TRANSPLANT Flashcards
Class I HLA antigen are found on what cells
all nucleated cells
Class II HLA are found on wet cells
antigen presenting cells: Macrophage Dendritic cells B. lymphocytes Monocytes
corticosteroid
use, mechanism, side effects
maintenance, rejection
IL1 released
Posttransplant diabetes, hypertension, osteonecrosis, Cushing’s
azathioprine
use, mechanism, side effects
maintenance
Azathioprine (purine) block
Inhibits nuclaic acid syntheis (DNA) - the we will do him suppressing proliferation of activated B and T-cells
bone marrow depression, hepatic venoocclusive disease, pancreatitis, RBC achalasia, arthralgia
cyclosporine
use, mechanism, side effects
maintenance
C=C CALCINEURIN cyst is in
L2 secretion and formation inhibition
Inhibits calcineurin
Nephrotoxic-interstitial fibrosis and arteriolar lesions blood Hepatotoxicity Hypertension Hyperkalemia Hirsutism Gingival hyperplasia Tremors Headache
drug inhibits IL-2 synthesis
tacrolimus
tacrolimus
use, mechanism, side effects
(FK506, Prograft)
maintenance refractory rejection (rescue)
IL-2 synth / production
Nephrotoxic
Glucose intolerance
Neuro toxic
hypertension
mycophenolate mofetil
use, mechanism, side effects
(CellCept)
Maintenance
Inosine monophosphate dehydrogenase inhibition
Neutropenia
GI
Sirolimus
use, mechanism, side effects
maintenance
TOR inhibitor
( target of rapamycin)
THROMBOCYTOPENIA
neutropenia
Impaired wound healing
Dyslipidemia
OKT3
use, mechanism, side effects
(Monoclonal antibody)
treatment of rejection
Depletion of T cells
receptors surface T-cell
fever/chills
Pulmonary edema
LYMPHOPROLIFERATIVE disorder
Polyclonal anti-lymphocyte
use, mechanism, side effects a
induction therapy
treatment of rejection
Decreased lymphocytes
ANAPHYLAXIS Leukopenia Thrombocytopenia LYMPHOPROLIFERATIVE disorder cytokine release syndrome Fever
Daclizumab and Basiliximab
induction therapy
IL2 receptor blockade
Minimal
how does cyclosporine inhibit T-cell activation
inhibit calcineurin As primary mechanism secondary effect is IL-2
University of Wisconsin solution
raffinose
hydroxyethyl starts
lactobionate
rejection and start on postoperative day 2
accelerated acute rejection
Hyperacute rejection
minutes to hours
Antibody mediated
Preformed antibiotics to ABO blood blood group or HLA antigens
In the field and necrosis Vascular thromboses Flaccid Cyanotic anuric PMNs packed and peri-capillary
Accelerated acute rejection
Days
Memory response to prior sensitization
Rare difficult to control
Early graft loss
Cellular and antibody mediated injury
More, and went recipient has been sensitized by previous antigen exposure
Kidney-oliguria
disseminated intravascular coagulation
Thrombocytopenia
Hemolysis
Swollen organ
Tender
Congestive
Arterial necrosis
Perry vasculitis
Glomerular basement membrane CD4 deposition
acute rejection
days to months
Predominantly cell-mediated:
Lymphocytes
Chronic rejection
slow progressive of months to years
Immune and nonimmune mechanisms involved
Vascular intimal hyperplasia
Lymphocytic infiltration
Atrophy
Fibrosis
Delayed type hypersensitivity
Chronic ischemia
Antibiotic formation
Causing her inhibitor toxicity is a risk
TGF beta may be a risk
the most significant side effect of s sirolimus
thrombocytopenia
Other side effects:
Neutropenia
Impaired wound healing
Increased lipids
cyclosporine levels are affected by what drugs
p450 complication
Inducers of the P450 system
Phenytoin ramp up p450
Inhibitors or competitive ears with the P450 system
Inhibitors or competitive ears with the P450 system
Erythromycin
Cimetidine
Ketoconazole
Fluconazole
Living donor bowel is removed for transplant
How much length
was blood supply
mid ileum to distal ileum-the good part
This is about 200 cm
ileocolic vessels
Acceptable cold ischemia time for kidney
36-40 hours
left delayed graft function
Acceptable cold ischemia for pancreas
less than 24 hours
left duodenal leaks due to pancreatitis
Acceptable cold ischemia for liver
less than 16 hours
Associated with left hepatic dysfunction
Biliary complications
The acceptable ischemia time the heart and lung
less than 6 hours! Cold ischemia not an option
Most appropriate treatment for lymphocele after renal transplant
Laparoscopic or open peritoneal window
another option is percutaneous catheter with or without sclerotherapy - associated with some risk of recurrence or infection
Not percutaneous aspiration
Describe complications associated with lymphocele after renal transplant
Easily over 2 weeks after transplant
Mass effect:
Ureter
Iliac pain
Allograft renal artery
Hypertension
Unilateral leg swelling
Elevated creatinine
Diagnoses:
Ultrasound for confirmation
the major cause of death after Renal transplantation
cardiovascular:
Myocardial infarction
Stroke
less common causes of death following renal transplantation
sepsis 3%
Malignancy 2%
The leading cause of graft loss following renal transplantation
recipient death-usually cardiovascular
Second most common past chronic allograft nephropathy-slow deterioration of graft function
Graft failure due to surgical technique percentage
2%
Back table preparation for donor pancreas prior to transplantation includes
Placement of arterial graft to connect the splenic and superior mesenteric arteries
the most common cause of liver failure in patient undergoing liver transplantation
hepatitis C United States
Left commonly hepatitis B
Milan criteria
single lesion less than 5
One-3 tumors each less than 30
Absence of vascular or lymphatic invasion
indications for liver transplant in acute liver failure
Fulminant hepatic failure different criteria and chronic:
acetaminophen:
PH less than 7.3
INR greater than 6.5
Creatinine greater than 3.4
NON--acetaminophen: INR greater than 6.5 Creatinine greater than 3.4 age less than 10 or greater than 40 non-a non-b hepatitis ( type C) Duration of jaundice before encephalopathy greater than 7 days
Defined fulminant hepatic failure
hepatic encephalopathy and profound coagulopathy short after the onset of symptoms such as jaundice and patient’s WITHOUT pre-existing liver disease
Most common causes of fulminant hepatic failure
United States in West acetaminophen Acute hepatitis B Hepatic toxins Wilson's disease Often idiopathic
Component of the MELD score
INR
Creatinine
Total bilirubin
Most, vascular complication after liver transplantation
Hepatic artery thrombosis
Most common early event
May cause ischemia to common bile duct with diffuse biliary leak or stricture
3-5% adult
5-10% children
Increase with partial transplant
Initial diagnosis Doppler
Treatment: Urgent reexploration Thrombectomy REVISION of anastomosis May require re\re transplant is extensive necrosis
Later events:
Stenosis
Pseudoaneurysm
posttransplant lymphoproliferative disorder as caused by, Presentation, treatment
Epstein-Barr he
asymptomatic is possible
mononucleosis syndrome
Hepatitis
Posttransplant lymphoproliferative disorder:
may present as localized tumor of the lymph nodes or GI tract or rarely rapidly progressive diffuse fatal lymphomatous infiltration
Most common indication for pediatric liver transplantation
Biliary atresia
Others:
Sclerosing cholangitis
Familial cholestasis syndrome
Lack of intrahepatic bile ducts (ALAGILLE syndrome
Metabolic disorder:
Alpha-1 antitrypsin deficiency-most common
Tyrosinemia - hereditary enzyme deficiency so cannot degrade tyrosine-results and cirrhosis with greatly increased risk of hepatocellular carcinoma
Wilson’s disease
Up for an anti-traction deficiency
Metabolic disorder
Presentation:
Jaundice as a neonate but then resolves often
Subsequent presentation:
Childhood or early less than
Cirrhosis
Portal hypertension
Wilson’s disease
Autosomal recessive
Proper cannulation in the liver, CNS, kidneys, eyes, other organs
May present form and, supplements, chronic liver failure
after transplantation, patient’s are at increased risk for which malignancy
Kaposi's sarcoma Skin cancers Lymphoproliferative disease Gynecologic cancer Urologic cancer
which transplant recipients are at the most increased risk for cancer
kidney 1%
Small bowel and multiple visceral transplants 5-6% of
5 year graft survival rate after renal transplantation
75-80%
60-65 cm
Main advantage of bladder drainage with pancreaticoduodenal transplant
Direct measure and enzyme activity in urine to follow exocrine function with urine amylase
serum amylase is less sensitive
Urine amylase decreases before hyperglycemia recurrence
Leak rate is the same for enteric anastomosis
Disadvantage of bladder drainage with pancreaticoduodenal transplant
Bladder leak is much more severe when compared to bile leak
Dehydration
Acidosis from loss of a clotted pancreatic secretions into the urine
Bladder infection, hematuria, stones, urethritis
10-20% of the bladder drained graft recipient are converted to an enteric drainage
Advancement of the enteric drainage for pancreatic transplant
More physiologic
decreased long-term complications
Powders rejection effect simultaneous pancreas and kidney transplant
almost always affects both kidney and pancreas
Therefore creatinine level can be used as a marker for rejection of pancreas
Most centers use enteric drainage for simultaneous pancreas and kidney transplant
His kidney and pancreas are from different donors or if there is pancreas transplant alone bladder drainage is preferred
absolute contraindication for orthotopic cardiac transplant
severe hypertension Advanced age over 65 Cardiac trauma Coronary artery disease medical noncompliance renal insufficiency
Active infection does not equal uncontrolled infection
Contraindications for organ specific donation
Medical problems Malignancy other than primary brain tumor ( or skin cancer which can be treated with excision) Prolonged cardiac arrest Uncontrolled infection HIV?
And a liver be transplanted with hepatitis B positive
yes
IF kidneys are normal
Recipient appropriate serologic and viral profile to oppose minimal risk
Hepatitis C positive liver donation
Yes
normal liver biopsy required
Can organ to be donated from patient’s with high risk factors
no except an emergency situation Sexual behavior Intravenous drug Correctional institution
expanded criteria for kidney donation
old and 60 with a history of hypertension, cerebrovascular accident as cause of death
And final procurement creatinine greater than 1.5
mild hypertension may not be a contraindication though severe hypertension is absolute contraindication
age as a contraindication for donation
relative
contraindications for kidney donation
pre-existing renal disease
Contraindication for pancreas donation
diabetes
contraindications for heart lung donation
cardiac trauma
Coronary artery disease
Pneumonia
age when donor is considered older - and workup needed
35-40
may require a coronary catheterization rule out significant and cardiac disease
contraindications for lung donation
pneumonia
Pulmonary trauma
Respiratory compromise
may require bronchoscopy for inspection evaluation
heterotopic cardiac transplant
patient’s native right heart continues to work against pulmonary hypertension - option sometimes used when patient has pulmonary hypertension
No heart supplies systemic circulation
Absolute contraindications for DONATION of heart
prolonged cardiac arrest
Carbon monoxide greater than 20%
Significant smoking history
most common cause of renal failure and United States
Diabetes
Best test to monitor the development of acute rejection and cardiac transplant
Endomyocardial biopsy
Current indications the patient clinically and for
absolute contraindications for renal transplant in a patient with chronic renal failure
chronic active hepatitis
Recent operation for colon cancer-recommend 5 year disease-free interval
Relative contraindications for renal transplant in patient with chronic renal failure
sickle cell disease
HIV?
absolute contraindications for kidney donation
age over 70
Chronic renal insufficiency
Intravenous drug use
Severe hypertension
which organ is ABO compatibility less important pretransplant
liver
criteria for brain death
clinical diagnosis only
No barbiturates
hypothermia not dead until warm and dead
acute metabolic derangement
No spontaneous respiration
Absent pupillary reflex
Absent corneal reflex
Apnea sustained with disconnection ventilator
transplant team is pronounced patient ( not transplant surgeon) the
confirmatory tests cannot be used for final diagnoses: cerebral angiography electroencephalography transcranial Doppler cerebral scintigraphy
preservation of bone skin dura
cryopreservation
Matching required bone skin dura
none ABO not required
how is cross-matching done
recipient screened for preformed HLA antibodies
screening:
Donor lymphocytes mixed with recipient serum to evaluate if there are recipient antibodies combined to donor lymphocytes
crossmatch:
Final test
Donor lymphocyte mixed with the patient’s serum
Absolute contraindication to kidney transplant crossmatch results
a positive T-cell CDC crossmatch
Isograft
identical monozygotic twin
Does not require immunosuppression
organ besides bone skin dura the does not require immunosuppression
the eyes are in no privileged site
because no lymphatic drainage
or ejection does occur palpable steroid used a
Percentage crossmatch and family genetics
each recipient shears one of 2 haplotype with each parent
25% chance assuring both haplo types: “ HLA identical”
25% chance of not showing any haplotype
50% chance of sharing one haplotype
along the most renal transplant recipients weight before organ is available
3-7 years
less than six-month weight time on dialysis 2 times better graft survival than waiting over 2 years
What is arterial inflow most commonly for renal transplant
external iliac
Which side is kidney transplant done on
right side external iliac vessels are more superficial
what side is preferred to donate kidney from
left to longer vein
How do you handle multiple renal vessels
extra artery must be used because of segmental perfusion-use epigastric vessel is extra inflow
Can tie off extra vein
most common complication after renal transplant
wound infection
4-7 days
Thrombosis of renal vein posttransplant
immediate exploration
Symptoms of decreased urine output
and should renal transplant patient received prophylactic antibiotics post transplant
yes:
Bactrim
Antifungal
CMV infection
Fever
Weakness
GI bleed
Esophagitis
Treatment
Valganciclovir
Artery inflow for pancreatic transplant
splenic
Superior mesenteric using iliac artery Y graft (iliac artery from the recipient)
doses portal enteric drainage for pancreatic transplant increased risk of pancreas thrombosis
no
and no increased risk of infection
urinary tract infections are higher with bladder drainage
Liver transplantation for hepatocellular carcinoma
Stage I-2
T1 or T2
No invasion of larger vascular structure
No extrahepatic disease
is crossmatch required for liver transplant
no
liver transplant in adults which lobe is donated from living donor
right
liver transplant in children which lobe was donated from living donor
left - because smaller
Specific indications for cardiac transplant
cardiomyopathy Ischemic cardiac disease Postpartum cardiomyopathy Terminal cardiac valvular disease Hypertensive cardiomyopathy
What can help bridge cardiac failure patient’s transplant
ventricular assist device
match requirement for an cardiac transplant
ABO
Tissue typing not usually done preoperatively
Under 6 hour preservation time
Cancers common after cardiac transplant
skin cancer
Posttransplant lymphoproliferative disorder
Lung cancer
heart-lung transplant
performed when
severe pulmonary hypertension with cardiac disease
associated with congenital heart disease: Eisenmenger’s
signs of acute and chronic rejection of lung transplant
bronchiolitis
one year survival rate for a heart-lung transplant recipients
63%
indicators for need of lung transplant
FEV1 less than 25%
PCO2 greater than 55
Increased pulmonary artery pressure
can patient with lung cancer a lung transplant
no
Does bilateral lung transplant have better survival than single lung
yes
what is likely to compromise single lung transplant
emphysema-air trapping in need of long compresses transplant lung
Cystic fibrosis
History of chronic wound infection
Contraindications for bowel transplant
uncontrolled infection
Uncontrolled malignancy
technical aspects of bowel transplant
heterotopic were orthotopic
anastomosis may be brought up to abdominal wall at ileostomy to allow observation and biopsy monitor rejection or ischemia
venous anastomosis easily to recipient cava but may be due to portal vein
arterial anastomosis to abdominal aorta
survival after bowel transplant
80% one year
67% 3 years
54% 5 years
43% 10 years
sirolimus most common complications
The most common adverse effects of sirolimus are hyperlipidemia and myelosuppression.
Postmarketing studies have revealed a number of unforeseen adverse effects, including impaired wound healing and possibly proteinuria, edema, pneumonitis, and thrombotic microangiopathy. The incidence of abnormal wound healing with sirolimus is 1% to 12%.
CMV infection after solid organ transplantation
one of the most common viral infections,
Presentation of early CMV colitis can be mild and nonspecific, including mild diarrhea, associated fever, and abdominal pain.
A more reliable diagnosis can be made via early and rapid colonoscopy with mucosal biopsies and documentation of the typical colonoscopic and histopathologic findings compatible with CMV colitis.
Although serology is helpful in the diagnosis, sometimes it is inadequate.
Serum CMV IgM and CMV pp65 antigenemia may be negative.
Standard antiviral (ganciclovir, foscarnet) treatment is recommended.
Operation (colectomy) is indicated for life-threatening complications (perforation, bleeding, ischemia) or lack of response to medical management.
Organ transplant recipients are at particular risk for what skin cancer
Organ transplant recipients are at particular risk for squamous cell carcinoma (SCC).
Heart transplant patients have a threefold risk of NMSC over renal transplant recipients who have more NMSC than liver recipients. Cancers in other organ systems are also more common in OTRs compared with nonimmunosuppressed age-matched controls; esophagus [RR 4.7], liver [RR 4.8], cervix [RR 4.6], bladder [RR 5.1], and thyroid [RR 4.5].
The incidence of de novo tumor occurrence is 7% after both kidney and liver transplantation. The median elapsed time from transplant to the diagnosis of de novo malignancy was 45 months for kidney and 37 months for liver transplants. Skin cancers were the most common in renal recipients, while gastroenteric cancers were more frequently seen in liver transplants
In renal transplant recipients, the mean incidence per year of NMSC is 8%, comprised equally by SCC and basal cell carcinoma (BCC) and less so by Bowen’s disease.
Cancers of the skin and lips comprise 40% of all cancers arising after transplantation.
type of cancer more commonly seen with liver transplant
gastroenteric cancers were more frequently seen in liver transplants
The definition of organ trafcking
the recruitment, transport, transfer, harboring or receipt of persons, by means of the threat or use of force or other forms of coercion, of abduction, of fraud, of deception, of the abuse of power, of a position of vulnerability, of the giving or receiving of payments or benefits to achieve the consent of a person having control over another person, for the purpose of exploitation by the removal of organs, tissues, or cells for transplantation.
Transplant tourism a
is a phrase often used interchangeably with organ trafficking but…
some medical tourism that entails the travel of transplant recipients or donors across national borders is not organ trafficking.
Examples of legal and appropriate transplant tourism include travel of a related donor and recipient pair from countries without transplant services to countries where organ transplantation is performed, or persons traveling across borders to donate or receive a transplant via a relative.
The United Network for Organ Sharing (UNOS) recently defined transplant tourism as:
the purchase of a transplant organ abroad that includes access to an organ while bypassing laws, rules, or processes of any or all countries involved.
reimbursement for personal expense is allowed for transplant donors
no!
Including no reimbursement for personal traveled stents, lost wages, housing…
followup care for donors is whose responsibility
is the responsibility of the donor