The phases of the metabolic response to injury

The metabolic response to injury has two phases, the ebb and the flow (Fig 55.2). The ebb phase is usually short and may correspond to clinical shock, resulting from reduced tissue perfusion. The physiological changes that occur here are designed to restore adequate vascular volume and maintain essential tissue perfusion. The severity of the ebb phase determines clinical outcome. If the ebb phase is mild or moderate, patients will have an uncomplicated transition to the flow phase. However, if severe, patients may develop the systemic inflammatory response syndrome (SIRS). The features of this are shown in Table 55.2. This is a complex pathophysiological state involving a vast array of inflammatory mediators and hormonal regulators, but the underlying mechanisms have yet to be clarified. No therapeutic strategies have been found to be helpful, perhaps because of our incomplete understanding of the SIRS. However, a proportion of patients will recover with intensive life support, including ventilation and dialysis.

A number of biochemical parameters are deranged in this syndrome, because the normal homeostatic mechanisms are overridden by the stress response. A low level of albumin, zinc, iron and selenium are characteristic along with disordered hormonal regulation, e.g low T₄, TSH and T₃, and nearly all of these patients will develop SIAD (see p. 16).

The flow phase may last for days to weeks depending on the extent of the injury. In this phase, metabolism is altered to ensure that energy is available for dependent tissues at the expense of muscle and fat stores (Table 55.3).

The acute phase protein response

The acute phase protein response leads to greatly increased de novo synthesis (principally by the liver) of a number of plasma proteins along with a decrease in the plasma concentration of some others. This response is stimulated by the release of cytokines such as interleukin 1 and 6 and tumour necrosis factor, and raised concentrations of the hormones cortisol and glucagon. The major human acute phase proteins are listed in Table 55.4.

The acute phase protein response is an adaptive response to disease. Its role is not fully understood but certain aspects can be seen to be of benefit to the individual. The increases in C-reactive protein (CRP) and complement will contain and eliminate infection; increased coagulation factors will aid and prevent excess blood loss; protease inhibitors will prevent the spread of tissue necrosis when lysosomal enzymes are released by damaged cells at the site of injury. The precise role of other proteins in this response such as caeruloplasmin and serum amyloid A remains to be established.

Clinical uses

In practice the major use of the acute phase response is to monitor the course of the inflammatory process in the patient. This is done in two ways:

In neonates and immunosuppressed patients, bacterial infection can be difficult to diagnose in its early stages. This includes patients with AIDS. Failure to make the diagnosis may have fatal consequences. In practice, a serum CRP concentration of >100 mg/L (normal <3 mg/L) is frequently taken to indicate the presence of infection.

Starvation and the metabolic response to injury

The metabolic responses to injury and to starvation are quite different. After injury the body is at war, defences are mobilized, metabolic activity increases and resources are directed to the site of action. In starvation, the body is in a state of famine, resources are rationed and metabolic activity is limited to the minimum for survival. Hypoalbuminaemia is often erroneously perceived as an index of nutritional status. In starvation not associated with inflammation, the serum albumin is characteristically within the reference interval or increased. In clinical practice a low serum albumin concentration is almost invariably caused by the inflammatory response, which results in an increased redistribution of the albumin from the intravascular to the interstitial fluid compartment..