Jaundice Differential Diagnosis PDF

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Summary

Jaundice Hepatic bilirubin) bilirubin) Genetic haemolytic anaemia Spherocytosis, pernicious anaemia G6DP deficiency, sickle cell anaemia, thalassaemia Obstructive bilirubin) Genetic: syndrome Common bile duct stone Drug induced (paracetamol) Cancer of the head of pancreas Congestive heart failure Pr...

Description

Jaundice

Hepatic (↑unconjugated bilirubin)

Pre-hapatic (↑unconjugated bilirubin) • Genetic haemolytic anaemia Spherocytosis, pernicious anaemia G6DP deficiency, sickle cell anaemia, thalassaemia • Autoimmune haemolytic anaemia Idiopathic, SLE, lymphoma, CLL, infectious mononucleosis

Obstructive (↑conjugated bilirubin)

• Genetic: Gilbert's syndrome

• Common bile duct stone

• Drug - induced (paracetamol)

• Cancer of the head of pancreas

• Congestive heart failure

• Primary biliary cirhhosis • Primary sclerosing cholangitis • Pancreatitis

Hepatic (↑conjugated bilirubin)

• Bile duct stricture - benign/tumour • Dubin-Johnson's syndrome

• Viral hepatitis - Hepatitis A, B, C

• Trauma/septicaemic haemolytic anaemia

• Alcoholic hepatitis/liver cirrhosis • Autoimmune hepatitis

DIC, haemolytic uraemic syndrome, TTP, infections (sepsis from UTI/pneumonia, malaria)

• Cholestasis in pregnancy

• Hepatocellular carcinoma • Wilson's disease

JAUNDICE DIFFERENTIAL DIAGNOSIS Condition

Symptoms

Signs

Investigations

Management

Jaundice + anaemia, normal dark stools and normal urine. ↑serum unconjugated bilirubin; evidence of haemolysis - ↑urinary urobilinogen, ↓serum haptoglobin, ↑reticulocytes, ↑LDH, ↓Hb

PRE-HEPATIC

Hereditary haemolytic anaemia

Sickle cell anaemia Thalassaemia G6DP/pyruvate kinase deficiency • May be asymptomatic

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Pallor, pale conjunctivae ↑RR, HR Leg ulcers Splenomegaly

Acquired haemolytic anaemia

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Sudden onset, later in life and on medication Weakness, angina

Septicaemic haemolysis

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Fever (UTI/pneumonia) Shock symptoms

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Signs of infection

Malaria

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Recent travel to malaria zone Periodic paroxysmal rigors, fever, nausea, sweating

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Fever, jaundice Splenomegaly Hepatomegaly Tender abdo

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Pallor, pale conjunctivae ↑RR, HR

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No fava beans in G6DP deficiency Folic acid administration – deficiency in active haemolysis Transfusion therapy Splenectomy – hereditary spherocytosis (+prior immunisation for H.influenza and S. pneumoniae)

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FBC (normocytic hypochromic anaemia) or ↑MCH+MHCH spherocytosis Blood films - Red cell morphology – spherocytes, schistocytes – TTP, HUS) Sickle cell screen LFT - ↑uBilirubin, enzymes – G6DP, PK Antibodies – IgG warm/cold autoimmune haemolytic anaemia Coombs test – acquired USS spleen/abdo, CXR, ECG FBC, LFT, CRP, blood culture + G+S and crossmatch

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Stop drugs that cause immune haemolysis – penicillin, quinine, L-dopa Folic acid +/- transfusion, iron therapy if severe intravascular haemolysis Corticosteroids/immunosuppressive drugs – Azathioprine/ Cyclophosphamide

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Fluids +/- transfusion if ↓BP + active haemolysis Paracetamol for fever, ABx for infection

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FBC ↓Hb, Plt, FBC, U+E, glucose, culture ABG, clotting, urine+stool culture, CXR Blood smear (thick & thin)

Non-falciparum malaria • 1st Chloroquine; quinine for resistant P.vivax. Primaquine to prevent relapse Falciparum • Admission, supportive (PCM if fever, blood transfusion if severe anaemia) • Severe: IV quinine; uncomplicated PO quinine 1/52, Atovaquone-proguanil

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CONGENITAL

Jaundice, normal-looking stools and urine. ↑serum unconjugated bilirubin, no conjugated bilirubin in urine. No urobilinogen in urine, normal haptoglobin, normal LFT Gilbert’s syndrome Tiredness

Precipitated by: • Intercurrent illness • Stress, dehydrated • Alcohol, lack of sleep

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Jaundice May be normal otherwise

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FBC – normal reticulocyte count LFT – normal including LDH ↑serum unconjugated bilirubin

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No treatment is required Avoid medications such as – Atazanavir/Indinavir (HIV Rx), Imatinib

Onset of jaundice over days/weeks, stools pale/normal, dark urine. ↑serum conjugated bilirubin, ↑urine bilirubin. Normal urine urobilinogen. LFT all ↑abnormal, ↑↑ALT

HEPATIC

Drug-induced hepatitis Paracetamol Halothane Methotrexate ↑unconjugated

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Abrupt onset Chills, fever, rash, pruritus, arthralgia Headache, N+V Abdo pain

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Jaundice Dark urine Hepatomegaly

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Withdrawal of drug causing the problem Avoid physical exertion, alcohol, paracetamol, hepatotoxic substance N-acetylcysteine to reverse paracetamol action Supportive care – fluids, analgesic

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LFT - ↑AST/ALT (hepatitis-PCM poisoning, statins), ↑ALP (cholestasis – chlorpromazine, erythromycin, oestrogen), mixed picture (co-amoxiclav) Hepatitis viral serology, ANA, copper, iron levels, FBC, U+E, CRP, Drug levels Abdo USS, CT/MRI, liver biopsy FBC, U+E, LFT, clotting (INR) Hepatitis serology USS/CT/MRI abdo – cirrhosis

Viral hepatitis

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N+V, fatigue, myalgia RUQ pain, coryza Photophobia, headache Diarrhoea (pale stools)

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Jaundice Hepatomegaly Splenomegaly Lymphadenopa thy

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Antipyretics for fever, IV fluids, antiemetic if N+V, colestyramine for pruritus Acute hepatic failure – Monitor BM, U+E, LFT, coag. 5% glucose IV, NG tube + NBM, neomycin PO, lactulose, vitamin K IV

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Jaundice Hepatomegaly Spider naevi

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FBC (macrocytic B12 deficiency anaemia) LFT (AST:ALT >2), ↑gGT Clotting screen USS abdo, liver biopsy

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Stop alcohol intake – detox Give folic acid, thiamine, vitamin K IV – if coagulopathy Acute hepatic failure - Monitor BM, U+E, LFT, coag. 5% glucose IV, NG tube + NBM, neomycin PO, lactulose, vitamin K IV Salt and fluid restriction Supportive – O2, IV furosemide +/- K+ supplement Beta-blocker, spironolactone

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bilirubin

Hep B (blood) Hep C (blood) Hep A (viral)

HEPATIC JAUNDICE

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Alcoholic hepatitis

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Lead to liver cirrhosis

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History of chronic alcohol dependency Nausea, malaise RUQ pain, nausea

Congestive heart failure impaired hepatic uptake

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SOB Leg swelling Tiredness Ascites

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↑JVP Hepatomegaly Ankle oedema

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CXR – cardiomegaly, effusion ECHO – dilated right ventricle FBC, LFT, U+E, Cr, lipids, coag, CRP BNP

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Wilson’s disease

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May be asymptomatic Acute liver failure picture – jaundice, ascites, abnormal bleed May be + FHx Psych – depression

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Jaundice Hepatic encephalopathy Neuroasymmetrical tremor KayserFleischer ring (copper)

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↓caeruloplasmin (copper-containing enzyme) ↑24hr urinary excretion of copper Enzymatic assay Liver biopsy – often diagnostic MRI head shows lesions – basal ganglia Family screening

• Monitor LFT, U+E, FBC, clotting • Avoid alcohol and drugs that are possibly hepatotoxic • Avoid food high in copper – liver, chocolate, nuts, mushrooms, shellfish • Annual slit-lamp exam of Kayser-Fleischer rings Medical • Penicillamine – copper chelating agents; Trientine – if penicillamine C/I • Zinc acetate – prevents absorption of copper Surgical – liver transplant, deep brain stimulation for neuro Sx

↑uBilirubin –

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Hepatocellular Carcinoma

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OBSTRUCTIVE JAUNDICE

Common bile duct stones

• • • Cancer of head of pancreas

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Primary biliary cirrhosis

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Fatigue – commonest Pruritus +/- jaundice RUQ pain Sjogren’s syndrome

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Cholestasis in Pregnancy

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Screening for at risk patients – AFP USS liver/CT/MRI – FNA or biopsy LFT – consistent with cirrhosis Clotting screen, albumin ↓ CXR – raised hemidiaphragm

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Surgical resection, thermal ablation Systemic chemotherapy/transarterial chemoembolisation/ selective internal radiation therapy Liver transplant Treat complications of cirrhosis – ascites, encephalopathy, varices

Jaundice + pale stools + dark urine. ↑serum conjugated bilirubin, ↑ urine bilirubin, normal urobilinogen in urine. ↑↑ALP, less abnormal LFT and ↑GGT Non-surgical • Tender • Urinalysis, CXR, ECG – exclude other RUQ/epigastric causes • Analgesia – morphine PO, IV pethidine, PR diclofenac • Jaundice • USS – IOC to see stones • Anti-emetic, fluid rehydration • Bloods – LFT (↑cBili, ↑ALT/AST, • Healthy lifestyle – regular physical activity, healthy diet ↑↑ALP), CRP, U+E, FBC (N) Surgical • ERCP – diagnose CBD stones • Laparoscopic cholecystitis – Elective • • •

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Jaundice Hepatomegaly Ascites Spider naevi Flapping tremor

Epigastric/RUQ pain (intermittent) May radiate to back Worse after fatty food, N+V common Jaundice – obstructed

Courvoisier’s sign – palpable GB + painless jaundice Weight loss, anorexia Epigastric pain radiates to the back Steatorrhoea Haematemesis May be asymptomatic Jaundice + pruritus RUQ pain Fatigue, weight loss Fever, sweats

Sclerosing cholangitis yOBSTRUCTIVE JAUNDICE

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Pruritus, jaundice Weight loss, ascites RUQ pain, haematemesis (varices) Confusion, hepatic encephalopathy

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Jaundice Epigastric mass Palpable GB

Jaundice Hepatomegaly/ Splenomegaly Cirrhosis, portal HTN, hepatic failure

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FBC – normochromic anaemia, ↑Plt LFT - ↑↑ALP, gGT, ↑bilirubin Glucose – hyperglycaemia CA19-9 Ultrasound of hepatobiliary + pancreas – dilatation of biliary ducts CT pancreas, ERCP/MRCP

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Child Pugh scale to assess severity LFT - ↑ALP & gGT, ↑bilirubin, Abnormal clotting – albumin and PTT ↑IgG, IgM, p-ANCA, aCL, ANA USS Abdo, MRCP (IOC), ERCP MRY/liver biopsy

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Low fat, high protein diet Pain control, pancreatic enzyme supplement, antiemetic (prokinetic) – metoclopramide/domperuidone • Phenothiazine/colestyramine for pruritus • Chemotherapy – adjuvant Surgical • Surgical resection of tumour (Whipple’s) + lymphadenectomy • Stenting – relieves itch and reverse jaundice Conservative • Fat-soluble vitamins supplements, avoid alcohol (RF for cholangioCa) Medical • Colestyramine, ursodeoxycholic acid – pruritus Surgical • Stents to relieve stricture, surgical drainage • Liver transplant – effective treatment • Modanafil – fatigue • Sedating antihistamine/colestyramine/rifampicin/ursodeoxycholic – pruritus • Immunosuppression – methotrexate, steroids, ciclosporin, azathioprine • Avoid COCP – oestrogen promote cholestasis • Liver failure – liver transplant is the only cure

Hepatomegaly • FBC – normal, ↑ESR Splenomegaly • LFT - ↑ALP, bilirubin Jaundice • Autoantibodies screen - ↑IgM, AMA + Xanthelasma • USS liver, CT/MRI, MRCP (exclude PSC) Ascites, spider • Transient elastography, liver biopsy naevi, portal HTN Jaundice during pregnancy which resolve following delivery – pruritus especially in palms and soles Ursodeoxycholic acid to relieve pruritus and improve LFT

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