evaluation_of_a_patient_with_jaundice_accs_june_2018.ppt

The best initial step in the evaluation of jaundice is history and physical examination. The next step is to classify jaundice by etiology and type-Hepatocellular, cholestatic or mixed. The basic mechanisms of jaundice include elevated production, decreased uptake, and faulty conjugation.

1. Evaluation of a patient Evaluation of a patient
with Jaundicewith Jaundice
ACCS 1 Training dayACCS 1 Training day
Thanks to Dr Yousif. A QariThanks to Dr Yousif. A Qari
Assist prof. consultant Assist prof. consultant
gastroenterologistgastroenterologist

2. Definition of JaundiceDefinition of Jaundice
Jaundice, as in the French Jaundice, as in the French jaune,jaune, refers to the refers to the
yellow discoloration of the skin.yellow discoloration of the skin.

Abnormal accumulation of bilirubin in body Abnormal accumulation of bilirubin in body
tissues, which occurs when the serum bilirubin tissues, which occurs when the serum bilirubin
level exceeds 3 mg/dL or 50 mmol/L. level exceeds 3 mg/dL or 50 mmol/L.
HyperbilirubinaemaHyperbilirubinaema

3. Investigation of a patient with jaundiceInvestigation of a patient with jaundice
History of presentationHistory of presentation
Medication useMedication use
Past medical historyPast medical history
Physical examinationPhysical examination
Evaluation of liver function testsEvaluation of liver function tests

4. First evaluating a patient with hyperbilirubinemia
Quick assessment of the emergency of the situation
• Fever,
• Leukocytosis
• Hypotension
Ascending
cholangitis
Immediate
therapy
• Asterixis
• Confusion
• Stupor
severe
hepatocellular
dysfunction
fulminant
hepatocellular
failure

5. History
Family history of liver disease
Alcohol and drug history
Sexual history
Transfusion history
Nutrition history

Exposure to

Environmental toxins

Persons with jaundice

Drugs (e.g., prescription, nonprescription, intravenous)

,
Outbreaks or epidemics in the community
Previous liver function tests are valuable
History of biliary or pancreatic disease.

6. History
Shaking chills or fevers point toward cholangitis or bacterial
infection

Abdominal pain may indicate pancreatic disease, especially
if it radiates to the back
Right upper quadrant ache point toward Viral hepatitis
Weight loss, anorexia, nausea, and vomiting are not helpful
signs because most patients with hepatobiliary disease or
obstruction have anorexia and some weight
Pruritus can be associated with both intrahepatic cholestasis
as well as biliary obstruction.

7. History
Age:
Children and young adults ——› congenital,viral
hepatitis
< 30 years ——› acute parenchymal disease
> 65 years ——› stones or malignancies
30 - 50 years ——› chronic liver disease

8. History
Sex:
Men are more likely to develop
Cirrhosis secondary to alcohol
Pancreatic cancer
Hepatocellular carcinoma,
Hemochromatosis
Women are more likely to have
Primary biliary cirrhosis
Gallstones
Chronic active hepatitis

9. Physical Examination

Jaundice must be differentiated from

Hypercarotenemia

Uremic pigmentation

Picric acid ingestion

Quinacrine therapy

10. Physical Examination
Shrunken, nodular liver may ——› cirrhosis
Palpable mass ——› abscess or malignancy
A liver span >15 cm ——› fatty infiltration, congestion
other infiltrative diseases, or malignancy
Liver tenderness ——› acute disease but is generally not
helpful

11. Physical Examination
Spider angioma
palmar erythema
distended abdominal veins
jaundice
Ascites
jaundice
Ascites
indicate cirrhosis
Acute hepatitis
Cirrhosis
Malignancy

12. Physical Examination
Splenomegaly
A palpable, distended gallbladder ——› malignant biliary obstruction
Asterixis
Fever
Infections
Infiltrative diseases
Fulminant hepatic failure
End-stage liver disease
Billiary colic
Infection

13. Laboratory Tests
Total bilirubin and direct bilirubin assays

.
Conjugated
hyperbilirubinemia
Unconjugated
hyperbilirubinemia

14. Heme MetabolismHeme Metabolism
Hemoglobin –
80%
Myoglobin
Cytochrome
P450s
Hemoproteins
Macrophage of the
reticuloendothelial
system
Hem
e
Heme
Oxygenase
Biliverd
in Biliverdin
Reductase
Biliru
bin
Blood
O
2
Fe
3+
+
CO
NADPH +
H
+
NAD
P+

15. The Fate of Bilirubin…The Fate of Bilirubin…
Alb = albumin B = bilirubin GST =
glutathione-S-transferase
UDPGA = uridine diphosphoglucuronic acid;CB =
conjugated bilirubin
UGT1A1 = UDP-glucuronosyltransferase 1A1
MRP2 = Multi-drug Resistance Protein 2
MR
P2
BB+ +
GSTGST
CC
BB
Plasma
Hepatic Cell Bil
e
AlbAlb
BB
AlbAlb
?
:GSTBB
sER
BB+
UDPG
A
UGT1A1

16. Bilirubin ExcretionBilirubin Excretion
Intestines
Liver
BB CC
BB
CC
BB
BB
Urobilin
ogen
B-
glucoronidase
bacter
ia
bacter
ia
Bile
Enterohepatic
circulation
o
x
Urobilin
Stercob
ilin
Stercobiling
ogen
fece
s

17. Bilirubin ExcretionBilirubin Excretion
Intestines
Liver
BB CC
BB
CC
BB
BB
Urobilin
ogen
B-
glucoronidase
bacter
ia
bacter
ia
Bile
Enterohep
atic
circulation
Kidne
y
Urob
ilin
o
x
Urobilinogen
Urobilin
Stercob
ilin
Stercobiling
ogen
fece
s
Urine
o
x

18. Causes Of Hyperbilirubinemia
UNCONJUGATED
HemolysisHemolysis

Glucose-6-phosphate Glucose-6-phosphate
deficiencydeficiency

Pyruvate kinase deficiencyPyruvate kinase deficiency

DrugsDrugs
Ineffective erythropoiesisIneffective erythropoiesis
Neonatal causesNeonatal causes

Physiologic abnormalitiesPhysiologic abnormalities

Lucy-Driscoll syndromeLucy-Driscoll syndrome

Breast milkBreast milk
Uridine diphosphate Uridine diphosphate
glucuronosyltransferase glucuronosyltransferase
deficienciesdeficiencies

Gilbert syndromeGilbert syndrome

Crigler-Najjar syndromes (I Crigler-Najjar syndromes (I
and II)and II)
Miscellaneous causesMiscellaneous causes

DrugsDrugs

HypothyroidismHypothyroidism

ThyrotoxicosisThyrotoxicosis

Pulmonary infarctPulmonary infarct

FastingFasting

19. Causes Of Hyperbilirubinemia
CONJUGATED FORM
Congenital causesCongenital causes

Rotor syndromeRotor syndrome

Dubin-Johnson syndromeDubin-Johnson syndrome

Choledochal cystsCholedochal cysts
Familial disordersFamilial disorders

Benign recurrent Benign recurrent
intrahepatic cholestasisintrahepatic cholestasis

Cholestasis of pregnancyCholestasis of pregnancy
Hepatocellular defectsHepatocellular defects

Alcohol abuseAlcohol abuse

Viral infectionViral infection
SepsisSepsis
CholestaticCholestatic

Primary biliary cirrhosisPrimary biliary cirrhosis

Primary sclerosing Primary sclerosing
cholangitischolangitis

Biliary obstructionBiliary obstruction

Pancreatic diseasePancreatic disease
Systemic diseaseSystemic disease
Infiltrative disordersInfiltrative disorders
Postoperative Postoperative
complicationscomplications
Renal diseaseRenal disease
DrugsDrugs

20. Several questions must be answered initiallySeveral questions must be answered initially
1. Is the elevated bilirubin conjugated or unconjugated?1. Is the elevated bilirubin conjugated or unconjugated?

2. If the hyperbilirubinemia is unconjugated, is it caused by 2. If the hyperbilirubinemia is unconjugated, is it caused by

increased productionincreased production

decreased uptakedecreased uptake

impaired conjugationimpaired conjugation
3. If the hyperbilirubinemia is conjugated, is the problem 3. If the hyperbilirubinemia is conjugated, is the problem

intrahepatic or intrahepatic or

extrahepatic?extrahepatic?

4. Is the process acute or chronic? 4. Is the process acute or chronic?

21. Conjugated hyperbilirubinemiaConjugated hyperbilirubinemia
Usually acquired disease
Intrahepatic or Extrahepatic (obstructive) cause.

Acute disease usually can be differentiated from chronic disease by the
patient's history, physical examination, and laboratory tests
clinical evaluation

xanthelasma,

spider angioma,

ascites,

hepatosplenomegaly.

Laboratory evidence of chronic disease

Hypoalbuminemia,

Thrombocytopenia,

uncorrectable prolongation of the prothrombin time.

22. CholestasisCholestasis
Chronic cholestasis may arise from Chronic cholestasis may arise from

Cirrhosis, Cirrhosis,

Primary sclerosing cholangitis, Primary sclerosing cholangitis,

Primary biliary cirrhosis, Primary biliary cirrhosis,

Secondary biliary cirrhosis, Secondary biliary cirrhosis,

Carcinoma Carcinoma

Drugs.Drugs.
Acute disease.Acute disease.

New-onset bilirubinuriaNew-onset bilirubinuria

Fever Fever

Right upper quadrant pain,Right upper quadrant pain,

Tenderness,Tenderness,

Hepatomegaly, Hepatomegaly,

23. Help from LFTsHelp from LFTs
ALT in hepatocyctesALT in hepatocyctes

Indicator of hepatocellular injuryIndicator of hepatocellular injury

High ALTHigh ALT↑↑↑, ALP ↑ ↑↑↑, ALP ↑ suggests hepatocellularsuggests hepatocellular
ALP liver/ bile duct/ boneALP liver/ bile duct/ bone

Raised in cholestasisRaised in cholestasis

ALP ↑↑, ALP ↑↑, ALTALT↑ ↑ suggests cholestasissuggests cholestasis

24. GGTGGT

Raised in biliary epithelium/ bile duct obstnRaised in biliary epithelium/ bile duct obstn

Raised in alcohol and phenytoinRaised in alcohol and phenytoin
ALP and GGT raised ALP and GGT raised →→cholestasischolestasis
ALP isolated = not hepatobiliaryALP isolated = not hepatobiliary

25. Jaundiced ALT/ALP normalJaundiced ALT/ALP normal
Causes Causes

PrehepaticPrehepatic
HaemolysisHaemolysis

Gilberts syndrome (most common) Gilberts syndrome (most common)

26. Urine - Jaundice Urine - Jaundice
Colour of urine and stools Colour of urine and stools

Normal urine + normal stools = pre-hepatic Normal urine + normal stools = pre-hepatic
causecause

Dark urine + normal stools = hepatic causeDark urine + normal stools = hepatic cause

Dark urine + pale stools = post-hepatic cause Dark urine + pale stools = post-hepatic cause
(obstructive)(obstructive)
Bilirubin/urobilinogenBilirubin/urobilinogen

27. Livers main synthetic functionsLivers main synthetic functions
Conjugation and elimination of bilirubinConjugation and elimination of bilirubin
Synthesis of Synthesis of albuminalbumin
Synthesis of Synthesis of clotting factorsclotting factors
GluconeogenesisGluconeogenesis

28. DiagnosisDiagnosis
Second-line tests for jaundice “focused” or “screen”

Anti-nuclear antibody
Anti-smooth muscle antibody
Immunoglobulins
Anti-mitochondrial antibody
hepatitis serologies
a1-antitrypsin
iron levels
Ceruloplasmin
a-fetoprotein

29. DiagnosisDiagnosis
Radiological tests:

Ultrasonography
Stones
Billiary ductal dilatation
Tumour masses, lymph nods etc.
Organomegaly
AsciCtes

CT scan abdomen

Endoscopic Retrograde Cholangiopancreatography (ERCP) MRCP
Liver Biopsy

30. Common Drugs Associated With
Hyperbilirubinemia
AcetominophenAcetominophen
AlcoholAlcohol
AmiodaroneAmiodarone
AzulfidineAzulfidine
CarbenicillinCarbenicillin
ClindamycinClindamycin
ColchicineColchicine
CyclophosphamideCyclophosphamide
DiltiazemDiltiazem
KetoconazoleKetoconazole
MethyldopaMethyldopa
NiacinNiacin
NifedipineNifedipine
NSAIDsNSAIDs
PropylthiouracilPropylthiouracil
PyridiumPyridium
PyrazinamidePyrazinamide
QuinidineQuinidine
RifampicinRifampicin
SalicylatesSalicylates
VerapamilVerapamil
HEPATOCELLULAR CAUSESHEPATOCELLULAR CAUSES

31. Common Drugs Associated With
Hyperbilirubinemia
AmitriptylineAmitriptyline
Androgenic steroids (Androgenic steroids (BB))
AtenololAtenolol
AugmentinAugmentin
AzathioprineAzathioprine
Bactrim (Bactrim (DD))
BenzodiazeprinesBenzodiazeprines
CaptoprilCaptopril
CarbamazoleCarbamazole
Chlordiazepoxide (Chlordiazepoxide (D))D))
ClofibrateClofibrate
CoumadinCoumadin
CyclosporineCyclosporine
Danazol (Danazol (BB))
DapsoneDapsone
DisopyramideDisopyramide
ErythromycinErythromycin
Estrogens (Estrogens (BB))
EthambutolEthambutol
FloxuridineFloxuridine
5-Flucytosine5-Flucytosine
FluoroquinolonesFluoroquinolones
GriseofulvinGriseofulvin
Haloperidol (Haloperidol (DD))
LabetololLabetolol
Nicotinic acidNicotinic acid
NSAIDsNSAIDs
PenicillinsPenicillins
PhenobarbitalPhenobarbital
Phenothiazines (Phenothiazines (DD))
PhenytoinPhenytoin
TamoxifenTamoxifen
TegretolTegretol
Thiabendazole (Thiabendazole (DD))
ThiazidesThiazides
ThiouracilThiouracil
Tolbutamide (Tolbutamide (DD))
Tricyclics (Tricyclics (DD))
VerapamilVerapamil
ZidovudineZidovudine
CHOLESTATIC CAUSES
B. bland or noninflammatory cholestasis: D. ductopenic cholestasis or vanishing bile duct syndrome.

32. Common Drugs Associated With
Hyperbilirubinemia
AcetohexamideAcetohexamide
AllopurinolAllopurinol
AmpicillinAmpicillin
AugmentinAugmentin
CimetidineCimetidine
DapsoneDapsone
DisulfiramDisulfiram
GoldGold
HydralazineHydralazine
LovostatinLovostatin
NitrofurantoinNitrofurantoin
NSAIDsNSAIDs
PhenytoinPhenytoin
RifampicinRifampicin
ThiouracilThiouracil
TetracyclineTetracycline
MIXED CAUSES

33. Any QuestionsAny Questions

34. Diagnosis of hyperbilirubinemia.
Identify red flags for immediate treatmentIdentify red flags for immediate treatment
PPatient's history
Physical examination
Laboratory tests

35. ReferencesReferences
Geekymedics.comGeekymedics.com
RCEM learning “search liver function” will RCEM learning “search liver function” will
link to Jaundice, ALF and Upper GI link to Jaundice, ALF and Upper GI
haemorrhagehaemorrhage