Transplant - Immunology - Medbullets Step 1

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

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

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