Snapshot A 60-year-old-man presents with nausea and vomiting to his primary care physician. Medical history is significant for a liver transplantation approximately 2 weeks prior to presentation. On physical examination there is scleral icterus and mild ascites. A liver biopsy shows lymphocytic infiltrates in the interstitium. (Acute rejection) Introduction Transplantation is a process by which cells, tissues, or organs (a graft) from the donor are transplanted into a host (or recipient) The immune system's ability to recognize and respond to foreign antigens bring challenges to transplantation There are several types of grafts autograft tissue is moved from one location to another in the same person e.g., skin graft and using the saphenous vein to replace a coronary artery the graft will not be considered foreign and thus will not require lifelong immunosuppresion syngeneic graft (isograft) tissue is transplanted from one genetically identical donor to the host e.g., transplantation between monozygotic twins allograft tissue is transplanted from one genetically different donor of the same species to the host e.g., kidney transplant xenograft tissue is transplanted from a donor of a different species to the host e.g., porcine heart valve Transplant Rejection Transplant Rejection Rejection Type Pathogenesis Comments Hyperacute Type II hypersensitivity reaction where pre-existing recipient antibodies attack the donor antigen resulting in complement activation endothelial damage inflammation thrombosis Time minutes to hours Findings capillary thrombosis which prevents graft vascularization Acute Cellular rejection type IV hypersensitivity reaction where recipient CD8+ T-cells react to donor antigens after activation by antigen presenting cells Humoral rejection just like in hyperacute rejection; however, the antibodies are formed after transplantation occured Time weeks to months Findings graft vessel vasculitis with lymphocytic infiltrates Chronic Type II and IV hypersensitivity reaction secondary to CD4+ T-cells responding to the host's antigen presenting cells Time months to years Findings cytokine secretion after T-cell activation leads to smooth muscle proliferation interstitial fibrosis parenchymal atrophy Graft-versus-host disease Type IV hypersensitivity reaction secondary to the donor's T-cells attacking the recipient's cells leading to organ dysfunction Time variable Findings maculopapular rash jaundice diarrhea hepatosplenomegaly Tissue Compatibility Testing ABO blood typing Tissue typing used to see if HLA antigens match and focuses on HLA-A HLA-B HLA-DR References
QUESTIONS 1 of 9 1 2 3 4 5 6 7 8 9 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + (M1.IM.77) A physician is describing a case to his residents where a kidney transplant was rapidly rejected by the recipient minutes after graft perfusion. The physician most likely describes all of the following manifestations EXCEPT? Review Topic QID: 100498 1 Graft mottling 7% (6/84) 2 Graft cyanosis 5% (4/84) 3 Low urine output with evidence of blood 18% (15/84) 4 Histological evidence of arteriosclerosis 64% (54/84) 5 Histological evidence of vascular damage 1% (1/84) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 (M1.IM.18) A 32-year-old Caucasian female required a kidney transplant 3 years ago. She presents with elevated creatinine levels (2.6 mg/dl) and an elevated blood pressure (160/90 mmHg). A biopsy is taken of the transplanted kidney. Following histological findings, a diagnosis of chronic graft rejection is made. Which of the following is NOT a likely finding? Review Topic QID: 100439 1 Interstitial fibrosis 7% (12/183) 2 Glomerular destruction 7% (12/183) 3 Tubular atrophy 11% (21/183) 4 Graft arteriosclerosis 15% (28/183) 5 Glomerular crescents 59% (108/183) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (M1.IM.52) Several weeks following a kidney transplantation, a 50-year-old Caucasian female presents for evaluation of the transplanted organ. Biopsy shows inflammation involving the endothelial cells of the kidney vasculature and the presence of mononuclear cells in the interstitium. Which cells are most likely responsible for this presentation? Review Topic QID: 100473 1 Donor T-cells 14% (37/256) 2 Recipient T-cells 59% (151/256) 3 Preformed recipient antibodies 11% (27/256) 4 Donor antibodies 4% (10/256) 5 Deposition of antibody immune complexes 8% (21/256) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 (M1.IM.76) A 62-year-old female with a history of uncontrolled hypertension undergoes kidney transplantation. One month following surgery she has elevated serum blood urea nitrogen and creatinine and the patient complains of fever and arthralgia. Her medications include tacrolimus and prednisone. If the patient were experiencing acute, cell-mediated rejection, which of the following would you most expect to see upon biopsy of the transplanted kidney? Review Topic QID: 101030 1 Sloughing of proximal tubular epithelial cells 9% (3/35) 2 Lymphocytic infiltrate of the tubules and interstitium 63% (22/35) 3 Drug precipitation in the renal tubules 11% (4/35) 4 Granular immunofluorescence around the glomerular basement membrane 9% (3/35) 5 Crescent formation in Bowman’s space 6% (2/35) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.IM.74) A 45-year-old female is undergoing renal transplantation for management of chronic renal failure secondary to glomerulonephritis. The transplant surgeon placed the donor kidney in the recipient and anastamosed the donor renal artery to the recipient's external iliac artery as well as the donor ureter to the recipient's bladder. After removing the clamps on the external iliac artery, the recipient's blood is allowed to perfuse the transplanted kidney. Within 3 minutes, the surgeon notes that the kidney does not appear to be sufficiently perfused. Upon further investigation, an inflammatory reaction is noted that led to clotting off of the donor renal artery, preventing blood flow to the transplanted organ. Which of the following best describes the pathophysiology of this complication? Review Topic QID: 106676 1 Type I hypersensitivity reaction 5% (1/22) 2 Type II hypersensitivity reaction 55% (12/22) 3 Type III hypersensitivity reaction 5% (1/22) 4 Type IV hypersensitivity reaction 5% (1/22) 5 Graft-versus-host disease 32% (7/22) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.IM.42) A 40-year-old male with a history of chronic alcoholism recently received a liver transplant. Two weeks following the transplant, the patient presents with a skin rash and frequent episodes of bloody diarrhea. A colonoscopy is performed and biopsy reveals apoptosis of colonic epithelial cells. What is most likely mediating these symptoms? Review Topic QID: 100463 1 Donor T-cells 54% (19/35) 2 Recipient T-cells 11% (4/35) 3 Donor B-cells 9% (3/35) 4 Recipient B-cells 3% (1/35) 5 Recipient antibodies 14% (5/35) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1