Organ Transplantation

Transplantation is a procedure that involves the removal of an organ or living tissue and placing it into a different part of the body or into a different person. Organ transplantations have become the therapeutic option of choice for many individuals with end-stage organ failure. Transplantation can offer the individual a definitive treatment for a given disease entity. Over the past 50 years, organ transplantation has become established worldwide, with ever-improving results, conferring an immense benefit to hundreds of thousands of individuals. Both solid organs and bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow–derived hematopoietic cells can be successfully transplanted for a number of different indications. Tolerance of the transplanted organ by the immune system of the host is achieved through the use of immunosuppressive and immunomodulating strategies. The main complications of transplantation are organ rejection or graft failure; however, chronic immunosuppression also carries the risk of serious complications, including potentially life-threatening infections.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Definitions

Transplanted tissue may be cells (e.g., hematopoietic stem cells), tissues (e.g., cornea), parts of an organ (e.g., liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin grafts), or entire organs (e.g., kidney, heart). There are many terms that are important to transplant medicine.

  • Graft: a piece of living tissue that is surgically transplanted
  • Autograft:
    • A graft from an individual’s own tissue
    • No tissue compatibility issues
    • High rate of success
    • Clinical uses:
      • Skin grafts from one part of the body to another
      • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones marrow harvest and reinfusion after intensive chemotherapy
  • Isografts:
    • Transplantations between 2 genetically identical individuals (monozygotic twins)
    • Still some risk of rejection; immunosuppressive therapy indicated
  • Allografts:
    • Transplantations between genetically nonidentical individuals
    • Most common type 
    • Closely matched to reduce the risk of rejection
    • Immunosuppressive therapy is always indicated.
  • Living donor grafts: 
    • Organs from a living donor
    • Classic example: kidney transplantation
  • Cadaveric grafts:
    • Organs that are procured after death from registered donors
    • Constitute the great majority of currently used transplants
    • Recipients are chosen from transplant-listed individuals based on histocompatibility.
  • Xenografts:
    • Tissues or organs that are derived from a different species
    • Xenografts undergo depletion of all animal cells to mitigate rejection from a human host
    • Clinical uses:
      • Pig heart valves in individuals who need valve replacement
      • Partial-thickness pig skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin grafts to treat individuals being treated for burn injuries
  • Heterotopic:
    • An organ grafted to a different site than the usual anatomic location
    • Example: a kidney transplanted into the iliac fossa
  • Orthotopic: tissue grafted to the usual anatomic site (heart, lung, and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplants)

Immunologic Matching

Immunologic matching between an organ donor and an organ recipient is important to improve the success of a transplantation and to reduce the risk of rejection. HLA tissue typing is important for the transplantation of hematopoietic stem cells and solid organs, including kidney, heart, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas, and lung transplants.

MHC antigens

  • Tissue cell-surface antigens that regulate immune response
  • Encoded by HLA genes:
    • Siblings have a 25% chance of having identical HLA genes. 
    • Identical twins can have 100% identical HLA genes, but not in all cases.
  • Determine the immune response to a transplanted organ
  • Controlled by genes on chromosome 6:
    • HLA-A to HLA-D genes are very close to each other.
    • Inherited as 1 block with minimal crossover
Major histocompatibility complex

Major histocompatibility complex

Image by Lecturio.

Classification of MHC antigens

  • Class I: 
    • Found on the cell surface of all nucleated cells
    • Encoded by HLA-A, HLA-B, and HLA-C genes
  • Class II: 
    • Found on activated T helper cells that express CD4
    • Found on antigen-presenting cells (APCs; e.g., B cells B cells B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. B Cells, macrophages)
    • Encoded by HLA-D genes
  • Class III: 
    • Determine the structure of some complement factors; tumor necrosis factor Tumor necrosis factor Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF) alpha ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF)-α) important in inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • Class III genes are located between the HLA-B and HLA-D loci.

Principles of donor–recipient matching

  • ABO antigens usually must be compatible.
  • One’s own HLA antigens do not trigger the immune system; exposure to another set of HLA antigens will trigger an immune response.
  • A close match between a donor’s and a recipient’s HLA antigens is essential.
  • A donor must match a minimum of 6 HLA antigens of the recipient.
  • HLA matching is performed by high-resolution molecular typing on peripheral blood or lymph node lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes.

Mechanisms of Transplant Rejection

Rejection may be acute or chronic, and the symptoms vary by organ system.

  • Transplanted tissue expresses damage-associated molecular patterns → recognized by toll-like receptors on innate immune cells → host innate immune system Innate immune system Innate immunity, the 1st protective layer of defense, is a system that recognizes threatening microbes, distinguishes self-tissues from pathogens, and subsequently eliminates the foreign invaders. The response is nonspecific and uses different layers of protection: barriers such as the skin, pattern recognition receptors (PRRs) as well as circulating proteins, and immune cells that help eliminate the microbe. Cells of the Innate Immune System is activated → immune cells rapidly release inflammatory mediators 
  • The innate immune system Innate immune system Innate immunity, the 1st protective layer of defense, is a system that recognizes threatening microbes, distinguishes self-tissues from pathogens, and subsequently eliminates the foreign invaders. The response is nonspecific and uses different layers of protection: barriers such as the skin, pattern recognition receptors (PRRs) as well as circulating proteins, and immune cells that help eliminate the microbe. Cells of the Innate Immune System by itself can also (rarely) cause transplant rejection.
  • T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells are very capable of responding to mismatched MHC molecules.
  • Priming of recipient T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells with alloantigen can occur by:
    • Direct allorecognition: Recipient T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells interact with MHC–peptide complexes presented by donor-derived APCs.
    • Indirect allorecognition: Recipient T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells interact with MHC–peptide complexes presented by recipient-derived APCs.
    • Costimulation: Antigen-specific signals are delivered to the T cell → T-cell proliferation and resistance to cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death by apoptosis 
  • Role of B cells B cells B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. B Cells:
    • Act as APCs, as they express MHCs and costimulatory molecules, including CD40
    • Interact with T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells and enable T-cell–mediated cytokine production
    • Produce alloantibodies against:
      • Mismatched MHC molecules
      • Minor histocompatibility molecules
      • Donor endothelial cells
    • Express complement receptors; interact with complement-coated damaged cells
    • Interact with natural killer (NK) cells and macrophages 
    • Antibody-mediated rejection begins early after transplantation but can also contribute to late graft loss.
  • Preformed alloantibodies at the time of transplantation lead to antibody-mediated rejection:
    • Seen with ABO blood group incompatibility
    • Leads to hyperacute rejection of the graft within minutes
    • Is extremely rare
  • Transplant rejection results in: 
    • Infiltration of transplanted tissue by host inflammatory cells
    • Vascular microthrombosis
    • Tissue death
Table: Transplantation rejection reponses
Rejection Time after transplantation Characteristics of rejection
Hyperacute Within 48 hours
  • Caused by preexisting complement-fixing antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to graft antigens (presensitization)
  • Small-vessel thrombosis and graft infarction are seen
  • Rare (1%) with adequate prescreening
  • Only treatment is graft removal
Accelerated 3–5 days
  • Caused by preexisting non–complement-fixing antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to graft antigens
  • Histopathology: cellular infiltrates with or without vascular changes
  • Rare
  • Treatment: high-dose steroids; plasma exchange
Acute > 5 days
  • T-cell–mediated delayed hypersensitivity reaction to graft MHC antigens
  • Mononuclear cellular infiltration with hemorrhage, edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, and necrosis but maintained vascular integrity
  • Histopathology: proliferation of smooth muscle cells in the blood vessels resulting in ischemia and fibrosis in the graft organ
  • About 50% of rejections within 10 years
  • Treatment: intensified immunosuppressive therapy
Chronic Months to years
  • Diverse causes: can involve antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins, immune complexes, T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells
  • Accounts for the other almost 50% of rejections
  • Progresses despite immunosuppression

Immunosuppressive Therapy

Recipients of solid organ transplants must take immunosuppressive drugs to prevent rejection of the graft. Current immunosuppressive drugs target T-cell activation and cytokine production, clonal expansion of T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells, or both.

Induction immunosuppressive therapy

  • Before and at the time of transplantation:
    • More intense than maintenance therapy
    • Goal: to prevent acute rejection and to avoid more toxic maintenance drugs
  • Induction immunosuppressive drugs:
    • Antithymocyte globulin (derived from rabbits)
    • Monoclonal antibody against interleukin-2 receptor complex expressed on activated T lymphocytes T lymphocytes T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells (basiliximab, brand name Simulect)
    • High-dose glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids

Maintenance immunosuppression

  • Targets multiple steps in T-cell activation
  • Initiated at the time of transplantation and continued long term
  • Combination therapy with 2 or 3 agents for 6 months to prevent organ rejection, then monotherapy: 
    • Glucocorticoids (e.g., prednisone):
      • Suppress the immune system and adrenal function
      • Bind to glucocorticoid response elements in the promoter regions of cytokine genes
      • Side effects: hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, hyperlipidemia, and glucose intolerance 
    • Calcineurin inhibitors (CNIs) (e.g., cyclosporine, tacrolimus)
      • Inhibit T-cell activation 
      • Side effects of cyclosporine: nephrotoxicity, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, dyslipidemia, hirsutism
      • Side effects of tacrolimus: diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, neurotoxicity, nephrotoxicity
    • Antimetabolic agent (e.g., mycophenolate mofetil):
      • Prevents the expansion of alloactivated T-cell and B-cell clones
      • Side effects: bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow suppression, infection, GI ( constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation or diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, gastric ulcer or bleeding)
    • mTOR inhibitors: CNI-sparing agents: (sirolimus, everolimus)
      • Inhibit T-lymphocyte activation and proliferation and inhibit antibody production
      • Side effects: glucose intolerance, impaired wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing, lung toxicity
  • Many drugs interact with immunosuppressive agents
  • Medical conditions worsened by immunosuppressive agents:
    • Infections
    • Hypertension
    • Diabetes
    • Obesity
    • Hyperlipidemia
    • CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
    • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis

Liver Transplantation

The scarcity of organs from donors is a significant factor in liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantation; many individuals die while waiting for an organ. Living-donor transplants are now used, in which only a portion of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver is removed from a healthy donor.

Epidemiology

  • Approximately 8900 liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantations are performed per year in the United States.
  • Waiting list (2018) in the United States: > 14,000 individuals
  • Approximately 7000 liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantation candidates will wait > 1 year.
  • The 1- and 5-year survival rates after liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantation are 90% and 80%.
  • Alcohol-associated cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis: 21% of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantations (2015)

Pretransplantation vaccinations required (for all solid-organ transplantations)

  • Pneumococcus
  • Influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza (high-dose)
  • Hepatitis A Hepatitis A Hepatitis A is caused by the hepatitis A virus (HAV), a nonenveloped virus of the Picornaviridae family with single-stranded RNA. HAV causes an acute, highly contagious hepatitis with unspecific prodromal symptoms such as fever and malaise followed by jaundice and elevated liver transaminases. Hepatitis A Virus and B
  • For at-risk individuals who have not been previously vaccinated:
    • Meningococcus
    • Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae
    • Human papillomavirus Human papillomavirus Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomaviridae: HPV ( HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomaviridae: HPV)
    • Measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus, mumps Mumps Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. Mumps is typically a disease of childhood, which manifests initially with fever, muscle pain, headache, poor appetite, and a general feeling of malaise, and is classically followed by parotitis. Mumps Virus/Mumps, rubella Rubella Rubella (also known as German measles or three-day measles) is caused by a single-stranded, positive-sense RNA virus of the Togaviridae family. Rubella only infects humans and spreads prenatally via vertical transmission or postnatally via droplet contact. Congenital rubella is associated with a classic triad of symptoms: cataracts, cardiac defects, and deafness. Infection in children and adults may be mild and present with constitutional symptoms along with a viral exanthem. Rubella Virus (MMR)
  • Tdap
  • Recombinant zoster vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination for individuals > 50 years

Clinical indications for liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantation

  • Acute life-threatening fulminant hepatic failure
  • Cirrhosis plus complications of portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension:
    • Variceal hemorrhage
    • Encephalopathy
    • Ascites 
  • Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases ( HCC HCC Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases): specific criteria
  • Metabolic conditions (with end-stage liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease or HCC HCC Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases):
    • Cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis
    • Alpha-1 antitrypsin deficiency
    • Hemochromatosis
    • Wilson disease
    • Tyrosinemia

Contraindications

  • Severe cardiopulmonary disease
  • AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS
  • Other malignancy
  • Sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock
  • Persistent noncompliance with medical care
  • Lack of adequate social support
  • Alcohol-associated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease without abstinence for 6 months (varies with transplant programs) or without participation in a structured support program

Medical therapy before liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantation

  • Optimization of medical management before transplantation is required.
  • Medical management involves treating:
    • Encephalopathy 
    • Ascites
    • Spontaneous bacterial peritonitis 
    • Infection
    • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
    • Concurrent renal or heart failure
  • Model for End-stage Liver Disease score:
    • Severity scoring system used to predict 3-month survival
    • Uses an individual’s lab results:
      • Serum bilirubin
      • Creatinine
      • INR
    • A higher score is associated with worsening liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver function.
    • Used to prioritize organ transplantations → sickest individuals 1st

Procedure

  • Orthotopic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantation includes the excision of: 
    • Native liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
    • Portal vein 
    • Hepatic artery Hepatic artery A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. Liver 
    • Common bile duct common bile duct The largest bile duct. It is formed by the junction of the cystic duct and the common hepatic duct. Acute Cholangitis
    • Parts of the inferior and superior vena cava Superior vena cava The venous trunk which returns blood from the head, neck, upper extremities and chest. Mediastinum and Great Vessels
  • A donor liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver is implanted at the anatomic site. 
  • 4 types of anastomoses are performed:
    • Arterial anastomosis
    • Venous inflow anastomosis: portal venous system 
    • Venous outflow anastomosis: hepatic vein and/or inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels
    • Biliary anastomosis

Posttransplantation

Complications:

  • Acute graft rejection (most common) 
  • Infections: bacterial, viral, and fungal
    • Leading cause of mortality following liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver transplantation
    • Can rapidly progress to sepsis with multiorgan failure
    • Prophylactic antibiotics are commonly used.
    • High vigilance is imperative.
  • Reactivation of infection from the organ donor or recipient can occur:
    • Herpes simplex virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview
    • Cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus (CMV)
    • Geographically restricted systemic mycoses (e.g., histoplasmosis Histoplasmosis Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. Transmission is through inhalation, and exposure to soils containing bird or bat droppings increases the risk of infection. Most infections are asymptomatic; however, immunocompromised individuals generally develop acute pulmonary infection, chronic infection, or even disseminated disease. Histoplasma/Histoplasmosis)
    • Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • Nosocomial infections:
    • Early posttransplantation period with prolonged hospitalization or mechanical ventilation
    • Gram-negative bacilli (e.g., Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas)
    • Gram-positive cocci, including vancomycin-resistant enterococci and MRSA
    • Fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology: Overview, including Aspergillus and Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis
    • Anaerobic gram-positive, spore-forming bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus: Clostridioides difficile

Complications of immunosuppression:

  • Development of malignancies
  • Acceleration of cardiovascular disease
  • Severe infection, possibly life-threatening

Immunizations for posttransplant/immunosuppressed individuals:

  • Usual schedule
  • Live attenuated vaccines are contraindicated:
    • Live zoster vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination (not recombinant)
    • Varicella vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination
    • MMR

Kidney Transplantation

Epidemiology

  • Most common solid organ transplantation
  • About 40% of donated kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys come from living donors
  • 1-year survival rates after kidney transplantation:
    • From living donors: 98% of recipients; 94% of grafts
    • From deceased donors: 95% of recipients; 88% of grafts

Clinical indications

  • End-stage renal failure
  • No clear age limit: Individuals > 70 years may be candidates if they have good overall health and a reasonably long life expectancy.

Contraindications

  • Absolute: severe heart disease, cancer
  • Relative: poorly controlled diabetes

Medical therapy before transplantation

  • Dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Overview and Types of Dialysis may be required  to ensure a relatively normal metabolic state.
  • Living-donor allografts fare slightly better in recipients who have not yet begun long-term dialysis.

Procedure

  • Deceased-donor kidney transplantation:
    • Kidney is surgically removed with the renal blood vessels and the ureter.
    • Immersed in iced saline for up to 24 hours
    • Renal vein and artery dissected free, excess perinephric fat removed, excess vena cava and aorta trimmed
  • Living donor:
    • Laparoscopic preparation of the kidney is done in situ prior to removal from the donor.
    • Kidney is transplanted heterotopically into the iliac fossa.
    • Native kidney in the recipient is left intact unless there is infection.
    • Renal vein then artery is anastomosed in the recipient.
    • Recipient is hydrated and given furosemide plus mannitol.
    • Transplanted kidney is reperfused.
    • Ureter is implanted/sewn into the bladder.

Complications

Rejection:

  • Approximately 20% of individuals have ≥ 1 episode in the 1st year → corticosteroid bolus
  • Most individuals return to normal activity after 3–4 months; require long-term immunosuppressive therapy
  • Rejection episodes contribute to long-term graft failure.
  • Symptoms of rejection:
    • Hyperacute/accelerated:
      • Fever
      • Anuria or oliguria 
    • Acute: 
      • Fever
      • Increased creatinine
      • Hypertension
      • Weight gain/swelling
      • Urinalysis with protein, lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes, and renal tubular cells in sediment
    • Chronic:
      • Proteinuria with or without hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
      • Nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome

Other complications:

  • Chronic allograft nephropathy: failure > 3 months after transplantation
    • May be attributable to nephrotoxic effects of CNI drugs, diabetic nephropathy or hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
    • Biopsy shows chronic interstitial fibrosis and tubular atrophy.
  • Cancer
    • Kidney transplant recipients are 10–15 times more likely to develop cancer.
    • Lymphoma: 30 times more common than in the general population (but overall incidence is still low)
    • Skin cancer: increased incidence owing to prolonged immunosuppression

Heart Transplantation

Heart transplantation may be offered to individuals who have intolerable symptoms despite optimal medical therapy and who are at risk of death due to cardiac disease.

Epidemiology

  • Substantial increase in heart donor offers and heart transplantations since 2003
  • More than 3000 heart transplantations per year (2016) 
  • Approximately 20% of candidates die while on the waiting list or are removed for being “too sick.”
  • 1-year survival rate: 85%–90%
  •  > 70% of individuals return to full-time employment.
  • 10-year survival rate is approximately 53% (for transplantations done between 1990 and 2007).

Clinical indications

  • Cardiogenic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock requiring continuous IV inotropic support or intraaortic balloon pump/left ventricular assist device
  • End-stage heart failure (New York Heart Association functional class IV)
  • Intractable or severe angina due to coronary artery disease and not amenable to other treatments
  • Intractable life-threatening arrhythmias unresponsive to other therapies
  • Restrictive and hypertrophic cardiomyopathies with heart failure

Contraindications

  • Absolute contraindications:
    • Life expectancy < 2 years despite transplantation
    • Irreversible pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
    • Severe symptomatic cerebrovascular disease
    • Active substance abuse, including tobacco, within 6 months
    • Persistent nonadherence with medical care
  • Relative contraindications:
    • Age > 70 years
    • Obesity: body mass index > 35
    • Diabetes mellitus with hemoglobin A1c > 7.5% despite optimal effort 
    • Irreversible renal dysfunction with glomerular filtration rate Glomerular filtration rate The volume of water filtered out of plasma through glomerular capillary walls into bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests < 30 ml/min/1.73 m2
    • Cancer
    • Infection
    • Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism within 6–8 weeks

Complications

  • Rejection: 
    • 50%–80% of individuals have 1–3 episodes 
    • Often asymptomatic; surveillance biopsy is done once a year
  • Risk factors for rejection:
    • Younger age
    • Female sex (recipient)
    • Female or Black donor
    • HLA mismatching
  • Death ≤ 1 year:
    • Acute rejection
    • Infection
  • Death > 1 year:
    • Vasculopathy in the heart graft
    • Lymphoproliferative disorder

Other Organ and Tissue Transplants

Hematopoietic stem cell transplantation ( bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow transplantation)

  • Indications:
    • Hematologic cancers:
      • Leukemias
      • Lymphomas
      • Multiple myeloma Multiple myeloma Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
    • Nonmalignant hematologic disorders:
      • Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia
      • Myelodysplastic syndromes Myelodysplastic Syndromes Myelodysplastic syndromes (MDS) are a group of clonal neoplasms with maturation defects characterized by dysplasia, cytopenia, and immature bone marrow precursors. Myelodysplastic syndromes can be idiopathic, or secondary to various injurious exposures such as cytotoxic chemotherapy, ionizing radiation, or environmental toxins. Myelodysplastic Syndromes
      • Primary immunodeficiency
    • May be used to restore bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow after high-dose chemotherapy
  • Procedure: 
    • Can be autologous (no contraindications) or allogeneic (contraindicated > age 50 or with significant comorbidities)
    • Stem cells can be harvested from:
      • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones marrow: donor’s posterior iliac crests
      • Peripheral blood: Donor is treated with recombinant growth factors and apheresis is done 4–6 days later; stem cells are infused over 1–2 hours through a central IV line.
      • Umbilical cord blood: newer procedure, HLA matching less crucial; higher percentage of naive T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells increases the risk of reactivating CMV or EBV infections.
  • Complications:
    • Rejection
    • Failure
    • Acute graft-versus-host disease (GVHD)

Lung transplantation

  • Indications:
    • Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD))
    • Idiopathic pulmonary fibrosis Pulmonary Fibrosis Idiopathic pulmonary fibrosis is a specific entity of the major idiopathic interstitial pneumonia classification of interstitial lung diseases. As implied by the name, the exact causes are poorly understood. Patients often present in the moderate to advanced stage with progressive dyspnea and nonproductive cough. Pulmonary Fibrosis
    • Cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis
    • Alpha-1 antitrypsin deficiency
    • Primary pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
  • Procedures:
    • Single- and double-lung transplantation
    • Lung-heart transplantation in combination for lung disorders with irreversible severe ventricular dysfunction
  • Prognosis:
    • 1-year survival: 84%
    • 5-year survival: 34%–46% (higher with primary pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension and pulmonary fibrosis Pulmonary Fibrosis Idiopathic pulmonary fibrosis is a specific entity of the major idiopathic interstitial pneumonia classification of interstitial lung diseases. As implied by the name, the exact causes are poorly understood. Patients often present in the moderate to advanced stage with progressive dyspnea and nonproductive cough. Pulmonary Fibrosis; lower for COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD))
    • Mortality: single-lung > double-lung transplantation
    • Lung-heart transplantation has an 80% survival rate at 1 year for individuals and grafts.

Pancreas transplantation

  • Indications:
    • Type 1 diabetes with renal failure 
    • > 90% of pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas transplantations also include a kidney.
  • Contraindications:
    • Age > 55 years
    • Significant cardiovascular disease
  • Prognosis:
    • Recipient survival > 95% at 1 year
    • Graft survival > 85% at 1 year
    • Recipients no longer need insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin therapy after transplantation.

Tissue transplantation

  • Composite transplants:
    • Hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand
    • Extremity
    • Face
  • Skin grafts
  • Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage transplantation
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones transplantation
  • Adrenal autografting

Corneal transplantation

  • Indications:
    • Bullous keratopathy
    • Keratoconus
    • Corneal stromal dystrophies
    • Keratomycosis due to molds with extension into the aqueous humor
    • Herpes simplex keratitis
  • Over 48,000 transplantations per year (2013)
  • Tissue matching is not routinely done; cadaveric donor tissue can be used.
  • Procedure: 
    • Full- or partial-thickness transplantation; endothelial keratoplasty
    • Done under general anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts or local anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts plus IV sedation
  • Complications:
    • Rejection: rate of 10%; can be treated
    • Other complications: infection, glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma, cataracts, refractive errors Refractive errors By refraction, the light that enters the eye is focused onto a particular point of the retina. The main refractive components of the eye are the cornea and the lens. When the corneal curvature, the refractive power of the lens, does not match the size of the eye, ametropia or a refractive error occurs. Refractive Errors

References

  1. Di Maira, T., Little, E.C., Berenguer, M. (2020). Immunosuppression in liver transplant. Best Practice & Research Clinical Gastroenterology 46–47:101681. 10.1016/j.bpg.2020.101681
  2. Wood, K.J., Goto, R. (2012). Mechanisms of rejection: current perspectives. Transplantation 93:1–10. 10.1097/TP.0b013e31823cab44
  3. Chandraker, A., Yeung, M. (2021). Kidney transplantation in adults: overview of care of the adult kidney transplant recipient. UpToDate. Retrieved October 20, 2021, from https://www.uptodate.com/contents/kidney-transplantation-in-adults-overview-of-care-of-the-adult-kidney-transplant-recipient
  4. Fishman, J.A. (2020) Infection in the solid organ transplant recipient. UpToDate. Retrieved October 20, 2021, from https://www.uptodate.com/contents/infection-in-the-solid-organ-transplant-recipient
  5. Hertl, M. (2020). Overview of transplantation. MSD Manual Professional Version. Retrieved October 20, 2021, from https://www.msdmanuals.com/professional/immunology-allergic-disorders/transplantation/overview-of-transplantation
  6. Dharmavaram, N., et al. (2021). National trend in heart donor usage rates: Are we efficiently transplanting more hearts? Journal of the American Heart Association. https://doi.org/10.1161/JAHA.120.019655
  7. Suarez-Pierre, A., et al. (2021). Long-term survival after heart transplantation: a population-based nested case-control study. Annals of Thoracic Surgery 111:889–898. 10.1016/j.athoracsur.2020.05.163

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