Transplant Rejection

Transplant Rejection

pediagenosis    September 30, 2023    Comment   

Transplant Rejection

Immunologically mediated allograft damage or rejection may be hyperacute, acute or chronic. Acute rejection is classified as acute cellular/T cell-mediated rejection or acute antibody-mediated/ humoral rejection, according to which arm of the immune system is principally involved in mediating allograft damage.

Stem Cell

Stem Cell

pediagenosis    September 26, 2023    Comment   

What is a Stem Cell?

In the popular media and even in some medical circles, stem cells are presented as miracle cells that can do anything. When administered to a patient with some serious disease they will rebuild the damaged tissues and make the patient young again. Alas, in reality there are no such cells. However, there are cells that exhibit stem cell behavior and the future of regenerative medicine will undoubtedly be built on a good scientific understanding of their properties. In this chapter these properties are briefly outlined, and in the remainder of the book each of them will be underpinned by an explanation of the relevant areas of science and technology.

Causes Of Liver Failure

Causes Of Liver Failure

pediagenosis    January 29, 2023    Comment   

Causes Of Liver Failure

Currently, approximately 85% of liver transplants in the UK are undertaken in adults, the remainder in children. Most (85%) are for chronic liver disease, with only a few for acute liver failure.

Islet Transplantation

Islet Transplantation

pediagenosis    January 29, 2023    Comment   

Islet Transplantation

Indications for islet transplantation

1.    Islet transplantation alone (ITA) is indicated for life-threatening hypoglycaemic unawareness.

2.   Islet after kidney transplantation (IAK), where patients are already taking immunosuppression and have life-threatening complications of their diabetes.

3.    Autologous islet transplantation in patients with chronic pancreatitis undergoing pancreatectomy. Their pancreas is processed, the islets extracted and then infused into their liver.

Pancreas Transplantation

Pancreas Transplantation

pediagenosis    January 29, 2023   

Pancreas Transplantation

Categories of transplant

Simultaneous pancreas and kidney (SPK, 80%)

The pancreas is transplanted at the same time as a kidney from the same deceased donor. The recipient is in kidney failure, and either on or within a few months of starting dialysis. This combination is a bigger surgical operation, but has the benefit that the kidney can be used as a surrogate to monitor rejection of both grafts.

Assessment For Liver Transplantation

Assessment For Liver Transplantation

pediagenosis    May 18, 2021    Comment   

Assessment For Liver Transplantation

Assessment of the transplant candidate

As with renal transplantation, assessment of a potential liver transplant recipient involves not only evaluation of the liver disease for which transplantation is indicated, but also determination of comorbidity that may affect peri or post-operative morbidity and mortality. Moreover, since liver transplantation is now a successful treatment for liver failure, focus has switched to ensuring longterm survival rather than just surviving the surgical assault. The shortage of organs has necessitated increased selectivity, favouring patients with better anticipated outcomes.

Evaluating the liver disease

Most liver screening tests are repeated to verify the diagnosis and rule out other diseases. These are illustrated in Figure 34.

Complications Of Liver Transplantation

Complications Of Liver Transplantation

pediagenosis    May 18, 2021    Comment   

Complications Of Liver Transplantation

Monitoring the liver

Careful and frequent clinical review is required post transplant to identify deterioration suggestive of complications. Post-transplant biochemical monitoring uses the same markers of liver dysfunction as were used before transplantation, namely:

1.    Prothrombin time, for synthetic function;

2.    Alanine transaminase (alt) and aspartate transaminase (ast), for hepatocellular damage;

3.    Alkaline phosphatase (alp): reflects bile duct damage;

4.    Serum lactate, should start to fall towards normal within an hour or two of reperfusion of the liver giving earliest sign of function;

5. Ultrasonography is used to detect biliary dilatation and assess blood flow to the liver, supplemented by ctyangiography.

Surgical complications

Non-specific complications of surgery

Bleeding is common due to a combination of factors:

·      The presence of abdominal varices

·      A coagulopathy, particularly if the liver is slow to resume full protein synthesis

·      Thrombocytopaenia due to splenomegaly

·      Multiple venous and arterial anastomoses.

Intestinal Failure And Assessment

Intestinal Failure And Assessment

pediagenosis    May 18, 2021    Comment   

Intestinal Failure And Assessment

Intestinal failure

Intestinal failure means that the patient can no longer maintain their nutritional needs by oral intake of food. In some patients, for example those who have had a recent bowel resection, this is a temporary state that will recover as the residual bowel adapts; in others with very diseased bowel or major resections the condition may be irreversible with a continued requirement for parenteral nutrition (PN).

Parenteral nutrition is the main treatment for patients with intestinal failure. It requires an indwelling central venous catheter to which the patient connects a bag of nutrition (typically 2.5 litres) every evening to run over 12 to 14 hours through the night. Most patients can live a reasonable existence on such therapy.

Complications of parenteral nutrition

The 1-year survival of a patient on home PN is 90%, falling to 65% at 5 years. There are three principal complications of long-term PN.

Assessment For Heart Transplantation

Assessment For Heart Transplantation

pediagenosis    May 18, 2021    Comment   

Assessment For Heart Transplantation

While heart transplantation remains an excellent treatment for advanced heart failure, the number of transplants performed in Europe is falling due to the lack of suitable donors. The assessment of potential recipients has therefore become more stringent in order to make optimal use of available organs. Many patients referred for transplantation can be improved with conventional cardiac surgery and/or improved medical management, including resynchronisation therapy with biventricular pacing. A classification of underlying diseases is given in Figure 39.

Assessment for transplantation

The assessment of potential recipients involves three components:

•   functional capacity

•   right heart catheterisation to assess pulmonary circulation

•   comorbidity.

Complications Of Heart Transplantation

Complications Of Heart Transplantation

pediagenosis    April 25, 2021    Comment   

Complications Of Heart Transplantation

Early complications

The initial complications of heart transplantation relate to donor events, damage due to cold ischaemia, reperfusion injury, technical complications and the haemodynamic challenge facing the new heart in the recipient.

·  Bradycardia – related to cold ischaemia, damage to the sinoatrial node or pre-transplant treatment with amiodarone. Treatment comprises either isoproterenol (isoprenaline) or temporary atrioventricular pacing.

·     Atrial fibrillation or flutter occurs in up to a fifth of patients.

·    Right ventricular failure – due to pre-existing pulmonary hypertension and high pulmonary vascular resistance. Isoproterenol is a pulmonary vasodilator as well as a chronotrope, and is used routinely. Inhaled nitric oxide can be a useful addition to reduce pulmonary artery pressure.

·      Systemic hypotension may be due to impaired left ventricular function, which may recover. Reduction in peripheral vascular resistance may occur due to acidosis and vasoconstricting inotropes such as noradrenaline or vasopressin may be required.

·     Valvular dysfunction. Tricuspid regurgitation is more common and may relate to dilatation of the tricuspid valve ring due to high pulmonary pressures. It typically recovers within 12 months.

·      Bleeding resulting in tamponade may occur.

·   Pericardial effusion may also occur and sometimes requires treatment, although it usually resolves within 6 weeks.

· Renal dysfunction is very common, particularly in patients with pre-existing renal impairment, those requiring prolonged bypass (retransplants, previous congenital heart disease) and as a consequence of calcineurin inhibitor immunosuppression. Short-term haemofiltration should be started early and does not confer any late disadvantage.

Immunosuppression

A typical immunosuppressive regimen would comprise an induction agent such as antithymocyte globulin or basiliximab, with maintenance therapy with tacrolimus, mycophenolate and steroids. In addition, statins such as pravastatin are also used in the early post-transplant period, regardless of serum cholesterol level.

Assessment For Lung Transplantation

Assessment For Lung Transplantation

pediagenosis    April 25, 2021    Comment   

Assessment For Lung Transplantation

Indications for lung transplantation

Lung transplantation is indicated for end-stage obstructive, septic, restrictive lung disease or pulmonary vascular disease. In broad terms, the presence of septic disease (e.g. cystic fibrosis) or pulmo- nary hypertension is an indication for bilateral lung transplantation; obstructive or restrictive disease may be treated by single or bilateral lung transplantation. Combined heart lung transplantation, popular in the 1990s, is now rarely performed, although may be indicated for some complex congenital heart diseases.

A decision to offer lung transplantation is based on physical status, quality of life and comorbidity.

Assessment investigations

Forced expiratory volume in one second (FEV₁) is the amount of breath forcibly exhaled in 1 second. It is usually expressed as a proportion of the value predicted for age, sex and build. A reduced FEV₁ signifies obstruction to air escaping.

Lung Transplantation: The Operation

Lung Transplantation: The Operation

pediagenosis    April 25, 2021    Comment   

Lung Transplantation: The Operation

The Lung Donor

Donor selection

Matching donor and recipient involves matching blood group and donor size, and avoiding any incompatible HLA antigens that might result in hyperacute or early humoral rejection. Size is very important, particularly avoiding putting large lungs into small chests, which will result in pulmonary collapse and infection.

Lung assessment differs between DCD and DBD donors.

Lung retrieval from donors following brain death

In DBD donors, where the heart is still beating, the donor undergoes bronchoscopy before retrieval surgery commences to look for evidence of infection or inflammation; bronchial aspirates are sent for Gram stain and culture to inform choice of antibiotics in the recipient. Once the operation begins the lungs are inspected externally and care is taken to ensure that all segments are fully inflated, with no evidence of atelectasis, consolidation, masses or trauma. Pulmonary vein oxygen levels are measured by aspirating blood directly from left and right upper and lower pulmonary veins. A PO₂ >40 kPa is desirable.

The lungs are preserved by perfusing a low-potassium/dextran preservation solution (Perfadex), together with a prostaglandin vasodilator, via the pulmonary artery, with the lungs ventilated to aid distribution of perfusate. Following this, additional retrograde perfusion is given via the pulmonary veins to wash out clots. This may also perfuse the bronchial arteries, which arise directly from the descending thoracic aorta.

Complications Of Lung Transplantation

Complications Of Lung Transplantation

pediagenosis    April 25, 2021    Comment   

Complications Of Lung Transplantation

Early Complications

Initial post-transplant management

The early management of patients post-lung transplantation involves limiting airway pressures (<35 mmHg) and physiotherapy to improve expectoration; tracheostomy may be indicated to facilitate tracheal toilet if prolonged intubation is anticipated. Fluid management aims to keep the recipient in a negative balance so as not to waterlog the lungs, and colloids may be preferred to crystalloids for the same reason.

Complications

The early complications following lung transplantation may be divided into four types.

1.    Technical complications relating to the surgery

These are now uncommon.

Composite Tissue Transplantation

Composite Tissue Transplantation

pediagenosis    April 25, 2021    Comment   

Composite Tissue Transplantation

Vascularised composite tissue allotransplantation (CTA) reflects the fact that the vascularised graft includes many different tissues, such as bone, nerve, muscle, tendons and skin. The most common example is hand transplantation, but face, laryngeal and abdominal wall transplantation are other examples. Abdominal wall transplants have been used in a few multivisceral transplant recipients to gain abdominal domain – in other words to make room for the bowel.

Hand transplantation

Indications

Loss of one hand causes significant disability and carries many psychological and social stigmata, but loss of both upper limbs is a devastating handicap. While prosthetics may provide a substitute that can be used to compensate for loss of a single limb, none can substitute for the tactile sense that is required for many activities of daily living. The benefits of such transplantation need to be balanced against the need for immunosuppression. Possible indications include:

Xenotransplantation

Xenotransplantation

pediagenosis    April 24, 2021    Comment   

Xenotransplantation

Aspirations for xenotransplantation

The shortfall between the number of available organs for transplantation and the number of patients on the transplant waiting lists is ever widening. One solution to this that has been explored since Jaboulay’s first efforts in the 1900s is the use of animal organs, so-called xenotransplantation. In spite of much research, xenotransplantation has failed to achieve the successes hoped for, and with every new finding more hurdles appear to slow its progress.

Many xenotransplants have been performed, ranging from kidney, liver and heart transplants using dog, goat, pig or primate organs, to the transplantation of specialised cells in an attempt to cure diabetes or Parkinson’s disease. None has yet been successful.

Barriers to success

Donor selection

It is generally agreed that the favoured animal for mass breeding as donors for transplantation is the pig, for the following reasons.

·     The animals are of a similar size to man, compared with primates such as baboons, which are much smaller.

·       Organs are anatomically similar to those in man.

·       Breeding programmes are well established, and gestation is short.

·      Genetic manipulation has been shown to be possible.

In the paragraphs that follow we have assumed that the pig is the donor; similar considerations apply whatever the species chosen.

History Of Transplantation

History Of Transplantation

pediagenosis    October 14, 2020   

History Of Transplantation

Fundamentals

Vascular anastom ses

Transplantation of any organ demands the ability to join blood vessels together without clot formation. Early attempts inverted the edges of the vessels, as is done in bowel surgery, and thrombosis was common. It wasn’t until the work of Jaboulay and Carrel that eversion of the edges was shown to overcome the early thrombotic problems, work that earned Alexis Carrel the Nobel Prize in 1912. Carrel also described two other techniques that are employed today, namely triangulation to avoid narrowing an anastomosis and the use of a patch of neighbouring vessel wall as a flange to facilitate sewing, now known as a Carrel patch.

Diagnosis Of Death And Its Physiology

Diagnosis Of Death And Its Physiology

pediagenosis    October 14, 2020   

Diagnosis Of Death And Its Physiology

Diagnosing death

Circulatory death

Traditionally, death has been certified by the absence of a circulation, usually taken as the point at which the heart stops beating. In the UK, current guidance suggests that death may be confirmed after 5 minutes of observation following cessation of cardiac function (e.g. absence of heart sounds, absence of palpable central pulse or asystole on a continuous electrocardiogram). Organ donation after circulatory death (DCD) may occur following confirmation that death has occurred (also called non-heart-beating donation). There are two sorts of DCD donation, controlled and uncontrolled.

Deceased Organ Donation

Deceased Organ Donation

pediagenosis    October 14, 2020   

Deceased Organ Donation

Opting in or opting out?

In the UK, as in most countries in the world, the next of kin are approached for consent/authorisation for organ donation, a system known colloquially as ‘opting in’. This system is facilitated by having a register, such as the UK organ donor register (ODR), where people can register their wishes to be a donor when they die; 29% of the UK population are on the register. However, opinion polls show that nearer to 90% of people are in favour of organ donation, suggesting that the shortfall is a consequence of apathy. When a person is on the ODR the relatives are much more likely (>90%) to consent to donation than where the wishes of the deceased were not known (∼60%).

Live Donor Kidney Transplantation

Live Donor Kidney Transplantation

pediagenosis    October 14, 2020   

Live Donor Kidney Transplantation

The limited supply of deceased donor organs and an ever-increasing number of patients waiting for kidney transplantation has led to the widespread use of living donors. Renal transplantation has the unique advantage, compared with other organs, that most individuals have two kidneys, and if not diseased, have sufficient reserve of renal function to survive unimpeded with a single kidney. The shortage of donors has also led to the use of parts of non-paired organs, such as liver and lung lobes, the tail of pancreas and lengths of intestine from living donors; indeed, even live donation of the heart has occurred, when the donor has lung disease and received a combined heart-lung transplant, with their own heart being transplanted to someone else, so called ‘domino transplantation’. For the purposes of this chapter we will focus on live kidney donation, but similar principles apply to other organs.

Live Donor Liver Transplantation

Live Donor Liver Transplantation

pediagenosis    October 14, 2020   

Live Donor Liver Transplantation

Live liver donation

Much of what has been said about the assessment of a kidney donor applies to a liver donor, with the exception that the full assessment of the liver, its function, exclusion of disease and assessment of its anatomy are paramount.