Organ Transplantation & Immunosuppressants Flashcards
Describe donor characteristics for organ transplantation
Donor Characteristics:
Doner has to have respirations and HR intact (may be artificial - on ventilator)
Kidneys still need to be functioning
Fixed, dilating pupils; no reflexes; brain dead
No chronic kidney disease
No cancer (except primary brain tumors - bc do not metastasize out of the brain)
No sepsis or HIV or other infectious processes
Describe recipient characteristics for organ transplantation:
Recipient Characteristics
End-stage disease in transplantable organ
Failure of conventional therapy
Absence of untreatable malignancy or irreversible infection
Absence of disease that would attack transplanted tissue
Ability of patient to survive procedure
Psychosocial characteristics
Identify criteria for brain death
What is considered brain dead?
No response to painful stimuli
No spontaneous movement
No spontaneous respirations
No cranial nerve response
EEG, cerebral angiography, apnea test (take patient off ventilator to see if CO2 levels rise and if patient doesn’t take breath)
Status unchanged for 6 hours
Describe absolute contraindications for transplantation
Active alcohol, drug, or tobacco abuse
Active infection
Acute pulmonary embolism
Bleeding disorders
AIDS
Psychopathology
Inability to comply with therapeutic regimen
Inability to understand risks involved
Recent malignancy
Severe damage in another organ
Describe relative contraindications for transplantation
Cachexia (less than 80% ideal body weight)
HIV
Lack of functioning psychosocial support
Morbid obesity (over 140% ideal body weight)
Severe osteoporosis
Understand role of immune system in transplantation
Histocompatibility - minimize rejection
ABO: blood type
HLA: human leukocyte antigen
Describe the PRA test
This test is done on patients that are going to be listed on the organ transplant list
Test detects performed HLA antibodies
From pregnancy, blood transfusion, previous transplantation - if pt has not had any of these then the body has not been exposed to any other HLA proteins
The more HLA a patient is exposed to, the more antibodies the body has developed, it could be much more difficult to find an organ
Can restrict access to transplantation
High PRA means that the body is reacting to a lot of HLA and more likely to reject an organ
Given as a % - 50% means that the patient’s serum reacts with 50% of the donors in the panel
0-19: means you react with none to very few HLA proteins - that is 60% of patients who waited 490 days
20-79: means you have preformed antibodies - that is 21% of patients who waited 1042 days
80+: means very restricted to to organs the body can accept - that is 19% of patients who waited 2322 days
hyperacute rejection
minutes to hours after transplant.
Kidney is most susceptible. Due to preformed antibodies to organ HLA. Organ must be removed immediately
acute rejection
highest risk in the first 3 months, risk declines after 1 year. Must be treated promptly. T-cell mediated.
chronic rejection
long-term loss of organ function due to fibrosis of vasculature, due to poorly understood chronic inflammatory and immune response.
physiologic dosing and effects of glucocorticoids
Metabolic: influence metabolism of carb, proteins, and fats. Elevates blood glucose levels (this is why we check glucose often even if pts are not diabetics), diverts proteins to form glucose
Cardio: most noticeable when levels are inadequate, capillaries are more permeable, vasoconstriction is suppressed, blood pressure falls
Stress Response: can be life saving, body produces a large amount of glucocorticoids to prevent bleeding out. Large quantities secreted during physiologic or psychological stress. Help maintain BP, glucose levels
F&E: similar in structure to aldosterone (mineralocorticoid). Can promote retention of sodium and water, promote excretion of K+. Also, important in maturation of lungs in neonates and premature infants.
pharmacologic dosing and effects of glucocorticoids
When giving glucocorticoids in super high doses, we are trying to provide anti-inflammatory effects and immunosuppressant
Inhibit synthesis of chemical mediators that are responsible for inflammation in our immune system
Suppress infiltration of phagocytes, so damage form release of lysosomal enzymes is averted
Suppressed proliferation of lymphocytes
These 3 effects together is what we are trying to achieve
However, there are really bad side effects with such high doses
Understand the negative feedback loop for endogenous glucocorticoid production
Normally, hypothalamus release CRH to anterior pituitary causing ACTH to release, which stimulates adrenal cortex to release glucocorticoids. Then, when glucocorticoids are at high levels, there will be feedback inhibition that will tell the hypothalamus and anterior pituitary to stop producing hormones related to glucocorticoids because body has enough.
Describe side effects of high-dose glucocorticoids
Adrenal insufficiency - adrenal medulla will stop making glucocorticoids because there is so many, there will be atrophy of the adreal cortex.
Need to taper off so adrenal medulla can start to support the body
In trauma situation, body won’t be able to pump any glucocorticoids
Metabolic: increased glucose production; diversion of proteins to make glucose; alteration in fat mobilization and distribution (buffalo hump, moon face)
Osteoporosis: ribs and vertebrae are most affected, can lead to pathologic fractures
Suppresses osteoblasts
Accelerates bone resorption by osteoclasts
Produce intestinal absorption of calcium - causing hypocalcemia, PTH increases, increased mobilization of calcium from bones
Glucocorticoids = terrible for bones
Describe action and adverse effects of cyclosporine (Sandimmune),
Class: Calcineurin inhibitor
MOA: inhibits an enzyme called calcineurin suppresses IL-2 and other cytokines, which is needed for T-cell proliferation. So, basically decreased T-cell production
AE: nephrotoxicity (75% of pts), infections (74% of pts), lymphomas, HTN, hirsutism, tremor
No grapefruit juice
