Path III: organ rejection Flashcards
4 causes of pathology in organ transplantations
- rejection
- effects of immunosuppression
- recurrence of the original disease
- effects of incomplete allograft preservation
Direct. vs. indirect rejection
donor cells mediate direct rejection: donor APCs present dono endogenous antigens. this involves cytotoxic T cells as well as B cells.
indirect rejection: host APCs present exogenous donor proteins. does not involve cytotoxic T cells.
What causes hyperacute rejection?
preformed antibodies and the complement system
What is acute humoral rejection?
rejection mediated by newly formed anti-donor antibodies. takes about 1 week
what is acute cellular rejection:
medated by T cells/delayed hypersensitivitiy
takes about 2 wks
What is accelerated rejection?
mediated by T cells
takes about 1-5 days
What is the primary cause/pathologic feature of chronic rejection?
arterial/arteriolar proliferation and fibrosis leading to ischemic graft dysfunction
What are the three most important organs involved in grading graft vs. host disease?
skin, liver, and GI tract
What is seen in hyperacute rejection?
necrotizing arteritis, arteriolitis, thromobsis, infarction
What cells are seen in accelerated rejection?
lymphocytes and PMNs
How would you ID acture humoral rejection?
stain for C3d or C4d complement in the microvasculature and/or donor-specific antibody in the blood
In graft vs. host disease, what three features do we look for?
dermatitis, hepatitids, and enteritis.
What are two major effects of corticosteroid use?
adrenal atrophy and Cushing syndrome
What are two major effects of azathioprine?
bone marrow suppression and pulmonary fibrosis
What are some major effects of calcineurin inhibitors like cyclosporin?
tubular necrosis, intrahepatic cholestasis (bile can’t flow from liver to the duodenum), gingeval hypetrophy (whatever), renal fibrosis, glomerular scelrosis, HUS
What are some differences btw TCAD and atherosclerosis?
TCAD= transplant coronary artery disease. this is diffuse, rich in cells, concentric, and involves multiple lesions
atherosclerosis is focal/segmental, rich in debris, eccentric, and solitary lesions are common
Anatomical vs. clinical pathologists
anatomical pathologists examine tissue samples (surgical) or cell preps (cytopathologists) for abnormal morphology
clinical pathologists oversee blood and other body fluid testing for abnormalities and accuracy
What are the 4 features of pathology?
etiology (intrinsic/genetic vs. acquired), pathogenesis (mechanisms that lead to morphologic changes), morphologic changes (gross/microscopic changes that define disease), functional derangements/clinical manifestations (effects of changes in specific tissues and how these affect treatment and prognosis)
What are examples of physiologic hypertrophy?
increased functional demand as in weight lifting or uterine expansion during pregnancy
What are pathologic hypertrophy examples?
hypertrophy in response to a pathologic process, as in cardiac responses to hypertension or valve disease
esterogen can cause what kind of cellular adaptation in the uterus?
hyperplasia: causes an increase in DNA synthesis and cell division. important during pregnancy
What is an example of compensatory hyperplasia?
cell growth and division in response to partial hepatectomy in liver; proliferative response in remaining kidney after loss of one kindney.
What are common causes of pahtologic hyperplasia? What is a danger of hyperplasia?
causes: imbalance/excess hormone production due to neoplasm or physiologic abnormality. danger: neoplasia may result
What is the definition of atrophy?
smaller cells with fewer functions and lower metabolic rate.
these cells are still alive
What are causes of atrophy?
decreased workload/disuse, decr. blood supply, damage to or loss of innervation, aging, insufficient nutrition, decreased hormonal stimulaiton
What is metaplasia?
reversible replacement of one tissue type for another
What is the most common type of metaplasia and where does it occur?
most common type of metaplasia is the replacement of columnar cells with squamous cells
occurs in the resp. tract of smokers and in the uterine cervix as a response to some infections with papillomavirus
What is Barrett’s esophagous?
replacement of normal stratified squamous epithelium with columnar type epithelium with goblet cells in response to ongoing GERD. may increase risk of cancer in that area. this cancer would be adenocarcinoma, NOT squamous cell carcinoma
What are examples of CT metaplasia?
cartilage, bone, or adipose tissue growth in tissues where it is not normally found. may occur at sites of inflammation in soft tissues.
What are two examples of reversible cell injury?
cell swelling and fatty change
what are some features of cell swelling>
plasma membrane alterations (blebbin, blunting, loss of microvilli), mitochondrial changes (swelling), dilation of the ER (polysome detachement), nuclear alterations (
What is autolysis?
not seen in vivo. enzymatic breakdown of tissues without accompanying inflammation
What is coagulative necrosis? gross and microscopic appearance?
eosinophilia of cytoplasm, dissolution of the nucleus. tissue is pale and looks cooked. may see ghosts on microscopic exam. seen during ischemic necrosis. inflammation at the edges.
What is liquefactive necrosis? What diesease(s)? Gross and microscopic appearance?
enzymatic digestion predominates and tissue liquifies. seen in ischemic damage in the CNS or in some bacterial infections. infected tissue will have cavities filled with pus. microscopically there will be sheets of PMNs/neutrophils
WHat is caseous necrosis? What disease? Gross and microscopic appearance?
mostly seen in TB. tissue is grossly white and friable (LIKE CHEESE, jesus, how many times do they have to make that analogy).
microscopically: granulomatous rxn (necrosis surrounded by epithelioid histiocyhtes and multinucleated giant cells).
What is enzymatic fat necrosis?
gross: chalky deposits of fat in and around the pancrease due to the release of lots of lipase from a damaged pancrease. factty acids forms soaps with serum Ca.
What are some causes of cell injury and death?
hypoxia, ischemia, physical injury chemical injury, immune-mediated injury, genetic defects, malnutrition, radiation, aging, and infectious agents.
What are five pathogenic mechanisms for cell injury and necrosis?
depeltion of cellular energy stores, damage to mitochondria, loss of calcium homeostasis, free radical damage, and loss of membrane integrity
How does depletion of cellular energy stores lead to cell death and necrosis?
everything needs ATP, including cellular compontents and TM transport. you can see cell swelling due to Na influx, anaerobic glcolysis leading to acidosis, protein misfolding
How does damage to mitochondria lead to cell injury and necrosis?
pores open, leading to release of cytocormome c, which triggers apoptosis
How does loss of calcium homeostasis lead to cell injury and necrosis?
actiaviton of enzymes like ATPases, proteases, endonucleases, and phospholipases
How does free radical damage lead to cell injury and necrosis?
membrane damage, protein closs-linking and loss of function, DNA rxns, ischemia
What might cause loss of membrane integrity?
ATP depletion, phospholipases, cytoskeletal breakdown, free radicals, lipid breakdown products, toxins, chemicals.
