16. Assessment of acute phase proteins, diagnosis and monitoring of sepsis

From greek.doctor

Acute phase proteins

Acute phase proteins (APPs), also called acute phase reactants, are proteins whose synthesis is up- or downregulated in case of inflammation, both acute and chronic (despite the name). This is called the acute phase reaction or acute phase response, which is part of the body's defence against microbes. Acute phase proteins are produced in the liver.

Triggers of the acute phase reaction

When certain immune cells, mostly macrophages and monocytes, are stimulated by a microbe or other noxious stimulus, they secrete cytokines. The cytokine interleukin 6 (IL-6), as well as IL-1 beta, tumor necrosis factor alpha, and interferon gamma, are released. These cytokines reach the liver and triggers the liver to regulate the acute phase proteins.

Positive acute phase proteins

Positive acute phase proteins are those proteins whose synthesis is upregulated during inflammation. Following the acute phase reaction the positive acute phase protein concenctration increases up to 1000-fold. The positive acute phase proteins have beneficial effects against microbes. The positive APPs are:

The increase in positive APPs, especially fibrinogen, causes the erythrocyte sedimentation rate to increase in case of inflammation.

Negative acute phase proteins

Negative acute phase proteins are those proteins whose synthesis is downregulated during inflammation. This is mostly so that the liver can redirect available amino acid to synthesis of positive acute phase proteins. The negative APPs are:

The levels of some non-protein compounds in the body also decreases in response to inflammation. This is true for iron, vitamin D, and zinc.

Sepsis

Sepsis is an acute life-threatening condition characterised by organ dysfunction caused by a dysregulated host response to infection, usually bacterial. It’s related to SIRS in pathomechanism. It has a very high mortality rate and can lead to multiple organ dysfunction syndrome (MODS) and death.

Diagnosis

Diagnosis of sepsis can be difficult. A series of criteria called qSOFA (quick SOFA) can be used to quickly create suspicion about whether the patient has sepsis. qSOFA is said to be positive of 2 or more of the following criteria are present:

  • Altered mental status (GCS < 15)
  • Respiratory rate > 22 breaths per minute
  • Systolic blood pressure < 100 mmHg

If qSOFA is positive, blood cultures should be performed to look for the pathogen. The function of important organ systems should be evaluated according to the SOFA system. Blood tests should be performed to measure the following:

  • CBC (complete blood count)
  • Procalcitonin – a serum protein that increases significantly in sepsis
  • CRP – which signals inflammation
  • Lactate – which is proportional to the degree of tissue hypoxia
  • Thrombocytes - thrombocytopaenia is common