Pathogenesis of anthrax

Cellular mechanisms and action of pathogenicity factors

The infectious process starts immediately after spores enter the organism. Within a few hours, they transform into vegetative forms that begin to produce key virulence factors:

• Capsule. It protects the bacterium from complete destruction by immune cells, resulting in the phenomenon of incomplete phagocytosis.
• Exotoxin. It is a complex consisting of three components: protective antigen, lethal factor, and edema factor.

Cell damage begins when the protective antigen binds to specific ATR receptors (anthrax toxin receptor) on the membrane of eukaryotic cells. Then, the lethal and edema factors attach to it. Through receptor-mediated endocytosis, the resulting toxins enter the macrophage cytoplasm.

Inside the cell, the toxins provoke a massive release of cytokines. Acting synergistically, they cause a marked increase in vascular permeability, massive hemolysis of red blood cells, and trigger severe dystrophic and necrobiotic processes.

Tissue changes and process generalization

The pathogen uses macrophages as a kind of "transport", migrating within them via the lymphatics to regional lymph nodes. There, the bacteria continue to actively multiply.

At the tissue level, classical serous-hemorrhagic inflammation develops, affecting the primary lesion, lymph nodes, and internal organs (showing congestion and marked edema). Increasing toxin production leads to severe vascular failure.

The further scenario depends on the state of immunity:

1. Favorable outcome: elimination of bacteria, localization of the process, rejection of necrotic masses, and tissue repair (typical for 80% of cutaneous cases).
2. Unfavorable outcome: the immune barrier is breached, and rapid hematogenous dissemination begins. The infection spreads both within macrophages and extracellularly. The result is the development of severe sepsis with a pronounced hemorrhagic syndrome and septic shock.

Pathogenesis features in different infection routes

The route of spore entry directly determines the specifics of morphological changes and the severity of the disease:

• Aerogenic route (pulmonary form): In the respiratory tract, a high oxygen concentration paradoxically slows down spore germination, which can stretch the incubation period to several weeks. Toxins provoke extensive necrosis of the mucosa of the trachea, bronchi, and mediastinal lymph nodes. Serous-hemorrhagic effusion occurs in the pleural and pericardial cavities, lung tissue becomes infiltrated with blood, and respiratory distress syndrome rapidly develops.
• Alimentary route (intestinal form): The histological picture is completely identical to pulmonary involvement (deep necrosis and hemorrhages), but the process is localized in the intestinal mucosa and mesenteric lymph nodes. Destruction of the digestive tract tissue rapidly leads to bacterial breakthrough into the bloodstream.
• Contact route (cutaneous form): The incubation period lasts 3–10 days. Spores enter the body through microtraumas of the epidermis. A primary affected focus is formed — the anthrax carbuncle. The lesion involves all layers of the dermis down to the subcutaneous adipose tissue, accompanied by serous-hemorrhagic inflammation and deep necrosis.

Evolution of the anthrax carbuncle

The development of the local lesion in the cutaneous form (pustula maligna) goes through a strict sequence of stages:

1. Macule: 1–3 mm in diameter, with a reddish or bluish tint.
2. Papule: forms within a few hours, rises above the skin, and acquires a copper-red or purple color. Subjectively accompanied by burning or itching.
3. Vesicle: appears after 12–24 hours, reaching 2–3 mm. The serous content is rapidly replaced by hemorrhagic fluid, coloring the vesicle a purplish-violet (this stage gave rise to the name pustula maligna). Symptoms of general intoxication join: fever up to 40 °C, headache, vomiting.
4. Ulcer: forms after spontaneous or traumatic rupture of the vesicle. The base of the ulcer becomes black, the edges raised. Within a day, the size of the defect can increase up to 15 mm, and the total diameter of the carbuncle varies from a few millimeters to 10 centimeters.

Crucial diagnostic sign: pain sensitivity is completely absent in the area of the formed carbuncle.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Clinical presentation and diagnosis of pulmonary and intestinal forms of anthrax
• Epidemiological potential of anthrax as a biological weapon
• Genetic engineering threats: insertion of toxins into the genome of other Bacillus species
• International Classification of Anthrax Forms (ICD-10)

Other topics in the section "Zoonotic infections — 2024 study guide"

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