Transplantation Flashcards
Why are organs transplanted?
Transplantations occur when organs are failing or have failed, or for reconstruction.
What are the two reasons for transplantation? Including examples.
LIFE-SAVING (when other life-supportive methods have reached the end of their use e.g. liver, heart and left ventricular assist device, and small bowel and total parenteral nutrition), and LIFE-ENHANCING (when other life-supportive methods are less good e.g. kidney and dialysis, pancreas and insulin injections; OR when organ is not vital but it will improve quality of life e.g. eye and reconstructive surgery).
What is the difference in long-term survival between transplanted organs from a living and deceased organ?
Living donor transplant has higher survival rates in the long-term than from deceased donors.
Why do organs fail: cornea (x3), skin (x4), bone marrow (x2), kidney (x4), liver (x2), heart (x3), lung (x3), pancreas (x1) and small bowel (x5)?
CORNEA: degenerative disease, infections and trauma. SKIN: burns, trauma, infections and tumours. BONE MARROW: tumours and hereditary diseases. KIDNEY: diabetes, hypertension, glomerulonephritis and hereditary conditions. LIVER: cirrhosis (hepatitis, alcohol, autoimmune, hereditary) and acute liver failure (paracetamol). HEART: coronary artery or valve disease, cardiomyopathy and congenital defects. LUNGS: COPD (smoking, environmental), interstitial lung disease (autoimmune, environmental), cystic fibrosis (hereditary). PANCREAS: T1DM. SMALL BOWEL: volvulus, gastroschisis, necrotising enteritis related to prematurity, Crohn’s disease, cancer.
What are the five types of transplantation?
□ AUTOGRAFTS: within the same individual e.g. skin, cardiac bypass surgery, or generating organs from own stem cells (this is experimental and is a developing area of medicine). □ ISOGRATS: between two genetically identical individuals of the same species. □ ALLOGRAFTS: between individuals of the same species. □ XENOGRAFTS: between individuals of different species (heart valves from pigs and cows). □ PROSTHETIC GRAFT: plastic, metal.
What are the two types of donor?
Deceased donor and living donor.
What type of organs can liver donor donate?
Only a limited number of organs, because something like a heart cannot be donated without the patient dying. Organs that can be donated from a living person include bone marrow, kidney and liver.
What are the two types of deceased donor? Which one is advantageous?
□ DBD – DONOR AFTER BRAIN STEM DEATH: majority of organ donors. Where brain injury has caused death before terminal apnoea has resulted in cardiac arrest and circulatory standstill. Occurs as a result of RTCs and intracranial haemorrhage. In these donors, the circulation has been established and sustained through resuscitation, but they are brain dead. This maintenance of circulation is advantageous because it reduces to chance of organ ischaemia. DEATH IS CONFIRMED USING NEUROLOGICAL CRITERIA. □ DCD – DONOR AFTER CIRULATORY DEATH: death occurs because of cardio-respiratory causes. Usually, it is controlled (people taken off life support) but can sometimes be uncontrolled (resuscitation unsuccessful). DEATH IS CONFIRMED USING CARDIO-RESPIRATORY CRITERIA.
What must be checked from deceased donors before their organs are donated? (x4)
Viral infections, malignancy, drug abuse/overdose/poison, and disease of the transplanted organ must be EXCLUDED.
How are donated organs processed before donation?
They are rapidly cooled and perfused. This cannot be done for long – the process is used because it SLOWS DOWN ischaemia; it doesn’t stop it.
What is needed for ethical transplant allocation? (x2)
□ EQUITY: what is fair? This considers factors such as time on waiting list, urgency of transplant. □ EFFICIENCY: what is the best use of the organ in terms of patient and graft survival. This considers factors such as match.
What tools are used to decide transplant allocation? (x2)
National guidelines and evidence-based computer algorithm.
What are the criteria for organ allocation? (x5)
□ WAITING TIME. □ HLA MATCH AND AGE COMBINED. □ DONOR-RECIPIENT AGE DIFFERENCE. □ AGE OF PATIENT. □ Blood group match.
What is the Organ Donation Taskforce?
UK Government organisation set up to identify barriers in organ donation and recommend actions to increase organ donation and procurement.
What is NHS Blood and Transplant?
Provides blood and organs to the NHS. It also establishes rules for organ allocation and monitors allocation.
Which chromosome is the MHC transcribed from?
Coded from HLA gene (human leukocyte antigens) on Chromosome 6.
What are the two mechanisms of transplant rejection?
From mismatched ABO blood group, and from HLA (and MHC).
What is the mechanism of ABO-incompatible transplant rejection?
□ RBCs have A and B proteins with carbohydrate chains – these are the ABO antigens. Endothelial lining of blood vessels in transplanted organs also have these antigens.
□ Our body produces anti-AB antibodies depending on blood group. In blood group AB, you produce none of these antibodies (see photo).
□ This means that donated organs from a donor with a different blood group to the recipient develops an immune response to the donated organ (unless recipient is AB, or donor is O): The recipient’s antibodies mediates rejection by binding to ABO antigens on donor endothelium.
□ Microcirculation is therefore thrombosed, and organ cannot be perfused –> dies.
How do you overcome ABO-incompatible transplantation?
Remove antibodies in the recipient with plasma exchange. This has good outcomes, even if the antibody comes back (we don’t understand why this is).
What is the mechanism of HLA-incompatible transplant rejection?
□ MHC (from the HLA gene) is found on cell surface and are highly variable between individuals. The variability of HLA molecules is important in defence against infections and neoplasia.
□ In donated organs, the donor graft cells shed their (foreign) HLA proteins into the circulation.
□ These foreign HLA proteins are taken up by APCs, broken down, and presented to immune cells as peptides by the donor’s own HLA proteins (in the peptide groove).
□ CD4+ T lymphocytes recognise these peptides in APCs and become stimulated. An ANTIBODY RESPONSE is subsequently mounted against the organ.
□ The immune reaction causes immune graft damage and failure = REJECTION.
What are the two types of HLA?
□ Class I (from A, B, C HLA genes) is expressed on all cells. MCH Class I molecules hold out a sample of the internal cell contents for CD8 T cells. □ Class II (DR, DQ, DP) is expressed on antigen-presenting cells but also upregulated on other cells – mediated by CD4 T cells.
How do the general responses of activated CD4 and CD8 T cells differ?
CD4 activates an antibody response; CD8 responds by directly killing cells.
What are the characteristics of HLA genes? (x3 points)
□ MHC is POLYGENIC with several class I and II loci i.e. there is more than one gene locus involved in expression of MHC. □ Expression of MHC is CO-DOMINANT meaning that maternal and paternal genes both expressed. □ Human MHC genes are highly POLYMORPHIC: meaning there are lots of different alleles (thousands) for the same gene in the population. These alleles are LINKED on the SAME chromosome (Chr 6) – this collection of alleles is called MHC HAPLOTYPE.
What is the structure of MHC Class I?
□ Has one transmembrane and cytoplasmic region.
□ Has three domains: alpha 1, 2 and 3 – comprising the heavy chain of the MHC.
□ The B2-microglobulin is the light chain – NON-COVALENTLY associated with the heavy chain.
□ The alpha 3 domain and B2-microglobulin are similar in structure to Ig – so are part of the immunoglobulin super-family.
□ The bit that binds the peptide (the thing the MHC holds out for T cells) is between the alpha 1 and 2 regions. This region can only hold peptides of 8-10 amino acids.
