RRT and Transplantation Flashcards
Describe Haemodialysis
Patient’s blood flows through an artificial kidney which is separated from dialysis fluid by a semi-permeable membrane. The dialysate fluid is pumped past the membrane in the opposite direction to the blood. Electrolytes and substances diffuse through the semi-permeable membrane until the equilibrium is reached.
The amount fo fluid removed by ultrafiltration is controlled by altering the hydrostatic pressure of the blood compared to the fluid.
Vascular acess in haemodialysis
Haemodialysis required two points of access to the circulation to remove blood and return it to the patient.
Temporary access is via a central venous catheter
For long term access an arterio-venous fistula is created in the arm by joining the brachaial or radial artery to a vein. Also possible to use an external shunt.
Complications (symptoms) in haemodialysis
Hypotension: movement of blood out of the circulation into the dialysis circuit
Muscle cramps: due to electrolyte shifts
Nausea and vomiting
Headache: vasodilation
Chest pain: hypokalemia can cause dysrrthmias
Back pain
Fever and chills
Peritoneal dialysis
Fluid is infused through a tube in the peritoneal cavity. Water and solutes move across the semi-permeable peritoneal membrane.
The dialysis solution has high glucose/amino acid concentration which creates the osmotic pressure that draws water from the blood.
Complications of peritoneal dialysis
Glucose is absorbed from the dialysis solution over time, resulting in hyperglycaemia, weight gain and hyperlipidaemia
Peritonitis caused by S. aureus or E. coli.
Hernias
Back pain due to increase in intra-abdominal pressure
Blocked tube can lead to constipation, abdominal adhesions, blood clots
Treatment of end-stage renal failure
Haemodialysis
Peritoneal dialysis
Transplantation
Supportive care
Relationship between antigen presentation and transplant rejection
Direct presentation: Host T cells recognise antigens presented on donor APCs. Cause of eary acute graft rejection
Indirect presentation: Donor antigens are processed and presented by self APCs which activate T cells. Involved in chronic rejection
Cytokines involved in the immunse response of transplantation
IFNg: induces MHC II, differentiation of Th1 and inhibits Th2
IL2: Induces T-cell proliferation, activates NK cells
Il10: promotes Th2 humoural response. Inhibits Th1 and APCs
IL4: promotes B-cell proliferation and Th2 response.
Immune mechanisms that affect graft outcome
HLA matching
Immune activation
Effector responses
Effects of immunosuppresive drugs
Immunosuppressive drugs used in transplantation
Steroids: Prednisolone, inhibit transciption of pro-inflammatory cytokine, T cells activation and phagocytic activity of macrophages and NK cells
Ciclosporin, Tacrolimus, Sirolimus: Inhibits IL-2 synthesis and T-cell activation
Azathioprine: metabolised to 6-mercaptopurine. Inhibits purine metabolism = inhibits nucleic acid synthesis and cell proliferation
Mycophenolate: Inhibits enzyme required for nucleic acid synthesis. Inhibits lymphocytes
Antibodies: ATG/ALG polycolonal IgG against human WBCs cause depletion and immunosuppression. Rituximab - anti-CD20 causes B cell depletion
OKT3 - mAb of CD3 TCR
Treatment of transplantation
Rejection prophylaxis:
Basiliximab (anti-CD25, blocks IL2R) , steroids.
High risk patients: tacrolimus
Low risk patients: cyclosporin, azathioprine
Hyperacute rejection
Patients have preformed antibodies to donor antigens. Organ fails immediately due to complement mediated lysis of the kidney endothelium.
Acute kidney rejection
Acute cellular rejection mediated by host lymphocytes.
Immune rejection causes rapid rise in creatinine
Chronic complications of transplantation
PTLD: lymphoma-like disease caused by EBV
BK virus: normally affects children but reactivates in immunosuppresed causiing renal impairment
Ciclosporin: causes hypertension, nephrotoxicity and hyperlipidaemia
