SHOCK

SHOCK

• Definition – Shock is characterised by systemic hypo tension due to either reduced cardiac output or  reduced effective circulating blood volume

• This leads to impaired tissue perfusion and cellular hypoxia

Types of shock depending on etiology

• Cardiogenic shock

• Hypovolemic shock

• Septic shock

• Neurogenic shock

• Anaphylactic shock

Cardiogenic shock

• Mechanism – Results from low cardiac output due to myocardial pump failure

• Causes

  • Myocardial damage (M.I)

  • Ventricular rupture

  •  Arrhythmias

  • Cardiac tamponade  (External compression)

  • Pulmonary embolism (outflow obstruction)

Hypovolemic shock

• Mechanism – loss of blood or plasma volume leads to decreased cardiac output and reduced tissue perfusion

• Causes – massive hemorrhage or fluid loss from severe burns

Neurogenic shock

• Mechanism – result due to anesthetic accident or spinal cord injury which leads to loss of vascular tone and peripheral pooling of blood

• This leads to decreased cardiac return and cardiac out put leading to tissue hypoxia

Anaphylactic shock

• Mechanism – in this there is systemic vasodilatation and increased vascular permeability caused by an Ig E- mediated hypersensitivity reaction

• Acute widespread vasodilatation results in tissue hypoperfusion and hypoxia

Septic shock

• Definition – Septic shock is defined as hypotension asoociated with severe sepsis and cannot be corrected by infusing fluids

• Causes for Septic shock

  • Overwhelming microbial infections (bacteria and fungi) 

  • Gram positive septicemia

  • Gram negative bacteria

  • Fungal sepsis

  • Rarely protozoa or Rickettsiae

PATHOGENESIS

Major factors contributing to the pathophysiology include

• Inflammatory mediators

• Endothelial activation and injury

• Induction of procoagulant state

• Metabolic abnormalities

• Organ dysfunction

• Immune suppression

Inflammatory mediators

• Microbial cell wall constituents (LPS) engage receptors on neutrophils, mononuclear inflammatory cells and endothelial cells leading to cellular activation

• Activated cells produce inflammatory mediators like TNF, IL-1, IFN-γ, IL-12, IL-18, HMGB 1 (High mobility group box 1 protein), prostaglandins and PAF. These mediators activate endothelial cells which express adhesion molecules

• They activate complement and coagulation cascade

• Complement cascade is activated by microbial components – results in production of anaphylotoxins (C3a, C5a), chemotactic fragments (C5a) and opsonins (C3b). All these contribute to proinflammatory state

• Microbial components activate coagulation directly through factor XII and indirectly through altered endothelial function

• Accompanying widespread activation of thrombin may further augment inflammation by triggering protease-activated receptors on inflammatory cells

Endothelial activation and injury

• Endothelial cell activation and inflammatory mediators produce 3 major sequelae

1. Thrombosis

2. Increased vascular permeability

3. Vasodilation

Induction of procoagulant state

• Pro inflammatory cytokine affects on endothelial cells

  • Increase in tissue factor production

  • Increased plasminogen activating inhibitors which prevent fibrinolysis

  • Diminshed endothelial anticoagulant factors such as thrombomodulin and protein C

• All these factors leads to formation of thrombi leading to Disseminated intravascular coagulation (DIC) which causes ischemic damage in various organs. 

• Later patient develops hemorrhage and bleeding due to the deficiency of platelets and coagulation factors

Metabolic abnormalities

• Septic patients exhibit insulin resistance and hyperglycemia

• Pro inflammatory cytokines suppress insulin release while simultaneously promoting insulin resistance in the liver and other tissues by impairing surface expression of GLUT-4 a glucose transporter

• Cytokines such as TNF and IL-1, stress induced hormones (glucagon, growth hormone and glycocorticoids) and catecholamines drive gluconeogenesis

• Hyperglycemia leads decreased neutrophil function – which suppresses bactericidal activity and increased expression of adhesion molecules on endothelial cells

• In sepsis – initially acute surge in glucocorticoid production followed by adrenal insufficiency

• Adrenal insufficiency – due to depression in sympathetic capacity of intact gland or due to adrenal necrosis because of DIC (Waterhouse Friderichsen syndrome)

• Hypoxia leads to metabolic acidosis and electrolyte imbalance due to sodium pump failure

Immune suppression

• Hyper inflammatory state initiated by sepsis can activate counter regulatory immunosuppressive mechanisms

• Shift from pro inflammatory to anti-inflammatory cytokine production (IL-10, IL-1 receptor antagonists etc)

• Lymphocyte apoptosis and induction of cellular ageing

Organ dysfunction

• Systemic hypotension, interstitial edema and small vessel thrombosis leads to decreased delivery of oxygen and nutrients to the tissues which produces alterations in cellular metabolism

• High levels of cytokines and secondary mediators diminish myocardial contractility, cardiac output, endothelial injury and increased vascular permeability

• These factors lead to multiple organ failure

Severity and outcome of septic shock depends upon

• Extent and virulence of the infection

• The immune status of the host

• The presence of other co-morbid conditions

• Levels of mediator production

Morphology

• Changes manifest mainly in brain, heart, lungs, kidney, adrenals and GIT

• Adrenals – there is cortical cell lipid depletion reflecting relatively inactive vacuolated cells to metabolically active cells that utilize stored lipids for the synthesis of steroids

• Heart – due to hypoxia and fall in cardiac output – myocardial infarction

• Brain – cerebral ischemia develops leading to altered state of consciousness

• Liver – congestion and centrilobular necrosis

• GIT –erosions of gastric mucosa and Diffuse ischemic necrosis of intestine

• Lungs

  • congestion and edema develops leading later to formation of hyaline membrane and alveolar collapse.

  • If patient survives organization and fibrosis occurs leading to emphysema and bronchiectasis

  Kidney

  • fall in the BP leads to reduction in glomerular filtrate which further produces uremia due to retention of waste products

  • Due to tubular ischemia, tubular necrosis develops which leads to anuria further leading to severe progressive uremia

References :

1. Robbins and Cotrans: Pathologic basis of diseases.8th edition