Sources of donor material and its preservation
The primary source of organs consists of donors in whom brain death has been declared. Cadaveric material or organs from close relatives are used significantly less frequently in clinical practice (permitted only for paired organs, such as kidneys).
Suitable candidates for successful retrieval include patients who died from accidents with severe trauma or who died suddenly (myocardial infarction, cerebral apoplexy). Infectious diseases (HIV, syphilis, tuberculosis, malaria), severe poisonings, and malignant neoplasms are absolute contraindications to donation.
Material harvesting is performed in specialized operating rooms with strict adherence to asepsis rules. Before preservation, organs are thoroughly washed free of blood and tissue fluid. The following preservation methods are used:
- Cooling: immersion of tissues in solutions containing antibiotics and antiseptics, or the recipient's blood or plasma at a temperature of 4 °C.
- Freezing: a sharp drop in temperature to ultra-low values (from -183 °C to -273 °C) followed by storage at -25...-30 °C.
- Lyophilization: vacuum drying after freezing (most commonly used for bone grafts).
- Chemical treatment: fixation of structures in paraffin or aldehyde solutions (glutaraldehyde, formaldehyde).
Types of transplants and tissue compatibility
The survival prognosis of transplanted tissues depends on the degree of genetic relationship. Ideal compatibility (complete engraftment) is achieved only with autotransplantation (transplantation of one's own tissues) and isotransplantation (between identical twins). In all other cases — in allotransplantation (from human to human) and xenotransplantation (interspecies transplantation) — a rejection reaction is inevitably triggered.
To minimize rejection risks, complex typing systems are used:
- By erythrocyte antigens (AB0 and Rh systems).
- By leukocyte histocompatibility antigens (HLA complex).
HLA sublocus antigens are unique to each individual and are located on cell membranes. The presence of a vast number of different determinants makes finding a suitable donor an extremely difficult task. To solve this problem, international organ banks and registries are established, storing detailed information on the immunological, hematological, and clinical status of thousands of potential recipients.
Dynamics and mechanisms of rejection
The transplantation immunity reaction typically unfolds on days 7–10 post-surgery. It is based on the interaction of T- and B-lymphocytes aimed at recognizing and destroying foreign tissue. Subpopulations of T-lymphocytes play the leading role in this process.
The development of rejection proceeds in stages:
- First 1–5 days: period of apparent engraftment. During this time, the immunocompetent cells of the recipient's body merely identify the foreign antigen.
- From days 4–5: a cascade of destructive reactions is triggered. Microcirculation in the graft vessels is impaired, marked edema increases, and tissue invasion by mononuclear cells occurs.
- Destruction: T-lymphocytes acquire cytotoxic properties (killer cells), and the B-lymphocyte system begins massive antibody synthesis. The result is complete rejection of the allo- or xenograft.
Clinical nuance: if a patient undergoes a repeated organ transplantation from the same donor, the rejection reaction will develop exactly twice as fast, since the recipient's body is already sensitized to these antigens.
Approaches to immunosuppression
To prevent the death of the transplanted organ, pharmacological blockade of the recipient's immunocompetent system is required. Several strategies are used:
- Nonspecific immunosuppression: use of glucocorticoids (prednisolone), antimitotic agents (azathioprine), and antilymphocyte sera. The method is effective, but leads to severe immunodeficiency and a sharp drop in resistance to infections.
- Selective immunosuppression: a more modern and precise approach. Drugs of selective action (e.g., cyclosporine) allow for the elimination of T-killer cells while simultaneously stimulating the activity of T-suppressor cells.
- Replacement of the hemolymphoid system: radical preparation for allotransplantation. It consists of total radiation suppression of the recipient's own lymphoid tissue followed by transplantation of donor bone marrow.
Briefly: answers to topical questions
What types of graft rejection are distinguished depending on the timing of development?
Depending on the timing of development, three types of graft rejection are distinguished.
- Hyperacute rejection — develops immediately or within 1–5 days post-surgery due to the presence of preformed antibodies in the recipient.
- Acute rejection — occurs within 5 to 30 days; the mechanism is driven by the activation of cellular immunity.
- Chronic rejection — develops after 6 months or more, and is also predominantly mediated by cellular immunity.
What clinical criteria are used to declare brain death in a donor?
To declare brain death in a donor, clinical criteria confirming irreversible impairment of central nervous system functions are applied. The following signs are distinguished:
- Absence of consciousness — persistent and irreversible.
- Impairment of brainstem functions — includes the absence of spontaneous breathing, swallowing, and disruption of systemic hemodynamics.
- Absence of reflexes — disappearance of pupillary, pharyngeal, and other reflexes.
The diagnosis is established by a medical board of specialists, with the mandatory exclusion of the effects of hypothermia, medications, endocrine, and metabolic disorders.
What organs and tissues are permitted to be transplanted from a living related donor?
Only paired organs are permitted to be transplanted from a living related donor.
- Kidneys — the only example explicitly specified in the materials of an organ retrieved from close relatives for transplantation.
When planning such a surgery, a genetic screening is mandatory. If no mutations are detected in either the donor or the recipient, or if variants of uncertain clinical significance are identified, related transplantation should be declined.
To remember the timeline of the reaction to a repeated transplant, use the "immune memory" rule: upon first encounter, the body "studies" foreign antigens for 7–10 days, whereas upon re-exposure to the same donor, it attacks twice as fast.
Class and exam questions
What are the main causes of transplanted organ failure?
The key reason is the transplantation immunity reaction. T-lymphocytes (killer cells) and antibodies produced by B-lymphocytes disrupt microcirculation in the organ, causing severe edema and tissue death.
How is the rejection problem solved in modern surgery?
Patients are prescribed lifelong immunosuppressive therapy. Most frequently, selective drugs (e.g., cyclosporine) are used, as well as glucocorticoids and antimitotic agents, although this increases the risk of infectious complications.
What else to study on this topic
- Structure of the histocompatibility complex (HLA): SD and LD determinants.
- Morphological picture and clinical manifestations of graft-versus-host disease (GVHD).
- Physicochemical bases of tissue lyophilization and cryopreservation methods.
- Side effects and complications of long-term glucocorticoid and cytostatic therapy.
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Other topics in "CHAPTER 17. PLASTIC (RECONSTRUCTIVE) SURGERY"
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