Updated: 1/17/2019

Transplant

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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

 

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Questions (10)
Lab Values
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/L
Female: 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/mL
Female: 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/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative 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/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 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/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 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/min
Female: 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 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 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
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(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

8%

(7/91)

2

Graft cyanosis

4%

(4/91)

3

Low urine output with evidence of blood

18%

(16/91)

4

Histological evidence of arteriosclerosis

65%

(59/91)

5

Histological evidence of vascular damage

1%

(1/91)

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(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

6%

(13/207)

2

Glomerular destruction

7%

(14/207)

3

Tubular atrophy

11%

(22/207)

4

Graft arteriosclerosis

15%

(31/207)

5

Glomerular crescents

60%

(125/207)

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(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

15%

(41/280)

2

Recipient T-cells

60%

(167/280)

3

Preformed recipient antibodies

11%

(30/280)

4

Donor antibodies

4%

(11/280)

5

Deposition of antibody immune complexes

8%

(21/280)

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(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

7%

(3/41)

2

Lymphocytic infiltrate of the tubules and interstitium

66%

(27/41)

3

Drug precipitation in the renal tubules

10%

(4/41)

4

Granular immunofluorescence around the glomerular basement membrane

10%

(4/41)

5

Crescent formation in Bowman’s space

5%

(2/41)

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(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

8%

(2/25)

2

Type II hypersensitivity reaction

56%

(14/25)

3

Type III hypersensitivity reaction

4%

(1/25)

4

Type IV hypersensitivity reaction

4%

(1/25)

5

Graft-versus-host disease

28%

(7/25)

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(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

52%

(21/40)

2

Recipient T-cells

12%

(5/40)

3

Donor B-cells

8%

(3/40)

4

Recipient B-cells

2%

(1/40)

5

Recipient antibodies

18%

(7/40)

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