Transplant Flashcards
Hyperacute. Onset time?
Minutes to hours
Hyperacute. Etiology
Preformed RECIPIENT antibodies against graft antigens
Hyperacute. Morphology
Gross mottling and cyanosis;
Arterial fibrinoid necrosis and capillary thrombotic occlusion
Acute. Onset time?
<6 monts
Acute. Etiology
Exposure to donor antigens induces activation of naive immune cells.
Predominantly CELL-MEDIATED
Acute. Morphology
CELLULAR (MAIN): lymphocytic interstitial infiltrate and endothelitis’
HUMORAL (not that dominant): C4d deposition, neutrophilic infiltrate, necrotizing vasculitis
Chronic. Onset time?
6 months to years
Chronic. Etiology
Chronic low-grade immune response refractory to immunosupression;
Mixed cell-mediated and humoral (aka antibody mediated)
Chronic. Morphology
Vascular wall thickening and luminal narrowing;
Interstitial fibrosis and parenchymal atrophy
Gross mottling and cyanosis;
Arterial fibrinoid necrosis and capillary thrombotic occlusion. What stage?
Hyperacute
CELLULAR: lymphocytic interstitial infiltrate and endothelitis’
HUMORAL: C4d deposition, neutrophilic infiltrate, necrotizing vasculitis
Acute
Vascular wall thickening and luminal narrowing;
Interstitial fibrosis and parenchymal atrophy
Chronic
KIDNEY from UW case.
Following transplant, T cells are activated and recipient antibodies are created against ……………
created against graft HLA and other antigens.
Donor graft MHC antigens (human leukocyte antigens).
KIDNEY from UW case.
The activated T cells can initially cause ……… acute rejection, which is generally reversible via an increase in immunosuppression (eg, high-dose glucocorticoids).
cell-mediated
KIDNEY from UW case.
The activated T cells can initially cause cell-mediated ACUTE rejection, which is generally reversible via ……………………
an increase in immunosuppression (eg, high-dose glucocorticoids)
KIDNEY from UW case.
Chronic rejection represents progression of cell-mediated and antibody-mediated inflammation (eg, via …………..) to the point that irreversible renal damage takes place;
activation of complement and recruitment of neutrophils
KIDNEY from UW case.
Chronic rejection represents progression of cell-mediated and antibody-mediated inflammation (eg, via activation of complement and recruitment of neutrophils) to the point that ………….. renal damage takes place.
irreversible
KIDNEY from UW case.
Chronic rejection. Kidney macro and micro?
The kidney grossly decreases in size;
histopathology shows obliterative vascular wall thickening with tubular atrophy and interstitial fibrosis.
KIDNEY from UW case.
Chronic. What metabolic changes are present?
Increased sodium retention, declining renal function in chronic rejection is also commonly accompanied by new or worsening hypertension.
KIDNEY from UW case.
Chronic. What is present due to metabolic changes?
declining renal function –> sodium retention –> HYPERTENSION
KIDNEY from UW case.
What is predominant glomerular injury in chronic?
Glomerular injury in chronic rejection is predominantly ischemic (no crescent formation nothing)
KIDNEY from UW case. What infiltration would be seen in acute phase?
A dense, interstitial, mononuclear (lymphocytic) infiltrate is characteristic of acute allograft rejection, which is most often a primarily T cell–mediated process.
KIDNEY from UW case.
Use of immunosupressants. Acute rejection often <6month. Why may occur acute but beyond 6 months?
Can occur later in a patient in whom posttransplant immunosuppression has been stopped.
KIDNEY from UW case.
Vascular fibrinoid necrosis with capillary thrombotic occlusion occurs in …….
hyperacute
KIDNEY from UW case.
Whats the course and scope of hyperacute?
A rapid and profound form of antibody-mediated rejection caused by preformed antibodies to graft antigen
.
.
KIDNEY from UW case.
Acute mechanism?
This process is mostly cell-mediated and results from sensitization of recipient T cells to donor graft MHC antigens (human leukocyte antigens).
KIDNEY from UW case.
In acute what parameter starts to raise and is ,,asymptomatic’’?
asymptomatic rise in serum creatinine
KIDNEY from UW case.
In acute what symptoms may have?
low-grade fever, malaise, joint pains, and graft tenderness
KIDNEY from UW case.
What microscopic finding in acute?
dense lymphocytic infiltrate sometimes accompanied by vascular inflammation (endothelitis)
KIDNEY from UW case. Acute reversible or not?
reversible with high-dose GK.
KIDNEY from UW case. What combination helps to prevent acute rejection episodes?
Chronic immunosuppression with a calcineurin inhibitor–based regimen (eg, tacrolimus plus mycophenolate and low-dose prednisone) helps prevent acute rejection episodes.
KIDNEY from UW case.
If in acute stage happens Host-B cells sensitization, what is seen in histopathology?
Histology is expected to show deposition of complement (eg, C4d), neutrophilic infiltrate, and necrotizing vasculitis; this patient’s mononuclear (lymphocytic) infiltrate is consistent with a cell-mediated T-cell response.
KIDNEY from UW case. HUMORAL - more pronounced in acute or chronic?
In chronic. In acute more cell-mediated.
LUNG UW table. Hyperacute etiology.
PREFORMED HOST antibodies to donor ABO or HLA
LUNG UW table. Hyperacute patho?
Neutrophilic infiltration with fibrinoid necrosis and thrombosis
LUNG UW table. Acute etiology?
Cell-mediated response to mismathched donor HLA.
LUNG UW table. Acute patho?
Perivascular (small lung vessels) and submucosal (bronchiole) lymphocytic infiltrates
LUNG UW table. Chronic etiology?
Chronic, low-grade, mixed cell-mediated and antibody response to HLA antigen
LUNG UW table. Chronic patho?
Submucosal inflammation –> granulation, scarring and BRONCHIOLITIS OBLITERANS
LUNG. The severity and timing of the rejection depends on ……?
degree of difference between the donor and recipient MHC antigens in addition to other variables.
LUNG. Chronic lung transplant rejection is marked by submucosal …….. inflammation in the walls of the small airways
lymphocytic
LUNG. Subsequent ingrowth of granulation tissue into the lumen leads to ……… and ………..
Airway obstruction and obliteration (bronchiolitis obliterans)
LUNG. What symptoms is present in chronic?
Patients usually present with slowly worsening dyspnea and dry cough that begins months or years after transplantation.
LUNG. Chronic. What lung examination findings?
Lung examination may reveal end-expiratory squeaks or pops, and spirometry typically demonstrates airflow limitation (obstructive pattern) with a drop in FEV1.
LUNG. Hyperacute. Histo findings?
Histology generally shows fibrinoid necrosis with hemorrhage and ischemia (“white graft” reaction).
LUNG. Acute. Histo findings?
Histology generally shows perivascular mononuclear infiltrates in the small blood vessels of the lung, which can expand to include the alveolar walls.
LUNG. Restrictive allograph syndrome, what is it?
Restrictive allograft syndrome, a less common type of chronic lung transplant rejection, can result in fibrotic changes to the pleurae. However, pulmonary function tests would reveal a restrictive (reduced FVC), not obstructive, pattern.
GVHD. Most commonly occurs after ……
Bone marrow transplantation
GVHD. GVHD can also occur following transplantation of organs rich in …………. (eg, liver) or ……………….
GVHD can also occur following transplantation of organs rich in lymphocytes (eg, liver) or transfusion of non-irradiated blood.
GVHD. Why it manifest in patients? What patients?
Patients affected by GVHD are generally severely immunodeficient due to the primary disease process or as a result of immunosuppressive medications.
GVHD. Immunosupression/immunodef of the host allows …….
This allows immunocompetent donor T cells from the graft to survive and migrate into host tissues, where they recognize host MHC antigens as foreign and become sensitized. On activation, donor CD4+ and CD8+ T cells (not B cells) participate in host cell destruction.
GVHD. What cells participate?
donor CD4+ and CD8+ T cells (not B cells) participate in host cell destruction.
GVHD. What organs are most frequently affected?
Any organ may be a target of GVHD, but the skin, liver, and gastrointestinal (GI) tract are the most frequently affected.
GVHD. Skin signs?
Early signs of GVHD include a diffuse maculopapular rash that has a predilection for the palms and soles and may desquamate in severe cases.
GVHD. GI signs?
GI tract involvement causes diarrhea, intestinal bleeding, and abdominal pain.
GVHD. Liver signs?
Liver damage will manifest as abnormal liver function tests.
