Principles Of Organ Transplantation

Transplantation is the process of surgically implanting an organ from one individual into another.

Organ transplantation becomes the treatment of choice for end stage organ failure where no other treatment exists, Ex : ESRD.

One year graft survival rate is close 90% of all types of transplants.

Several organs are now successfully being transplanted, such as kidneys, bone marrow, heart, lungs, liver, small bowel, pancreas and cornea

Types Of Transplants

  • Allograft
    • Transplant of tissue from genetically non identical donor from the same species
  • Isograft 
    • Graft of tissue between two individuals who are genetically identical
  • Autograft
    • Transplantation of organs or tissues from one part of the body to another in the same individual
  • Xeongraft
    • Transplantation of tissues of another species 

The major problem faced following an organ transplantation is graft rejection, this is because the adaptive immune system treats the new graft as foreign and directs immune responses again it. 

Pathophysiology Of Graft Rejection

Allograft of a kidney
Non self antigens become expose to the immune system
Adaptive humoral and cellular mechanisms attack the antigens expressed on the graft 
Leading to graft rejection 

Overcome Transplantation Barrier

Most patients will have at least one episode of acute rejection. 
Graft rejection is inevitable, but it should be reduced to a level which can be controlled. 

This is achieved by….

  • Matching the transplant antigens
  • Immunosuppression
  • Development of donor-specific tolerance 

Matching Transplant Antigens / Tissue Typing

  • Transplant antigens are….
    • Human leukocyte antigen (HLA)
      • Most important HLA antigens are….
        • Class I – HLA-A, HLA-B, HLA-C
        • Class II – HLA-DR
      • HLA-DR matching is most important as it can cause severe graft rejection 
      • Assessed by PCR using donor and recipient blood
    • Direct cross-matching for anti-HLA alloantibodies 
      • Degree of antigen mismatch should be assessed between recipient antibodies and donor MHC antigens 
      • Pre-formed antibodies may have occurred due to previous blood transfusions, pregnancy and previous organ transplantation 
      • Assessed by flow cytometry shows more accurate results
    • ABO blood grouping
      • ABO incompatibility will result in early organ rejection (hyperacute)
      • Group O donors can give organs to any type of ABO recipient
      • Group AB donor can only donate to AB recipient

An ideal organ match would be one in which all 8 alleles are matched 
2 genes from each parent makes up this 8 alleles 

Types Graft Rejection

  • Hyperacute
    • Caused by pre-existing complement-fixing antibodies 
    • Due to the presence of ABO incompatibility
    • Proper ABO blood grouping can prevent this occurrence 
    • Results in neutrophilic infiltration, coagulopathy and infarction
  • Accelerated rejection (Less than 5 days)
    • Mediated by pre-existing non-complement-fixing anti-HLA antibodies in sensitized patients
    • Flow cytometry done to prevent this mismatch
  • Acute rejection (Less than 100 days)
    • All organs may undergo acute rejection
    • Mediated by cellular rejection and acute vascular rejection (Antibodies mediated by endothelial damage)
    • Mononuclear cell infiltrates predominate
  • Chronic rejection (More than 100 days)
    • Most common cause of graft rejection 
    • Reflects the antibodies responding to antigen mismatch 
    • Cannot be effectively suppressed by immunnosuppressive agents 

Ishaemia And Reperfusion (I-RI)

Organ procurement and implantation results in severe physical stress to organs 
This stress occurs due to….

  • Initial ischaemia 
    • Seen in cadaveric donors 
    • Anaerobic respiration – Build up of lactic acid
  • Later reperfusion injury
    • Because of the development of free radicals 

I-RI will make the transplanted organ to be more visible to the immune system and may worse the success of the graft 

Ischaemic Time 

  • Warm ischaemic time
    • Seen in live donors 
    • Remains at normal body temperature
    • Time between cutting of blood supply from the donor and reconnection of organ in the recipient  the warm ischaemic time 
    • It is less than 30 mins
  • Cold ischaemic time
    • Seen in cadaveric patients 
    • Time between organ preservation till reconnection of organ in the recipient is called cold ischaemic time 
    • It is prolonged in compared to warm ischaemic time 
    • This leads to cellular swelling 

Organ Preservation

Stored in a suitable cold preservation solution with in-situ irrigation at 0 – 4 C
Preservation solution is called as impermeants

Impermeants help to….

  • Prevent cellular edema
  • Maintain pH
  • Prevent intracellular build up of calcium
  • Reduces I-RI

Donor-Specific Tolerance

A form of tolerance maybe developed after a long time following transplantation where an antigen-specific immunological unresponsiveness occur in the patients body.
Patient will be able to discontinue immonosuppressive mediation without graft loss 
This occur in renal transplantation

Immunosupression In Transplantation

After transplantation, immunosuppressive therapy should be initiated to improve graft survival
For some patients, it should be continued for life
Major drawback of this is that patient become vulnerable for infections 

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