Download Document

Organ Transplantation
►Autograft - describes tissue transfer within the
same individual (e.g., skin graft).
► Isograft - describes tissue transfer between
genetically identical individuals (e.g., identical
twins).
► Allograft - describes tissue transfer between
genetically nonidentical members of the same
species (includes living related donor and
cadaver donor human transplants).
Immunosuppression is required
► Xenograft - describes tissue transfer between
different species. Immunosuppression is
required.
5/7/2017
Dr.yekehfallah-PHd of nursing
2
Surgical Position
► Orthotopic: The old organ is
removed, and the new one is placed
in the same position.
►Heterotopic: The new organ is placed
in a different position
5/7/2017
Dr.yekehfallah-PHd of nursing
3
Donors
► Cadaver donors are individuals with
severe brain injury resulting in brain
death, which is defined as complete
irreversible cessation of all brain function,
including the brain stem
► Diagnosis: The mainstay of diagnosis is the
neurologic examination, which must demonstrate
unresponsiveness, absence of spontaneous
movement, and absence of reflexes from the brain
stem and higher
5/7/2017
Dr.yekehfallah-PHd of nursing
4
►The patient must be normothermic.
►Depressant drugs (especially barbiturates)
must not be present.
►An apnea test result must be negative (i.e.,
no respiratory effort despite a high arterial
carbon dioxide level).
►Electroencephalogram (EEG) and cerebral
blood flow studies are optional.
5/7/2017
Dr.yekehfallah-PHd of nursing
5
Causes
Cerebrovascular disease is most common
followed by trauma
5/7/2017
Dr.yekehfallah-PHd of nursing
6
Mechanism of Cerebral Death
5/7/2017
Dr.yekehfallah-PHd of nursing
7
Causes of Brain Death
Trauma
Cerebral Hemorrhage
Normal
Subarachnoid Hemorrhage
5/7/2017
Dr.yekehfallah-PHd of nursing
Cerebral Anoxia
8
exclusions
► Disseminated or uncured
Extracranial cancers, sepsis, or
poor organ function
►not contraindicated to donation
5/7/2017
Dr.yekehfallah-PHd of nursing
9
Living donors are individuals
motivated by altruism
► Living unrelated donors on average share
no more genes with a recipient than a
cadaver donor. An example is the patient's
spouse.
►Living related donors share a substantial
portion of their genomes with the recipient
5/7/2017
Dr.yekehfallah-PHd of nursing
10
Requirements
Living donors must be in almost perfect health, have
normal function of the organ under consideration, and be
good candidates for anesthesia and the operative
procedure. The workup includes:
► ABO typing, tissue typing, and cross matching
► Complete history and physical examination; chest radiography;
ECG; complete blood count
► 24-hour creatinine clearance and protein; serology for hepatitis B
and C, CMV, and HIV; urinalysis; PPD
► For renal donors, arteriography and intravenous pyelogram
(now combined as a helical computed tomography [CT] scan).
5/7/2017
Dr.yekehfallah-PHd of nursing
11
Risks
► Perioperative mortality for living kidney donors is
0.03% (3 per 10,000).
► A living donor provides one kidney, and the
remaining kidney hypertrophies and achieves 80%
of creatinine clearance before donation.
► Newer procedures include donation of the left
lateral segment or a lobe of the liver and segment(s)
or lobe(s) of the lung.
►
5/7/2017
Dr.yekehfallah-PHd of nursing
12
Risks
► ► In these procedures, the safety of the donor is not
assured.
► Although, traditionally, most living kidney donations
are performed as an open surgical procedure, there
is increasing experience with laparoscopically
performed nephrectomy.
► This method potentially offers the advantage of
minimally invasive surgery while still producing an
excellent kidney.
5/7/2017
Dr.yekehfallah-PHd of nursing
13
5/7/2017
Dr.yekehfallah-PHd of nursing
14
Removal of the donor organ
►The donor organ is removed in a formal
surgical procedure, wherein the blood
supply of the organ is controlled and
then the organ is rapidly flushed with a
cold (4 0C) solution to render it cold
and ischemic. All organs are more
tolerant of cold ischemia than warm
(normothermic) ischemia
5/7/2017
Dr.yekehfallah-PHd of nursing
15
VIASPAN
► pentafraction 50 g,
► lactobionic acid 35.83 g,
► potassium phosphate monobasic 3.4 g,
► magnesium sulfate heptahydrate 1.23 g,
► raffinose pentahydrate 17.83 g,
► adenosine 1.34 g,
► allopurinol 0.136 g,
► total glutathione 0.922 g,
► potassium hydroxide 5.61 g,
► sodium hydroxide
► hydrochloric acid adjust to pH 7.4,
► water for injection q.s.
► The solution has an approximate calculated osmolarity of
320 mOsM, a sodium concentration of 29 mEq/L, and a
potassium concentration of 125 mEq/L, and a pH of
approximately 7.4 at room temperature. Litre bags of 1 000
mL.
5/7/2017
Dr.yekehfallah-PHd of nursing
16
►The limit of cold ischemia with
current preservation methods is 4
hours for the heart, 6 hours for a
lung, 12 hours for the liver, 36
hours for the pancreas, and 40–
48 hours for a kidney. As the limit
is approached or passed, the risk
increases for delayed function,
damage, or nonfunction of the
organ
5/7/2017
Dr.yekehfallah-PHd of nursing
17
The immunologic compatibility of the donor and recipient
influences the outcome for any type of organ transplant
5/7/2017
Dr.yekehfallah-PHd of nursing
18
5/7/2017
Dr.yekehfallah-PHd of nursing
19
► ABO blood group compatibility. The same rules apply as
for red blood cell transfusions
► The recipient's serum is tested for the presence of cytotoxic
antibodies directed against surface antigens (usually antihuman
leukocyte antigen [HLA]) on the T lymphocytes of the donor. If
antidonor cytotoxic antibodies are present, the donor is unacceptable
because the recipient's antibodies will immediately attack the new
kidney and rapidly destroy it (hyperacute rejection; The recipient's
serum is tested for the presence of cytotoxic antibodies directed
against surface antigens (usually antihuman leukocyte antigen [HLA])
on the T lymphocytes of the donor.
5/7/2017
Dr.yekehfallah-PHd of nursing
20
5/7/2017
Dr.yekehfallah-PHd of nursing
21
► A positive crossmatch is positive for the presence of
preformed antidonor antibodies in the serum of the
prospective recipient and precludes transplantation
between that donor and the recipient.
► A negative crossmatch (i.e., absence of antidonor
antibodies) is mandatory before the transplant.
► A few patients have antibodies against most other
humans (so-called high panel-reactive antibody [PRA]
patients).High-PRA patients have formed antibodies
against a high proportion of a panel of human cells ,
which is used to screen for reactivity; therefore,
acceptable donors are difficult to find. Also, high-PRA
patients are at higher risk for early graft failure.
5/7/2017
Dr.yekehfallah-PHd of nursing
22
Human Leukocyte antigen (HLA)
►Six human HLA genes (HLA-A, -B, -C, -R, DP, and -DQ) are located on chromosome
6.
►HLA-C, -DP, and -DQ are not believed to be
important in clinical transplantation
5/7/2017
Dr.yekehfallah-PHd of nursing
23
► The contents of each chromosome 6 is a haplotype, and
all humans have two of these chromosomes—one from
the mother and one from the father. Therefore, six
HLA antigens are defined by tissue typing (i.e.,
two each for HLA-A, -B, and -DR).
► HLA-A and -B have more than 40 defined types,
which are designated numerically. HLA-DR has
more than 10 defined types. An example of an
HLA type is HLA-A2, 27; B1, 44; DR 3, 7. An
example of a haplotype is HLA-A2; B1; DR7
5/7/2017
Dr.yekehfallah-PHd of nursing
24
Rejection
The three types of rejection are:
►hyperacute
►acute
►chronic
5/7/2017
Dr.yekehfallah-PHd of nursing
25
Acute rejection
• is a cell-mediated immune response
initiated by helper T cells. The pace of
proliferation of alloreactive T cell clones
dictates that acute rejection usually occurs
after the sixth post-transplant day. In
some cases, a memory immune response
can trigger cellular rejection sooner
5/7/2017
Dr.yekehfallah-PHd of nursing
26
► The diagnosis is usually made via the detection and
workup of graft dysfunction, culminating in a biopsy.
► Acute rejection is treatable and reversible by a short
course of high-dose immunosuppressive drugs.
► When acute rejection is refractory to treatment or
recurs, graft failure can result.
► Acute rejection usually takes place within 3 months of
transplant and rarely occurs after 1 year, unless
triggered by an event such as infection or lack of
adequate immunosuppression.
5/7/2017
Dr.yekehfallah-PHd of nursing
27
5/7/2017
Dr.yekehfallah-PHd of nursing
28
Chronic rejection
usually occurs late. It has an insidious onset
and is multifactorial, with both the
cellmediated
and humoral arms of the immune system
involved.
Chronic rejection is poorly understood and
therefore not treatable or reversible.
5/7/2017
Dr.yekehfallah-PHd of nursing
29
5/7/2017
Dr.yekehfallah-PHd of nursing
30
Immunosuppression
►Almost all allografts require
indefinite suppression of the
recipient's immune system to
prevent rejection. This is in contrast
to tolerance, in which the recipient's
immune system responds normally to
all antigens except those of the
donor (i.e., the donor antigens
are “tolerated”).
5/7/2017
Dr.yekehfallah-PHd of nursing
31
► Immunosuppression attempts to disable or
destroy, components of the immune response
(typically lymphocytes).
CONVENTİONAL is created by drug therapy;
administration of biologic reagents (sera); and,
rarely, radiation therapy.
MULTIPLE DRUG THERAPY is standard and
ims for synergistic immunosuppression while
minimizing the side effects.
5/7/2017
Dr.yekehfallah-PHd of nursing
32
►Immunosuppression can be loosely
classified into THREE TYPES:
►induction regimens
►antirejection regimens
►maintenance therapy
5/7/2017
Dr.yekehfallah-PHd of nursing
33
► Induction regimens aim to avoid rejection and
establish good graft function within the first two
post-transplant weeks. Induction regimens use
an antilymphocyte serum plus part of the
maintenance regimen, withholding one drug to
avoid unwanted side effects.
► The nephrotoxicity of cyclosporine and
tacrolimus is of particular concern after any
transplant.
► Impaired healing of the bronchial anastomosis
from high-dose steroids is disadvantageous after
lung transplantation
5/7/2017
Dr.yekehfallah-PHd of nursing
34
► Antirejection regimens are highdose, short-term (<3 weeks)
treatments aimed at reversing acute
rejection episodes. These regimens
include high-dose (pulse)
corticosteroids, typically
methylprednisolone, antilymphocyte
sera, or monoclonal antibodies.
5/7/2017
Dr.yekehfallah-PHd of nursing
35
► Maintenance therapy provides long-term
immunosuppression to prevent
rejection. These regimens usually include
two or three drugs. The principal drugs
are cyclosporine or tacrolimus. One of
these is combined with a corticosteroid
(e.g., prednisone), and a third drug may
be added. More recently, coritcosteroids
have been eliminated from maintenance
regimens
5/7/2017
Dr.yekehfallah-PHd of nursing
36
corticosteroids
► have broad anti-inflammatory and
immunosuppressive effects. Generally,
they inhibit all types of leukocytes, in
contrast to the other immunosuppressive
drugs, which are more lymphocyte
selective.
5/7/2017
Dr.yekehfallah-PHd of nursing
37
► Methylprednisolon is used intravenously
for induction or antirejection therapy.
► Prednison or prednisolon is given orally
as maintenance therapy With good
bioavailability.
► Side effects are common and include
obesity, cushingoid facies, poor wound
healing, atrophic skin, striae, and acne.
5/7/2017
Dr.yekehfallah-PHd of nursing
38
►In contrast to the prevalent side effects,
complications include diabetes,
hypertension, osteoporosis, aseptic
necrosis (usually of the hips), cataracts,
peptic ulcer disease, and psychiatric
disturbances. These broad complications
have led many centers to successfully
eliminate steroids from maintenance
protocols
5/7/2017
Dr.yekehfallah-PHd of nursing
39
Calcineurin inhibitors
►have become the mainstays of most
immunosuppressive regimens owing to their
superior effectiveness.
►These drugs block the calcineurindependent
pathway of helper T-cell activation, thus
blocking transcription of cytokine genes that
initiate and amplify the immune response
5/7/2017
Dr.yekehfallah-PHd of nursing
40
Cyclosporine
dosing is adjusted to achieve a desired
trough blood level because bioavailability
is low and varies greatly.
►Toxicity includes nephrotoxicity, hypertension,
neurotoxicity, hirsutism, gingival hyperplasia,
and hyperlipidemia.
►At appropriate levels, cyclosporine does not
cause progressive deterioration in renal function.
5/7/2017
Dr.yekehfallah-PHd of nursing
41
Tacrolimus (FK-506)
is more potent than cyclosporine. Dosing is
done by trough levels. Toxicity is similar to
cyclosporine without hirsutism, hyperlipidemia,
and gingival hyperplasia but with headache,
diarrhea, and an increased risk of diabetes.
5/7/2017
Dr.yekehfallah-PHd of nursing
42
5/7/2017
Dr.yekehfallah-PHd of nursing
43
Antimetabolites
►are drugs that inhibit purine or pyrimidine
metabolism, thereby inhibiting rapidly dividing
cells, including clonally proliferating alloreactive
T cells. They are usually used as third
maintenance immunosuppressants with
corticosteroids and a calcineurin inhibitor
5/7/2017
Dr.yekehfallah-PHd of nursing
44
Azathioprine
►is a purine metabolism inhibitor.
Toxicity causes leukopenia
5/7/2017
Dr.yekehfallah-PHd of nursing
45
Mycophenolate mofetil
►is a purine metabolism inhibitor that appears to
be more lymphocyte specific than azathioprine.
When used as a third drug, the incidence of
acute rejection is significantly decreased.
Toxicity includes reversible bone marrow
suppression and gastrointestinal side effects
5/7/2017
Dr.yekehfallah-PHd of nursing
46
Antilymphocyte sera
• are biologic agents derived from animals
immunized against human determinants.
Two agents that are used for either induction or
antirejection therapy are muromonab CD3
(OKT3) and antithymocyte globulin (ATG).
Muromonab CD3 is a murine monoclonal
immunoglobulin (IgG) to an antibody that binds
to the CD3 antigen on human T cells.
Antithymocyte globulin is a polyclonal
antilymphocyte serum harvested from horses or
rabbits, which depletes T cells.
5/7/2017
Dr.yekehfallah-PHd of nursing
47
Interleukin-2 (IL-2) receptor
blockers.
► Two IL-2 receptor blockers have been
developed. Studies have suggested that when
used as part of an immunosuppressive regimen
including steroids and cyclosporine, these agents
can reduce the frequency of acute rejection in
kidney transplant recipients. IL-2 receptor
blockers bind to the IL-2 receptor alpha chain on
the surface of activated T lymphocytes
5/7/2017
Dr.yekehfallah-PHd of nursing
48
• One agent is a humanized monoclonal antibody,
dacliximab (Zenapax) and the other a
mousehuman chimeric monoclonal antibody,
basiliximab (Simulect). Simulect is given at
transplant and is repeated 4 days later, whereas
Zenapax is given within 24 hours of transplant
and then at 14-day intervals for four doses. No
significant adverse reactions or drug interactions
have been reported with these agents. The longterm effects of these agents are not yet known.
5/7/2017
Dr.yekehfallah-PHd of nursing
49
Sirolimus (Rapamycin)
• is the newest drug. It binds to the same
intracellular carrier site as does tacrolimus
and may partially antagonize its effects. It
is synergistic with cyclosporine. It acts at
a separate, later site of T-cell activation
than the calcineurin inhibitors. Side effects
include hypercholesterolemia,
hypertriglyceridemia, and mild bone
marrow suppression.
5/7/2017
Dr.yekehfallah-PHd of nursing
50
?
5/7/2017
Dr.yekehfallah-PHd of nursing
51