7. SIRS
• Two or more of the following conditions:
– Fever or hypothermia
– Tachypnea
– Tachycardia
– Leukocytosis or leukopenia or >10% bands
• Infectious / Noninfectious
7
9. Severe sepsis
• Sepsis with signs of one or more organ dysfunction
– Cardiovascular: hypotension that responds to
administration of IV fluids
– Renal
– Respiratory
– Hematologic
– Unexplained metabolic acidosis
9
10. Septic shock
• Sepsis with
–Hypotension, for at least 1 h, despite
adequate fluid resuscitation
–Need for vasopressor
10
17. LBPBacteria
LP
S Phagocyte
MD-
2
TLR-
4
TLR4 – transmembrane
protein, transmits the LPS
recognition signal to the
interior of the cell, where
signal transduction and
gene transcription
pathways promote the
production and/or
secretion of numerous
molecules that mediate
the inflammatory
response
LP
S
MD-2
Extracellular protein
which binds the lipid A
moiety of LPS
Toxin Recognition by the Host
Signaling complex
Mandell Principles of Infectious Disease
21. • Patients usually manifests symptoms and signs related to
primary infection.
• Manifestations of Systemic Inflammatory Response
• Evidence of shock
• (-) fever: most common in neonates, elderly
patients and in persons with uremia or
alcoholism
Harrison’ s Internal Medicine 18th edition
23. MAJOR COMPLICATIONS
l. Cardiopulmonary Complications
– Acute respiratory distress syndrome
– Hypotension
– Decrease Myocardial function
II. Renal Complications
o Oliguira
o Azotemia
o Proteinuria
o Nonspecific casts
24. III. Coagulopathy
• Thrombocytopenia
• Platelet usually very low <50,000/uL
in pt with DIC
IV. Neurological Complications
• DDX: Guillain-Barre syndrome,
metabolic disturbance, toxin activity
MAJOR COMPLICATIONS
Harrison’ s Internal Medicine 18th edition
These mediators include cytokines (in particular, tumor necrosis factor [TNF]; interleukin [IL]-1â, IL-12); chemokines (IL-8, macrophage inflammatory protein [MIP]-1á); lipid mediators (prostaglandins, leukotrienes); and others, and they result in the familiar elements of local inflammation: increased capil- lary permeability and blood flow, infiltration of neutrophils, and pain.
In addition, local deposition of fibrin that is initiated by the expression of tissue factor on activated macrophages and endothelial cells helps wall off the infected tissue and provides an important impediment to bloodstream invasion.
Although neutrophils circulate in the bloodstream, they carry out phagocytosis largely in tissue spaces, where they can attach to extracel- lular matrix, spread out, get traction, and ingest. Because phagocytes may regurgitate the contents of their lysosomes as they eat, limiting this activity to local tissues minimizes the release of digestive enzymes and oxidants into the circulating blood. The major inherited mecha- nisms for killing microbes in the blood are soluble molecules: the mannose-binding lectin and C-reactive protein (CRP) pathways for activating complement, the alternative complement pathway, antibac- terial proteins (such as bactericidal permeability-increasing protein [BPI]), and natural IgM antibodies. Increased capillary permeability allows these molecules to diffuse into tissues where there is local inflammation.
These mediators include cytokines (in particular, tumor necrosis factor [TNF]; interleukin [IL]-1â, IL-12); chemokines (IL-8, macrophage inflammatory protein [MIP]-1á); lipid mediators (prostaglandins, leukotrienes); and others, and they result in the familiar elements of local inflammation: increased capil- lary permeability and blood flow, infiltration of neutrophils, and pain.
In addition, local deposition of fibrin that is initiated by the expression of tissue factor on activated macrophages and endothelial cells helps wall off the infected tissue and provides an important impediment to bloodstream invasion.
Although neutrophils circulate in the bloodstream, they carry out phagocytosis largely in tissue spaces, where they can attach to extracel- lular matrix, spread out, get traction, and ingest. Because phagocytes may regurgitate the contents of their lysosomes as they eat, limiting this activity to local tissues minimizes the release of digestive enzymes and oxidants into the circulating blood. The major inherited mecha- nisms for killing microbes in the blood are soluble molecules: the mannose-binding lectin and C-reactive protein (CRP) pathways for activating complement, the alternative complement pathway, antibac- terial proteins (such as bactericidal permeability-increasing protein [BPI]), and natural IgM antibodies. Increased capillary permeability allows these molecules to diffuse into tissues where there is local inflammation.
Ex: Pneumonia ( cough, dypnea, productive sputum)
Fever, chills, hypothermia,
Hypotension, lactic acidemia, progressive organ system dysfunction.
S/S rate differ from px to px
• Different variations, too
• Some sepsis are normo or hypothermic
• Absence of fever MOST COMMON
Hyperventilation – earliest sign
Encephalopathy (disorientation, confusion)
Hypotension
DIC, acrocyanosis, ischemic necrosis of peripheral tissues (e.g., digits)
• Skin: hemorrhagic lesions, bullae, cellulitis.
Skin lesions may suggest specific pathogens—e.g., petechiae and purpura with Neisseria meningitidis, ecthyma gangrenosum with Pseudomonas aeruginosa.
• Gastrointestinal: nausea, vomiting, diarrhea, ileus, cholestatic jaundice
• Hypoxemia: ventilation-perfusion mismatchand increased alveolar capillary permeability with increased pulmonary water content
Acute respiratory distress syndrome
VQ mismatch → fall in arterial PO2 early in course
Inc alveolar capillary permeability
↓
pulmonary water content
↓
decrease compliance and interferes with gas exchange
(progressive diffuse pulmonary infiltrates
and arterial hypoxemia (PaO2/FIO2 <200)) is ARD which develops in 50% of pts with severe
sepsis or septic shock.
Hypotension: Normal or increased cardiac output and decreased systemic
vascular resistance distinguish septic shock from cardiogenic or hypovolemic
shock.
a. generalized maldistribution of blood flow and blood volume
b. hypovolemia (dt diffuse capillary leakage of intravascular fluid)
c. Dehydration from atecedent dse or insensible fluid losses, v/d, and polyuria
Myocardial function is depressed manifested with
Decreased Ejection fraction
• Increased end-diastolic and systolic ventricular volumes
*CO normal even if decrease Ejection Fraction because of ventricular dilatation which permits normal stroke
volume
Renal complications
2) Renal Complications
• Oliguira
• Azotemia
• Proteinuria
• Nonspecific casts
• Polyuric (Hypergly can exacerbate)
• Most renal failure dt ATN induced by hypotension or capillary injury
• Some may have glomerulonephritis, renal cortical necrosis or interstitial nephritis
• Drug induced renal damage can complicate therapy
