphadenopathy

P i Bili Ci h i


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Primary Biliary Cirrhosis Cholestatic liver disease (ALP)

Most common symptoms: pruritus andfatigue

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 Cholangitis


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Primary 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


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Diagnosis ofImmune-Mediated Liver Disease

LFT Serology QuantitativeImmunoglobulins

Biopsy

AIH SGPT ANA

ASMA

IgG Portalinflammation

Plasmacytes

Piecemealnecrosis

PBC ALP AMA IgMBile duct

destruction

granulomas

PSC ALP none normalPeriductalconcentric

fibrosis


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Common causes of Jaundice

Hepatitis

Obstructive jaundice

Primary liver cancer

Liver secondaries

Cirrhosis

Haemolysis

Gilberts syndrome

Septicaemia

U l C f J di


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Unusual Causes of Jaundice

Ischemic hepatitis

Congestive hepatopathy

Wilsons disease

AIDS cholangiopathy

Amanita phalloides (mushrooms)

Jamaican bush tea

Infiltrative diseases of the liver

Amyloidosis

Sarcoidosis

Malignancy: lymphoma, metastatic dz

Wilsons Disease


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Wilson 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


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LFTs and urine summary

Blood Urine

SGPT ALP Bil Urobilinogen Bilirubin

Pre-hepatic

N N Present absent

Hepatic N or N Present

Post-hepatic

N or absent Present

B d Diff i l Di i


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Broad Differential Diagnosisproduction transport or

conjugation

Impaired

excretion

Biliary

obstruction Unconjugate Unconjugate Conjugated Conjugated

Hemolysis Gilberts Rotors CH/CBD stone

Transfusions Crigler-Najarr DubinJohnson Stricture

Txfusion rxn Neonatal Cancer Cancer

Sepsis Cirrhosis Cirrhosis Chronic

pancreatitisBurns Hepatitis Hepatitis PSC

Hgb-opathies Drug inhibition Amyloidosis

Pregnancy


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Causes 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 Gillberts syndrome Crigler-Najjar syndrome ( I and II)

Miscellaneous causes Hypothyroidism Thyrotoxicosis Fasting

Causes of Jaundice


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Causes of JaundiceConjugated hyperbilirubinemia

Congenital causes Rotors 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

History


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History

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.

Hepatotoxins


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Hepatotoxins

Molibdinum

Nickel.

Phosphorus.

Selenium.

Thallium.

Tin.

Antimony

Arsenic

Barium

Bismuth.

Cadmium.

Chromium.

Copper.

Iron. Lead.

Manganese.

Occupational Exposure


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Occupational 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.


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History 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

SYMPTOMS


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SYMPTOMS

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


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Physical Examination


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y

Ascites+Jaundice.

Laennecs(Alcohol

ic)+other cirrhosis

Cirrhosis

Malignancy

Abd.Malignancy

Murphys sign :Severe RUQ tenderness

with resp arrest in inspiration.

Enlarged tender liver,

Jugular venous distention, edema, Enlargedtender liver.

Enl supracl node(Virchows node),Periumbilical

node(sister marryjosephs node),Nodular hard liver.

Spider nevi,palmar erythema,gynecomastia,caputmedusae,Dupuytrens contracture,Enlaged parotids,testicular

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

.

CholecystitisAcute Cholangitis

ViralHepatitis,Amyloidosis,

R.Heart failure.

R.Sided Heartfailure

Spider Nevi


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Spider Nevi

Palmar Erythema


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Palmar Erythema

Gynecomastia


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Gynecomastia

Caput Medusae


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Caput Medusae

Dupuytrens contracture


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Dupuytren s contracture

Virchows Node


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Virchow s Node

Sister Marry Josephs Nodule.


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y p


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Gross specimen of cirrhosis


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pof the liver

Evaluation of the Jaundiced Patient


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PHYSICAL EXAM

BP/HR/Temp

Mental status

Asterixis

Abd tenderness

Liver size

Splenomegaly

Ascites

Edema

Spider angiomata

Hyperpigmentation

Kayser-Fleischerrings

Xanthomas

Gynecomastia

Left supraclavicularadenopathy(Virchows node)

Common causes of Jaundice and


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Common causes of Jaundice andrelevant 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



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Common causes of Jaundice andrelevant 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



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Common causes of Jaundice andrelevant investigations - contd

Haemolysis

Reticulocyte count

Haptoglobin

Direct and indirect Coombs Test

G-6-P-D level

Gilberts Syndrome

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

Tips on Interpretation of Lab Tests


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p p SGPT?OT > ALPHepatocellular Process ALP > SGPT/ OTCholestatic Process Bilirubin : Increased in both but if

D>I : Cholestatic

I>D : Prehepatic.

D=I : Hepatocellular

.Albumin if normal Acute cause likeHepatits,Choledocolithiasis.

Prothrombin time: chronic cause + Signific hepatocelldysfunction.

If PT improves after inj Vit K Good liver functions.If PT doesnt im rove afterKSev he atocellular in ur .


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Haemolytic anaemia

Mechanism Examples

Abnormal red cell Hereditary spherocytosismembrane Drug e.g. Sulphonamides

sulphonylureas, alpha-

methyldopa, levodopaPrimary immunedeficiency

Rigid red cell membrane Sickle cell , Thalassaemia

Trauma to red cells Cardiac haemolysis (prostheticvalves) Microangiopathichaemolysis

Commonly used drugs causing jaundice


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Commonly 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

Causes of postoperative jaundice


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Causes 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 cardiopulmonarybypass pump

Cholestasis following major abdominal surgery &TPN

Sepsis (pneumonia,urinary tract infection)

Liver biopsy indications


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Liver 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 ofunknown 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. Wilsonsdisease, hemochromatosis, autoimmune hepatitis, chronic viral hepatitis)

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

Li bi t i di ti


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Liver 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

Critical Questions in the Evaluation


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Critical Questions in the Evaluationof 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?

Evaluation of the Jaundiced PatientLAB EVALUATION


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LAB EVALUATION

AST-ALT-ALP

Bilirubintotal/indirect

Albumin

INR

Glucose

Na-K-PO4, acid-base

Acetaminophen level

CBC/ lt

Ammonia

Viral serologies

ANA-ASMA-AMA

Quantitative Ig

Ceruloplasmin

Iron profile

Blood cultures

D i hi h SGPT/OT


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Drugs causing high SGPT/OT

Aspirin,PCM

Brufen,Naproxen

Phenytoin,Sod

valproate

Carbamazepine

Tetra,Sulpha,TMP

INH,NFT,Fluconaz

Statins

Niacin

Amiodarone

Hydralazine

Quinidine

Tricyclic Antidep

Oth di i b OT/PT


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Other disease causing abn OT/PT

Hemachromatosis

Wilsons disease

Alpha 1 antitrypsin def(with emphysema)

Celiac sprue

Crohns disease

Ulcerative colitis



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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


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Utility of Liver Function Test

Sensitive and non invasive method of screening forthe 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 !


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THANK YOU ALL !

Thanks to my sonVishwas

for helping me inpreparing this PPT

presentation !

38257492 Jaundice Master PPT

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