Flashcards in Sepsis, Hemorrhagic Fever, and EBV Deck (36):
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
-WBC count > 12,000 or 10%bands (young neutrophils)
-Organisms found in normally sterile sites
-inflammatory response to microorganisms
-invasion of normally sterile tissues
-bacteremia: cultivatable bacteria in the blood stream
SIRS plus infection
-systemic response to infection
-systolic blood pressure 40mmHg from baseline
Define Severe Sepsis.
-dysfunction of organ(s) distant from site of infection
May include lactic acidosis, oliguria (decreased output of urine), altered mental status, acute lung injury
Define septic shock.
Sepsis plus hypotension despite fluid resuscitation
What is the pathophysiology of shock?
cellular level: oxygen demand greater than supply
1. Initial stage: hypoperfusion-->hypoxia
2. Compensatory "cold shock"
-hyperventilation (decrease CO2)
-low urine output
3. Progressive "warm shock"
-compensatory mechanisms fail
-leakage of protein and fluid into tissues
-ischemia of organs
-shock can't be reversed
What are the causes of shock?
1. Hypovolemic shock
-dehydration or blood loss
-most common cause
2. cardiac shock
3. Obstructive shock
-pulmonary embolism, aortic stenosis, tension pneumothorax, cardiac tamponade
4. Distributive shock
-septic, anaphylactic, neurogenic
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
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
-shunting of blood flow and micro thrombosis--> disordered blood flow-->organ failure
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
-hemorrhagic necrosis from ischemia
-CNS: confusion, delirium, stupor, coma
What are the therapeutic approaches to sepsis?
-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
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
What are the etiologies or classic FUO?
In the order of most common to least common
What are infectious causes of classic FUO?
-abscess: classic hiding place in retroperitoneal area
-granulomatous disease: disseminated Tb, hitoplasmosis, coccidioidomycosis, blastomycosis
-viral infections: CMV, EBV, HIV, parvo, Hep
-Zoonoses: brucellosis, leptospirosis, lyme
What are the diagnostic possibilities in the investigation of classic FUO?
CBC with differential
Urinalysis and culture
Blood cultures (at least 3)
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
Serologic tests: Salmonella, Brucella, rickettsia. Lyme, RPR
Antigen detection: Cryptococcus
Biopsies (average of 2.8 to 4.6 biopsies per case)
Liver, lymph node, temporal artery
Exploratory laporotomy (rare today)
What is the prognosis of FUO?
-8% remain undiagnosed
-most of cases resolve spontaneously without sequelae
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
What is the mechanism behind viral hemorrhagic fever?
Primary marrow dysfunction
-Hemodynamic compromise leading to shock
What are the causes of viral hemorrhagic fever?
-all enveloped RNA viruses
-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
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
-nervous system malfunction, coma, delirium, seizures
-some types of VHF are associated with renal failure
Describe 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)
What are some specific organisms/diseases that cause viral hemorrhagic fever?
-flaviviridae: dengue, yellow fever
-Arenaviridae: lassa fever
-filoviridae: ebola, marburg
Describe Lassa Fever.
-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
-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
-incubation period 2-21 days
-sudden onset: fever, intense weakness, muscle pain, headache, sore throat
-vomiting, diarrhea, rash, impaired kidney and liver function
-strict airborne and contact precautions
Describe the properties of Epstein-Bar Virus.
-belongs to gamma herpes virus subfamily
-protein core, icosohedral nucleocapsid
-Viral genome forms circular episomes that reside in host nucleus, doesn't integrate into DNA
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
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
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
Discuss the chronic conditions associated with EBV infection
-symptoms up to 4 months
-may progress to lymphoproliferative diseases, lymphoma
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)
What are diseases associated with EBV?
Chronic infectious mononucleosis
Fever of Unknown Origin (FUO)
AIDS associated: Oral hairy leukoplakia , Chronic interstitial pneumonitis (LIP)
Lymphoproliferative disease: Lymphoma in the immunosuppressed, Hemophagocytic lymphohistiocytosis
X-linked lymphoproliferative syndrome
What is the differential diagnosis of infectious mononucleosis?
-Acute retroviral syndrome: HIV
What are the laboratory findings in infectious mononucleosis?
-lymphocytosis: >50% circulating mononuclear cells
-atypical lymphoctyes, cytotoxic T cells directed against infected B cells
Positive heterophile antibody test: monospot test, agglutination rxn to Ags of horse RBCs, represents nonspecific B cell activation
What is the therapy for EBV infection?
No antivirals effective
Avoid ampicillin/amoxicillin: often causes a rash in patients with EBV/acute IM
Corticosteriods for complications