Involves the principles of organ transplantation - basics of immunology and organ donation, preservation and eventual transplantation in the recipient.
Involves the principles of organ transplantation - basics of immunology and organ donation, preservation and eventual transplantation in the recipient.
Power point presentation about general principles of organ transplantation and pioneer surgons and investigators, Specific discussion about Heart, Heart lung and Lung transplantation is given
Immunology of Transplantation and Rejection A. Rakha
This file gives info about transplantation and the immunological problem like tissue rejection. MHC role in transplantation, laws, and types of tissue transplantation. Explains all kinds of tissue rejection and source of tissue. Some immunological terms plus transplantation history, it also includes the genetic basis of Transplantation. Hope it's helpful
Transplantation basics explained with history . For details look at the subtext for every slide. Immune suppression drugs. Body reaction to grafts are all explained
Power point presentation about general principles of organ transplantation and pioneer surgons and investigators, Specific discussion about Heart, Heart lung and Lung transplantation is given
Immunology of Transplantation and Rejection A. Rakha
This file gives info about transplantation and the immunological problem like tissue rejection. MHC role in transplantation, laws, and types of tissue transplantation. Explains all kinds of tissue rejection and source of tissue. Some immunological terms plus transplantation history, it also includes the genetic basis of Transplantation. Hope it's helpful
Transplantation basics explained with history . For details look at the subtext for every slide. Immune suppression drugs. Body reaction to grafts are all explained
biology of evil, basic understanding of the neuropsychological basis of evilmusayansa
gives a biological understanding of the evil side of mankind.
trying to lay down the neuropsychological basis of evil.
fun to read and easy to understand.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
2. Introduction
• Attempts at tissue transplantation have been recorded over the
centuries. The earliest reports of transplantation in humans included
several miracles.
• One of the best known examples is the thirteenth century story of
Cosmas and Damian. The Christian Arab saints who were martyred
around AD 300 and were reputed to have successfully replaced the
diseased leg of a sexton with that from a Moor who had died several
days earlier.
De Pope
3. continua…………..
• The use of autologous tissue transplants for restoring mutilation of
the nose dates back to an even earlier period. The practice originated
in India and was modified to great effect in Europe.
• Frenchman Serge Voronoff at the beginning of the century
popularized the transplantation of monkey testis into man, in the
mistaken belief that the procedure would stave off age-related
deterioration in physical and mental agility.
De Pope
4. The First Human Kidney Transplants
• Yu Yu Voronoy in 1936 performed the world's first human to human
kidney transplantation operation.
• He had already carried out kidney transplantation in dogs and was the
first person to describe the appearance of complement fixing
antibodies after transplantation.
• Encountered a number of patients who died in acute renal failure
after swallowing corrosive sublimate (mercuric chloride).
De Pope
5. Continua…………
• He foresaw the need for suppressing the recipient's immune system
after kidney transplantation and argued that since mercury poisoning
caused atrophy of the spleen and lymph nodes, its presence might
favor kidney graft survival.
De Pope
6. Continua…….
• The receipt was a 26-year-old female who had been admitted to
hospital in a semicomatose state after purposely ingesting 4 grams of
mercuric chloride. The donor kidney was obtained from an elderly
male who had died after a head injury and was blood group
incompatible with the recipient.
• Donor had died 6 hours earlier, the long warm ischemic time did not
disturb Voronoy unduly because he believed, mistakenly, like others,
that warm, rather than cold, preservation would favor graft viability.
De Pope
7. Continua…….
• The operation was carried out under local anaesthetic and the donor
kidney was placed in the thigh with anastomosis of the renal artery
and vein to the femoral vessels, leaving the ureter to drain
cutaneously.
• Voronoy noted during the procedure that the graft perfused with
blood and he judged the operation to be a technical success. Not
surprisingly, however, in view of the blood group incompatibility and
long ischemic time, the graft never functioned and the recipient died
2 days later.
De Pope
9. The Scientific Foundations of Transplantation
• Peter Medawar and colleagues showed that the loss of a tissue
allograft was brought about by the immune response it provoked in
the recipient and not as a result of some kind of non-specific
inflammatory reaction. This observation provided a firm scientific
basis from which clinical transplantation can be made.
De Pope
10. Continua……..
• Gibson grafted the woman's burns with a series of small "pinch" skin
grafts taken from her brother and Medawar proceeded to study the
fate of the skin grafts by taking biopsies of them for histological
examination.
• As expected, the grafts were destroyed after some days and when a
second set of grafts from the same donor was applied 2 weeks later,
these were destroyed even more quickly. This so-called 'second set'
phenomenon was taken as clear evidence that the rejection response
was due to actively acquired immunity and not to a nonspecific
inflammatory reaction. Medawar and Gibson published their findings
in the Journal of Anatomy in 1943.
De Pope
12. INDICATIONS
• When an organ or tissue becomes irreparably damaged (disease or
injury)
• When congenitally defective or absent.
De Pope
13. TYPES OF TRANSPLANT;
• Orthotopic transplants; Implantation in the same anatomic location in the
recipient as it was in the donor. Require the removal of the diseased organ
(heart, lungs, liver, or intestine).
• Heterotopic transplants; implantation in another anatomic location. The
diseased organ is kept in place (kidney, pancreas).
• Autotransplant; From one body site to another in the same individual, no
immunosuppression is required. Eg; skin
• Allotransplant; Between genetically different individuals from the same
species .
• Isotransplant: Between isogenic individuals e.g identical twins
• Xenotransplant; Between members of different species (still experimental).
De Pope
14. GRAFT REJECTION
• Allografts provoke a powerful immune response that results in rapid
graft rejection unless immunosuppressive therapy is given.
• Reason-allelic differences at polymorphic genes that give rise to the
histocompatibility antigens (transplant antigens) of which ABO blood
group antigens and HLA are the most important.
De Pope
15. ABO blood group antigens
• ABO blood group antigens are expressed not only by red blood cells
but also by most other cell types.
• For all types of organ allografts, its important to ensure that a recipient
graft is ABO blood group compatible otherwise it will likely cause
hyperacute graft rejection.
• There is no need to take account of Rhesus antigen compatibility.
De Pope
16. Human Leukocyte Antigen (HLA) System
• Are the most common cause of graft rejection.
• Their physiological function is to act as antigen recognition units.
• They are highly polymorphic (amino acid sequence differs widely between individuals).
Classes ;
• Class I: located in nucleated cells, HLA-A-B and C.
• Class II: located in dendritic cells, macrophages, B cells HLA-DR, DP and DQ. (antigen
presenting cells)
Located on the short arm of chromosome 6
• T cells recognize HLA molecules via their T-cell receptor
• Each individual will inherit two half sets, one from each parent, called haplotypes,
therefore individuals have a 25% chance of having an HLA identical sibling
De Pope
17. Effector mechanisms of rejection
• HLA antigens expressed by graft cells activate T cells and stimulate them to
proliferate in response to IL-2 and other T-cell growth factor (TCGF).
• The cellular effectors of graft rejection include:
• Cytotoxic CD8 T cells; recognises donor HLA class I antigens and cause target
cell death by releasing lytic molecules such as perforin and granzyme.
• Graft infiltrating CD4 T cells; recognise donor HLA class II antigens, releases
proinflammatory cytokines such as IFN-γ, which recruits and activates
macrophages.
• CD4 T cells also facilitate differentiation of B lymphocytes into plasma cells that
produce alloantibodies that bind to graft antigen and induce target cell injury.
De Pope
18. Types of allograft rejection:
1. Hyperacute rejection:
• Occurs within minutes to hours after organ reperfusion.
• Triggered by preformed antibodies against the donor’s HLA or ABO blood group antigens.
• Causes: previous blood transfusion, a failed transplant and pregnancy.
• After revascularization of the graft, these antibodies bind immediately to the vasculature and activate
the complement system that result in diffuse intravascular thrombosis, causing ischemic necrosis of
the graft within minutes and hours.
• Kidney transplants are particularly vulnerable to hyperacute graft rejection, whereas heart and liver
transplants are relatively resistant. Possibly because of dual blood supply
• Can be avoided by ensuring ABO blood group compatibility and cross matching.
De Pope
19. 2. Acute rejection:
• Occurs during the first 6 months of transplantation but may occur later.
• It is mediated predominantly by T lymphocytes, but alloantibodies may also play a role.
• Characterised by mononuclear cell infiltration of the graft, consisting of cytotoxic T cells,
B cells, NK cells and activated macrophages.
• Antibody-mediated damage may also be present, evidenced by deposition of complement
within the graft microvasculature.
• All types of organ allograft are susceptible to acute rejection, most episodes can be
reversed by additional immunosuppressive therapy.
De Pope
20. 3. Chronic rejection
• Occurs after the first six months, it is the major cause of allograft failure.
• Alloantibodies are the major cause (transplant antibodies).
• Characterised by myo intimal proliferation in graft arteries leading to ischaemia and
fibrosis.
• The risk factors for chronic rejection of a kidney transplant are:
• previous episodes of acute rejection (most important)
• poor HLA match
• long cold ischaemia time
• cytomegalovirus (CMV) infection
• raised blood lipids
• inadequate immunosuppression (including poor compliance).
De Pope
22. Graft-versus-host disease
• The graft mounts an immune response against the antigens of the host
• Essential components for GVHD
The graft contains immunocompetent T cells.
The recipient possesses transplantation antigens that are absent in the graft.
The recipient must not reject the graft.
• GVHD frequently involves the skin, causing a purpuric rash on the palms and soles.
• Bone marrow transplant is the most affected.
• May also occur after liver or small bowel transplant.
• Acute GVHD
• Characterized by epithelial cell death in the skin, GI tract, and liver
• Chronic GVHD
• Characterized by atrophy and fibrosis of one or more of these same target organs
De Pope
23. Tissue Typing Laboratory
• To determine the HLA type of blood for both donor and recipient by
PCR
• Lymphocyte cross matching to exclude circulating antibodies in
recipient against HLA expressed by donor
• HLA antibody screening and specificity in recipient before and after
transplant to guide immunosuppressive therapy
De Pope
24. Continua……….
Positive cross matching, implies recipient antibodies attack donor’s
and hence not suitable for transplant
Negative cross matching; implies that recipient antibodies do not
attack donor’s and hence suitable for transplant
De Pope
25. Immunosupressive Therapy:
• A range of agents that act at different sites during T-cell activation to
prevent rejection.
1. Calcineurin inhibitors (ciclosporin and tacrolimus)
• Block IL-2 gene transcription.
2. Corticosteroids:
• Causes widespread anti-inflammatory effect
3. Antibody therapies ( anti CD25mAb, alemtuzumab and rituximab)
• Directed against the IL-2 receptor on T lymphocytes
4. Antiproliferative agents (Azathioprine and mycophenolate)
• Inhibit lymphocytes proliferation
De Pope
26. Immunosuppressive Regimens
Principles of Immunosuppression
• The principles are the same for all types of organ transplant
• Aim is to maximize graft protection and minimize side effects
• Most regimens are based on calcineurin blockade and are steroids and
an anti-proliferative agent
• The need for immunosuppression is highest in the first 3 months but
indefinite treatment is needed
• It increases the risk of infection and malignancy
De Pope
27. Regimens
Immunosuppressive agents are given as
1. Induction therapy; started at the time of transplantation
2. Maintenance therapy; given for life
3. Rescue Agents; to reverse acute rejection
De Pope
28. Induction regimen
Most current
CNI+ anti CD25 monoclonal antibody
• Triple therapy: CNI plus antiproliferative agent like mycophenolate
mofetil (MMF) plus steroid
• Dual therapy: CNI+MMF alone or steroid alone
De Pope
29. Maintenance therapy
• mTOR-inhibitors these are not nephrotoxic as compared to CNI
NB; In acute rejection, polyclonal or monoclonal antibody preparations
are administered followed by triple therapy
If acute rejection recurs, Rx with antilymphocyte globulin (ALG)
De Pope
32. Complications of immunosuppression;
• Infections; high risk of opportunistic infections.
1. Bacterial infections. These are common during first month after
transplantation. Sources of infection may include wound infection, UTI
which may be catheter related, community acquired infections
• Pathogens involved include staph aureus, pseudomonas aeruginosa
De Pope
33. Continua………
2. Viral infections. Highest in first six months, include CMV, herpes
simples virus, herpes zoster infection
3. Fungal infections. Pneumocystis jiroveci, candidiasis. Usually
occurs in the first 3 months after transplantation.
De Pope
34. Malignancy
• Post transplant lymphoprolipherative disease (PTSD)
• Squamous cell carcinoma. 50% of transplant patients would develop
skin malignancy in 20 years
• Basal cell Ca and malignant melanoma
• Kaposi sarcoma (still uncommon)
De Pope
35. Organ Donation
• Most of the organs used for transplantation are obtained from
brainstem dead and heart beating deceased donors.
• However the number of organs required to satisfy the need of
transplantation is high.
De Pope
36. Preoperative donor evaluation
• General evaluation; CVS, GIT, Renal Status, cancer screening
• Immunologogic evaluation; Serology for Hepatitis, HIV, CMV
Source of organs for transplantation
• Living donors:
• The donor remains alive and donates a renewable tissue or organ, eg; skin,
blood, kidney, liver lobe, lung lobe.
• Deceased donor:
• The donor is declared brain dead
• Organs are kept viable by ventilators or other mechanical mechanisms until
they can be excised for transplantation.
De Pope
37. Donation after brain death donors
• Brain death is defined in terms of permanent functional death of the
brain stem as neither consciousness nor spontaneous respiration is
possible in the absence of a functional brain stem.
• Occurs when severe brain injury causes irreversible loss of the
capacity for breathing
• Most deceased donor organs are obtained from patients in whom brain
stem death has been diagnosed.
De Pope
38. Clinical testing for brain stem death
• Absence of spontaneous respiration
After preventilation with 100% O2 for at least 5 minutes, the patient is
disconnected from the ventilator for 10 minutes to confirm absence of respiratory
effort
• Absence of cranial reflexes (Pupillary reflex, Corneal reflex, Pharngeal (gag) and
tracheal (cough) reflex, Oculovestibular (caloric) reflex)
• Absence of motor response
The absence of a motor response to painful stimuli applied to the head/face and
the absence of a motor response within the cranial nerve distribution to adequate
stimulation of any somatic area is an indicator of brainstem death
De Pope
39. Criteria for brain death
• Irreversible causes
• Absence of cerebral blood flow
• Isoelectric EEG
• Sustained apnoea with elevated CO2
De Pope
40. Organ procurement (organ recovery from
deceased donors)
• When brainstem death has been confirmed, management of the donor
is aimed at preserving the functional integrity of the organs.
• Brainstem death produces profound metabolic and neuroendocrine
disturbances leading to cardiovascular instability.
• Careful monitoring and management of fluid balance is essential.
De Pope
41. Organ procurement
• Brain death is confirmed in the donor, after giving inotropic support drugs
(triiodothyronine,T3 and argipressin)
• Various organs are removed carefully, preserving their vessels
• Organs are flushed with chilled preservative solution
• Placed in sterile bags, containing saline and preservatives
• Immersed in 0-40C box containing ice
De Pope
42. Non Heart Beating Donors (NHBD)
The Maastricht Classification
• Category I : dead on arrival to hospital
• Category II : Unsuccessful resuscitation
• Category III: Awaiting cardiac arrest after support withdraw
• Category IV: Cardiac arrest with brain death
• Category V: Cardiac arrest and unsuccessful resuscitation in hospital
De Pope
43. Non Heart Beating Donors (NHBD)
• Maastricht category 1, 2 and 5 donors are sometimes referred to as
uncontrolled NHBD.
• The warm ischaemic time of organs from these three categories of
donor is usually longer and less predictable than in the case of
categories 3 and 4 (controlled) donors.
• The majority of NHBD organs used for transplantation are from
controlled (category 3) donors.
De Pope
44. Non Heart Beating Donors (NHBD)
• NHBD are not generally suitable for organs other than the kidney and
liver.
• To minimise additional ischaemic damage it is essential that organs
from NHBD are transplanted with the minimum possible cold storage
time.
De Pope
45. Non Heart Beating Donors (NHBD)
Maximum and optimal cold storage times in hours
optimal time safe maximum storage time
Kidney <24 48
Liver <12 24
Pancreas <10 24
Small I <4 8
Heart <3 6
Lung <3 8
De Pope
46. Renal Transplantation
Evaluation of Living donor
• Tissue typing, ABO, MHC typing
• RFTs, BUN, serum creatinine
• Selective renal angiogram
• serology: HIV, Hepatitis
N.B: usually the Lt Kidney is preferred because of the long Lt renal
vein.
It’s placed in the right iliac fossa and vasculature anastomosed.
De Pope
47. Pretransplant evaluation
• Identify any factors that would contraindicate a transplant or any risk
factors that could be minimized pretransplant.
• Divided into four parts: medical, surgical, immunologic, and
psychosocial.
• The purpose of the medical evaluation: identify risk factors for the
surgical procedure. Mortality posttransplant usually is because of
underlying CVS disease, so a detailed cardiac evaluation is necessary.
De Pope
48. Continua……..
• Untreated malignancy and active infection are absolute
contraindications to a transplant, bcoz of the requisite lifelong
immunosuppression. After curative txt of malignancy, an interval of
2–5 years is recommended pretransplant.
• The medical evaluation also should concentrate on GI problems such
as peptic ulcer disease, symptomatic cholelithiasis, and hepatitis. Pts
with serologic evidence of hepatitis C or B, but without evidence of
active hepatic inflammation or cirrhosis, are acceptable transplant
candidates.
De Pope
49. Continua……….
• Surgical evaluation: identify vascular or urologic abnormalities that
may contraindicate or complicate a transplant. Evidence of vascular
disease revealed by the history (claudication or rest pain) or the
physical examination (diminished or absent pulse or bruit) should be
evaluated further by Doppler studies or angiography.
• Urologic evaluation shld exclude chronic infection in the native
kidney, which may require nephrectomy pretransplant. Other
indications for nephrectomy include huge polycystic kidneys,
significant vesicoureteral reflux, or uncontrollable renovascular
hypertension.
De Pope
50. Continua………
• Immunologic evaluation: determining blood type, tissue type (HLA-A,
-B, or -DR antigens), and presence of any cytotoxic antibodies against
HLA antigens (because of prior transplants, blood transfusions, or
pregnancies). If a living-donor transplant is planned, a cross-match
should be performed early on during the initial evaluation.
De Pope
51. Continua……..
• Psychosocial evaluation: ensure that transplant candidates
understand the nature of the transplant procedure and its attendant
risk. They must be capable of rigorously adhering to the medical
regimen posttransplant.
• Pts who have not been compliant with their medical regimen in the
past must demonstrate a willingness and capability to do so before
they undergo the transplant.
De Pope
53. Technique
• Donor first receives IV mannitol, diuretics and Heparin
• Azathioprine, cyclosporine and prednisolone should be started 3 days
prior to surgery as diuretics and mannitol are continued
• After removal, protamine sulphate is administered.
• Removed kidney is then preserved ( Euro Collins solution / University
of Wisconsin solution)
N.B: Kidney will stand cold ischemia for 72hrs.
De Pope
54. Continua……..
Bilateral nephrectomy in recipient is required only in;
• Polycystic kidney disease
• persistent symptomatic renal infection -Hematuria
• Severe Hypertension resistant to medical therapy
De Pope
56. Early Postoperative Care
The immediate postop care of all recipients involves:
• Stabilizing the major organ systems (e.g., cardiovascular, pulmonary,
and renal)
• Evaluating graft function
• Achieving adequate immunosuppression
• Monitoring and treating complications directly and indirectly related
to the transplant.
De Pope
57. Continua……..
• Fluid and electrolyte management.
• Recipients should be kept euvolemic or slightly hypervolemic.
• If initial graft function is good, fluid replacement can be regulated by
hourly replacement of urine. Half-normal saline is a good solution to
use for urine replacement.
• Aggressive replacement of electrolytes, including calcium,
magnesium, and potassium, necessary, especially for recipients
undergoing brisk diuresis.
De Pope
58. Continua………
• Those with acute tubular necrosis (ATN) and fluid overload or
hyperkalemia need fluid restriction and even hemodialysis.
Magnesium levels should be kept above 2 mEq/L to prevent seizures,
and phosphate levels kept between 2 and 5 mEq/L for proper support
of the respiratory and alimentary tracts.
• NOTE: Repeated evaluation of graft function, which in fact begins
intraoperatively, soon after the kidney is reperfused. Signs of good
kidney function: appropriate color and texture, along with evidence
of urine production.
De Pope
59. Continua…………..
• Postoperatively, urine output is the most readily available and easily
measured indicator of graft function. Urine volume may range from
none (anuria) to large quantities (polyuria). Some knowledge of base
line urine output.
• Labs: serum blood urea nitrogen (BUN) and creatinine levels.
De Pope
60. Postoperative recipient classification
Recipients can be divided into three groups (by initial graft function as
indicated by their urine output and serum creatinine):
(1) Immediate graft function (IGF), xtd by a brisk diuresis
posttransplant and rapidly falling serum creatinine level;
(2) Slow graft function (SGF), xtd by a moderate degree of kidney
dysfunction posttransplant, with modest amounts of urine and a
slowly falling creatinine level, but no need for dialysis at any time
posttransplant
(3) Delayed graft function (DGF), which represents the far end of the
spectrum of posttransplant graft dysfunction and is defined by the
need for dialysis posttransplant.
De Pope
61. Continua………
• Decreased or minimal urine output is a frequent concern
posttransplant. Most commonly, because of an alteration in volume
status.
• Other causes: blocked urinary catheter, vascular thrombosis, a urinary
leak or obstruction, early acute rejection, drug toxicity, or DGF.
• Early dx important, begins with an assessment of the recipient’s
volume status. Urinary catheter is checked-exclude the presence of
occlusion with clots or debris. Other diagnostic tests: Doppler
ultrasound, nuclear medicine scan, or a biopsy.
• N.B: overall survival is 90% in one year an 80% in 5 years
De Pope
62. Late posttransplant care
Goal of late posttransplant care:
• Optimize immunosuppression
• Carefully monitor graft function
• Screen and monitor for complications that are directly or indirectly
related to immunosuppressive medications
• Detect compliance.
• Manage hypercholestemia, hypertriglycerides, screen for
malignancy(especially skin, colorectal, breast, cervical, and prostate),
HTN.
De Pope
64. LIVER TRANSPLANTATION
Indications
• Primary biliary atresia, metabolic liver disease.
• Cirrhosis.
• Malignant disease of the liver.
• Acute fulminant liver failure
• Children respond better for liver transplantation. Tissue typing and
cross matching are not that necessary and do not influence the results.
De Pope
65. BONE MARROW TRANSPLANTATION
Indications
• Leukaemias.
• Aplastic anaemias.
• Immune deficiencies etc.
• Recipients are initially treated with total body irradiation. As bone
marrow is an active immune system, proper tissue typing is essential.
Infant bone marrow is better marrow as a donor. Immunosuppression
with cyclosporin-A is always needed. It will take few weeks to show
the response
De Pope
66. PANCREATIC TRANSPLANTATION
• It is used in diabetic patients, taken from cadaver donor to replace
insulin.
• It can be combined with kidney transplantation to patients who have
diabetes with end stage kidney disease.
• Donor criteria are individuals without pancreatitis.
• Entire pancreas with duodenum or part of the pancreas (body and tail
of the pancreas) can be transplanted.
• It is placed in the right iliac fossa with anastomosis done between
portal vein and iliac vein, duodenum fixed to bladder.
• Graft take up is 60-70%.
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68. Isolated Pancreatic Islet Transplantation
• Islets of Langerhans are obtained by mechanical disruption of pancreas by
injecting collagenase into the pancreatic duct.
• Tissue disrupted is collected and purified by density gradient centrifugation.
• These islet cells are injected into the liver through portal vein.
• Islet cell rejection is prevented by covering them with semipermeable
membrane which prevents antibodies reaching islet cells but allowing
insulin to get secreted
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69. SMALL BOWEL TRANSPLANTATION
• Indication is short bowel syndrome following massive resection,
atresia, necrotising enteritis, Crohn’s disease.
• Bowel anastomosis with a stoma (ileostomy) is usual method.
• As small bowel is rich in lymphoid tissue, graft versus host reaction is
a major problem. So graft take up is poor.
• It is an immunological challenge even though technically easier.
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70. HEART AND LUNG TRANSPLANTATION
Indications
• Dilated cardiac failure
• Intractable angina
• Primary restrictive
cardiomyopathy,
• primary valvular disease and
congenital heart disease
• Pulmonary HTN
Contraindications
• Advanced age >60
• Obesity/Cachexia (>25% ideal
body weight, <80% ideal body
weight)
• Active infections
• Previous or Current Neoplastic
Disease
• Coexisting Systemic Disease
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71. Continua………
indications
• EisenMenger syndrome
• Think of more others
Contraindications
• Dysfunction of Other Major
Organ Systems
• Unresolved Pulmonary Infarction
• Psychosocial Instability/Non-
compliance
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72. postop care
• Not so diff from others
• Prohylaxis antibiotics (increased risk of infections than others)
• Maintenance immunosuppressive therapy is started immediately
posttransplant.
• Cardiac output is sustained by establishing a heart rate of 90–110
beats per minute, using either temporary epicardial atrial pacing or
low-dose isoproterenol.
• For recipients who may suffer transient right-sided heart failure,
adequate preload is important.
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73. Continua………
• Use of an oximetric Swan-Ganz catheter can be helpful to monitor
pulmonary artery pressure and measure cardiac output.
• Urine output and arterial blood gases must be carefully monitored.
Hypotension and a low cardiac output usually respond to an infusion
of volume and to minor adjustments in inotropic support
• Complications both surgical and medical
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74. Privileged sites:
• Sites where grafts are not likely to be rejected
• Eg:
• Brain; lacks lymphatic vessels, and its blood vessel walls are impermeable to lymphocytes
such as T- cells
• Cornea; lacks blood vessels
• Eyes and testes; contain naturally high levels of immunosuppressive molecules
• The fetus is considered an allograft but it is not rejected
• Early embryos do not express MHC molecules
• Placenta generates a hormone which is locally immunosuppressive
• High concentration of AFP in fetal blood- immunosuppressive properties
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75. SKIN GRAFTS
• They are autografts (one body site to another)
Types of skin grafts;
• Partial thickness graft (Split Skin Graft/Thiersch graft)
• Epidermis and varying portions of dermis from donor
Indications
well granulated ulcer(5Ps)
Clean wound or defect which can not be apposed
To cover the excision area after surgery e.g mastectomy
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79. Donor Site Selection and Graft Harvest
• Selection of a graft donor site is based on three factors:
1) whether a full-thickness skin graft or a split-thickness skin graft is to
be used
2) whether the intended donor site matches the recipient bed in color;
3) potential morbidity of graft harvest at that site.
Appropriate color match is particularly important in head and neck
reconstruction with skin grafts. Skin graft taken below the clavicles and
applied above the clavicle will result in a lifelong color mismatch
extremely difficult, if not impossible, to correct.
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80. Continua………
• Common full-thickness graft donor sites: the groin, postauricular
area, and clavicular region, preputium as a source of graft skin in
children.
• Splitskin grafts are usually harvested from the outer thigh because
technical ease and convenience of intraoperative positioning and
postoperative dressings.
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81. Continua………
Prerequisite;
Healthy granulation area
B-hemolytic streptococci load< 105/g of tissue
Contraindications;
SSG cannot be done over bone, tendon, cartilage, joint.
Technique;
Donor area is commonly thigh, occasionally arm, leg, fore arm
Humby’s knife and eschmann blade/Down’s blade
Graft is taken and puctate bleeding observed at donor site
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83. continua….
Donor area is dressed and opened after 10 days
Recipient area is scraped well and the graft is placed after making window
cuts in the graft to prevent the development of seroma.
Graft is fixed and tie-over dressing is placed.
If graft is placed near the joint, then the part is immobilised to prevent
friction which may separate the graft.
On 5th day, dressing is opened and observed for graft take up
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84. Continua………
Stages of graft intake;
• Plasmatic imbibition: lasts 24-48hrs Thin, uniform, layer of plasma forms
between recipient bed and graft. Allows grafts to survive the immediate
postgraft ischaemic period until such time as graft vasculature is
established. Thick FTSGs-3days, thin FTSGs-5days, STGs-4days.
• Inosculation: from 48 hrs, Linking of host and graft which is temporary,
capillary buds from the blood vessels in the receipt bed make contact with
graft vessels, open channels are formed. Skin graft becomes pink.
• Neovascularization: New capillaries proliferate into graft from the recipient
bed which attains circulation later.
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85. Advantages and disadvantages of SSG
Advantages Disadvantages
• Technically easier
• Wide recipient area can be
covered. Mesher can be used.
• Graft take up is better
• Donor area heals on its on
• Contractures
• Seroma and hematoma
formation.
• Infection
• Loss of hair growth, blunted
sensations
• Dry, scaling skin (Rx; coconut
oil)
• Graft failure
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86. Full Thickness Skin Graft
• Includes both the epidermis and full dermis with variable amounts of
subcutaneous tissue
• Used over the face, eyelid, hands and over the joints
• Removed using a scapel blade, and underlying fat is cleared
• The deeper raw donor area is closed by suturing
Common donor sites
Post auricular area.
Supraclavicular area.
Groin crease area.
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87. Advantages and disadvantages of FSG
Advantages Disadvantages
• Good color match
• No contractures
• Sensations, function of
sebaceous glands all retained
• Better function and cosmesis
• Only for small areas
• Wider donor area has to be
covered with SSG
• Cannot be used to cover ulcers
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88. Other common grafts
• Composite graft (skin+fat+other tissues)
• Tendon graft
• Bone graft
• Nerve graft
• Venous graft
• Corneal graft
• Combined graft (allograft + autograft)
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89. FLAPS
• Transfer of donor tissue with its blood supply to recipient area.
Indications;
Wider deep defects
Over bone, tendon, cartilage
If skin graft repeatedly fails
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90. Types of flaps
• 1. Random pattern flaps: Here vascular basis is subdermal plexus of
blood vessels. No known blood vessel is supplying it. Rectangular flap
with length to width ratios 1 : 1 or less than 1.5 : 1.
• 2. Axial pattern flaps: Here superficial vascular pedicles pass along
their long axes, e.g. forehead flap, deltopectoral flap, groin flap
• 3. Muscle flap: Gluteus maximus muscle flap, gracilis flap, tensor
fascia lata muscle flap
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92. Continua……….
4. Myocutaneous flap: Pectoralis major myocutaneous flap,
latissimus dorsi flap - composite flap.
• 5. Osteomyocutaneous flaps: Radius with brachioradialis and skin,
rib with intercostal muscles and skin - commosite flap.
• 6. Local rotation flaps, transposition flaps: When the flap moves
laterally it is called a transposition flap. When the flap rotates laterally
towards defect it is called a rotation flap.
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93. • 8. Free flaps: Vascular pedicle of the flap, both artery and vein are
anastomosed to recipient vessels using operating binocular
microscopes.
• 9. Omental flaps.
• 10. Island flap: Localised flap is swung around a stalk from the donor
area to the recipient area often with the pedicle buried underneath the
skin bridge in between
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94. Advantages Disadvantages
• Good blood supply, good take
up
• Gives bulk, texture, color to the
area.
• Allows required movements in
the recipient area
• Cosmetically better
• Long term hospitalization
• Infection
• Kinking, rotation, flap necrosis
(especially the tip)
staged procedure is done to
decrease necrosis( 10-14 days)
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99. References
• Bailey and Love's Short Practice of Surgery 27th Ed
• Schwartz principles of surgery 10th edition
• Transplantation surgey 5th edition
• Operative techiniques in transplant surgery 1st edition
KNOWLEDGE MUST BE FREE FOR ALL
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