Sepsis, Hemorrhagic Fever, and EBV Flashcards
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)
Define infection.
- Organisms found in normally sterile sites
- inflammatory response to microorganisms
- invasion of normally sterile tissues
- bacteremia: cultivatable bacteria in the blood stream
Define sepsis.
SIRS plus infection
-systemic response to infection
Define hypotension.
-systolic blood pressure 40mmHg from baseline
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
Define septic shock.
Sepsis plus hypotension despite fluid resuscitation
What is the pathophysiology of shock?
cellular level: oxygen demand greater than supply
- Initial stage: hypoperfusion–>hypoxia
- lactic acidosis - Compensatory “cold shock”
- hyperventilation (decrease CO2)
- vasoconstriction
- low urine output - Progressive “warm shock”
- compensatory mechanisms fail
- leakage of protein and fluid into tissues
- ischemia of organs - Refractory
- organ failure
- shock can’t be reversed
What are the causes of shock?
- Hypovolemic shock
- dehydration or blood loss
- most common cause - cardiac shock
- MI
- cardiomyopathy - Obstructive shock
- pulmonary embolism, aortic stenosis, tension pneumothorax, cardiac tamponade - 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
-immunosuppression
-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
-liver: jaundice
-hemorrhagic necrosis from ischemia
-CNS: confusion, delirium, stupor, coma
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
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
- infections
- neoplasms
- CT disease
- Misc
- undiagnosed
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
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
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?
-Capillary leak
-Bleeding diathesis
DIC
Hepatic damage
Consumptive coagulopathy
Primary marrow dysfunction
-Hemodynamic compromise leading to shock
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
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
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)
What are some specific organisms/diseases that cause viral hemorrhagic fever?
- flaviviridae: dengue, yellow fever
- Arenaviridae: lassa fever
- filoviridae: ebola, marburg
- bunyaviradae: hantavirus
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
