Septic shock 

Definition: This is a kind of shock caused by systemic microbial infection, most commonly by gram – negative infection (endotoxic shock)  but can also occur with gram – positive or fungal infections. 

   or

It can be defined as sepsis with

1. Hypotention, arterial blood pressure less than 90mmHg or 40mmHg less than the patient’s normal blood pressure,

2. Organ dysfunction, & 

3. Unresponsiveness to fluid administration.

Pathogenesis of septic shock: 

 Septic shock has a mortality rate of over 50% ranking the first among the causes of death in intensive care units. It results from the spread & expansion of an initially localized infection like pneumonia into the blood stream. 

 Most causes of septic shock (~70%) are caused by endotoxin-producing gram-negative bacilli, hence the term endotoxic shock.  Endotoxins are bacterial wall lipopolyschardes (LPS) released when cell walls are degraded. Analogues molecules in the walls of gram-positive bacteria & fungi can also elicit septic shock. LPS bind with CD14 molecule on leucocytes, especially monocytes & macrophages, endothelial cells & others. Depending on the dosage of LPS – protein complex, initiation of a cascade of cytokine-mediated events take place. 

The mononuclear phagocytes respond to LPS by producing TNF which, in turn, induces IL –1 synthesis. TNF & IL-1 both act on endothelial cells to produce further cytokines like IL-6, IL-8, & secondary effectors like NO & PAF (platelet aggregating factor).  

•  High levels of the above molecules or mediators (TNF-α, IL-1, etc…) cause septic shock by acting on: 

→ The heart – causing decreased myocardial contractility which results in low cardiac output, 

→ Blood vessel – causing systemic vasodilation which decreases the peripheral arteries.

The mediators also cause widespread endothelial injury & activation of the coagulation system resulting in DIC, & 

→ Lung – causing alveolar capillary damage resulting in adult respiratory distress syndrome (ARDS).

Stages of shock 

Uncorrected shock passes through 3 important stages:

1) An initial nonprogressive phase

-   It is also called a period of early compensatory period, during which compensatory mechanisms are activated & perfusion of vital organs maintained. 

Mechanisms 

-   A variety of neurohumoral mechanisms operate: 

i)  A decrease in cardiac output will stimulate peripheral & central baro receptors with subsequent intense sympatho-adrenal stimulation. This sometimes leads to up to 200 fold increase in plasma catecholamine level. The net effect is → Tachycardia, ↑ HR  →  ↑ CO  → Peripheral vasoconstriction  →  ↑ BP. This is a major autocompensatory response. 

ii)  The fall in renal perfusion stimulates the renin – aldosterone secretion mechanism → renal conservation of fluid. 

 2. Progressive stage (Established shock) 

•  This is characterized by tissue hypoperfusion with onset of worsening circulatory & metabolic imbalances including acidosis. 

•  There is a widespread tissue hypoxia. 

•  Anaerobic glycolysis results in excessive lactic acid production. The lactic acid reduces tissue PH & blunts vasomotor response. The hypoxic cells leak glucose leading to insulin-resistant hyperglycemia and increased glycogenolysis. Impaired carbohydrate metabolism causes a fall in production of ATP, failure in function of Na+ - K+ ATPase, result in Na & water entrance into the cell, causing cellular swelling also called sick cell syndrome. Anoxic injury to endothelial cells results in DIC. 

3. An irreversible stage 

•  A sage at which, even if hemodynamic disorders are corrected survival is not possible. 

•  Transition to irreversible damage is mediated via various mechanisms.  

Morphology of septic shock: 

•  All organs are affected in severe shock. In shock, there is widespread tissue hypoperfusion involving various organs such as the heart, brain, & kidney. This leads to widespread hypoxic tissue necrosis. The widespread tissue necrosis manifests as multiple organ dysfunction [MODS]. Various organs may fail to perform their normal functions. And lungs may show ARDS or Shock lung.

Clinical course of shock 

•  Patient with shock may manifest as having a weak and rapid pulse, tachypenia, & cool, clammy, cyanotic skin. In septic shock, the skin will initially be warm & flushed because of peripheral vasodilation. The patient may present with confusion, restlessnes, decreased urine output, coma, and death.

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.

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Distributive shock

Cardiogenic shock

Hypovolemic shock

Shock

Disseminated Intravascular Coagulation

Infarction