Transcript Final jaundice without movie

Jaundice
1.0= Normal Vigilance
Medical Audience Attention Span
In Tens of Minutes
Overview
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What is “jaundice”?
Types
Etiologies
Diagnosis
What is jaundice?
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The french word jaune - yellow.
Icterus - yellowish discoloration
Skin, conjunctiva, sclera, mucous membranes
Appears 'top to bottom' (face to feet)
Resolves 'bottom to top'.
Technical definition
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Hyperbilirubinemia
Normal less than 1.2 mg/ml
Less than 5 percent conjugated
Not visual until greater than 2.5 mg/ml
Best seen in sclera and oral mucous membranes
(look at soft palate)
Bilirubin
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RBC destruction
Hemoglobin degraded to heme
Spleen turns into unconjugated
bilirubin
Transported to liver
Conjugated with glucuronic acid
Passed into bile
Small bowel bacteria convert to
stercobilinogen
Oxidised to stercobilin.
Some reabsorbed, excreted renally
as urobilinogen
Oxidised into urobilin
A Tale of Two Hyperbilirubinemias
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Unconjugated
Overproduction
 Impaired uptake
 Conjugation abnormalities
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Mixed
Hepatocellular disease
 Impaired canalicular excretion
 Obstruction
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Or…
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Pre-hepatic or hemolytic causes
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Hepatic causes
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Hemolysis
Conjugation problems
Post-hepatic or extrahepatic
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Excretion of bile disrupted
Unconjugated Hyperbilirubinemia
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Overproduction
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Hemolysis
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Extravascular vs intravascular
Extravasation
 Dyserythropoiesis
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Reduced hepatic uptake
Impaired conjugation
Physiologic jaundice of newborn
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Consists of all three
Overproduction
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Normal liver can keep up
 Bilirubin < 4-5 mg/dl
 Conjugated bilirubin remains 3-5 percent
Hepatic disease affects canilicular excretion
 Bilirubin diffuses back into plasma
Conjugation Function
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Gilbert’s
Crigler-Najjar
What about Gilbert?
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Reduced levels of Uridinediphosphoglucuronate
glucuronosyltransferases (UGTs)
Mutation in the promoter region
Deficiency in isoform that conjugates bilirubin
to glucuronic acid
Creates a backflow equilibrium
And Crigler-Najjar?
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Type I - UGT with no activity
Kernicterus
 Fatal without liver transplant
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Type II – UGT with reduced activity
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Less severe than type I
Genetic lesions in bilirubin-UGT deficiency syndromes
Are you new here?
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Conjugating activity low in neonates
Turn over of fetohemoglobin to adult forms
May need light therapy
Other Effects on Activity
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Decreased UGT activity
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Antibiotics
Hepatitis
Chronic hepatitis
Advanced cirrhosis
Wilson’s disease
Hyperthyroidism
Ethinyl Estradiol
Increased activity
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Progestational and estrogenic steroids
Conjugated Hyperbilirubinemia
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Intrahepatic cholestasis
Extrahepatic cholestasis/obstruction
Hepatocellular injury
Dubin-Johnson
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Autosomal recessive
Human canalicular multispecific organic anion
transporter (cMOAT) mutation (multidrug resistance
protein 2 (MRP2))
Impaired transport
Accumulation of hepatocellular pigment.
Rare, Sephardic Jews
Prevalence 1:1300.
Life expectancy normal
Reduced prothrombin and factor VII activity
Nonpruritic jaundice in teenage years.
Rotor Syndrome
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Rare, Autosomal Recessive
Mechanism not clear
chronic mixed hyperbilirubinemia
Storage defect
Benign
Labs and histology normal
Biopsy not required
Urinary coproporphyrin 250 to 500% normal, 65%
coproporphyrin I
Dubin-Johnson syndrome - urinary coproporphyrin normal,
80% coproporphyrin I
Normal – urinary porphyrins 75% coproporphyrin III
Bilirubin throughput in hepatocytes
Obstruction
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Bilirubin retained
Glucuronidation reversed
Unconjugated bilirubin diffuses into plasma
Mixed bilirubin transported into plasma by MRP
transporters.
Primary Sclerosing Cholangitis
Cholangiocarcinoma
Differential Dx
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Cholelithiasis
Tumors
Primary sclerosing cholangitis
Parasites
Pancreatitis
Strictures (benign/malignant)
AIDS cholangiopathy
AIDS Cholangiopathy
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Cryptosporidium
CMV
HIV
Biopsies or bile cultures for dx
Other HIV Possibilities
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Viral Hepatitis
HSV
EBV
Tumors
Lymphoma
Kaposi’s
Drugs
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Mycobacterium TB
Atypical mycobacterium
Fungi
Cryptococcus
Histoplasma
Candida
Coccidioides
Pneumocystis carinii
Intrahepatic Cholestasis
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Jaundice
Bile ducts are patent
Etiologies
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Viral Hepatitis
Alcoholic Hepatitis
Non-Alcoholic
Steatohepatitis
Primary Biliary Cirrhosis
Drugs
Toxins
End-stage liver disease
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Sepsis
Low perfusion states
Malignancy
Liver infiltration
TPN
Post-operative
Post-transplant
Sickle Cell disease
Pregnancy
Alcoholic Hepatitis
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Cholestasis
Fever
Leukocytosis
History of EtOH
AST to ALT exceeds 2.0
AST and ALT each less than 500
NASH
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Similar to EtOH but NO
EtOH
Obesity
DM
Female
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Amiodarone
Antiviral drugs (nucleoside
analogues)
Aspirin / NSAIDS
Statins
Corticosteroids
Methotrexate
Nifedipine
Perhexiline
Tamoxifen
Tetracycline
Valproic acid
PBC
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Cholestatic and hepatocellular injury picture
Antimitochondrial antibodies
Present in 95 percent
 95 percent sensitive, 98 percent specific
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Anti-nuclear antibodies
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In 70 percent of patients
Drugs
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Dose related
Allergic reactions
Idiosyncratic
Mixed hepatocellular/cholestatic picture
Thorough drug history imperative
Low Perfusion States
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Sepsis
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Hyperbilirubinemia can promote sepsis
CHF
Hypotension
Hypoxemia
Paraneoplastic Syndromes
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Stauffer’s Syndrome
Uncommon in RCC
Absence of metastases
Cholestasis, elevated alkaline phosphatase.
Fever
Weight loss
Fatigue
Poor prognosis
Related to tumor cytokines
Nephrectomy may ameliorate
Recurrence - maybe more cancer or metastases
Infiltration
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Amyloidosis
Sarcoidosis
Lymphoma
TB
TPN
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Steatosis
Lipidosis
Cholestasis (after 2-3 weeks of Rx)
Bacterial overgrowth
Post Operative
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Multifactorial
Transfusions
Hematomas
Hemolysis
Sepsis
TPN
Drugs (anesthetics)
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Hypoxia
Hypotension
Viral Hepatitis
Renal Failure
Post Transplant
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Bone Marrow and Liver
mostly
TPN
Drugs
Immunosuppressives
Radiation
Chemotherapy
Graft rejection
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Preservation injury
Operative complications
Sickle Cell Disease
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Chronic hemolysis
Hepatic dysfunction
Cirrhosis
Secondary hemochromatosis
Hepatic crisis
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Hepatomegaly and tenderness
Severe hyperbilirubinemia
Bilirubin microliths, sludge, stones common
Obstruction rare
Intrahepatic Cholestasis of
Pregnancy (IHCP)
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Third Trimester
Possibly genetic
Pruritus >> cholestasis >> Jaundice
Maybe more premature/still births
Distinguish from acute fatty liver and HELLP
Acute Fatty Liver of Pregnancy
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microvesicular fatty infiltration of hepatocytes
1 in 7000 to 1 in 16000 deliveries
Second half of pregnancy, usually third trimester
Nausea, vomiting, abdominal pain, anorexia, and
jaundice, preeclampsia
Delivery is curative (and mandatory!)
HELLP
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Hemolysis, Elevated Liver enzymes, Low
Platelets
1 of 1000 pregnancies
10 to 20 percent with preeclampsia or eclampsia
Diagnosed between 28 and 36 weeks of
gestation
70 percent occurred prior to delivery
Delivery is mandatory!
End Stage Liver Disease
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Supportive Care
Transplant
Hepatocellular Injury
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Neoplasms
Viral
Bacterial
Congenital
Parasitic
Fungal
Systemic
Immunologic
Toxic
Viral
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Hepatitis A, B, C, D, E
HSV
Hemorrhagic viruses
Adenoviruses
Enteroviruses
Bacterial
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TB
Leptospirosis
Syphilis
Brucella
Rickettsia
Tropheryma Whippelii
Rochalimea
Congenital
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Wilson’s disease (rare after age 40)
Alpha-1-antitrypsin deficiency
Hemochromatosis
Porphyrias (a 24 hour urine for porphyrins is
best test to rule out all the porphyria subtypes)
Systemic
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Acute Ischemia
Cardiac causes
Thromboembolic disease
Telangiectasias
Amyloid
Sarcoid
Immunologic
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Autoimmune Hepatitis
PBC
PSC
Diagnosis
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History
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Diseases/therapies
Medications/herbals/exposures
Risk factors/HIV status/travel
Surgeries
Complications
Physical
Screening labs
Differential
Further testing
Findings
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Primary biliary cirrhosis
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Viral Hepatitis
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Xanthomas
Anorexia
Malaise
Myalgias
Liver failure/portal HTN
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Ascites
Splenomegaly
Spider Angiomata
Gynecomastia
Overload Findings
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Hyperpigmentation
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Hemochromotosis
Kayser-Fleischer rings
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Wilson’s disease
Labs
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Transaminases – biliary or hepatic injury
Alkaline Phosphatase
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GGT/5’-nucleotidase - biliary tract (overly sensitive
test)
Prothombin time
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obstruction or intrahepatic cholestasis
TB
Sarcoid
Correctable with vitamin K?
Albumin – hepatic synthetic insufficiency
Non-obstructed
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Viral hepatitis
AMA
ASMA and LKM
Iron panel and ferritin (ferritin is an APR, can be
elevated for multiple causes); iron saturation is
key
Ceruloplasmin level
Alpha-1-antitrypsin activity
Obstructed?
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US
EUS
Helical CT/CT
ERCP
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0.2% mortality, pancreatitis 3 %
MRCP – non-therapeutic, interpretation difficult
Pecutaneous Transhepatic Cholangiography
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Good for proximal lesions or if ERCP not available
Emergencies
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Massive hemolysis (sepsis, malaria)
Ascending cholangitis
Fever
 Chills
 RUQ pain
 Prior biliary surgery
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Neonates
Fulminant hepatic failure
Summary
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Many etiologies for jaundice
History and physical is key
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Medical history
Medications
Risk factors
Surgeries
Labs
Differential
Further testing
Diagnosis