Organ Transplants

Organ Transplant Definition

Surgical removal of a failing/damaged organ and replacement with a functioning one from a deceased donor, living donor, or animal

Tissue Transplant Definition

Transfer of tissues (cornea, skin, bone, tendons, vessels, hands, face) to restore structure or function

Most Common Organ Transplants

1. Kidney 2. Liver 3. Heart

Transplant Types: Autograft

Transplant within same person (skin graft)

Transplant Types: Allograft

Transplant between two humans (most common)

Transplant Types: Isograft

Transplant between genetically identical individuals (twins)

Transplant Types: Xenograft

Transplant between species (pig → human)

Donor–Recipient Matching: Three Factors

Blood type, HLA match, plasma crossmatch

Blood Type Compatibility Rule

Same as blood transfusion; mismatched blood type causes immediate rejection

HLA Matching Definition

Human Leukocyte Antigen proteins on cells; 6 major antigens determine compatibility

HLA Antibody Issue

If recipient has antibodies against donor HLA → high rejection risk → donor declined

Crossmatch Test

Mix donor blood with recipient serum; if recipient antibodies attack donor cells → positive (incompatible)

Negative Crossmatch

Recipient immune system does NOT attack donor cells → SAFE to transplant

Organ Allocation System

Managed by UNOS to prioritize survival benefit and fair distribution

Organ Allocation Factors

Distance to hospital, age, medical urgency, time on waitlist, comorbidities, infection, mental status, substance use, weight, diabetes

Survival Benefit Calculation

Difference in expected lifespan with vs without transplant; prioritizes those who gain most years

Comorbidity Definition

Existence of two or more diseases which decrease surgical and post-transplant survival

Immunosuppressants Purpose

Prevent organ rejection by suppressing immune system (T cells, B cells, glucocorticoid signaling)

Immunosuppressant Outcomes

Reduced rejection from 30% → 12%; 1-year organ survival ~95%

Immunosuppressant Side Effect Risk

Opportunistic infections due to weakened immune system

Heart Surgery Challenge 1

How to operate on an organ that constantly moves

Heart Surgery Challenge 2

How to maintain oxygenation without a beating heart

Cardioplegia Definition

Drug (high K+ solution) used to arrest the heart during surgery by stopping action potentials

Cardioplegia Additional Feature

Ice-cold solution reduces metabolism and puts heart into a resting state

Cardiopulmonary Bypass (CPB) Machine

Heart-lung machine maintaining circulation and oxygenation during surgery

CPB Operator

Perfusionist

Heart Transplant Need vs Supply

Over 100k waiting; 17 die daily; heart viability only 4–6 hours after harvest; must come from brain-dead donors

Heart Transplant Limiting Factors

Short organ lifespan, few hospitals perform surgery, distance constraints

Xenotransplantation Definition

Transplanting organs from one species into another

Why Pigs Are Used

Similar anatomy/physiology to humans; accessible; scalable

Early Xenotransplant Attempts

Chimp-to-human kidney transplants (1960s) failed rapidly due to rejection

Genetically Engineered Pigs Purpose

Reduce rejection by modifying pig genome to make organs human-compatible

Genetic Modifications in Transplant Pigs

3 pig genes knocked out (reduce rejection), 6 human HLA genes inserted, 1 growth gene inactivated (organ size)

CRISPR Role

Genome editing technology allowing precise modification of pig genes for xenotransplantation

Xenotransplant Milestones

2021: GEP kidneys in brain-dead patients with no rejection; 2022: first pig-to-human heart transplant

Pig-to-Human Heart Transplant Result

Heart initially worked; no early rejection; patient died 2 months later (autopsy concerns)

Xenotransplantation Risks

Viral transmission, unknown physiology of pig organs in humans, microbiome mismatch, ethical concerns

Ethical Considerations of Xenografts

Experimental nature, long-term monitoring, “violating natural order,” biotech competition concerns

Factors Allowing Matching of Donor to Recipient

Blood type compatibility, HLA protein similarity, negative crossmatch

Post-Transplant Immunosuppression Purpose

Prevent immune-mediated organ rejection by inhibiting T/B-cell activation

Why Immunosuppression Is Lifelong

Immune system continuously recognizes donor organ as foreign

Cardioplegia in Heart Transplants

Used to stop heart safely to allow transplantation or surgical repair

CPB in Heart Transplants

Temporarily replaces heart/lung function for oxygenation and circulation