This is for Sepsis.. | Study Guides, Projects, Research Pathology

W9_Sepsis

SIRS = systemic inflammatory response

syndrome; non-septic, localized

infection 

Fever or hypothermia

Tachycardia

Tachypnea

Leukocytosis or leukopenia

Sepsis = 2+ bedside end-organ abnormalities, AMS, tachypnea or BP < 100 mmHg 

Hypotension; systolic BP < 100 mmHg

Oliguria

Hypoxemia; PaO2 < 70mmHg or RR > 22

Increased blood lactate

DIC; thrombocytopenia,  PT or PTT, or  D-dimer

Altered mental status

Septic shock = sepsis +

MAP not rising above 65

mmHg after IV bolus

(short cut = about 90/50

or less)

Serum lactate > 2 mmol/L

Progressions of sepsis

Hours to days  untreated patient starts with chills and fever  localized infection  sepsis  septic shock

Risk factors = elderly, immunocompromised; underlying chronic diseases  cancer, diabetes, emphysema, renal failure, cirrhosis; urinary catheter, indwelling IV

catheter, hospitalization, recent surgery or trauma, burns, splenectomy

Etiology

On blood culture 

Gram + = Staph aureus, staph epidermidis, strep pneumo

Gram - = E. coli, pseudomonas aeruginoa, N. meningitides

Polymicrobial

Anaerobic = Bacteroides fragilis

Fungal = Candida albicans

Blood culture is not a requirement for diagnosis; bacteremia or fungemia may be intermittent or not the major causes of sepsis; consider exotoxins

Sources of sepsis

Lung Pneumonia Strep pneumo

URI Meningococcus

Abdomen Abscess, perforation E. coli, Bacteroides

Splenectomy = strep pneumo

Kidney Pyelonephritis, urinary catheter E. coli

Skin/soft tissue Burns, trauma, IV catheter, surgical

wounds

Burns = pseudomonas

IV catheter or surgical wound = Staph

Vagina Neonatal sepsis, postpartum sepsis Strep agalactiae

Pregnancy = listeria monocytogenes

Pathogenesis

1. Bacteria or fungi multiply in body to high numbers and enter blood

omore likely if immune deficiency, neutropenia, splenectomy, neonates, trauma, post-operative, or post-partum

2. Cytokines (pro-inflammatory and anti-inflammatory) affect cells and proteins – other cytokines, neutrophils ( # & adhesion), vascular injury (vasculitis),

complement activation (C3a, C5a), DIC, lymphocytes (immunodeficiency)

oExcess C5a in blood vessels keeps PMNs in lumen where they release protease & reactive oxidants

oDIC triggered by inflammation via extrinsic pathways using tissue factor to make thrombin (tx: activated protein C = inactivates V & VIII)

  Thrombin,  anticoagulation,  fibrinolysis

3. Multi-organ failure  kidneys, lungs, heart and brain due to inadequate perfusion  drive up serum lactate

4. Shock, coma and death

Inflammation/Immunosuppression

In gram + bacteria  LPS interactions with TLR4 and CD14 driving NF-kB pathway and cytokine production

In gram - bacteria  lipoteichoic acid and peptidoglycan interact with TLR2 to drive NF-kB pathway

Inflammation =

IL-8  chemotactic cytokine for PMNs

TNF and IL-6 are pro-inflammatory cytokines

i. More severe sepsis – higher level of cytokines

Anti-inflammatory =

Cytokines, IL-10   CD4 cells, CD8 cells and NK cells  inhibition of immune cells

i. Patients often anergic

Toxins of bacteria

Toxinemia = endotoxemia – toxic shock syndrome toxins (TSST) of Staph aureus & Strep pyogenes

Toxic shock syndrome = tampon-related, fever, erythema, hypotension, multi-organ failure

Toxins are superantigens that cause cytokine synthesis

Labs

Blood culture

WBC with differential & platelets

Organ function 

oPaO2 (low)

olactate (high)

okidney and liver function

oDIC (PT, PTT, D-dimer – all high)

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W9_Sepsis SIRS = systemic inflammatory response syndrome; non-septic, localized infection   Fever or hypothermia  Tachycardia  Tachypnea  Leukocytosis or leukopenia Sepsis = 2+ bedside end-organ abnormalities, AMS, tachypnea or BP < 100 mmHg   Hypotension; systolic BP < 100 mmHg  Oliguria  Hypoxemia; PaO2 < 70mmHg or RR > 22  Increased blood lactate  DIC; thrombocytopenia,  PT or PTT, or  D-dimer  Altered mental status Septic shock = sepsis + MAP not rising above 65 mmHg after IV bolus (short cut = about 90/ or less) OR Serum lactate > 2 mmol/L Progressions of sepsis Hours to days  untreated patient starts with chills and fever  localized infection  sepsis  septic shock Risk factors = elderly, immunocompromised; underlying chronic diseases  cancer, diabetes, emphysema, renal failure, cirrhosis; urinary catheter, indwelling IV catheter, hospitalization, recent surgery or trauma, burns, splenectomy Etiology On blood culture   Gram + = Staph aureus , staph epidermidis, strep pneumo  Gram - = E. coli , pseudomonas aeruginoa, N. meningitides  Polymicrobial  Anaerobic = Bacteroides fragilis  Fungal = Candida albicans Blood culture is not a requirement for diagnosis; bacteremia or fungemia may be intermittent or not the major causes of sepsis; consider exotoxins Sources of sepsis Lung Pneumonia Strep pneumo URI Meningococcus Abdomen Abscess, perforation E. coli, Bacteroides Splenectomy = strep pneumo Kidney Pyelonephritis, urinary catheter E. coli Skin/soft tissue Burns, trauma, IV catheter, surgical wounds Burns = pseudomonas IV catheter or surgical wound = Staph Vagina Neonatal sepsis, postpartum sepsis Strep agalactiae Pregnancy = listeria monocytogenes Pathogenesis

Bacteria or fungi multiply in body to high numbers and enter blood o more likely if immune deficiency, neutropenia, splenectomy, neonates, trauma, post-operative, or post-partum
Cytokines (pro-inflammatory and anti-inflammatory) affect cells and proteins – other cytokines , neutrophils ( # & adhesion), vascular injury (vasculitis), complement activation (C3a, C5a), DIC , lymphocytes (immunodeficiency) o Excess C5a in blood vessels keeps PMNs in lumen where they release protease & reactive oxidants o DIC triggered by inflammation via extrinsic pathways using tissue factor to make thrombin (tx: activated protein C = inactivates V & VIII)   Thrombin,  anticoagulation,  fibrinolysis
Multi-organ failure  kidneys, lungs, heart and brain due to inadequate perfusion  drive up serum lactate 4. Shock, coma and death Inflammation/Immunosuppression  In gram + bacteria  LPS interactions with TLR4 and CD14 driving NF-kB pathway and cytokine production  In gram - bacteria  lipoteichoic acid and peptidoglycan interact with TLR2 to drive NF-kB pathway  Inflammation =  IL-8  chemotactic cytokine for PMNs  TNF and IL-6 are pro-inflammatory cytokines i. More severe sepsis – higher level of cytokines  Anti-inflammatory =  Cytokines, IL-10   CD4 cells, CD8 cells and NK cells  inhibition of immune cells i. Patients often anergic Toxins of bacteria  Toxinemia = endotoxemia – toxic shock syndrome toxins (TSST) of Staph aureus & Strep pyogenes  Toxic shock syndrome = tampon-related, fever, erythema, hypotension, multi-organ failure  Toxins are superantigens that cause cytokine synthesis Labs  Blood culture  WBC with differential & platelets  Organ function  o PaO2 (low) o lactate (high) o kidney and liver function o DIC (PT, PTT, D-dimer – all high)

Prognosis  Sepsis mortality declining, but still high  worse prognosis in neonates, elderly and black men  Mortality rate for septic shock > 50%  Cause of death = circulatory failure & multi-organ system failure

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