Transplantation V. Žampachová I. PAÚ Transplantation •Transfer of living tissue •Cells: stem cells, blood cells – platelets, … •Tissue: blood, bone marrow, skin, bone, cartilage, cornea, vessel, heart valve, fat tissue •Organ: kidney, heart, lung, liver, pancreas, small intestine, uterus, spleen, ovary •Body parts: hand/upper limb, face • • Types of transplantations •The four major types of grafts are: •Autografts – graft transplanted from one site on the body to another in the same person (skin, vessel, blood, ovary, heart valve) •Isografts – grafts between identical twins (1. successfull transplantation – kidney 1954) •Allografts – transplants between individuals that are not identical twins, but belong to same species (human-human), most common •Xenografts – grafts taken from another animal species (skin, heart valves; pig-human) • Types of transplantations - localization •Heterotopic: to a different position (kidney into pelvic region, pancreatic islets into mesenterium), the recipient‘s own organ remains in its place •Orthotopic: to the same anatomic position •Necessity of prior removal of the recipient‘s own organ (heart, lung, liver) – explantation •Implantation of the donor organ (graft) • Types of transplantations •Combined organ transplantations possible, many combinations •Heart + kidney •Heart + lungs •Heart + liver + kidney •Liver + kidney + pancreas + intestine + spleen • • Organ transplantation •Treatment of end-stage organ failure •Temporary/auxiliar functional replacement (uterus, liver) •Waiting list normal /urgent •Cadaver donor most common •Living donor for kidney, part of the liver, skin, … •Selection of most suitable donor and recipient - AB0-system most important • •Ultimate goal: most possible immunologic tolerance • Organ transplantation problems •Shortage of available and suitable organs •Preservation of donor organs (time outside the blood circulation) •Surgical techniques of transplantation •Immunosuppression therapy to prevent rejection •Diagnosis of possible rejection, infections, surgical complications • Posttransplantational complications •Ischemic injury (stop of blood flow), reperfusion injury (after implantation) •Rejection, GVHD – graft-versus-host-disease (bone marrow transpl.) •Immunosuppression complications (opportunistic infections, neoplasia – 100x increased incidence; drug cytotoxicity) •Other complications (surgical, original disease recurrence) •Organ retransplantation sometimes possible Organ transplantation problems •Rejection: complex immunologic process, cellular and humoral reaction •Factors – genetic diversity, type of tissue (vascularisation, number of antigen presenting cells), host immune system activity (immunosuppression), graft condition •Rejection in reaction on presence (+ demasking grade) of foreign antigenes •Hyperacute, acute, chronic rejection Opportunistic infections •Risk due to acquired immunodeficiency • •Viral – activation of opportunistic microorganisms – cytomegalovirus CMV, Ebstein-Barr virus EBV •Mycotic – ubiquitous fungi (aspergillus) •Bacterial – TB, common bacteria •Parasitic - toxoplasma Organ transplantation and exercise, activity •Postoperatively: •Long recovery period •Side effects of long-term immunosuppression •Diabetes mellitus, accelerated hyperlipidemia •Lifelong changes – drug compliance, diet changes, … Organ transplantation and exercise, activity •Before transplantation: long term poor health, severe deconditioning, exercise intolerance •Pretransplantation activity necessary to maintain function •Training to maintain/increase muscle strength before adverse effects of steroid therapy Organ transplantation and exercise, activity •Immediate start of physical therapy after transplantation necessary •Various training programs – aerobic, muscle endurance, resistive training •Improved quality of life •Persistent limitations common (decrease in workload, earlier onset of anaerobic threshold, lower exercise capacity) •Denervation of transplanted organs – loss of autonomic response (heart, kidney); no problems in liver •Lungs – delay in bronchodilatation – longer warm-up period necessary Organ transplantation and exercise, activity •Musculoskeletal effects: osteoporosis, vertebral fractures, myopathies •Neurotoxic reactions: tremor, paresthesia •GIT problems •Decreased wound healing • • Hematopoietic cell transplantation – implications for the therapist •Treatment of hematologic neoplasias (leukemia, lymphoma, myeloma) •Non-neoplastic blood disorders (bone marrow failure – aplastic anemia, inborn severe combined immunodeficiency) Hematopoietic cell transplantation – implications for the therapist •Short and/or long-term complications – 30% lower life expectancy •Immunodeficiency •Loss of immune memory (vaccines, after infections, …) •Bone marrow failure •Sterility •Neurocognitive impairment •Cardiopulmonary toxicity •Graft-versus-host disease • Hematopoietic cell transplantation – implications for the therapist •Assessment of past life/medical history, •Prior level of function/exercise/activities •Assessment of general/specific condition •Knowledge of specific medical regimen • •Risk for imobility, pneumonia, pressure ulcers, muscle weakness •Skin care •Oral mucositis GVHD, implications for the therapist •GVH disease occurs in any situation in which immunologically competent cells or their precursors are transplanted into immunologically crippled recipients, and the transferred cells recognize alloantigens in the host •May be fatal •Most important complication of hematopoietic cell transplantation • Graft-versus-host disease •In most patient with bone marrow transplantation, possible in organs with higher amount of lymph. tissue – intestine, liver (immunologic competent T cells + precursors → in immunodeficient host) •HLA typization necessary •hyperacute 7-14 d., fever, generalized erythrodermia •acute –skin rash, mucosal ulceration, liver cholestatic lesions, thrombocytopenia, anaemia •chronic – chron. lichenoid lesions + atrophy of skin, mucosa, bronchiolitis obliterans, chron. hepatitis,… • GVHD GVHD-skin-ma GVHDchr-oral-ma Graft-versus-host disease •Possible signs observed by the therapist: •Progressive dyspnea •Heart palpitations •Chest pain •Increasing fatigue •Neuromusculoskeletal problems •Generalized polyneuropathy •Muscle wasting •Joint pain + stiffness, contractures (in chronic GVHD) •Deep tendon reflexes changes