Dialysis + Transplant Flashcards
Haemodialysis Principles
Blood + dialysate flow in opposite directions –> countercurrant mechanisms maintain conc. gradient throughout exchange surface
For diffusion losses to occur–> small amounts K+ and other solutes in dialysate, so K+ diffuses out of blood
For additions to occur–> large vol of bicarbonate in dialysate, flows into blood
For water loss–> increase pressure of blood + decrease pressure of dialysate
Haemodialysis Circulatory access- temporary
Central venous catheter (enters internal jugular + sits in right atrium)
Haemodialysis Circulatory access- permanent
Arterio-venous fistula (artery + vein joined together to arterialise vein) where blood can be removed + added back in
Haemodialysis- GFR
When patient on machine, clearance is excellent, but rest of time have no kidney function
Averages out to GFR 10-12ml/min
Haemodialysis Advantages
Better clearance
Short time for treatment
Not dependent on patient competence
Haemodialysis Disadvantages
Hospital Limited by staff and spaces Requires circulatory access- complications including thrombosis + infection (LMWH + antibiotics) Cardiovascularly demanding Restricted diet
Peritoneal dialysis Principle
Catheter placed in patient’s abdomen –> travels under skin + enters peritoneal cavity at midline
Uses peritoneum as semi-permeable membrane
Capillaries run outside the peritoneal membrane carrying solutes etc.
Dialysate pumped into peritoneal cavity + exchange processes occur across the peritoneal membrane
Dialysate contains low conc. of waste product (to encourage to diffuse out of blood) and high conc. glucose + larger molecules (to promote diffusing into blood)
Can also deliver things to patient such as bicarb/lactate for buffering + amino acids for nutrition
Closed space –> conc. gradients equal out –> have to drain fluid + replace
Peritoneal dialysis GFR
Slightly less efficient than haemodialysis
GFR around 7-8ml/min
Some renal function must remain
Can be done almost continuously unlike haemodialysis
4 x 2L exchanges per day- 30 mins per exchange
Peritoneal Dialysis advantages
Easy access
Haemodynamically stable
Increased patient mobility –> do not have to remain close to hospital
Home based –> maintains patient independence
Peritoneal Dialysis disadvantages
Lower rate of clearance Infection (peritonitis) and adhesions can occur Membrane failure Intra-abdominal catheter required Dependent on patient competence
Renal transplant prognosis
Lower risk of death compared to both types of dialysis
Initial risk of death is higher in those receiving a transplant due to surgical complications, immunosuppression and recovery period
Takes about half a year for RR of death to become lower than patients remaining on transplant risk, but after this time risk is continuously getting lower
Renal transplant advantages
Increased survival Continuous therapy (dialysis) not needed
Renal transplant disadvantages
Risk of rejection
Lifelong immunosuppression
Have to find suitable donor
Psychological problems
Blood group
People can’t receive transplant to which they have pre-formed antibodies against
All blood groups can donate to themselves
O can donate to anybody but only receive from O
A and B can donate to AB
A and B cannot donate to each other
HLA Class I
Present in all cells
A,B,C
HLA Class II
Present in APCs
DR, DQ, DP
HLA genetics
Found on chromosome 6
Inherited via simple Mendelian inheritance
Everyone has 2 alleles for each HLA subtype
HLA compatibility
0MM= all same types
6MM= none of same types
HLA DR, B and A most important
Antibodies
Sensitising events- pregnancy, previous transplant, blood transfusion
Detected via direct cross match- Patients serum mixed with donor tissue- if reaction occurs, transplant contraindicated
Non-immunological matching
Age
Comorbidity
Gender
Cold ischaemia time (longer= poorer function)
Donor type (DBD better outcome than DCD as circulation intact for longer)
MHC
Presents fragments of non-self proteins to T cells in order to initiate an immune response
HLA Class I immune response
HLA A,B,C subtypes
Present on all nucleated cells
Present endogenous antigens to CD8 T cells
Self antigens do not stimulate response due to immunological tolerance
HLA Class II immune response
HLA DR, DQ, DP subtypes
Present on antigen presenting cells
Present exogenous peptides to CD4 T cells
HLA recognition- Direct pathway
Donor APCs present foreign particles to recipient CD8 T cells leading to their activation
Response for acute, cell mediated rejection
HLA rejection- Indirect pathway
Donor cells/proteins are shed from graft + are engulfed and presented by recipient APCs to CD4 T cells
Mediated more chronic graft rejection
T cells
Th1- activate macrophages + synthesis of important inflammatory cytokines
Th2- help with B cell responses
B cells
Responsible for antibody production
CD4 T cells can activate B cells + cause differentiation into plasma cells that churn out large quantities of antibodies
Antibodies can play a role in graft rejection via activation of complement + cell mediated damage
Calcineurin inhibitors examples
Tacrolimus
Cyclosporine
Tacrolimus, Cyclosporine
Calcineurin inhibitors
Calcineurin inhibitors MOA
Prevent action of calcineurin on stimulating transcription of T cell activating genes (including IL2) to prevent T cell clonal expansion
Calcineurin inhibitors SE
Nephrotoxicity Headaches New onset diabetes after transplant hypertension Liver dysfunction Increases risk of post-transplant malignancy
Azathioprine
Anti-metabolite agent
Purine analogue that selectively inhibits purine synthesis which inhibits cell proliferation
SE= Myelosuppression, hepatitis, cholestasis
Mycophenolate
Antimetabolite Inhibits enzymes (IMPDH) involved in purine synthesis to prevent cell proliferation SE= GI, myelosuppression, infections (CMV)
mTOR inhibitors examples
Everolimus
Sirolimus (rapamycin)
Everolimus, sirolimus
mTOR inhibitors
mTOR inhibitors MOA
Inhibits IL2 + other cytokines signal transduction via action on mTOR
Decreases T and B cell activation
mTOR inhibitors SE
Impaired wound healing
Lymphocele formation
Pneumonitis
Mouth ulcers
Corticosteroids
Decrease cytokine gene transcription to decrease cytokine regulated lymphocyte signalling which decreases proliferation
Corticosteroid SE
Insomnia Wright gain Hypertension CV risk increased Impaired glucose tolerance Poor wound healing Osteoporosis
IL 2 monoclonal antibodies
Basiliximab
Prevents IL2 induced T cell proliferation + clonal expansion
SE= few
Co-stimulation inhibitors
Belatacept
Fusion protein of Fc portion of IgG and CTLA-4
Inhibit T cell signalling
Anti-rejection therapy- Infection
Bacterial- UTI, pneumonia, TB
Fungal
Viral:
-CMV (4 weeks–> 6months after transplant–> mono, retinitis, colitis)
-EBV= >6months after transplant –> mono like illness, PTLD
- BK –> BK virus nephritis
Anti-rejection therapy- cancer
Skin–> mostly non melanoma skin cancer
Lymphoma
Kaposi sarcoma (caused by HHV8)
Anti-rejection conditions- metabolic
Diabetes mellitus
Hypertension
Osteoporosis
Heart beating donations
Live donors
Donation after brain death (DBD)
Donation after brain death criteria
Absence of 6 reflexes (pupillary, corneal, vestibule-ocular, gag, cough, pain)
Confirmed apnoea
At least 2 doctors registered with GMC >5 years and at least 1 is consultant
Tests performed twice
Heart+ lungs still working while on life supported
Organs transplanted are in better conditions
Non heart beating donations
Donation after cardiac death (DCD)- organs in worse condition
Controlled- donor taken to theatre before life support turned off
Uncontrolled- donor taken to theatre after
