Sepsis and Septic Shock Flashcards Preview

Semester II Pathology > Sepsis and Septic Shock > Flashcards

Flashcards in Sepsis and Septic Shock Deck (19):
1

SPECTRUM OF SEPSIS

The sepsis syndrome can be considered as a spectrum of increasing severity:
SYSTEMIC INFLAMMATORY RESPONSE (SIRS)
SEPSIS
SEVERE SEPSIS
SEPTIC SHOCK
MULTIPLE ORGAN DYSFUNCTION

2

SYSTEMIC INFLAMMATORY RESPONSE (SIRS)

Systemic inflammatory response to a variety of severe clinical insults, manifested by TWO or more of:
1. FEVER OR HYPOTHERMIA (temperature derangement)
2. TACHYCARDIA
3. TACHYPNOEA OR HYPOCAPNIA (decreased CO2)
4. LEUKOPAENIA, LEUKOCYTOSIS or LEFT SHIFT.

3

SEPSIS

Systemic Inflammatory Response (SIRS) induced by INFECTION.

4

SEVERE SEPSIS

Sepsis associated with organ dysfunction, hypoperfusion (decreased blood flow to organs), hypotension (low blood pressure)

5

SEPTIC SHOCK

Sepsis-induced hypotension DESPITE ADEQUATE FLUID RESUSCITATION, along with presence of perfusion abnormalities eg. lactic acidosis, oliguria, altered mentation.

6

MULTIPLE ORGAN DYSFUNCTION

Presence of organ dysfunction in an acutely ill patient, such that homeostasis cannot be maintained without interventions (medical treatment to aid organ function)

7

ENDOTOXIC SHOCK

Results from spread or expansion of an initially localised infection.
Many cases are caused by endotoxin-producing Gram negative bacilli.
ENDOTOXIN- lipopolysaccharide released during rapid organism proliferation or cell wall degradation/lysis.
Endotoxin release is one of the most common causes of septic shock.

8

PATHOPHYSIOLOGY

Bacteria or their products are recognised by monocytes and macrophages via their Toll-like receptors (TLR4).
Profound activation of monocytes and macrophages leads to release of inflammatory cytokines (TNFa, IL-1)
Cytokines are responsible for SOME clinical features of sepsis, activation of the complement and coagulation cascades, inhibition of fibrinolysis.
The EXTRINSIC coagulation cascade is activated by release of Tissue Factor.

9

ACTION OF LIPOPOLYSACCHARIDE AND TLR4

Lipopolysaccharide (LPS) binds to LPS binding protein.
LPS-LPS binding protein complex binds to CD14 (coreceptor on monocyte surface)
LPS can then bind to TLR4
ACTIVATED TLR4 activates vascular wall cells and leukocytes, initiates cytokine mediators, and downregulates natural anticoagulants.

10

CYTOKINE CASCADE IN SEPSIS

LPS
Initiates TNF release
And IL1 release
then IL6/8.
Cytokines are released in successive waves following activation of TLR4 by LPS binding.

11

PATHOPHYSIOLOGY OF SEPSIS

Stimulation of polymorphic cells to marginate (to edges of vessels)
Migration of polymorphs to tissues
Release of lytic substances by polymorphs- ROIs, lysosomes etc.
If this occurs on vascular endothelial walls, then endothelial cells are damaged.

Vasoactive substances- cytokines, bradykinin- induce INAPPROPRIATE vasodilaton and vasoconstriction.
->Shunting of blood within microcirculation/stasis in capillary beds.
->Impaired oxygen delivery
-> Oxygen delivery further impaired by exudaton of erythrocytes/intravascular fluid, DIC, and extrinsic compression of capillaries by interstitial oedema.

12

LOW DOSES OF LPS

Causes activation of monocytes and macrophages.
Enhances their ability to eliminate bacteria.
They produce TNFa, IL1, IL6.
TNF and IL1 ACTIVATE ENDOTHELIAL CELLS.
This stimulates expression of adhesion molecules.
Monocyte/macrophage activation can directly activate the complement cascade, which contributes to local eradication of bacteria.
(Remember- complement- classical, alternative and lectin binding pathway)
LOCAL INFLAMMATION

13

MODERATE DOSES OF LPS

Augments cytokine cascade.
Cytokine induced secondary effectors are seen eg. NO (vasodilator)
SYSTEMIC EFFECTS of TNF and IL1 are seen: Fever, increased Acute Phase Proteins, decreased thrombomodulin (anticoagulant), decreased Tissue Factor Pathway Inhibitor (TFPI, an anticoagulant)
-> increased coagulation.

14

HIGH LEVELS OF LPS

Same cytokines and secondary effectors are seen with high doses as moderate doses.
Systemic vasodilation and decreased myocardial contractility decrease perfusion.
Widespread endothelial injury and activation
-> systemic leukocyte adhesion
-> pulmonary alveolar capillary damage (acute respiratory distress syndrome)
Activation of coagulation system leads to DIC.
High levels of LPS cause SEPTIC SHOCK.

15

3 PHASES OF SHOCK

Shock is a progressive disorder. It has three stages:
1. NONPROGRESSIVE PHASE
2. PROGRESSIVE PHASE
3. IRREVERSIBLE PHASE

16

SHOCK PHASE 1: NONPROGRESSIVE PHASE

Reflex compensatory mechanisms are activated.
Perfusion of vital organs is maintained.

17

SHOCK PHASE 2: PROGRESSIVE PHASE

Blood abnormalities, endothelial cell damage etc.
Tissues are hypoperfused.
Worsening circulatory and metabolic imbalances.

18

SHOCK PHASE 3: IRREVERSIBLE PHASE

Severe cellular and tissue injury
Correction of haemodynamic defects
Death occurs EVEN IF haemodynamic defects are resolved.

19

SEPTIC SHOCK: MAJOR ELEMENTS

-Haemodynamic derangements (leads to hypoperfusion)
-Temperature derangement (pyrexia or hypothermia)
-Progressive hypoperfusion of microcirculation
-Hypoxic injury to susceptible cells
-Quantitative adjustments to blood leukocytes and platelets (leukopaenia/leukocytosis/left shift/thrombocytopaenia
-DIC
-Multiple organ failure- azotaemia, oliguria etc
-DEATH