1. 2010 pa tho physiology and clinical presentation

8/2/2019 1. 2010 Pa Tho Physiology and Clinical Presentation

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Pathophysiology

and

Clinical Presentation


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Introduction

Dengue fever is the fastest emerging arboviral

infection spread by theAedes

The global incidence has grown dramatically

over the past decade


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Key facts

2.5 billion people in tropical and subtropical countries

are at risk of dengue infection

An estimated 50 million dengue infections occur

annually An estimated 500 000 people with DHF require

hospitalisation

Dengue infection is endemic in over 100 countries.South East Asia and Western Pacific regions are the

most affected


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Dengue virus

The dengue virus is a single stranded RNA

Belongs to the genus Flavivirus and family

Flaviviridae 4 serologically distinct serotypes

DENV: 1 to 4

Dengue infection provides life long immunity to only that serotype

Transient protection to other serotypes


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Vectors and host

The two principal vectors of dengue are theAedes

aegyptiandAedes albopictus

The virus is maintained by the vector transovariallyvia the eggs

Both monkeys and humans are the amplifying host


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Pathophysiology


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Evidence of plasma leakage

The hallmark of DHF is increased vascular

permeability resulting in plasma leakage

The unique feature of the plasma leakage is

Selective leakage into the pleural and peritoneal

space

Period of leakage: 24 48 hours


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Evidence of plasma leakage

The evidence of plasma leakage includes

hemoconcentration

pleural effusion

ascites

hypovolemia and shock


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Bleeding tendency

Vasculopathy

Increase capillary fragility as indicated by a

positive tourniquet test

Seen usually early in the febrile phase

Thrombocytopenia and platelet dysfuction

Due to decreased platelet production and increase

peripheral destruction


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Bleeding tendency

Coagulopathy

There is a variable but no significant reduction in a

number of coagulation factors: prothrombin,

factors V, VII, VIII, IX and X

Low levels of protein C, protein S and prothrombin

were also seen in DSS

These coagulation abnormalities are well

compensated in the majority of patients

without circulatory shock.


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Clinical presentation


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Manifestations of the dengue syndrome

Incubation period: 4 - 10 days Spectrum of illness:

Asymptomatic

Undifferentiated

fever

No

hemorrhageUnusual

hemorrhage

Dengue Fever

DHF 1& 2 DHF 3&4DSS

Dengue Hemorrhagic Fever

(plasma leakage)

Symptomatic

Dengue virusInfection


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Clinical course of dengue infection

FebrilePhase

CriticalPhase

RecoveryPhase

Lasts for 2 7 daysClinical features are indistinguishable between DF and DHF

Happens often after the 3rd day of feverClinical presentation depends on the presence and degree ofplasma leakageLasts for about 24-48 hours

In DHF patients plasma leakage stops and is followed byreabsorption of extravascular fluid


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Febrile phase

Sudden onset of high grade fever, may bebiphasic, lasting for 2 -7 days

Flushed face Headache and retro-orbital pain

Severe myalgia and arthralgia: Breakbone

fever Rash


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Skin manifestations

Facial flush in first 24 to 48hours

Petechiae with positive Hesstest

Erythematous maculo-

papular rash : Isles of whitein a sea of red


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Hemorrhagic manifestations

Gum bleeding and epistaxis

Menorrhagia

GIT hemaorrhage Massive bleeding is rare in dengue fever

Dengue fever with hemorrhagic manifestationsmust be differentiated from DHF


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Clinical Lab findings

Leucopenia with decreasing neutrophils throughout

the febrile phase

Thrombocytopenia: < 100 000 cells/mm3

Mild rise in hct ( ~ 10%) may be seen as a

consequence of dehydration

Clinical lab findings


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Clinical Lab findings

Liver enzymes: ALT/AST may be elevated

Coagulation profile: APTT may be prolonged

Clinical lab findings


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FebrilePhase

CriticalPhase

RecoveryPhase





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Risk factors for DHF

Secondary infection

Due to antibody-dependent enhancement

Viral virulence

Viral load

Host genetic background


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High risk patients

Infants and the elderly

Obesity

Pregnant women

Peptic ulcer disease

Chronic diseases: DM, Hypertension, IHD,

asthma, liver cirrhosis


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Critical phase

Usually occurs on days 3 7

Drop in temperture

Plasma leakage, if occurs usually lasts for 24to 48 hours

Progressive leucopenia with

thrombocytopenia precedes plasma leakage


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Critical Phase

During this phase

Minimal or no plasma

leakage occurs

Patient feels better as thetemperature subsides

Critical volume of plasma leakageoccurs

Patient develops DHF

Varying degrees ofcirculatory disturbancesoccur depending on thedegree of plasma leakage


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Warning signs

Lethargy and restlessness

Mucosal bleeding

Persistent vomiting Abdominal pain or tenderness

Liver enlarged > 2 cm

Clinical fluid accumulation

Lab: increase in HCT with a concurrent rapid

decrease in platelet count


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Critical phase

Thrombocytopenia and hemoconcentration are usuallydetectable before the onset of shock

HCT level correlates well with plasma volume loss anddisease severity.

However HCT values may be equivocal and hence

unhelpful when there is frank hemorrhage or with

untimely HCT determinations


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Rising Hematocrit

Upper limit normal Hct 0.4 for children and adult

female

0.45 for adult male

A > 20% rise in the Hct

from the baseline isconsidered significant


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Third space fluid accumulation

Pleural effusion: Dyspnoeic,

tachypnoeic,hypoxemic

CXR: pleuraleffusion

Ascites Abdominal distension

and tenderness


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Hemodynamic instablity

In more severe form of plasma leakage

Tachycardia

Cool extremities and prolonged capillary filling

time

Systolic pressure remains normal initially

Diastolic BP increases and the pulse pressure

narrows Poor urine output

Patients remain conscious and lucid


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Critical Phase

With profound shock

Restless and agitated

Multiple organ failure with

advanced DIC


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Hepatitis

May be mild or severe regardless of the degreeof plasma leakage

Patients with liver failure have a high

propensity to bleed esp. GIT bleeding

Other important manifestations


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Neurological manifestations: mainly encephalitisor encephalopathy.

Encephalopathy is usually secondary to liver failure. These manifestations may coincide with onset of

clinical features of DHF or may present on admissionwith no other features suggestive of dengue.



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Acute abdomen

Other causes include acalculous cholecystitis, acuteappendicitis

Need to differentiate from surgical causes

Fever before abdominal pain

Leucopenia, thrombocytopenia, prolonged APTT withnormal PT

Improvement of pain with fluid resuscitation

Most recover within 48-72 hours with conservativetreatment


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FebrilePhase

CriticalPhase

RecoveryPhase





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Recovery Phase

Plasma leakage stops after 24-48 hours ofdefervescence

This is followed by reabsorption of extravascular fluid

Patients general well being improves, appetite

returns, gastrointestinal symptoms abate,

hemodynamic status stabilises and diuresis ensues.

Recovery of platelet count is typically preceded bythe recovery of WCC count


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Summary

Dengue infection has a wide spectrum of clinicalpresentation

Death is preventable if the warning signs ofdengue are detected early and patients arepromptly resuscitated


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Thank You

1. 2010 pa tho physiology and clinical presentation

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