Sepsis and viral infections Flashcards
1
Q
Sepsis
A
- The body’s systemic response to infection: abnormal generalized inflammatory rxn (due to microbial products) in organs remote from initial insult
- SIRS (systemic inflammatory response syndrome) + infection (of normally sterile sites) = sepsis
- SIRS is 2 or more of: temp change (≥38 or ≤36), HR≥90, RR≥20, WBC≥12,000 or ≤4,000 (or 10% bands)
- Septic shock when accompanied by hypotension (systolic BP 40 mmHg from baseline) despite fluid resuscitation
2
Q
Pathophysiology of sepsis
A
- Triggered by infection (mostly GN and GP bacteria, can also be fungi)
- First host response is walling off and killing by tissue macs, mast cells, dendritic cells + innate immune system
- Also increase in procoagulants to wall off infection
- Systemic response: fever, leukocytosis, APRs (acute phase reactants)
- Severe sepsis: hypo perfusion of distant organs, dysfunction of those organs, hypotension
3
Q
Mediators of sepsis
A
- GP bacteria: teichoic acid, lipoteichoic acid, peptidoglycan
- GN bacteria: LPS (leads to production and secretion of inflammatory mediators TNF and IL1B)
- In effect LPS endotoxin increases capillary permeability, leads to infiltration of PMNs, and local fibrin deposition to impede infection
4
Q
Host responses to sepsis
A
- Microcirculatory and mitochondrial dysfunction
- Activation or injury of vascular epithelium
- Septic shock due to TNF and IL1
- Complement activation, and repression of anticoagulation and fibrinolysis
- The unbalance btwn coagulation and fibrinolysis can lead to DIC
- Disordered microcirculation due to shunting of blood and microthrombi
5
Q
Clinical manifestations of sepsis
A
- Systemic: fever, chills
- Hemodynamic: tachychardia, hypotenision
- Organ systems: endothelial damage, microthrombi, DIC (due to unbalanced hemostasis)
- Lung damage leads to fluid leakage into interstitium and alveoli, inadequate air exchange and ARDS
- Renal failure in kidney, jaundice due to liver failure, hemorrhagic necrosis from ischemia in intestines
- CNS symptoms: confusion, delirium, stupor, coma
6
Q
Rx for sepsis
A
- Medical emergency
- Goal directed Rx: achieve adequate O2
- Achieve adequate BP and end organ perfusion (fluid resuscitation, vasoactive agents)
- Transfusions for anemia
- RAPID eradication of microbes: draining or removing infectious foci, effective antimicrobial agents (broad spectrum)
- Possible low doses of corticosteroids (hydrocortisone)
- Modulation of harmful inflammatory response (Abs to endotoxin, TNF, ect)
7
Q
FUO: Fever of unknown origin
A
- Fevers due to: exogenous pyrogens and endogenous pyrogens
- Endogenous: IL1 and IL6, TNFa, CNF (ciliary neurotropic factor), INF
- Classic FUO, nosocomial FUO (not present on admission), Neutropenic FUO (PMNs <500), immune deficient FUO, HIV-related FUO
8
Q
Classical FUO
A
- Fever of >38.3 (101F) (lasting more than 3 weeks)
- No Dx after 3 days in hospital or 2 outpatient visits
9
Q
Etiologies of classic FUO
A
- Mostly infections, neoplasms, connective tissue (CT) disease (often AID), others
- Infectious FUO: abscess, endocarditis, granulomatous disease (TB, histoplasmosis, coccidiodomycosis, ect), viral infections (CMV, EBV, HIV, parvovirus B19, hepatitis), zoonoses (brucella, leptospirosis, lyme disease), typhoid fever, malaria, leshmania
10
Q
Viral hemorrhagic fever (VHF)
A
- Severe multisystem syndrome
- Vascular system is damaged and self-regulation impaired (accompanied by hemorrhage)
- Some cases are mild others are fatal
- Hemorrhage due to capillary leak, bleeding diathesis (DIC, hepatic damage, consumptive coagulopathy, primary marrow dysfunction)
- Hemodynamic compromise leading to shock
- Cause of all hemorrhagic fevers are enveloped RNA viruses (geographically restricted, survival depends on insect or animal host)
11
Q
Clinical symptoms of hemorrhagic fever
A
- Fever, malaise, myalgia, exhaustion, headache, dizziness, vomiting, diarrhea
- Also petechia, edema, bleeding, hypotension and shock
- Bleeding under the skin, in internal organs, from mouth, eyes, or ears
- Pts rarely die from blood loss, usually from shock
- Shock leads to CNS malfunction, coma, delirium, and seizures
- Some VHF are associated w/ kidney failure
12
Q
Causes of VHF
A
- Flaviviridae: yellow fever, dengue
- Arenaviridae: lassa fever
- Filoviridae: ebola, marbug
- Bunyaviridae: hantavirus, rift valley
13
Q
Yellow fever
A
- Mosquito transmitted (africa and south america)
- Replicates in LNs, spreads via blood to macrophages, liver, lung, kidney, adrenals, spleen
- Leads to petechial hemorrhaging (liver damage + coagulation + thrombocytopenia + endothelial damage)
- Jaundice due to liver damage
- No Rx, only vaccine
14
Q
Lassa fever
A
- Endemic in africa, host is a wild shrew-rat
- Endothelial cell damage/leak
- Platelet dysfunction
- Cytokines and other mediators induce shock and inflammation
- Majority only have non-specific flu symptoms
- Most sever in pregnant women, deafness is a common sequela
- Rx is supportive care and ribavirin
15
Q
Ebola
A
- Endemic to africa
- Sudden onset of fever, weakness, myalgias, headache, sore throat, vomiting, diarrhea, rash, impaired kidneys and liver
- Fatality rate as high as 90%
- Rx is supportive care (strict airborne and contact precautions)
