SHOCK
DR. SAPANA SEDHAIN
MD PATHOLOGY
OBJECTIVES
• Definitions
• Morphological changes in target organs
• Aetiopathogenesis
CASE HISTORY
• 56 year old male, known case of diabetes had right foot trauma 5 days
back. He presented in the ER with fever, tachycardia, tachypnea,
hypotension and swelling of his right [Link] was presence of
discharge from the trauma site. His total count was 21000/cumm with
95% neutrophils, RBS-254mg/dl. Microbial culture of the pus showed
Proteus species.
• What is the diagnosis?
• What is the pathogenesis?
DEFINITION
• State of circulatory failure that impairs tissue perfusion
and leads to cellular hypoxia.
• Cellular injury is reversible;
• Prolonged shock eventually leads to irreversible tissue
injury.
TYPES
Cardiogenic shock
• results from low cardiac output due to myocardial pump failure.
• intrinsic myocardial damage (infarction),
• ventricular arrhythmias,
• extrinsic compression (cardiac tamponade;or out flow
obstruction (e.g., pulmonary embolism).
TYPES
Hypovolemic shock
• results from low cardiac output due to low blood volume,
• massive hemorrhage or
• fluid loss from severe burns.
TYPES
Sepsis, septic shock and the systemic inflammatory
response syndrome.
• are interrelated and somewhat overlapping conditions.
TYPES
• Sepsis:
• life-threatening organ dysfunction caused by a dysregulated host
response to infection.
• Septic shock:
• subset of sepsis
• profound circulatory, cellular, and metabolic abnormalities
• greater risk of mortality than with sepsis alone.
TYPES
• Systemic inflammatory response syndrome SIRS
• sepsis-like condition associated with systemic
inflammation
• non- microbial insults
• triggered by burns, trauma, and/or pancreatitis.
Pathogenic feature common to SIRS and septic shock:
• massive outpouring of inflammatory mediators from innate and
adaptive immune cells
• arterial vasodilation, vascular leakage, and venous blood pooling.
• tissue hypoperfusion, cellular hypoxia, and metabolic derangements
• organ dysfunction and, if severe and persistent, organ failure and
death
PATHOGENSIS
• Most commonly triggered by gram-positive bacterial infections,
followed by gram-negative bacteria and fungi.
• Substances from these microorganisms
Stimulate and activate
• Macrophages, neutrophils, dendritic cells, endothelial cells and
Inflammatory and
complement pathway counter-inflammatory Septic Shock
response Organ failure
PATHOGENSIS
• Ligation of these receptors activation and nuclear translocation of
the transcription factor nuclear factor-κB (NF-κB)
• increased expression of the genes encoding inflammatory mediators.
• mediators include numerous cytokines such as tumor necrosis factor (TNF),
interleukin 1 (IL-1), IL-12, IL-18, and interferon-γ (IFN-γ), as well as other
inflammatory mediators such as high-mobility group box 1 protein (HMGB1).
PATHOPHYSIOLOGY
[Link] and counter inflammatory responses.
Microbial cell wall constituent activate:
• innate immune system and produce inflammatory cytokines.
• Complementary cascade - production of anaphylotoxin C3a, C5a;
Chemotactic fragment C5a; Opsonin(C3b) - pro inflammatory state.
• Activate coagulation (Factor XII) - widespread activation of
thrombin.
PATHOPHYSIOLOGY
• Shift from pro-inflammatory (Th1) to anti-inflammatory (Th2).
activat
e
• Hyperinflammatory state counter regulatory
immunosuppressive mechanism.
• Production of anti-inflammatory mediators IL-1 receptor
antagonist, IL-10 and apoptosis).
• Immunosuppression.
PATHOPHYSIOLOGY
2. Endothelial cell activation and injury:
• Widespread vascular leakage, tissue edema - tissue hypo
perfusion.
• production of nitric oxide and other inflammatory
mediators - vascular smooth muscle relaxation -
hypotension
PATHOPHYSIOLOGY
3. Induction of a procoagulant state:
• Derangement of coagulation - DIC- Consumption of coagulation factor and
platelet - concomitant bleeding and hemorrhage.
Pro-inflammatory cytokines
• increase tissue factor production by monocytes and endothelial cells.
• decrease production of endothelial anticoagulant factors, such as
tissue factor pathway inhibitor, thrombomodulin, and protein C
• Decrease fibrinolysis by increasing PAI-1 expression
PATHOPHYSIOLOGY
4. Metabolic abnormaties:
• Insulin resistance and hyperglycemia
• Decrease bactericidal activity
• Initially - acute surge in glucocorticoid production, followed by
adrenal insuffciency - deficit of glucocorticoids. (Waterhouse Friderichsen
syndrome)
• Lactic Acidosis (cellular hypoxia and diminished oxidative phosphorylation)
PATHOPHYSIOLOGY
5. Organ Dysfunction:
• Systemic hypotension, interstitial edema, microvascular dysfunction,
and small vessel thrombosis
all decrease the delivery of oxygen and nutrients to the tissues
tissue hypoxia
• diminish myocardial contractility and cardiac output
• acute respiratory distress syndrome
Severity and outcome of Septic
Shock
Depends on:
• Extent and virulence of infection
• Host immune status
• comorbidity
• pattern and level of mediator production
SATGES OF SHOCK
• Initial nonprogressive stage: reflex compensatory mechanisms
are activated and vital organ perfusion is maintained.
• Progressive stage: tissue hypoperfusion and onset of worsening
circulatory and metabolic derangement, including acidosis
• Irreversible stage: severe cellular and tissue injury even if the
hemodynamic defects are corrected, survival is not possible
MORPHOLOGY
• Cellular and tissue effects of shock are essentially those of hypoxic injury
• caused by a combination of hypoperfusion and microvascular thrombosis.
Any organ can be affected,
• Kidney: Fibrin thrombi in renal glomeruli.
• Adrenal: cortical cell lipid depletion reflects increased use of stored
lipids for steroid synthesis.
• Lungs: diffuse alveolar damage leading to so-called “shock lung.”
CLINICAL FEATURES
• Hypovolemic and cardiogenic shock: hypotension, a weak
rapid pulse, tachypnea, and cool, clammy, cyanotic skin.
• Septic shock: the skin may be warm and flushed owing to
peripheral vasodilation.
• myocardial infarction, severe hemorrhage, bacterial
infection - initiating event that threat life.
TAKE HOME MESSAGE
• Shock is defined as a state of systemic tissue hypo perfusion resulting from
reduced cardiac output and /or reduced circulatory blood volume.
• Major types: Cardiogenic (MI), Hypovolemic (blood loss), Septic (infection)
• Can lead to hypoxic tissue injury if not treated .
• Caused by dysregulated host response to bacterial, fungal infections.
• Characterized by endothelial cell activation, vasodilatation, edema, DIC and
metabolic derangements.
THANK YOU!
