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 systemic inflammatory response syndrome (SIRS) in pathomechanism. It has a very high mortality rate and can lead to multiple organ dysfunction syndrome (MODS) and death.

Diagnosis and evaluation

Organ dysfunction must be present for the diagnosis of sepsis. The definition of “organ dysfunction” can itself be difficult to accurately establish. To help with this, a set of assessment criteria called “sequential organ failure assessment score” or SOFA score can help. These criteria assess the function of important organ systems like lungs, liver, CNS, kidneys, circulation and the coagulation and gives scores from 0 (normal function) to 4 (worst function). The score for each organ system is then summed up. Acute organ dysfunction is defined as an acute change in total SOFA score of 2 points or more.

Sepsis used to be evaluated by the criteria of “systemic inflammatory response syndrome” (SIRS), but that is not recommended anymore. Sepsis now has its own criteria (SOFA).

Diagnosis of sepsis can be difficult. A series of criteria called qSOFA (quick SOFA) can be used to screen for 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 and the patient should be evaluated for organ dysfunction 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