Sepsis, Hemorrhagic Fever, and EBV Flashcards Preview

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Flashcards in Sepsis, Hemorrhagic Fever, and EBV Deck (36):
1

Define SIRS (systemic inflammatory response syndrome)

-clinical response arising from a nonspecific insult manifested by 2 or more of the following:
-temperature outside range of 98.6-100.4
-HR>90 beats/min
-respirations>20/min
-WBC count > 12,000 or 10%bands (young neutrophils)

2

Define infection.

-Organisms found in normally sterile sites
-inflammatory response to microorganisms
-invasion of normally sterile tissues
-bacteremia: cultivatable bacteria in the blood stream

3

Define sepsis.

SIRS plus infection
-systemic response to infection

4

Define hypotension.

-systolic blood pressure 40mmHg from baseline

5

Define Severe Sepsis.

Sepsis with:
-dysfunction of organ(s) distant from site of infection
-hypotension
-hypoperfusion
May include lactic acidosis, oliguria (decreased output of urine), altered mental status, acute lung injury

6

Define septic shock.

Sepsis plus hypotension despite fluid resuscitation

7

What is the pathophysiology of shock?

cellular level: oxygen demand greater than supply
1. Initial stage: hypoperfusion-->hypoxia
-lactic acidosis
2. Compensatory "cold shock"
-hyperventilation (decrease CO2)
-vasoconstriction
-low urine output
3. Progressive "warm shock"
-compensatory mechanisms fail
-leakage of protein and fluid into tissues
-ischemia of organs
4. Refractory
-organ failure
-shock can't be reversed

8

What are the causes of shock?

1. Hypovolemic shock
-dehydration or blood loss
-most common cause
2. cardiac shock
-MI
-cardiomyopathy
3. Obstructive shock
-pulmonary embolism, aortic stenosis, tension pneumothorax, cardiac tamponade
4. Distributive shock
-septic, anaphylactic, neurogenic

9

What causes sepsis?

-triggered by infection
-used to be mainly gram neg bacteria, but now gram positive make up at least >30% of bacterial infections that cause sepsis
-Gram positive: teichoic acid, lipoteichoic acid, peptidoglycan
-Gram neg: lipopolysaccharide (LPS)
-viral: viral dsRNA

10

Describe the pathological host response to infection.

-microcirculatory and mitochondrial dysfunction
-activation or injury of vascular epithelium
-pro-inflammatory cytokines: TNF, Il-1
-complement activation: repression of anticoag and fibrinolysis
+activation of coagulation cascade-->coagulopathy
-immunosuppression
-shunting of blood flow and micro thrombosis--> disordered blood flow-->organ failure

11

What are the clinical manifestations of sepsis?

-systemic: fevers and chills
-hemodynamic: tachycardia, hypotension
Organ system dysfunction
-clotting system: endothelial damage, microvascular thrombosis, DIC
-heart: depressed myocardial contractility (decreased cardiac output), tachycardia (increased cardiac output)
-lung: capillary endothelial damage--> fluid leaking into interstitium and alveoli, inadequate air exchange, ARDS
-acute renal failure
-liver: jaundice
-hemorrhagic necrosis from ischemia
-CNS: confusion, delirium, stupor, coma

12

What are the therapeutic approaches to sepsis?

-Goal-Directed therapy
-Achieve adequate oxygenation: nasal O2 or intubation
-achieve adequate blood pressure and end organ perfusion: fluid resuscitation and vasoactive agents
-transfusion therapy for anemia
-rapid eradication of microbes: IND, effective antimicrobial agents,
-corticosteroids in low doses
-modulation of harmful inflammatory response

13

Describe the features of classical FUO (fever of unknown origin).

-fever >101 F (38.3 C) on several occasions
-duration of fever >3 weeks
-no diagnosis after 1 week after intensive and intelligent investigation or after 2 outpatient visits or 3 days in the hospital

14

What are the etiologies or classic FUO?

In the order of most common to least common
-infections
-neoplasms
-CT disease
-Misc
-undiagnosed

15

What are infectious causes of classic FUO?

-abscess: classic hiding place in retroperitoneal area
-endocarditis
-granulomatous disease: disseminated Tb, hitoplasmosis, coccidioidomycosis, blastomycosis
-viral infections: CMV, EBV, HIV, parvo, Hep
-Zoonoses: brucellosis, leptospirosis, lyme
-typhoid fever
-malaria
-leshmaniasis

16

What are the diagnostic possibilities in the investigation of classic FUO?

-History
-physical exam
-Lab studies
CBC with differential
ESR/CRP
Liver panel
Urinalysis and culture
Blood cultures (at least 3)
Chest X-ray
PPD
-Non-invasive Studies
CT scan of abdomen/pelvis, chest
Labeled WBC scan (Indium or 99mTc)
Gallium scan (particularly effective in imaging chronic infections)
Venous duplex imaging of lower extremities
-Specialized studies
Serologic tests: Salmonella, Brucella, rickettsia. Lyme, RPR
Antigen detection: Cryptococcus
Malaria smears
O&P
Rheumatologic panels
-Invasive procedures
Biopsies (average of 2.8 to 4.6 biopsies per case)
Liver, lymph node, temporal artery
Exploratory laporotomy (rare today)
Lumbar puncture

17

What is the prognosis of FUO?

-8% remain undiagnosed
-most of cases resolve spontaneously without sequelae

18

Define viral hemorrhagic fever.

-Severe multisystem syndrome
-Overall vascular system is damaged, and self-regulation is impaired
-Accompanied by hemorrhage
-Some types can cause relatively mild illnesses, but many cause severe, life-threatening disease

19

What is the mechanism behind viral hemorrhagic fever?

-Capillary leak
-Bleeding diathesis
DIC
Hepatic damage
Consumptive coagulopathy
Primary marrow dysfunction
-Hemodynamic compromise leading to shock

20

What are the causes of viral hemorrhagic fever?

-all enveloped RNA viruses
-geographically restricted
-humans not natural reservoir for any of these viruses: infected when they come into contact with infected host
-human cases or outbreaks occur sporadically and irregularly

21

What is the clinical presentation of viral hemorrhagic fever?

-fever and bleeding diathesis (predisposition)
-symptoms: marked fever, malaise, myalgias, exhaustion, headache, dizziness, vomiting, and diarrhea
-physical exam: flushing of face and chest, edema, petechiae, frank bleeding, hypotension and shock
-severe cases: signs of bleeding under skin, in internal organs, body orifices
-shock
-nervous system malfunction, coma, delirium, seizures
-some types of VHF are associated with renal failure

22

Describe Yellow fever.

Yellow fever:
-In Africa and South America
-transmitted by mosquitos, replicates in lymph nodes, have widespread petechial hemorrhages and bleeding (liver damage-->decrease clotting factors, intravascular coat, thrombocytopenia, endothelial damage), hepatocellular damage (jaundice)

23

What are some specific organisms/diseases that cause viral hemorrhagic fever?

-flaviviridae: dengue, yellow fever
-Arenaviridae: lassa fever
-filoviridae: ebola, marburg
-bunyaviradae: hantavirus

24

Describe Lassa Fever.

-West Africa
-Mastomys species complex
-rodent to human transmission
-secondary human to human transmission with potential for nosocomial outbreaks with high fatality
-pathogenesis: endothelial cell damage/capillary leak, platelet dysfunction, suppressed cardiac fxn, cytokines other mediators of shock and inflammation
-clinical: gradual onset fever, headache, malaise. Also pharyngitis, myalgias, retrosternal pain, cough, GI. Minority have: bleeding, neck/face swelling, shock
-deafness common sequela
-Tx: supportive measures, ribavirin

25

Describe Ebola.

-central africa
Transmission
-Close contact with the blood, secretions, organs or other bodily fluids of infected animals.
-Chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines
-Health-care workers have frequently been infected
Clinical
-incubation period 2-21 days
-sudden onset: fever, intense weakness, muscle pain, headache, sore throat
-vomiting, diarrhea, rash, impaired kidney and liver function
Tx:
-supportive care
-strict airborne and contact precautions

26

Describe the properties of Epstein-Bar Virus.

-belongs to gamma herpes virus subfamily
-Linear dsDNA
-protein core, icosohedral nucleocapsid
-enveloped
-Viral genome forms circular episomes that reside in host nucleus, doesn't integrate into DNA

27

Understand the epidemiology of EBV infection

90-95% of adults have EBV Abs
-50% of population in US has seroconversion before age 5
-humans only reservoir
-in oropharyngeal secretions of asymptomatic people
-not very contagious, need large viral load to transmit

28

Understand the pathophysiology of EBV infection

-Primary infection from exposure to oral secretions of seropositive individuals: kissing, food sharing, anything that shares oral secretions
-Infects B cells and nasopharyngeal epithelial cells
-EBV receptor: C3d gp=CD21=CR2
-Infected B cells cause cytotoxic T cell response
-most cleared but quiescently infected B cells remain as life long reservoir
-Latent infection: no viral production, viral DNA is present, gene products convert B lymphocytes into immortalized lymphoblastic cells capable of continuous growth
-First genes expressed:EBNA1, 2, 3A, 3B, 3C, LP, EBNA2 essential for transformation of B lymphocyte
-latent: LMP1 dominant transforming gene in latent infection

29

Describe the symptoms of acute EBV infection

children: asymptomatic, FUO
teens and adults: 30-50% chance of infectious mononucleosis (IM) with acute infection
clinical presentation of IM:
-incubation 4-6 weeks
-self limited disease
-Triad: fever, lymphadenopathy, pharyngitis
Also: heptaosplenomegaly (week 2 of illness)
-periorbital edema, jaundice, rash less common

30

Discuss the chronic conditions associated with EBV infection

-symptoms up to 4 months
-may progress to lymphoproliferative diseases, lymphoma

31

How does the host immune system respond to EBV infection?

-challenge for immune system: up to 20% of B cells in circulation express EBNA
-Cell mediated response: CD8 and CD4 CTLs, NK cells
-Humoral response: IgM against VCA, IgG VCA (viral capsid antigen)
-

32

What are diseases associated with EBV?

Infectious Mononucleosis
Chronic infectious mononucleosis
Fever of Unknown Origin (FUO)
AIDS associated: Oral hairy leukoplakia , Chronic interstitial pneumonitis (LIP)
Burkitt's lymphoma
Nasopharyngeal carcinoma
Lymphoproliferative disease: Lymphoma in the immunosuppressed, Hemophagocytic lymphohistiocytosis
X-linked lymphoproliferative syndrome

33

What is the differential diagnosis of infectious mononucleosis?

-Acute EBV
-Acute CMV
-acute toxoplasmosis
-Acute retroviral syndrome: HIV

34

What are the laboratory findings in infectious mononucleosis?

Hematologic:
-lymphocytosis: >50% circulating mononuclear cells
-atypical lymphoctyes, cytotoxic T cells directed against infected B cells
Mild Hepatis
-elevated ALT/AST
-ocasional jaundice
Positive heterophile antibody test: monospot test, agglutination rxn to Ags of horse RBCs, represents nonspecific B cell activation

35

What is the therapy for EBV infection?

Supportive care
No antivirals effective
Avoid ampicillin/amoxicillin: often causes a rash in patients with EBV/acute IM
Corticosteriods for complications

36

What are serious complications of EBV infection?

serious complications are rare
-splenic rupture
-meningoencephalitis
-pharyngeal obstruction