Incubation and viral entry
The disease begins with an incubation period lasting from one week to 50 days. A minimal infectious dose is sufficient for the infection to develop.
With the most common aerosol route of transmission, viral particles settle on the epithelium of alveoli and terminal bronchioles, after which they invade alveolar macrophages. It is here that primary accumulation of the pathogen takes place.
Subsequently, primary viremia develops, and the virus spreads throughout the body, forming secondary replication foci. Favorite targets include the kidneys, adrenal glands, and the anterior pituitary gland. In response to contamination, cells activate non-specific defense genes, starting the production of interferons, while antigen-presenting cells trigger adaptive immunity mechanisms.
Initial period: immune response and intoxication
The initial period lasts from 1 to 6 days. During this time, viremia continues, but the effects of the unfolding immune response come to the forefront.
Immune-mediated cytolysis of infected cells occurs. Inflammatory mediators (cytokines TNF-$\alpha$, IL-1, IL-6, interferon-$\gamma$), growth factors, and cell breakdown products (prostaglandins, thromboxanes) are massively released. This "cytokine storm" leads to a sharp increase in vascular permeability.
Clinically, the stage manifests as acute fever, severe intoxication, myalgia, and headache. A pathognomonic sign is visual disturbances ("mist before the eyes"), which arise due to local edema and hyperemia of the optic nerve. Examination reveals vasodilation: facial and neck hyperemia, scleral injection.
Oliguric period: peak of vascular disorders
At the height of the disease (from days 2–4 to 8–11), viremia subsides, but the patient's condition paradoxically worsens even against the background of normalized temperature. This is associated with the maximal activity of adaptive immunity.
Target cells are destroyed by cytotoxic lymphocytes and the activated complement system. The resulting immune complexes become fixed in the endothelium where viral replication took place. The outcome is massive vascular wall damage, plasmorrhea, hypoproteinemia, and pronounced interstitial edema.
Mechanisms of renal injury:
- Massive edema of the peritubular zone of the distal nephron develops.
- Obstrutctional nephrosis occurs (tubules are compressed from the outside and blocked from the inside).
- The clinical consequence is oliguria (or anuria) with rapid progression of azotemia (elevation of blood urea and creatinine).
Progressive microcirculatory disorders cause organ ischemia and can lead to infectious-toxic shock (ITS), disseminated intravascular coagulation (DIC) syndrome, and multiple organ dysfunction syndrome.
Polyuria and convalescence
With a favorable course, the polyuric period begins from days 7–10 of the disease. The virus is eliminated from the body, and protective immunity is formed.
Pathogenetically, this stage is characterized by the resolution of interstitial edema. The lumen of the renal tubules is freed from fibrin casts, and their patency is restored. The functional ability of the kidneys to concentrate urine is still reduced, leading to hyposthenuria and marked polyuria accompanied by severe thirst.
The period of convalescence starts from the moment diuresis normalizes (usually days 15–21 of the disease). At this stage, tissue repair processes dominate, and asthenia gradually disappears.
Morphological picture
Pathological anatomical changes in HFRS are extremely specific:
- Kidneys: markedly enlarged, their capsule is overstretched (tears with hemorrhage into the perirenal adipose tissue are possible). Pallor of the cortical substance is observed against the background of dark crimson pyramids saturated with blood. The stroma is in a state of serous-hemorrhagic edema.
- Endocrine glands: necrosis and local hemorrhages in the tissues of the adrenal glands and anterior pituitary are characteristic.
- Microvasculature: widespread petechial rashes and hemorrhages in the mucous membranes (e.g., the "cherry-red" symptom on the sclerae).
Briefly: answers to topical questions
What specific cellular receptors does the HFRS virus use to penetrate endotheliocytes?
The HFRS virus uses specific integrin receptors of various classes on the membrane of target cells.
It is the presence of these receptors that ensures viral entry into cells and determines its organ tropism.
What changes in the complete blood count are characteristic of the initial and oliguric periods of HFRS?
Changes in the complete blood count in HFRS depend on the period of the disease:
- Initial period: increased erythrocyte count, leukocyte count is normal or leukopenia is observed.
- Oliguric period: marked leukocytosis (up to 20,000 – 40,000 per $\mu$l), left shift of the leukogram (band neutrophils 10–40%, segmented neutrophils 80–90%), an increase in the number of monocytes and plasma cells, as well as thrombocytopenia.
To easily remember the cyclical course of HFRS, use the acronym INOPR: Incubation, Nitial period, Oliguria, Polyuria, Reconvalescence.
Class and exam questions
The subsidence of fever usually coincides with the transition to the oliguric period. At this time, immunopathological reactions reach their peak, causing vascular damage, massive renal interstitial edema, and acute renal failure.
The subsidence of fever usually coincides with the transition to the oliguric period. At this time, immunopathological reactions reach their peak, causing vascular damage, massive renal interstitial edema, and acute renal failure.
Is an HFRS patient contagious to others?
No, patients who have contracted hemorrhagic fever with renal syndrome are not a source of infection for others.
What underlies the visual impairment in HFRS?
Specific visual disturbances are caused by damage to the microvasculature: edema, capillary congestion, and increased venous stasis in the optic nerve develop.
What else to study on this topic
- Features of the hemorrhagic syndrome and localization of the rash in HFRS
- Pathogenesis of infectious-toxic shock (ITS) in severe forms
- Specific hemorrhages: the "cherry-red" symptom and enanthema
- Differential diagnosis of peripheral blood changes in the initial period
- Mechanisms of formation and resolution of obstructive nephrosis
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