27. Systemic inflammation - etiology and pathogenesis.

Systemic inflammation – etiology and pathogenesis.

Systemic inflammation refers to a generalized inflammatory response affecting the entire body, rather than being confined to a local site.

Also called systemic inflammatory response (SIR).

Etiology (Causes)

1. 1 Severe infections (sepsis)

Bacterial infections (common), especially Gram-negative bacteria (due to endotoxins —LPS).

Gram-positive bacteria (e.g., Staphylococcus aureus toxins).

Fungi, viruses in severe cases.

1. 2 Extensive tissue injury

Major trauma, crush injuries.

Extensive burns.

1. 3 Pancreatitis

Release of digestive enzymes and inflammatory mediators into circulation.

1. 4 Massive ischemia/reperfusion injury

Restoration of blood supply after prolonged ischemia releases ROS and inflammatory mediators.

1. 5 Severe immune reactions

Severe allergic reactions (anaphylaxis).

Transfusion reactions.

Pathogenesis of Systemic Inflammation - Mnemonic: "C-V-C-M-O" for systemic effects

1. 1 Triggering of systemic cytokine release ("cytokine storm")

Initial stimuli: microbial products (e.g., LPS), DAMPs from tissue injury.

Main cytokines involved:

• TNF-α, IL-1, IL-6, IFN-γ.

1. 2 Activation of endothelial cells

Increased expression of adhesion molecules → widespread leukocyte adhesion.

Loss of barrier integrity → capillary leakage → edema, hypovolemia.

1. 3 Systemic vasodilation

Mediated by nitric oxide (NO), prostaglandins.

Leads to hypotension, reduced organ perfusion → potential for shock.

1. 4 Activation of coagulation cascade

Disseminated intravascular coagulation (DIC):

• Systemic microthrombi formation.
• Consumption of clotting factors → risk of bleeding.

1. 5 Metabolic changes

Fever (due to IL-1, TNF-α → PGE2 in hypothalamus).

Increased catabolism → muscle wasting.

Insulin resistance → hyperglycemia.

1. 6 Multi-organ dysfunction

Prolonged or severe systemic inflammation may lead to multi-organ failure:

• Acute respiratory distress syndrome (ARDS).
• Acute renal failure.
• Hepatic dysfunction.

Clinical Features

Fever, chills.

Tachycardia, tachypnea.

Hypotension.

Altered mental status.

Laboratory: Elevated CRP, procalcitonin, high or low WBC counts, coagulopathy markers (e.g., elevated D-dimers).