cp_najma_97

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BY:

DR.FAIZA

RESIDENT MEDICAL UNIT 4CHK.

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BIODATA

Name Najma

Husband name Zaheer Ahmad

Age 27 Y

Sex Female

Marital status Married D.O.A May 12, 2011

M.O.A Emergency

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PRESENTING COMPLAINTS

Yellowish discoloration of Sclera and body since 15days

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HISTORY OF PRESENTING COMPLAINS

According to the patient she was in usual statehealth of 15 days back then she developed yellowishdiscoloration of sclera followed by yellowish

discoloration of body. This was associated withnausea and vomiting but not associated withpuruitis, pale stools, malena, hematemesis,abdominal pain, ALOC.

According to her she noticed this yellowishdiscoloration after taking some medication forvaginal discharge that she developed after anabortion one month prior. She developed nauseaand vomiting soon after starting the medication thatwas prescribed by a local GP.

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HISTORY OF PRESENTING COMPLAINS (contd)

For these complaints she visited a hospital butthe problem did not settle and the jaundice

became more worse over the following days forwhich she was referred to CHK.

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SYSTEMIC REVIEW: Gastrointestinal system: No Epigastric pain, no

diarrhea or constipation

Respiratory system: No SOB,no cough, no chest pain.

CVS: No PND, orthopnea, pedal edema, central chest

pain or any other complains. CNS: no dizzy spells, blackouts, headache,no gait or

speech abnormality, vertigo or any other complains.

Genitourinary: No complains.

Musculoskeletal: No complains of joint pains.

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PAST MEDICAL HISTORY:

Nothing Significant

History of vaginal discharge 2 weeks prior to Jaundice

Before this, she aborted a seven weeks old fetusalmost a month back

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PAST SURGICAL HISTORY:

Nothing significant

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DRUG HISTORY:

As already mentioned. Can not

specify the name.

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HISTORY OF BLOOD TRANSFUSION:

None

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PERSONAL HISTORY:

Appetite Decreased

Sleep Disturbed

Bowel habits Normal

Micturition Normal Addiction None

Weight loss Present

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FAMILY HISTORY:

Husband Alive and Healthy

A 3 years old baby boy, NVD

No history of any fimalial disease running in thefamily

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SOCIO ECONOMIC HISTORY:

Low income family

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EXAMINATION

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VITALS ( ON ADMISSION):

BP 110/70

Pulse 80

R/R 20

Temp A/F

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GENERAL PHYSICAL EXAMINATION

Anemia Nil Jaundice +++ Clubbing Nil

Cyanosis Nil Pedal Edema Nil Koilonychia Nil Dehydration Nil Lymph nodes Not palpable Palmar erythema Nil Spider naevi Nil Thyroid Not enlarged JVP Not raised

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ABDOMINAL EXAMINATION

INSPECTION: Moving equally with respiration, noscar marks, pigmentations.

PALPATION:Soft and non tender

Liver not palpable, liver span 8 cms Spleen not palpable

Kidneys and Abdominal Aorta not palpable.

PERCUSSION: No signs of free fluid

AUSCULTATION: Gut sounds audible

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RESPIRATORY SYSTEM

No pigmentation or scars noted.

Moving equally with respiration.

On auscultation normal vesicular breathing with noadded sounds.

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CARDIOVASCULAR SYSTEM

H/R: 80/min & regular, No radio-radial or radio-femoral delay on comparison of pulses.

APEX BEAT: 5th intercostal space medial to midclavicular line.

S1 & S2 audible , no murmur heard in all 4 areas.

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CENTRAL NERVOUS SYSTEM

HMF Intact

SPEECH & GAIT Normal

SOMI Negative CRANIAL NERVES Intact

PUPILS BERLA

CEREBELLAR SIGNS Negative

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MOTOR SYSTEM:

Left lowerlimb

Left upperlimb

Right lowerlimb

Rightupper limb

NormalNormalNormalNormalBULK

NormalNormalNormalNormalTONE

5/55/55/55/5POWERS

NormalNormalNormalNormalREFLEXES

Down going___Down going___PLANTARS

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SENSORY SYSTEM:

Pain & temperature Intact

Fine touch Normal Vibration Normal

Joint position & proprioception Intact

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CASE SUMMARY

Najma, w/o Zaheer Ahmad, 27, resident ofmodel colony presented with complaints ofdiscoloration of sclera and body for 15 days

that was associated with nausea, vomiting butnot associated with puruitis, pale stools,malena, hematemesis, abdominal pain, ALOC.History of drug intake two weeks back for

vaginal discharge. on examination vitallystable. No organomegaly, no peripheralstigmata of chronic liver disease noted.

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DIFFERENTIAL DIAGNOSIS

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Differential Diagnosis Acute Viral Hepatitis

Drug Induced Hepatitis

Cholestasis secondary to drugs.

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INVESTIGATIONS

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CBCs 12/5 13/5 16/5 21/5

HB 10.20 9.10 9.3 9.9

MCV 94.30 96 97.40 101.00

TLC 6300 6700 6800 1300

Platlets 149000 131000 128000 129000

PT 24/13 20 15.3

APTT 55/36 40 32.4

INR 1.62 1.4

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LFTs 12/5 13/5 13/5 16/5 20/5 21/5

Total Bili 76.46 65.79 59.89 58.3 50.15 38.88

Direct Bili 41.20 35.90 53.40 31.78 27.70 21.16

Indirect Bili 35.26 29.89 6.49 26.25 22.45 17.72

SGPT 425 226 290 95 71 53

ALK. Phos 87 67 90 65 58 73

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UCE 12/5 13/5 16/5 20/5

Na 135 140 138 136

K 2.7 2.9 2.7 2.6

Cl 95 105 104 102

BUN 11 4 5 4

Cr 1.1 0.8 0.9 0.9

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Fasting blood sugar 92mg%

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VIRAL MARKERS:

HBsAg & Anti HCV Non reactive

Anti HEV & anti HAV Awaited

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A/G RATIO:

Total proteins 5.6 gm/dl

Albumin 3.8 gm/dl

Globulin 1.8 gm/dl A/G ratio 2.1

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U/S ABDOMEN

Liver normal in size measuring 14.8 cm withsubtle coarse eco-texture, intra hepatic andbiliary ducts are not dialated, portal vein 1.1cm, free fluid not present.

Spleen normal in size and shape measuring12.1 cms.

Rest of the scan is Normal.

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Evaluation of Abnormal Liver

Function Tests

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Markers of Hepatocellular damage

(Transaminases)

AST- liver, heart skeletal muscle, kidneys, brain, RBCs In liver 20% activity is cytosolic and 80% mitochondrial

Clearance performed by sinusoidal cells, half-life 17hrs

ALT more specific to liver, v.low concentrations inkidney and skeletal muscles.

In liver totally cytosolic.

Half-life 47hrs

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Gamma-GT hepatocytes and biliary epithelialcells, pancreas, renal tubules and intestine Very sensitive but Non-specific

Raised in ANY liver discease hepatocellular orcholestatic

Usefulness limited

Confirm hepatic source for a raised ALP

Alcohol

Isolated increase does not require any furtherevaluation, suggest watch and rpt 3/12 only if otherLFTs become abnormal then investigate

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Markers of Cholestasis

ALP liver and bone (placenta, kidneys, intestines orWCC)

Hepatic ALP present on surface of bile duct epitheliaand accumulating bile salts increase its release from cellsurface. Takes time for induction of enzyme levels somay not be first enzyme to rise and half-life is 1 week.

ALP isoenzymes, 5-NT or gamma GT may be necessaryto evaluate the origin of ALP

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Bilirubin, Albumin and Prothrombin time

(INR)

Useful indicators of liver syntheticfunction

In primary care when associated withliver disease abnormalities should raise

concern

Thrombocytopaenia is a sensitiveindicator of liver fibrosis

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Transaminases May not be elevated in chronic liver disease

HCV- apoptosis

Cirrhosis

Minimal ALT elevations (

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Mild Transaminitis AST/ALT < 5 times upper limit of normal

Etiologies

Hepatic: ALT-predominant

Chronic Hep C Hemochromatosis

Chronic Hep B Medications/Toxins

Acute viral hep Autoimmune Hep Steatosis Alpha1 Antitrypsin Def

Wilsons Disease Celiac Disease

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Mild Transaminitis Hepatic: AST predominant

Alcohol Steatosis Cirrhosis

Non-hepatic Hemolysis Myopathy Thyroid disease Strenuous exercise

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Elevated AST &ALT,

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Hepatotoxic Medications Analgesics- acetaminophen, NSAIDS

Antimicrobials

Amox-clav, nitrofurantoin, sulfonamides

INH

Azoles

Protease Inhibitors Anticonvulsants- carbamazepine, valproic acid,phenyton

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Hepatotoxic Medications Cardiovascular- alpha-methyldopa, amiodarone,

labetalol

Hyperglycemics- glyburide, troglidazone Psychiatric- trazadone, disulfiram Heparin Propylthiouracil

Statins Zafirlukast Dantrolene, Halothane, Nicotinic acid,

Phenylbutazone

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Hepatotoxic Herbals

Chaparral leaf

Ephedra Gentian

Germander

Jin Bu Huan

Senna, Kavakava

Scutellaria(skullcap)

Shark cartilage

Vitamin A

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Stop EtOH & meds; wtloss; glucose control

Repeat LFTs

ObservationUltrasound, ANA, smoothmuscle Ab, ceruloplasmin,

antitrypsin, gliadin &endomysial Ab

Negative Serology- Asymptomatic

Liver biopsy

Abnormal Normal

6 months

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Consider ultrasound,ANA, smooth muscle

Ab, ceruloplasmin,antitrypsin

Liver biopsy

Negative Serology- Clinical

Signs/Symptoms of Liver Disease

Abnormal

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+ Hep C/Binfection

Observation

Positive Serologies

Hep A IgM

Follow clinically,

serial LFTsObservation

Persistentelevated LFTs > 6

mos

Clinicalimprovement, LFTs

normalize in

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Serologic Tests for Viral Hepatitis HAV Hep A IgM- in acute infxn

Hep A IgG- in previous infxn or vaccination

HCV HCV Ab- during or after infection

HCV-RNA- during infection

Detectable prior to HCV Ab turning positive

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Serologic Tests for Viral Hepatitis HBV

Hep B Surface Ag- in active infxn

Hep B Surface Ab- in prior infxn or vaccinated Hep B Core Ab IgM- in active infxn

Hep B Core Ab IgG- in current or prior infxn

HBV-DNA- in active infxn

Hep B e Ag & Ab- markers of viral presence andpotential infectivity

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Symptoms

HBeAg anti-HBe

Total anti-HBc

IgM anti-HBc anti-HBsHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Acute Hepatitis B Virus Infection with Recovery

Typical Serologic Course

Weeks after Exposure

Titre

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Bilirubin Product of hemoglobin breakdown

2 Forms

Unconjugated (indirect)- insoluble

in hemolysis, Gilbert syndrome, meds

Conjugated (direct)- soluble

in obstruction, cholestasis, cirrhosis,hepatitis, primary biliary cirrhosis, etc.

No elevation until loss of > 50% capacity

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Conjugated bili;Abnormal alk phos,

ALT, AST

Unconjugated bili;Normal alk phos,

ALT, AST

RUQ u/s to assessductal dilatation

Hemolysis studies,review meds

ALT eval,review meds,

AMA, ERCP orMRCP, liver bx

ERCP orMRCP

Elevated Bilirubin

+ -

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Other Liver Labs Albumin

Poor marker of liver function- decreased by

trauma, inflammatory conditions, malnutrition Prothrombin time (PT)

Insensitive: no change until liver loses 80%capacity

Ammonia

No correlation between brain & serum values

Only one contributor to encephalopathy

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Acute hepatitis (ALT>10xULN)

Viral

Ischaemic

Toxins

Autoimmune

Early phase of acute obstruction

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Viral Hep A, B, C, E, CMV, EBV

ALT levels usually peak before jaundice appears.

Jaundice occurs in 70% Hep A, 35% acute HepB, 25% Hep C

Check for exposure

Check Hep A IgM, Hep B core IgM andHepBsAg, Hep C IgG or Hep C RNA

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Acute hepatitis (ALT>10xULN) Ischaemic- sepsis, hypotension

?most common cause in-patients

Often extremely high >50x Decrease rapidly

LDH raised 80%

Rarely jaundiced

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Toxins - paracetamol (up to 50% of all cases ofAcute Liver Failure)

Ecstasy ( 2nd most common cause in the young2 in 70%

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Autoimmune

Rarely presents with acute hepatitis

Usually jaundiced and progressive liver failure

Raised IgG and autoantibodies (anti-SM, -LKM,-SLA)

Liver biopsy Steroids and azathioprine

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Early phase- extrahepaticobstruction/cholangitis

Usually have history of pain USS dilated CBD ? ERCP or lap chole

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Alkaline Phosphatase Produced by biliary epithelial cells

Non-specific to liver: bone, intestine, placenta

Elevations Biliary duct obstruction

Primary biliary cirrhosis

Primary sclerosing cholangitis

Infiltrative liver disease- ie sarcoid, lymphoma

Hepatitis/cirrhosis

Medications

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Medications Hormones- anabolic steroids, estrogen,

methyltestosterone

Antimicrobials- augmentin, erythromycin,flucloxacillin, TMP-SMX, HIV meds

Cardiovascular- captopril, diltiazem, quinidine

Hyperglycemics- chlorpropamide, tolbutamide

Psychiatric- fluphenazine, imipramine, iprindole Others- allopurinol, carbamazepine

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RUQ us, medreview, AMA

Abnormal LFTsNormal LFTs, bili

RUQ u/s for ductaldilatationGGT or 5-NNT

ALT eval, liver

bx, ERCP orMRCP

Other source

ObservationLiver bx

No dilatation

- +

ERCP AMA

NoYes

Neg

AP > 6mo

Elevated Alk Phos

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Cholestasis

Isolated ALP 3rd trimester, adolescents Bone exclude by raised GGT, 5-NT or

isoenzymes May suggest biliary obstruction, chronic liver

disease or hepatic mass/tumour Liver USS/CT most important investigation-

dilated ducts Ca pancreas, CBD stones, cholangioca or liver

mets

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Cholestasis non-dilated ducts

Cholestatic jaundice Drugs- Antibiotics,Nsaids, Hormones, ACEI

PBC anti- mitochondrial Ab, M2 fraction,IgM

PSC associated with IBD 70%, p-ANCA,MRCP and liver biopsy Chronic liver disease Cholangiocarcinoma beware fluctuating

levels Primary or Metastatic cancer, lymphoma Infiltrative sarcoid, inflammatory-PMR,

IBD Liver biopsy often required

I ti ti f Ab l LFT

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Investigation of Abnormal LFTs

PRINCIPLES

2.5% of population have raised LFTs Normal LFTs do not exclude liver disease Interpret LFTs in clinical context Take a careful history for risk factors, drugs (inc

OTCs), alcohol, comorbidity, autoimmunity

Physical examination for liver disease Chase likely diagnosis rather than follow algorithmunless there are no clues

If mild abnormalities and no risk factors orsuggestion of serious liver disease , repeat LFTsafter an interval (with lifestyle modification)

I i i f Ab l LFT

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Investigation of Abnormal LFTs -

ALT/AST 2-5x normal

History and Examination Discontinue hepatotoxic drugs Continue statins but monitor LFTs monthly Lifestyle modification (lose wt, reduce

alcohol, diabetic control) Repeat LFTs at 1 month and 6 months


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- Raised ALT / AST

If still abnormal at 6 months: Consider referral to secondary care Hepatitis serology (B, C)

Iron studies transferrin saturation +ferritin

Autoantibodies & immunoglobulins Consider caeruloplasmin Alpha-1- antitrypsin Coeliac serology TFTs, lipids/glucose Consider liver biopsy esp if ALT > 100)

Wh t i th V l f Li Bi i

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What is the Value of Liver Biopsy in

Abnormal LFTs?

The most accurate way to grade the severity ofliver disease

Aminotransferase levels correlate poorly withhistological activity

Narrows the diagnostic options, if notdiagnostic

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Abnormal LFTs - Conclusions

Many abnormal LFTs will return to normalspontaneously

An important minority of patients with

abnormal LFTs will have importantdiagnoses, including communicable andpotentially life threatening diseases

Investigation requires clinical assessment

and should be timely and pragmatic

GUIDELINES TO IX AND BX OF PATIENTS WITH ABNORMAL LFTs AND NO CLEAR

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GUIDELINES TO IX AND BX OF PATIENTS WITH ABNORMAL LFTs AND NO CLEARDIAGNOSIS AFTER ROUTINE TESTS: WITH EMPHASIS ON FATTY LIVER AND NASH AS

UNDERLYING DIAGNOSIS

SCREEN FOR XS ALCOHOL CONSUMPTION

SCREEN FOR OCT/PD/RD DRUGS

INTERVENE AND REVIEW

INTERVENE AND REVIEW

SEROLOGICAL INVESTIGATIONS* NEGATIVEUSS NO SPECIFIC DIAGNOSISNO CLEAR CLINICAL (e.g. FHx A1 disease/xanthelasma/Signs CLD)ASSOCIATIONS WITH LIVER DISEASE

RE-EVALUATE DIAGNOSISAND BIOPSY

ABNORMAL CLINICALSIGNSPRESENT

NO CLINICAL SIGNSPERSISTENT ABNORMALLFTs > 6/12

NO CLINICAL SIGNSALT >3x normal

High risk LFT profile

MEASURE:TGChol.AST/ALT RatioTFTsBPFasting Blood SugarCalculate BM1

CONFIRMTREATMENTEFFECTIVE

LIFESTYLE MODIFICATION

LFTs NOT IMPROVED

RE-EVALUATE CLINICAL RISKFACTORSCONSIDER BIOPSY ANDFURTHER IMAGINGSEE GUIDANCE NOTES

LFTs IMPROVED

LFTs WORSEN ORBECOME ABNORMAL

RETURN TO NORMAL ORIMPROVE

MONITOR EFFECTIVENESS

MONITOR

LFTs WORSEN ORBECOME ABNORMAL

IF ABNORMALTREAT

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GUIDANCE NOTES

PREDICTIVE OF PATHOLOGYVS NORMAL:

ALT > 2 x NormalAST: ALT >1Age > 50 Low Platelet Count

OTHER GROUPS WITH HIGH RISKPATHOLOGY:

Raised Conjugated Bili with: ALT ALK P

Consider: BX; MRCP; ERCP Any abnormality of ALK P in addition to

abnormality ALT/ASTConsider BXPREDICTORS OF NASH AND FIBROSIS IN

PRESENCE OF NASH

ALT > 2 x Normal AST > ALT Moderate Central Obesity BM1 > 28 NIDDM/Impaired GTT BP TGs.

SUGGESTED ROUTINE SEROLOGICAL INVESTIGATIONS:

Alpha 1 AT; HAV; HBV; HCV; AIP and Igs; Fe Studies and HFE genotype; Caeruloplasmin; USS Fatty Change or Normalecho only; Bilirubin and haemolysis studies if appropriate

- ANY ABNORMALITIES IN THESE PARAMETERS, RE-EVALUATE POTENTIAL DIAGNOSIS AND CONSIDER BIOPSY

N.B. THESE NOTES/ALGORITHMS ARE FOR GUIDANCE ONLY. THIS IS A MOVING FIELD AND DESPITE IMPROVEMENTS INSEROLOGICAL AND RADIOLOGICAL TECHNIQUES, THERE REMAIN SMALL NUMBERS OF PATIENTS WHO HAVE SIGNIFICANT LIVERDISEASE WITH ONLY MILDLY ABNORMAL LFTs. THE ALGORITHM IS NO SUBSTITUTE FOR CAREFUL AND REPEATED CLINICALEVALUATION AND CLINICAL VIGILANCE.

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THANK YOU

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