liver in fever

8/12/2019 LIver in Fever

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. .


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Fever is the most ancient landmark of

disease. It is an increase in body

temperature above normal with its

circadian rhythm. It is the most common

presenting symptom of the pediatric

emergencies department ,representing 15-

30 % of all cases.


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Fever is an elevation ofbody temperature thatexceeds the normal daily

variation, inconjunction with an

increase in hypothalamic

set point


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Maximum normal oral

temperatureAt 6 AM: 37.2

At 4 PM: 37.7


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Pyrogens is any substance thatcauses fever

Exogenous pyrogens

Derived from outside the patient

Microbial products, toxins or whole

microorganisms


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Endogenous pyrogensCytokines are small proteins that regulate

immune, inflammatory and hematopoieticprocesses.

Cytokines that cause fever are calledpyrogenic cytokines. Produced from

monocytes, neutrophils and lymphocytes.

IL1, IL6, TNF, Ciliary neurotropic factor, andInterferon .

Each cytokine is encoded by a specific gene


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Endogenous pyrogensCytokines are small proteins that regulate

immune, inflammatory and hematopoieticprocesses.

Cytokines that cause fever are calledpyrogenic cytokines. Produced from

monocytes, neutrophils and lymphocytes.

IL1, IL6, TNF, Ciliary neurotropic factor, andInterferon .

Each cytokine is encoded by a specific gene


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Exogenouspyrogen

Activatedleukocytes

Endogenouspyrogen(IL1,TNF,)

Acute PhaseResponse

Pre-optic areaof anterior

hypothalamus(PGE2)

increase of setpoint

Brain cortex,

Vasoconstriction ,Muscle contraction

Heat production

Heat conservation

Fever


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IN FEVER


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Major causes of hepatitisare specific

hepatotropichepatitis A,B,C and deltaviruses.

Less common causes include other viralinfections (eg, infectious mononucleosis,yellow fever, cytomegalovirus infection).

Bacterial liver involvement with TB ,Leptospirosis ,etc may result ingranulomatous hepatitis.


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VIRUSES Bacterial

Q Fever

Leptospirosis

Relapsing Feve

Syphilis

Typhoid fever

Brucellosis

Tuberculosis

Leprosy

Yellow fever

ADENOVIRUSES

Rift Valley FevervirusCytomegalovirusDengue fever

Epstein-Barr virus

COXSACKIEVIRUSES

RUBELLA VIRUS

Lassa fever


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CLINICAL SIGNS OF LIVER DISEASE


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VIRUSES AFFECTING

LIVER


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Yellow fever

is an acuteviraldisease.It is animportant cause of

hemorrhagicillnessin manyAfricanand South

Americancountries.
http://en.wikipedia.org/wiki/Virushttp://en.wikipedia.org/wiki/Hemorrhagehttp://en.wikipedia.org/wiki/Africahttp://en.wikipedia.org/wiki/South_Americahttp://en.wikipedia.org/wiki/South_Americahttp://en.wikipedia.org/wiki/South_Americahttp://en.wikipedia.org/wiki/South_Americahttp://en.wikipedia.org/wiki/Africahttp://en.wikipedia.org/wiki/Hemorrhagehttp://en.wikipedia.org/wiki/Virus


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Yellowfever

(YF) is

caused byan

arbovirus.


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Yellow fever

(YF) istransmitted

by theAedes

aegyptimosquito.


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Yellow fever (YF) istransmitted by the

Aedes aegyptimosquito from :

1-one humanto

another (theurban form of YF)or from:

2- monkeystohumans (thejungle or sylvanform of YF).


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Pathogenesis of arboviruses


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Yellow feverAfter a 12-24 hourremission,

there is an "intoxication" orhepatorenal stagethat featuresreemergence of generalizedsymptoms including increasedtemperature,jaundice, andprostration.

Jaundiceusually appears on the

second or third day. After thethird day the symptoms recede,only to return with increasedseverity in the final stage.


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Rift Valley Fever


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Rift Valley Fever

Rift Valley Fever is aninfectious zoonoticdiseaseaffecting sheep, goats, and

cattle.

The disease is caused bytheRift Valley Fever (RVF) virus,

a member of the genusPhlebovirus.

The disease is transmittedby

Aedes aegyptimosquitoes.


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In severe cases,the disease becomes serious .Symptoms include fever, myalgias, and encephalitis,

including headache, coma, and seizures


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Rift Valley Fever

Severe cases of RVF fallinto three categories:

1 Liver necrosis(focal ordiffuse ) with hemorrhaging.

2 Retinitis with visualimpairment.

3 Meningoencephalitis

1977 outbreak in Egypt:


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1977 outbreak in Egypt:petechial haemorrhages and

hyphema in a womans face


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MODE OF TRANSMISSION


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Dengue hemorrhagic fever

Dengue fever(West Nile fever), isthe world's most important viralhemorrhagic fever disease; it is

the most geographically wide-spread of the arthropod-bornviruses, especially in the

Americas, the Pacific islands andon continental Asia.


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Dengue virus infection can present adiverse clinical spectrum,rangingfrom asymptomatic illness to dengueshock syndrome, as well as unusualmanifestations, such as hepatitis,

encephalitis, myocarditis, Reye'ssyndrome, hemolytic uremicsyndrome.


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Liver injurydue to dengue infection isnot uncommon and has beendescribed since 1970 .

Painful hepatomegaly, the mainclinical symptom observed, is seen in

up to 30% of patients.


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Barr virus-Epstein

Synonyms and related keywords:

glandular fever,infectious mono,infectious mononucleosis,Epstein-Barr virus, EBV, fever.

Infectious Mononucleosis
http://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htmhttp://www.emedicine.com/ped/topic705.htm


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Pathophysiology

EBV is transmittedvia intimate contactwith body secretions, primarilyoropharyngeal secretions. EBV infects the

B cellsin the oropharyngeal epithelium.

Circulating B cellsspread the infection

throughout the entire reticularendothelial system (RES), ie, liver, spleen,and peripheral lymph nodes.


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I f ti M l i


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Infectious MononucleosisMOUTH


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Later physical


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p yfindingsincludehepatomegaly,

palatal petechiae,jaundice( less than10%),uvular edema,splenomegaly, and,

rarely, (1-2%)findings associatedwith splenic rupture.

Splenic tendernessmay be present inpatients with

splenomegaly.

M l i h titi i


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Mononucleosis hepatitisischaracterized by peculiar

necroinflammatory changeswhich,at the difference of classical viralhepatitides consist of moreinflammation and less necrosis.

The sinusoidsare filled and

distended with mononuclearcellswhich are large and sometimesclustered to resemble granulomassometimes similar to sarcoidosis.

f i l i


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Infectious mononucleosishepatitis:Marked mononuclear cellinfiltration of the sinusoidswithout

significant necrosis


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Mononucleosis hepatitis

Another peculiar feature isthe presence of a marked

regenerative activity ofhepatocyteswith presence ofincreased number of

binucleate cells, polyploidnuclei and mitotic figures.


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Infectious mononucleosisheapatitis:High power of previous

illustration showing the signs of highregenerative activity


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ATYPICAL LYMPHOCYTE


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Liver function testsshowelevation of liver enzymelevels in nearly90% of

people with glandular fever.

An early, transient,mildincrease in serumtransaminases ischaracteristic of EBVinfectious mononucleosis.


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Cytomegalovirus


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Cytomegalovirus

Cytomegalovirusan encapsulatedDNAvirus, Is amember of the

herpesviridaefamily ,is foundworldwide, though

it is more commonin developingnations.


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Cytomegalovirus

Only occasionally will the virus inducemononucleosis-like syndrome, prolongedfever, and or mild hepatitis. Otherwise,once the individual is infected, the virus

will remain dormant, and for most people,recurrent infections will not develop.

For immunocompromised individuals, thevirus is able to reactivate, which can leadto diseases such as CMV retinitis.

Cytomegalovirus


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Cytomegalovirus


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CMV inclusion body: Hepatocyte


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CMV inclusion body: Hepatocytewith a large intranuclear inclusion body.

Surrounded by a clear halo. Dark punctiforminclusions are seen also in the cytoplasm.

ViralHepatitis

Toxoplasmosis

Cytomegalovirus

Epstein-Barr Virus


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HepatitismosisalovirusBarr Virus

++/-++Fatigue

+-++Malaise

+/-+/-++Mild sore throat

+/---+Earlymaculopapularrash

---+Early bilateral

upper eyelidedema

-+--Unilaterallocalizedadenopathy

Viralh i i

Toxoplasmosis

Cytomegalovirus

Epstein-Barr Virus


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hepatitissmosisusBarr Virus

+/--++Bilateralposterior

cervicaladenopathy

+-+/-+/-Tenderhepatomegaly

-+/-+/-+Splenomegaly

-NN/-N/-WBC count

++++/-+++ElevatedSGOT/SGPT

-+++Atypicallymphocytes

(>10%)

Viralh titi

Toxoplasmosis

Cytomegalovirus

Epstein-Barr Virus


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hepatitisosisovirusBarr Virus

+/--+/-+/-Thrombocytopenia

--+-Elevated IgMCMV titer

---+Elevated IgMEBV VCAII titer

-+--Elevated IgMtoxoplasmosistiter

+---Elevatedhepatitis (eg, A,

B, D) IgM titer


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OTHER VIRUSESRARELY AFFECTING

THE LIVER


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ADENOVIRUSES:Severe and fatal hepatitiswith severe respiratory infection may

develop in these individuals. Intranuclearviral antigen has been detected in cases ofhepatitis .

COXSACKIE VIRUSES:Hepatitis isfrequently associated with myocarditis and

consists of necroinflammatory changesinvolving lobules and porta tracts, to bedistinguished from congestive changes due

to heart failure.

RUBELLA VIRUS :The liver may be


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RUBELLA VIRUS:The liver may beinvolved with variable degree of acute

hepatitis, biliary obstruction anddestruction.

Lassa fever:There is markedhepatocyte damage in the liverconsisting in eosinophilic necrosis ofindividual cells but jaundice is rare.


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Bacterial infections


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Q Fever

Q Fever


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Q Fever

Q fever is causedby a microbecalled "Coxiellaburnetii, Gram-negative

obligateorganisms.
http://images.google.com.eg/imgres?imgurl=http://www.pbs.org/wgbh/nova/bioterror/images/agen_qfever.jpg&imgrefurl=http://www.pbs.org/wgbh/nova/bioterror/agen_qfever.html&h=175&w=250&sz=26&hl=ar&start=18&tbnid=9-vwRBRAhDCW3M:&tbnh=78&tbnw=111&prev=/images%3Fq%3D%2522Q%2BFEVER%2522%26gbv%3D2%26hl%3Dar%26sa%3DG


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Animalssuch ascattle, sheep, and

goats can carry the Qfever microbeintissues involved inbirth--the uterus,placenta, and birthfluids.

Infected animals also

release the microbe inmilk and manure.
http://images.google.com.eg/imgres?imgurl=http://www.abc.net.au/health/library/img/Q_Fever_m1348706.jpg&imgrefurl=http://www.abc.net.au/health/library/stories/2003/06/19/1831554.htm&h=150&w=300&sz=10&hl=ar&start=11&tbnid=xieUYMoXRaLc8M:&tbnh=58&tbnw=116&prev=/images%3Fq%3D%2522Q%2BFEVER%2522%26gbv%3D2%26hl%3Dar%26sa%3DGhttp://images.google.com.eg/imgres?imgurl=http://www.pbs.org/wgbh/nova/bioterror/images/agen_qfever.jpg&imgrefurl=http://www.pbs.org/wgbh/nova/bioterror/agen_qfever.html&h=175&w=250&sz=26&hl=ar&start=18&tbnid=9-vwRBRAhDCW3M:&tbnh=78&tbnw=111&prev=/images%3Fq%3D%2522Q%2BFEVER%2522%26gbv%3D2%26hl%3Dar%26sa%3DG


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Q Fever

People acquire the infection byinhalinginfectious aerosols andcontaminated dusts generated by

animals or animal products.

People can also get Q fever by

drinking infected milk, but mostinfections are spread through the air.


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Q fever PATHOGENESIS


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Q feverPATHOGENESIS

Q Fever: signs and symptoms


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Q g y p

A small percentage of patients develop

hepatitis and jaundice. Other rare clinical syndromesincluding

endocarditis, have been reported.

Hepato/splenomegalyand endocarditisare also common in chronicQ fever.

Q fever-focal hepatic granuloma (intra-


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Q fever focal hepatic granuloma(intraacinar granuloma with a central fat vacule

surrounded by fibrin ring and macrophages)


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L t i i


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Leptospirosis

Leptospirosis CAUSED BYLeptospira interrogans(Leptospiraicterohaemorrhagiae) : aflexible, spiral-shaped,Gram-negativespirochete with internalflagella.

Transmission occurs by contamination of


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water, soil, or vegetation by urineexcreted from infected animals.


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http://www.accuratepestmanagement.com/rat%20pic.jpg


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Interesting Fact:Brown ratscarrydiseases, including Weil's disease,Viral

hemorrhagic fever(VHF), Q fever.They can also act as reservoirs ofbubonic plague.

Leptospirosis:PATHOGENESIS
http://en.wikipedia.org/wiki/Weil%27s_diseasehttp://en.wikipedia.org/wiki/Viral_hemorrhagic_feverhttp://en.wikipedia.org/wiki/Viral_hemorrhagic_feverhttp://en.wikipedia.org/wiki/Q_feverhttp://en.wikipedia.org/wiki/Bubonic_plaguehttp://www.accuratepestmanagement.com/rat%20pic.jpghttp://en.wikipedia.org/wiki/Bubonic_plaguehttp://en.wikipedia.org/wiki/Q_feverhttp://en.wikipedia.org/wiki/Viral_hemorrhagic_feverhttp://en.wikipedia.org/wiki/Viral_hemorrhagic_feverhttp://en.wikipedia.org/wiki/Weil%27s_disease


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Icteric
http://microbewiki.kenyon.edu/index.php/Image:Humanlepto.jpg


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leptospirosis orWeil's syndromeis the more severeform and ischaracterized by

deepjaundice(blilirubin

May exceed

30mg/dl)

Leptospirosis
http://microbewiki.kenyon.edu/index.php/Image:Humanlepto.jpg


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Leptospirosis

Liver involvement is marked by centrilobularnecrosis and Kupffer cellproliferation, withhepatocellular dysfunction.

Abdominal examination can reveal liverenlargement and tendernessfrom hepatitis.

A positive Murphy sign can be observed inpatients who develop acalculouscholecystitis.


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Relapsing Fever

Relapsing Fever


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Relapsing fever istransmitted to humans

by 2 vectors, ticks andlice.

Relapsing Fever

RFs are spirochetal infectionswithBorrel ia sp)gram negative

helical bacteria).

Relapsing Fever-transmission
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Relapsing Fever-pathogenesis


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Relapsing Fever


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Relapsing Fever-CLINICAL


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Hepatosplenomegalyis common.

Conjunctival injection, epistaxis, cough,and slight hemoptysis may also occur.

Symptoms last for 3-10 days, whenthere is a crisis (>fever and severity ofother symptoms), followed by recoveryand relapsein about 7-14 days .

Petechial or maculopapular rash.

Rales , Rhonchi . Nuchal rigidity& Lymphadenopathy.

Iritis and iridocyclitis .

Jaundice in Relapsing Fever


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Jaundice in Relapsing Fever

The liver showsnecroinflammatory

changes withelevation of serumtransaminasesand

serumbilirubinup to15mg/100ml


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Syphilis


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Syphilis


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This historical disease used toproduce the "hepar lobatum" in itscongenital form due to dissecting

fibrosis produced by granulationtissue containing spirochetaepallidae and hepatic granulomas inany form.


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Typhoid and paratyphoidfever

Typhoid and paratyphoid fever


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Typhoid andparatyphoid fever

Typhoid feveris anacute systemicfebrile illnesscaused bySalmonella typhi.

S. Paratyphicauses the lesssevere paratyphoidfever.



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The liver is enlargedAND TENDER

Infarction abscessesand acute yellow

atrophy occur in rareinstances.

Moderate elevation in

serumtransaminasesandserumbilirubin

Salmonellosismay infect the liverwhere they produce histiocytic granulomas


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where they produce histiocytic granulomas.Typhoid noduleconsists of an intra

parenchymal focus of necrosis withhistiocytes, some neutrophils an will contain

the gram negative organisms.

Typhoid fever-focal hepatic necrosis


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Typhoid fever focal hepatic necrosis


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Brucellosis or undulant fever:B ll i i d
http://frontier.k-state.edu/Images/ResearchAndAnalysis/Updates/OverlapAgents/Brucellosis_lg.jpghttp://frontier.k-state.edu/Images/ResearchAndAnalysis/Updates/OverlapAgents/Brucellosis_lg.jpg


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Brucellosis is causedby gram negativecoccobacilli(Brucella abortusand other B.

biovars) transmitted through

contaminated milk,and animalproducts.

Sources of Brucella infection
http://frontier.k-state.edu/Images/ResearchAndAnalysis/Updates/OverlapAgents/Brucellosis_lg.jpghttp://frontier.k-state.edu/Images/ResearchAndAnalysis/Updates/OverlapAgents/Brucellosis_lg.jpg


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Sources of Brucella infection

Portals of entry for Brucella species


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Portals of entry for Brucella species

Spread of Brucella in the body


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Spread of Brucella in the body


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Brucellosis in the chronic form


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Brucellosisin the chronicform

will cause LIVER noncaseatinggranuloma lesions, sometimeswith atypical nuclei of their

histiocytes as to mimic Hodgkinsgranulomas.


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HEPATIC Tuberculosis



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It involves the liver most frequently

in miliary tuberculosiswhere it formsmultiple granulomas with or withoutgiant cells or caseation necrosis.

If the granulomas are numerous, theonly functional changemay beelevation of serum alkalinephosphatase due to the local

compression of the liver parenchymaaround each single granuloma.



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TB granulomasin the liver may bevery similar to those of sarcoidosisbecause caseation necrosis is oftenabsent.

Because the organismsare rarelyseen in TB granulomas of the liver,

the histological differential diagnosiswith sarcoidosis may be difficult.

Same TB granuloma of the liver


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Leprosy


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Liver granulomas are observed in the

lepromatous form of the disease.They contain acid-fast bacilli and the"lepra histiocyte" which are large

histiocyte with clear cytoplasm.

Hepatic granulomas may be the

cause of relapseafter an apparentsuccessful therapy.

Liver Lepromatous granulomawith H&E stain.


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Liver Lepromatous granuloma


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RICKETTSIAL INFECTIONS


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*Rocky Mountain Spotted Fever : It is due to a rickettsia transmitted by

ticks. The organisms after infectionproliferate in endothelial cells of variousorgans.

The clinical syndrome 2 to 14 days afterthe tick bite starts with fever,malaise,vomiting. On the third day a skin rashappears on the limbs. Later the rash

disappears leaving hemorrhagic spots. Jaundiceis present in 1/3 of the cases

with portal inflammation and presence ofrickettsiae in the portal spaces.


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Causes of Hepatic Granulomas


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p

Bacterial Infections: brucellosis,cat-scratch fever, syphilis, TB*, othermycobacterial infections, Leprosy,tularemia, Q fever, Rickettsia,

Actinomycosis and Typhoid fever.

Viral infections, which are lesscommon (eg, infectious

mononucleosis, cytomegalovirus andCoxsackie) .

Hepatic Granulomas


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p

Hepatic granulomas are usuallyasymptomatic. However, theunderlying disorder may causeextrahepatic manifestations, hepaticinflammation, fibrosis, portalhypertension, or a combination.

The liver may enlarge slightly, andmild jaundice may develop.


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Hepatic granulomas


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Diagnosisis based on Liver function tests

&Imaging, but biopsyis necessary only if atreatable underlying disorder (eg, infection) issuspected or if other liver disorders need to beruled out.

liver function testresults are only mildlyderanged, usually with a disproportionateelevation of alkalinephosphatase. Bilirubinlevelsare typically normal or only mildly

elevated, unless concomitant hepatocellularinjury coexists. Enzymevalues may simulateviral hepatitis if extensive hepatocellularnecrosis is present (eg, in infectious

mononucleosis)


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Conclusion


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* A large number of viral and bacterial

organisms can involve the liver .

* These systemic infections can causehepatic derangements, ranging from mildliver function tests abnormalities to frankjaundice and, rarely, hepatic failure.

* They should be put in mind indifferential diagnosisof abnorml liverfunction tests.


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liver in fever

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