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 half-century, organ transplantation has become a successful and evolving practice which provides benefit to over 100,000 individuals yearly worldwide. Both solid organs and bone marrowBone marrowThe soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Bone Marrow: Composition and Hematopoiesis–derived hematopoietic cells can be successfully transplanted for a number of different indications. ToleranceTolerancePharmacokinetics and Pharmacodynamics of the transplanted organ by the immune systemImmune systemThe body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs 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 infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease.
Transplanted tissue may be cells (e.g., hematopoietic stem cellsHematopoietic stem cellsProgenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.Bone Marrow: Composition and Hematopoiesis), tissues (e.g., corneaCorneaThe transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye.Eye: Anatomy), parts of an organ (e.g., liverLiverThe 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: Anatomy and skinSkinThe 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.Skin: Structure and Functions 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:
SkinSkinThe 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.Skin: Structure and Functions grafts from one part of the body to another
Bone marrowBone marrowThe soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Bone Marrow: Composition and Hematopoiesis harvest and reinfusion after intensive chemotherapyChemotherapyOsteosarcoma
Isografts:
Transplantations between 2 genetically identical individuals (monozygotic twinsMonozygotic twinsResult from the division of a single zygote; share the same genetic materialMultiple Pregnancy)
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 skinSkinThe 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.Skin: Structure and Functions 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 liverLiverThe 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: Anatomy 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 cellsHematopoietic stem cellsProgenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.Bone Marrow: Composition and Hematopoiesis and solid organs, including kidney, heart, liverLiverThe 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: Anatomy, pancreasPancreasThe 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: Anatomy, and lung transplants.
MHC antigens
Tissue cell-surface antigens that regulate immune response
Encoded by HLA genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure:
Siblings have a 25% chance of having identical HLA genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure.
Identical twinsIdentical twinsResult from the division of a single zygote; share the same genetic materialMultiple Pregnancy can have 100% identical HLA genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure, but not in all cases.
Determine the immune response to a transplanted organ
Controlled by genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure on chromosomeChromosomeIn a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.Basic Terms of Genetics 6:
HLA-A to HLA-D genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure are very close to each other.
Inherited as 1 block with minimal crossover
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 genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure
Class II:
Found on activated T helper cells that express CD4
Found on antigen-presenting cellsAntigen-presenting cellsA heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include macrophages; dendritic cells; langerhans cells; and B-lymphocytes. Follicular dendritic cells are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of immune complexes for b-cell recognition they are considered so by some authors.Adaptive Immune Response (APCs; e.g., B cellsB cellsLymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.B cells: Types and Functions, macrophagesMacrophagesThe relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells.Innate Immunity: Phagocytes and Antigen Presentation)
Encoded by HLA-D genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure
Class III:
Determine the structure of some complement factors; tumorTumorInflammationnecrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage factor alpha (TNF-α) important in inflammationInflammationInflammation 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 genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure 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 triggerTriggerThe type of signal that initiates the inspiratory phase by the ventilatorInvasive Mechanical Ventilation the immune systemImmune systemThe body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs; exposure to another set of HLA antigens will triggerTriggerThe type of signal that initiates the inspiratory phase by the ventilatorInvasive Mechanical Ventilation 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 lymphLymphThe interstitial fluid that is in the lymphatic system.Secondary Lymphatic Organs node lymphocytesLymphocytesLymphocytes 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: Histology.
Mechanisms of Transplant Rejection
Rejection may be acute or chronic, and the symptoms vary by organ system.
Transplanted tissue expresses damage-associated molecular patternsDamage-Associated Molecular PatternsSepsis and Septic Shock → recognized by toll-like receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors on innate immune cells → host innate immune systemImmune systemThe body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs is activated → immune cells rapidly release inflammatory mediators
The innate immune systemImmune systemThe body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs by itself can also (rarely) cause transplant rejection.
T cellsT cellsLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions are very capable of responding to mismatched MHC molecules.
Priming of recipient T cellsT cellsLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions with alloantigen can occur by:
Direct allorecognition: Recipient T cellsT cellsLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions interact with MHC–peptide complexes presented by donor-derived APCs.
Indirect allorecognition: Recipient T cellsT cellsLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions interact with MHC–peptide complexes presented by recipient-derived APCs.
CostimulationCostimulationAdaptive Cell-mediated Immunity: Antigen-specific signals are delivered to the T cell → T-cell proliferation and resistanceResistancePhysiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.Ventilation: Mechanics of Breathing to cell deathCell deathInjurious 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 apoptosisApoptosisA regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Ischemic Cell Damage
Role of B cellsB cellsLymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.B cells: Types and Functions:
Act as APCs, as they express MHCs and costimulatory molecules, including CD40CD40Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors.Hyper-IgM Syndrome
Interact with T cellsT cellsLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions and enable T-cell–mediated cytokine production
Produce alloantibodies against:
Mismatched MHC molecules
Minor histocompatibility molecules
Donor endothelial cells
Express complement receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors; interact with complement-coated damaged cells
Interact with natural killer (NK) cells and macrophagesMacrophagesThe relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells.Innate Immunity: Phagocytes and Antigen Presentation
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 antibodiesAntibodiesImmunoglobulins (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: Types and Functions to graft antigens (presensitization)
Small-vessel thrombosisThrombosisFormation and development of a thrombus or blood clot in the blood vessel.Epidemic Typhus 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 antibodiesAntibodiesImmunoglobulins (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: Types and Functions to graft antigens
Histopathology: cellular infiltrates with or without vascular changes
Rare
Treatment: high-dose steroidsSteroidsA group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus.Benign Liver Tumors; plasma exchangePlasma exchangeRemoval of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (ppf), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions.Thrombotic Thrombocytopenic Purpura
Histopathology: mononuclear cellular infiltration with hemorrhage, edemaEdemaEdema 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 necrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage but maintained vascular integrity
About 50% of rejections within 10 years
Treatment: intensified immunosuppressive therapy
Chronic
Months to years
Diverse causes: can involve antibodiesAntibodiesImmunoglobulins (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: Types and Functions, immune complexesImmune complexesThe complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases.C3 Deficiency, T cellsT cellsLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions
Histopathology: proliferation of smooth muscle cells in the blood vessels resulting in ischemiaIschemiaA hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation.Ischemic Cell Damage and fibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans in the graft organ
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 expansionClonal ExpansionSeborrheic Keratosis of T cellsT cellsLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions, 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-2Interleukin-2A soluble substance elaborated by antigen- or mitogen-stimulated T-lymphocytes which induces DNA synthesis in naive lymphocytes.InterleukinsreceptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors complex expressed on activated T lymphocytesT lymphocytesLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions (basiliximab, brand name Simulect)
High-dose glucocorticoidsGlucocorticoidsGlucocorticoids 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:
GlucocorticoidsGlucocorticoidsGlucocorticoids 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 (e.g., prednisonePrednisoneA synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver.Immunosuppressants):
Suppress the immune systemImmune systemThe body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs and adrenal function
BindBINDHyperbilirubinemia of the Newborn to glucocorticoid response elements in the promoter regions of cytokine genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure
Side effects: hypertensionHypertensionHypertension, 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 glucoseGlucoseA primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Lactose Intolerance intolerance
Calcineurin inhibitorsCalcineurin InhibitorsCompounds that inhibit or block the phosphatase activity of calcineurin.Immunosuppressants (CNIs) (e.g., cyclosporineCyclosporineA cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation.Immunosuppressants, tacrolimusTacrolimusA macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.Immunosuppressants)
Inhibit T-cell activation
Side effects of cyclosporineCyclosporineA cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation.Immunosuppressants: nephrotoxicityNephrotoxicityGlycopeptides, hypertensionHypertensionHypertension, 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, hirsutismHirsutismA condition observed in women and children when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated androgens from the ovaries, the adrenal glands, or exogenous sources. The concept does not include hypertrichosis, which is an androgen-independent excessive hair growth.Polycystic Ovarian Syndrome
Side effects of tacrolimusTacrolimusA macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.Immunosuppressants: diabetesDiabetesDiabetes 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 mellitus, hyperkalemiaHyperkalemiaHyperkalemia 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, hypertensionHypertensionHypertension, 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, nephrotoxicityNephrotoxicityGlycopeptides
Prevents the expansion of alloactivated T-cell and B-cell clones
Side effects: bone marrowBone marrowThe soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Bone Marrow: Composition and HematopoiesissuppressionSuppressionDefense Mechanisms, infection, GI (constipationConstipationConstipation 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 diarrheaDiarrheaDiarrhea 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 painAbdominal PainAcute Abdomen, gastric ulcerGastric ulcerUlceration of the gastric mucosa due to contact with gastric juice. It is often associated with Helicobacter pylori infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDS).Peptic Ulcer Disease or bleeding)
mTORmTORPeutz-Jeghers Syndrome inhibitors: CNI-sparing agents: (sirolimusSirolimusA macrolide compound obtained from streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.Immunosuppressants, everolimusEverolimusA derivative of sirolimus and an inhibitor of tor serine-threonine kinases. It is used to prevent graft rejection in heart and kidney transplant patients by blocking cell proliferation signals. It is also an antineoplastic agent.Immunosuppressants)
Inhibit T-lymphocyte activation and proliferation and inhibit antibody production
Side effects: glucoseGlucoseA primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Lactose Intolerance intolerance, impaired wound healingWound healingWound 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 toxicityToxicityDosage Calculation
Many drugs interact with immunosuppressive agents
Medical conditions worsened by immunosuppressive agents:
InfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
HypertensionHypertensionHypertension, 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
DiabetesDiabetesDiabetes 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
ObesityObesityObesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
Hyperlipidemia
CKDCKDChronic 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
OsteoporosisOsteoporosisOsteoporosis 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 transplantationLiver transplantationThe transference of a part of or an entire liver from one human or animal to another.Hepatocellular Carcinoma (HCC) and Liver Metastases; many individuals die while waiting for an organ. Living-donor transplants are now used, in which only a portion of the liverLiverThe 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: Anatomy is removed from a healthy donor.
Epidemiology
Approximately 8900 liverLiverThe 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: Anatomy transplantations are performed per year in the United States.
Waiting list (2018) in the United States: > 14,000 individuals
Alcohol-associated cirrhosisCirrhosisCirrhosis 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 liverLiverThe 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: Anatomy transplantations (2015)
Pretransplantation vaccinations required (for all solid-organ transplantations)
Pneumococcus
InfluenzaInfluenzaInfluenza 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 AHepatitis AHepatitis 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 influenzaeHaemophilus InfluenzaeA species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii.Haemophilus
Human papillomavirusHuman papillomavirusHuman 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. Papillomavirus (HPV) (HPVHPVHuman 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. Papillomavirus (HPV))
MeaslesMeaslesMeasles (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, mumpsMumpsMumps 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, rubellaRubellaAn acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system.Rubella Virus (MMRMMRA DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base.Lynch syndrome)
Tdap
Recombinant zoster vaccineVaccineSuspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases.Vaccination for individuals > 50 years
Acute life-threatening fulminant hepatic failureHepatic failureSevere inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio.Autoimmune Hepatitis
CirrhosisCirrhosisCirrhosis 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 plus complications of portal hypertensionPortal hypertensionPortal 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:
AscitesAscitesAscites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection).Ascites
Hepatocellular carcinomaHepatocellular carcinomaHepatocellular 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 (HCCHCCHepatocellular 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 liverLiverThe 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: Anatomy disease or HCCHCCHepatocellular 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):
HemochromatosisHemochromatosisA disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption.Hereditary Hemochromatosis
Wilson diseaseWilson diseaseWilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease
TyrosinemiaTyrosinemiaA group of disorders which have in common elevations of tyrosine in the blood and urine secondary to an enzyme deficiency. Type I tyrosinemia features episodic weakness, self-mutilation, hepatic necrosis, renal tubular injury, and seizures and is caused by a deficiency of the enzyme fumarylacetoacetase. Type II tyrosinemia features intellectual disability, painful corneal ulcers, and keratosis of the palms and plantar surfaces and is caused by a deficiency of the enzyme tyrosine transaminase. Type III tyrosinemia features intellectual disability and is caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase.Renal Tubular Acidosis
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
SepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock
Alcohol-associated liverLiverThe 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: Anatomy disease without abstinence for 6 months (varies with transplant programs) or without participation in a structured support program
AscitesAscitesAscites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection).Ascites
MalnutritionMalnutritionMalnutrition 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 failureHeart FailureA heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction.Total Anomalous Pulmonary Venous Return (TAPVR)
Model for End-stage LiverLiverThe 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: Anatomy Disease score:
Severity scoring system used to predict 3-month survival
A higher score is associated with worsening liverLiverThe 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: Anatomy function.
Used to prioritize organ transplantations → sickest individuals 1st
Native liverLiverThe 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: Anatomy
Portal veinPortal veinA short thick vein formed by union of the superior mesenteric vein and the splenic vein.Liver: Anatomy
Hepatic arteryHepatic arteryA branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum.Liver: Anatomy
Common bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy duct
A donor liverLiverThe 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: Anatomy is implanted at the anatomic site.
InfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease:bacterial, viral, and fungal
Can rapidly progress to sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock with multiorgan failure
Herpes simplexHerpes SimplexA group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection.Congenital TORCH InfectionsvirusVirusViruses 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
CytomegalovirusCytomegalovirusCMV 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 mycosesSystemic mycosesMycology (e.g., histoplasmosisHistoplasmosisHistoplasmosis 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 tuberculosisMycobacterium tuberculosisTuberculosis (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 infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease:
Gram-negative bacilliBacilliShigella (e.g., PseudomonasPseudomonasPseudomonas 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)
FungiFungiA 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, including AspergillusAspergillusA genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae.Echinocandins and CandidaCandidaCandida 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-positiveGram-PositivePenicillins, spore-forming bacillusBacillusBacillus 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 vaccineVaccineSuspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases.Vaccination (not recombinant)
Varicella vaccineVaccineSuspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases.Vaccination
MMRMMRA DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base.Lynch syndrome
Kidney Transplantation
Epidemiology
Most common solid organ transplantation
About 40% of donated kidneysKidneysThe 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: Anatomy 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 failureRenal failureConditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate.Crush Syndrome
No clear age limitLimitA value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lungInvasive Mechanical Ventilation: Individuals > 70 years may be candidates if they have good overall health and a reasonably long life expectancyLife expectancyBased on known statistical data, the number of years which any person of a given age may reasonably expected to live.Population Pyramids.
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
Absolute: severe heart disease, cancer
Relative: poorly controlled diabetesDiabetesDiabetes 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
Medical therapy before transplantation
DialysisDialysisRenal 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).Peritoneal Dialysis and Hemodialysis 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 dialysisDialysisRenal 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).Peritoneal Dialysis and Hemodialysis.
Procedure
Deceased-donor kidney transplantation:
Kidney is surgically removed with the renal blood vessels and the ureter.
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 veinRenal veinShort thick veins which return blood from the kidneys to the vena cava.Glomerular Filtration then artery is anastomosed in the recipient.
Recipient is hydrated and given furosemideFurosemideA benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency.Loop Diuretics plus mannitolMannitolA diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity.Osmotic Diuretics.
Transplanted kidney is reperfused.
Ureter is implanted/sewn into the bladderBladderA musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination.Pyelonephritis and Perinephric Abscess.
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:
FeverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
AnuriaAnuriaAbsence of urine formation. It is usually associated with complete bilateral ureteral (ureter) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present.Acute Kidney Injury or oliguriaOliguriaDecreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age.Renal Potassium Regulation
Acute:
FeverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
Increased creatinine
HypertensionHypertensionHypertension, 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
UrinalysisUrinalysisExamination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically.Urinary Tract Infections (UTIs) in Children with protein, lymphocytesLymphocytesLymphocytes 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: Histology, and renal tubular cells in sediment
Chronic:
ProteinuriaProteinuriaThe presence of proteins in the urine, an indicator of kidney diseases.Nephrotic Syndrome in Children with or without hypertensionHypertensionHypertension, 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 syndromeNephrotic syndromeNephrotic 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 nephropathyDiabetic nephropathyKidney injuries associated with diabetes mellitus and affecting kidney glomerulus; arterioles; kidney tubules; and the interstitium. Clinical signs include persistent proteinuria, from microalbuminuria progressing to albuminuria of greater than 300 mg/24 h, leading to reduced glomerular filtration rate and end-stage renal disease.Chronic Diabetic Complications or hypertensionHypertensionHypertension, 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
BiopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma shows chronic interstitial fibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans and tubular atrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation.
Cancer
Kidney transplant recipients are 10–15 times more likely to develop cancer.
LymphomaLymphomaA general term for various neoplastic diseases of the lymphoid tissue.Imaging of the Mediastinum: 30 times more common than in the general population (but overall incidenceIncidenceThe number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time.Measures of Disease Frequency is still low)
SkinSkinThe 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.Skin: Structure and Functions cancer: increased incidenceIncidenceThe number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time.Measures of Disease Frequency 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).
End-stage heart failureHeart FailureA heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction.Total Anomalous Pulmonary Venous Return (TAPVR) (New York Heart Association functional class IV)
Intractable life-threatening arrhythmias unresponsive to other therapies
Restrictive and hypertrophic cardiomyopathiesCardiomyopathiesA group of diseases in which the dominant feature is the involvement of the cardiac muscle itself. Cardiomyopathies are classified according to their predominant pathophysiological features (dilated cardiomyopathy; hypertrophic cardiomyopathy; restrictive cardiomyopathy) or their etiological/pathological factors (cardiomyopathy, alcoholic; endocardial fibroelastosis).Cardiomyopathy: Overview and Types with heart failureHeart FailureA heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction.Total Anomalous Pulmonary Venous Return (TAPVR)
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
Absolute contraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation:
Life expectancyLife expectancyBased on known statistical data, the number of years which any person of a given age may reasonably expected to live.Population Pyramids < 2 years despite transplantation
Irreversible pulmonary hypertensionPulmonary HypertensionPulmonary 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 use disorder, including tobacco, within 6 months
Relative contraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation:
Age > 70 years
ObesityObesityObesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity: body mass indexBody mass indexAn indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese).Obesity > 35
DiabetesDiabetesDiabetes 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 mellitus with hemoglobin A1c > 7.5% despite optimal effort
Irreversible renal dysfunction with glomerular filtration rateGlomerular filtration rateThe 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 embolismPulmonary EmbolismPulmonary 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
Female sexSexThe totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism.Gender Dysphoria (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 marrowBone marrowThe soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Bone Marrow: Composition and Hematopoiesis transplantation)
Indications:
Hematologic cancers:
Leukemias
Lymphomas
Multiple myeloma
Nonmalignant hematologic disorders:
Aplastic anemiaAplastic AnemiaAplastic 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 syndromesMyelodysplastic SyndromesMyelodysplastic 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
May be used to restore bone marrowBone marrowThe soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Bone Marrow: Composition and Hematopoiesis after high-dose chemotherapyChemotherapyOsteosarcoma
Procedure:
Can be autologous (no contraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation) or allogeneic (contraindicated > age 50 or with significant comorbiditiesComorbiditiesThe presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.St. Louis Encephalitis Virus)
Stem cells can be harvested from:
Bone marrowBone marrowThe soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Bone Marrow: Composition and Hematopoiesis: 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 lineIv LineCentral Venous Catheter.
Umbilical cordUmbilical cordThe flexible rope-like structure that connects a developing fetus to the placenta in mammals. The cord contains blood vessels which carry oxygen and nutrients from the mother to the fetus and waste products away from the fetus.Placenta, Umbilical Cord, and Amniotic Cavity blood: newer procedure, HLA matching less crucial; higher percentage of naive T cellsT cellsLymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.T cells: Types and Functions increases the risk of reactivating CMV or EBVEBVEpstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency.Epstein-Barr VirusinfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease.
Complications:
Rejection
Failure
Acute graft-versus-host diseaseGraft-versus-host diseaseThe clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the graft vs host reaction.Transfusion Reactions (GVHD)
Lung transplantation
Indications:
Chronic obstructive pulmonary diseasePulmonary diseaseDiseases involving the respiratory system.Blastomyces/Blastomycosis (COPDCOPDChronic 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))
Lung-heart transplantation in combination for lung disorders with irreversible severe ventricular dysfunction
PrognosisPrognosisA prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations.Non-Hodgkin Lymphomas:
1-year survival: 84%
5-year survival: 34%–46% (higher with primary pulmonary hypertensionprimary pulmonary hypertensionIncreased pulmonary arterial pressure in the absence of underlying heart or lung disease.Pulmonary Hypertension and pulmonary fibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans; lower for COPDCOPDChronic 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))
Lung-heart transplantation has an 80% survival rate at 1 year for individuals and grafts.
PancreasPancreasThe 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: Anatomy transplantation
Indications:
Type 1Type 1Spinal Muscular AtrophydiabetesDiabetesDiabetes 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 with renal failureRenal failureConditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate.Crush Syndrome
> 90% of pancreasPancreasThe 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: Anatomy transplantations also include a kidney.
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation:
Age > 55 years
Significant cardiovascular disease
PrognosisPrognosisA prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations.Non-Hodgkin Lymphomas:
Recipient survival > 95% at 1 year
Graft survival > 85% at 1 year
Recipients no longer need insulinInsulinInsulin 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:
HandHandThe 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: Anatomy
Extremity
Face
SkinSkinThe 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.Skin: Structure and Functions grafts
CartilageCartilageCartilage 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: Histology transplantation
BoneBoneBone 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. Bones: Structure and Types transplantation
Adrenal autografting
Corneal transplantation
Indications:
Bullous keratopathy
KeratoconusKeratoconusA noninflammatory, usually bilateral protrusion of the cornea, the apex being displaced downward and nasally. It occurs most commonly in females at about puberty. The cause is unknown but hereditary factors may play a role. The -conus refers to the cone shape of the corneal protrusion. .Anomalies of the Cornea
Herpes simplexHerpes SimplexA group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection.Congenital TORCH InfectionskeratitisKeratitisInflammation of the cornea.Herpes Simplex Virus 1 and 2
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 anesthesiaGeneral anesthesiaProcedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery.Anesthesiology: History and Basic Concepts or local anesthesiaAnesthesiaA state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.Anesthesiology: History and Basic Concepts plus IV sedation
Complications:
Rejection: rate of 10%; can be treated
Other complications: infection, glaucomaGlaucomaGlaucoma 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 errorsRefractive errorsBy 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
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
Wood, K.J., Goto, R. (2012). Mechanisms of rejection: current perspectives. Transplantation 93:1–10. 10.1097/TP.0b013e31823cab44
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
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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