**5.2 Uncompensated shock**

When compensatory mechanisms are inadequate and DO2 begins to fall beyond the critical point, shock has progressed to the **uncompensated stage**. During this stage there is rapid deterioration of the patient due to prolonged hypoxia and anaerobic respiration. When this state persists, a cascade of events occurs resulting in various pathophysiological outcomes outlined in **Figure 3**.

Lactic acid accumulation has an effect on several organs systems. Cardiac contractility has been shown to be reduced in states of acidosis further worsening DO2. Acidosis also causes a predisposition to ventricular arrhythmias. At the cellular level, the function of pH dependent enzymes such as 6-phosphofructokinase, essential in glycolysis, are compromised further retarding ATP production. As hypoxia progresses, cells begin to deplete their ATP stores resulting in the dysfunction of various ATP dependent enzymatic reactions. Of key importance is the dysfunction of ion pumps which maintain membrane potential and cellular fluid dynamics. About 70 percent of ATP produced by cells is used to maintain sodium-potassium ATPase pumps. In the setting of hypoxemia there is decreased ATP production resulting in Na+/K+ ATPase pumps failure. Improper functioning ion pumps results in an influx of sodium and efflux of potassium altering the osmotic equilibrium between extracellular and intracellular fluids. This results in cellular edema leading to cell dysfunction and rupture. This is the underlying issue of all types of shock and leads to the most damaging outcome of hypoxia. Cellular hypoxia also activates monocytes which result in the release of cytokines. This triggers a cascade

**Figure 3.** *Cellular response to hypoxia.*


#### **Table 2.**

*Findings in compensated and uncompensated shock.*

ultimately leading to more vasodilation and increased vascular permeability further contributing to reduced tissue perfusion and hypotension. Additionally, lysosomal ion channel dysfunction disrupts lysosomal membrane potential leading to their dysfunction and release of contents. Both lysosome and cellular rupture lead to the release of toxic substances into extracellular fluids and circulation resulting in a cascade of capillary endothelial damage and cell death. Ultimately, these events produce findings such as hyperkalemia, hyponatremia, prerenal azotemia and lactic acidosis.

Clinical findings for both compensated and uncompensated shock are contrasted on **Table 2**.

#### **5.3 Irreversible shock**

The final stage of shock is irreversible shock which is also referred to as refractory shock. This final stage of shock carries a 96–99% mortality rate. There is loss of almost all compensatory mechanisms. Decreased perfusion exacerbates anaerobic metabolism processes due to lack of oxygen delivery to end-organs. Vasodilation and increased vascular permeability results in plasma leaving the vascular space, contributing to profound interstitial edema and loss of intravascular volume. This results in refractory hypotension, end organ ischemia, Multiple Organ Dysfunction Syndrome (MODS) and ultimately death.
