Path III: organ rejection

Question 1

4 causes of pathology in organ transplantations

Answer 1

1. rejection
2. effects of immunosuppression
3. recurrence of the original disease
4. effects of incomplete allograft preservation

Question 2

Direct. vs. indirect rejection

Answer 2

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.

Question 3

What causes hyperacute rejection?

Answer 3

preformed antibodies and the complement system

Question 4

What is acute humoral rejection?

Answer 4

rejection mediated by newly formed anti-donor antibodies. takes about 1 week

Question 5

what is acute cellular rejection:

Answer 5

medated by T cells/delayed hypersensitivitiy

takes about 2 wks

Question 6

What is accelerated rejection?

Answer 6

mediated by T cells

takes about 1-5 days

Question 7

What is the primary cause/pathologic feature of chronic rejection?

Answer 7

arterial/arteriolar proliferation and fibrosis leading to ischemic graft dysfunction

Question 8

What are the three most important organs involved in grading graft vs. host disease?

Answer 8

skin, liver, and GI tract

Question 9

What is seen in hyperacute rejection?

Answer 9

necrotizing arteritis, arteriolitis, thromobsis, infarction

Question 10

What cells are seen in accelerated rejection?

Answer 10

lymphocytes and PMNs

Question 11

How would you ID acture humoral rejection?

Answer 11

stain for C3d or C4d complement in the microvasculature and/or donor-specific antibody in the blood

Question 12

In graft vs. host disease, what three features do we look for?

Answer 12

dermatitis, hepatitids, and enteritis.

Question 13

What are two major effects of corticosteroid use?

Answer 13

adrenal atrophy and Cushing syndrome

Question 14

What are two major effects of azathioprine?

Answer 14

bone marrow suppression and pulmonary fibrosis

Question 15

What are some major effects of calcineurin inhibitors like cyclosporin?

Answer 15

tubular necrosis, intrahepatic cholestasis (bile can’t flow from liver to the duodenum), gingeval hypetrophy (whatever), renal fibrosis, glomerular scelrosis, HUS

Question 16

What are some differences btw TCAD and atherosclerosis?

Answer 16

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

Question 17

Anatomical vs. clinical pathologists

Answer 17

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

Question 18

What are the 4 features of pathology?

Answer 18

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)

Question 19

What are examples of physiologic hypertrophy?

Answer 19

increased functional demand as in weight lifting or uterine expansion during pregnancy

Question 20

What are pathologic hypertrophy examples?

Answer 20

hypertrophy in response to a pathologic process, as in cardiac responses to hypertension or valve disease

Question 21

esterogen can cause what kind of cellular adaptation in the uterus?

Answer 21

hyperplasia: causes an increase in DNA synthesis and cell division. important during pregnancy

Question 22

What is an example of compensatory hyperplasia?

Answer 22

cell growth and division in response to partial hepatectomy in liver; proliferative response in remaining kidney after loss of one kindney.

Question 23

What are common causes of pahtologic hyperplasia? What is a danger of hyperplasia?

Answer 23

causes: imbalance/excess hormone production due to neoplasm or physiologic abnormality. danger: neoplasia may result

Question 24

What is the definition of atrophy?

Answer 24

smaller cells with fewer functions and lower metabolic rate.

these cells are still alive

Question 25

What are causes of atrophy?

Answer 25

decreased workload/disuse, decr. blood supply, damage to or loss of innervation, aging, insufficient nutrition, decreased hormonal stimulaiton

Question 26

What is metaplasia?

Answer 26

reversible replacement of one tissue type for another

Question 27

What is the most common type of metaplasia and where does it occur?

Answer 27

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

Question 28

What is Barrett’s esophagous?

Answer 28

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

Question 29

What are examples of CT metaplasia?

Answer 29

cartilage, bone, or adipose tissue growth in tissues where it is not normally found. may occur at sites of inflammation in soft tissues.

Question 30

What are two examples of reversible cell injury?

Answer 30

cell swelling and fatty change

Question 31

what are some features of cell swelling>

Answer 31

plasma membrane alterations (blebbin, blunting, loss of microvilli), mitochondrial changes (swelling), dilation of the ER (polysome detachement), nuclear alterations (

Question 32

What is autolysis?

Answer 32

not seen in vivo. enzymatic breakdown of tissues without accompanying inflammation

Question 33

What is coagulative necrosis? gross and microscopic appearance?

Answer 33

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.

Question 34

What is liquefactive necrosis? What diesease(s)? Gross and microscopic appearance?

Answer 34

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

Question 35

WHat is caseous necrosis? What disease? Gross and microscopic appearance?

Answer 35

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).

Question 36

What is enzymatic fat necrosis?

Answer 36

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.

Question 37

What are some causes of cell injury and death?

Answer 37

hypoxia, ischemia, physical injury chemical injury, immune-mediated injury, genetic defects, malnutrition, radiation, aging, and infectious agents.

Question 38

What are five pathogenic mechanisms for cell injury and necrosis?

Answer 38

depeltion of cellular energy stores, damage to mitochondria, loss of calcium homeostasis, free radical damage, and loss of membrane integrity

Question 39

How does depletion of cellular energy stores lead to cell death and necrosis?

Answer 39

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

Question 40

How does damage to mitochondria lead to cell injury and necrosis?

Answer 40

pores open, leading to release of cytocormome c, which triggers apoptosis

Question 41

How does loss of calcium homeostasis lead to cell injury and necrosis?

Answer 41

actiaviton of enzymes like ATPases, proteases, endonucleases, and phospholipases

Question 42

How does free radical damage lead to cell injury and necrosis?

Answer 42

membrane damage, protein closs-linking and loss of function, DNA rxns, ischemia

Question 43

What might cause loss of membrane integrity?

Answer 43

ATP depletion, phospholipases, cytoskeletal breakdown, free radicals, lipid breakdown products, toxins, chemicals.