Jaundice Dr Monika Pathania - PowerPoint Presentation

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Jaundice

Dr Monika Pathania

Slide2

Overview

Definition

Production & metabolism

Measurement of

bilirubin

– serum & urine

Approach to the patient

Broad Differential Diagnosis

Work-up for “Medical” Jaundice

Work-up if Obstructive Jaundice

Slide3

Definition

Yellowish discoloration of tissue resulting from the deposition of

bilirubin

in

hyperbilirubinemia

.

Detected by examining

sclerae

– ELASTIN

Scleral

icterus

-serum

bilirubin

of 3.0 mg/Dl

As serum

bilirubin

levels rise skin yellow in light-skinned &green if long-standing, oxidation of

bilirubin

to

biliverdin

.

Slide4

Differential diagnosis for yellowing of skin :

Drugs – quinacrine, phenols.

Carotenoderma -ingest excessive amounts of carotene. palms, soles, forehead, and nasolabial folds. sparing of the sclerae.

Slide5

Production and Metabolism of

Bilirubin

:

Bilirubin

, a

tetrapyrrole

pigment.

Slide6

Production steps:

Slide7

To be transported in blood,

bilirubin

must be

solubilized

by

noncovalent

binding to albumin.

Bilirubin

+ albumin=

unconjugated bilirubin transported to liver.

Bilirubin

minus albumin enters

hepatocyte

.

Slide8

Slide9

Measurement of Serum Bilirubin

van den Bergh reaction- direct- and indirect

the normal serum

bilirubin

is <1 mg/

dL

Up to 30% of the total may be direct-reacting (conjugated)

bilirubin

Slide10

Measurement of Urine

Bilirubin

Unconjugated

bilirubin

is always bound to albumin in the serum -not filtered by the kidney-not found in the urine.

Conjugated

bilirubin

is filtered at the

glomerulus

and the majority is reabsorbed by the proximal tubules; a small fraction is excreted in the urine

Any

bilirubin

found in the urine is conjugated

bilirubin

. The presence of

bilirubinuria

implies the presence of liver disease

Slide11

Approach to the Patient: JAUNDICE

Slide12

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Hepatocellular

Conditions that May Produce Jaundice

Viral

hepatitis – Viral serology, ALT>=AST

  Hepatitis A, B, C, D, and E

  Epstein-Barr virus

  Cytomegalovirus

  Herpes simplex

Alcohol – AST/ALT -2:1,AST rarely > 300

Drug toxicity

  Predictable, dose-dependent, e.g., acetaminophen

  Unpredictable,

idosyncratic

, e.g.,

isoniazid

Environmental toxins

  Vinyl chloride

  Jamaica bush tea—

pyrrolizidine

alkaloids

  Kava

Kava

  Wild mushrooms—

Amanita

phalloides

or

A.

verna

Wilson's

disease – young adult males where no

othr

cause of jaundice found

Autoimmune

hepatitis – middle aged females,

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Initial Evaluation: History

Jaundice, acholic stools, tea-colored urine

Fever/chills, RUQ pain (cholangitis)

Could lead to life-threatening septic shock

Reasons to have hepatitis or cirrhosis?

Alcohol, Viral, risk factors for viral hepatitis

Exposure to toxins or offending drugs

Inherited disorders or hemolytic conditions

Recent blood transfusions or blood loss?

Is patient septic or on TPN?

Recent gallbladder surgery? (CBD injury)

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While ALT and AST values less than 8 times normal may be seen in either

hepatocellular

or

cholestatic

liver disease, values 25 times normal or higher are seen primarily in acute

hepatocellular

diseases.

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Initial Evaluation: Physical Exam

Signs of end stage liver disease (cirrhosis)

Ascites, splenomegaly, spider angiomata, and gynecomastia

Jaundice evident first underneath the tongue, also evident in sclerae or skin

Courvoisier’s sign = painless, but palpable or distended gallbladder on exam

Could indicate

malignant

obstruction

Slide17

When the pattern of the liver tests suggests a

cholestatic

disorder, the next step is to determine whether it is intra- or

extrahepatic

cholestasis

Appropriate test is an ultrasound

Biliary

dilatation indicates

extrahepatic

cholestasis

– SURGICAL JAUNDICE

Absence of

biliary

dilatation suggests

intrahepatic

cholestasis

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Intrahepatic

A. Viral hepatitis

1.

Fibrosing

cholestatic

hepatitis—hepatitis B and C

2. Hepatitis A, Epstein-Barr virus, cytomegalovirus

B. Alcoholic hepatitis

C. Drug toxicity

1. Pure

cholestasis

—anabolic and contraceptive steroids

2.

Cholestatic

hepatitis—chlorpromazine, erythromycin

estolate

3. Chronic

cholestasis

—chlorpromazine and

prochlorperazine

D. Primary

biliary

cirrhosis

E. Primary

sclerosing

cholangitis

F. Vanishing bile duct syndrome

1. Chronic rejection of liver transplants

2.

Sarcoidosis

3. Drugs

G. Inherited

1. Progressive familial

intrahepatic

cholestasis

2. Benign recurrent

cholestasis

H.

Cholestasis

of pregnancy

I. Total

parenteral

nutrition

J.

Nonhepatobiliary

sepsis

K. Benign postoperative

cholestasis

L.

Paraneoplastic

syndrome

M.

Venoocclusive

disease

N. Graft-versus-host disease

O. Infiltrative disease-.

TB,Lymphoma

Slide19

DDx: Unconjugated bilirubinemia

↑production

Extravascular hemolysis

Extravasation of blood into tissues

Intravascular hemolysis

Errors in production of red blood cells

Impaired hepatic bilirubin uptake(trnsport)

CHF

Portosystemic shunts

Drug inhibition: rifampin, probenecid

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DDx: Unconjugated bilirubinemia

Impaired bilirubin conjugation

Gilbert’s disease

Crigler-Najarr syndrome

Neonatal jaundice (this is physiologic)

Hyperthyroidism

Estrogens

Liver diseases

chronic hepatitis, cirrhosis, Wilson’s disease

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DDx: Conjugated Bilirubinemia

Intrahepatic cholestasis/impaired excretion

Hepatitis (viral, alcoholic, and non-alcoholic)

Any cause of hepatocellular injury

Primary biliary cirrhosis or end-stage liver dz

Sepsis and hypoperfusion states

TPN

Pregnancy

Infiltrative dz: TB, amyloid, sarcoid, lymphoma

Drugs/toxins i.e. chlorpromazine, arsenic

Post-op patient or post-organ transplantation

Hepatic crisis in sickle cell disease

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DDx: Obstructive Jaundice

Obstructive Jaundice–

extrahepatic

cholestasis

Choledocholithiasis

(CBD or CHD stone)

Cancer

(

peri-ampullary

or

cholangioCA

)

Strictures

after invasive procedures

Acute and chronic

pancreatitis

Primary

sclerosing

cholangitis

(PSC)

Parasitic infections

Ascaris

lumbricoides

, liver flukes

Slide23

Screening Labs

NL LFT r/o hepatic injury or biliary tract dz

Consider inherited disorders or hemolysis

↑Alk Phos moreso than AST/ALT implies “cholestasis” (intrahepatic vs obstruction)

↑Alk Phos also seen in sarcoid, TB, bone

In this case, GGT is specific for biliary origin

Predominant

↑AST/ALT implies intrinsic hepatocellular disease

AST/ALT ratio > 2 in alcoholic hepatitis

↓albumin or ↑INR c/w advanced liver dz

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Subsequent Labs

If no concern for obstructive jaundice:

Viral (Hep B&C) serologies for viral hepatitis

anti-mitochondrial Ab (PBC)

anti-smooth muscle Ab (Auto-immune)

iron studies (hemochromatosis)

ceruloplasmin (Wilson’s)

Alpha-1 anti-trypsin activity (for deficiency)

Slide25

Imaging for Obstructive Jaundice

RUQ Ultrasound

See stones, CBD diameter

CT scan

Identify both type & level of obstruction

ERCP

Direct visualization of biliary tree/panc ducts

Procedure of choice for choledocholithiasis

Diagnostic –AND- therapeutic (unlike MRCP)

PTC useul of obstruction is prox to CHD

Endoscopic Ultrasound or EUS

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Treatment

If Medical, then treat the etiology

If Obstructive Jaundice:

Should r/o ascending

cholangitis

, ABC/

resusc

For

cholangitis

: IVF, IV Antibiotics, Decompression

Stones (remove stones

vs

stent

vs

drainage)

Done via ERCP or PTC or open (surgery)

Benign stricture (stent

vs

drainage catheter)

Cancer (Stent

vs

drainage +/-

resect

the CA)

Slide27

Thanks