Path Ch 2 Flashcards
1
Q
increase in lactic acid –>
A
decrease pH –> denaturation of proteins (may precipitate) = decreased activity of many enzymes
2
Q
fatty change seen in
A
liver, kidney, heart (organs involved in/dependent on fat metabolism)
3
Q
CCl4
A
- carbon tetrachloride
- dry cleaning
- causes liver cell necrosis
- first converted to free radicals (CCl3) in SER
4
Q
tylenol toxicity
A
- main cause of drug-induced hepatic necrosis
- converted by hepatocyte p450 into free radical
- FR neutralized by glutathione GSH (part of pentose phosphate pathway)
- reduction in GSH –> damage to hepatocyte by FR
- pathogenesis: FR acts on sulfhydryl groups in hepatocyte cell membrane
5
Q
Vit A def
A
- night blindness, squamous metaplasia (renal squamous cell stones (keratin pearls), immune deficiency (increased # of bacterial infections)
- Vit A –> cell proliferation and maturation, therefore give Vit A to AML patients
- bumps on skin where hair follicles are = squamous metaplasia of hair follicles
6
Q
vitamin C def
A
- scurvy (poor wound healing from lack of collagen I and III; petechiae, poor bones)
- if petechiae + purpura –> scurvy
- remember, Vit C hydroxylates collagen, without it have weak collagen –> bowing of long bones in kids or lots of bleeding when brush teeth
- 1st affects collagen w/ highest hydroxyproline content (i.e. blood vessels–> early symptom = bleeding gums)
7
Q
vit D def
A
rickets (bowing of long bones in kids) and osteomalacia
8
Q
vitamin K def
A
- bleeding diathesis
- kids with CF will often have Vit K deficiency from malabsorption
- adults with vitamin K def = warfarin patients or someone who lost a colon (bc lost the bacteria)
9
Q
Vit B12 def
A
- megaloblastic anemia, neuropathy, spinal cord degeneration
- megaloblastic anemia with neurologic deficits –> B12 deficiency
10
Q
folate def
A
megaloblastic anemia and neural tube defects
11
Q
niacin (Vit B3) def
A
pellagra, rough skin (diarrhea, dermatitis and dementia, death if don’t treat)
12
Q
kwashiorkor
A
- decrease in total protein intake –> decreased oncotic pressure –> edema in eyes, belly, hands
13
Q
Thiamine (Vit B1) def
A
wernicke-korsakoff, dilated cardiomyopathy (beri beri)
14
Q
Excess Vit A
A
- stored in Ito cells (liver) –> liver disease, jaundice
15
Q
excess Vit D
A
- excess Vit D –> increased calcium –> irritability, fatigue, muscle weakness, bone resorption and metastatic calcifications
16
Q
superoxide dismutase
A
superoxide O2- –> H202
17
Q
glutathione peroxidase
A
hydroxyl ions or H2O2 –> H2O
18
Q
catalase
A
H2O2 –> H20 + O2
19
Q
decrease in Na/K+ pump
A
- influx of Na+ and efflux of K+ –> cell swelling, ER swelling, loss of microvilli, membrane blebs
20
Q
apoptosis on H and E
A
- deeply eosinophilic cytoplasm and basophilic nucleus
- pyknosis (nuclear shrinkage)
- karyorrhexis (gragmentatino caused by endonuclease-mediated cleavage)
- cell membrane typical remains intact without significant inflammation (unlike necrosis)
- both intrinsic and extrinsic pathways (both activate caspases aka cytosolic proteases) –> cellular breakdown including cell shrinkage, chromatin condensation, membrane blabbing and formation of apoptotic bodies (which are then phagocytosed)
- DNA laddering: fragments in multiples of 180bp is a sensitive indicator of apoptosis
21
Q
intrinsic pathway for apoptosis
A
- mitochondrial pathway
- involved in tissue remodeling in embryogenesis
- occurs when regulating factor is withdrawn from a proliferating cell population (i.e. decrease in IL-2 after a completed immunologic reaction –> apoptosis of proliferating effector cells)
- also occurs after exposure to injurious stimuli (i.e. radiation, toxins, hypoxia) –> p53 activation –> BAX/BAK –> cytochrome c released from mitochondria –> initiator caspases –> apoptosis
- regulated by Bcl-2 family of proteins. BAX and BAK are proapoptotic, while Bcl-2 and Bcl-x are antiapoptotic
22
Q
extrinsic pathway for apoptosis
A
2 pathways:
- ligand receptor interactions (FasL binding to Fas [CD95] or TNF-α binding to its receptor)
- immune cell (cytotoxic T cell release of perforin and granzyme B
- Fas-FasL interaction is necessary in thymic medullary negative selection. Mutations in Fas –> increased numbers of circulating self-reacting lymphocytes due to failure of clonal deletion
- defective Fas-FasL interactions –> autoimmune lymphoproliferative syndrome
23
Q
fibrinoid necrosis
A
- immune reactions in vessels (ie PAN, preeclampsia, malignant HTN)
- immune complexes combine with fibrin –> vessel wall damage (Type 3 hypersensitivity reaction)
24
Q
antiapoptotic proteins
A
- Bcl-2 and Bcl-x are antiapoptotic
- Bcl-2 keeps the mitochondrial outer membrane impermeable and therefore prevents cytochrome c release from the inner mitochondrial matrix
- Bcl-2 overexpression (ex follicular lymphoma t[14,18] –> decreased caspase activation –> tumorigenesis
25
wet gangrene
- liquefactive necrosis (resulting from superinfection) superimposed on coagulative necrosis
- in coagulative necrosis proteins denature then enzymes degrade. In liquefactive necrosis neutrophils release lysosomal enzymes that digest the tissues. Enzymes degrade first and proteins denature 2nd.
26
pro-apoptotic proteins
Bcl-2 family of proteins. BAX and BAK are proapoptotic
27
Regions of brain most vulnerable to hypoxia/ischemia and subsequent infarction
- ACA/MCA/PCA boundary areas.
- ACA/MCA = anterior watershed area
- MCA/PCA = posterior watershed area
- watershed area = border zone that receives blood from most distal branches of 2 arteries with limited collateral vascularity. These areas are susceptible to ischemia from hypoperfusion
- neurons most vulnerable to hypoxic-ischemic insults include parking cells of cerebellum and pyramidal cells of hippocampus and neocortex (zones 3, 5, 6)
28
Regions of kidney most vulnerable to hypoxia/ischemia and subsequent infarction
- straight segment of proximal tubule (medulla)
| - thick ascending limb (medulla)
29
Regions of liver most vulnerable to hypoxia/ischemia and subsequent infarction
area around central vein (zone III)
30
Regions of colon most vulnerable to hypoxia/ischemia and subsequent infarction
splenic flexure, colon
31
increased alkaline phosphatase in the blood signifies
biliary tract obstruction --> cell damage --> leaking enzymes into blood
32
heterolysis
- release of proteolytic enzymes from inflammatory cells
| - seen in liquefactive necrosis
33
liquefactive necrosis occurs in
brain infarcts, abscesses and pancreatic necrosis
34
genetic control of apoptosis
- bcl-2 (which inhibits apoptosis) prevents release of cytochrome c from mito and binds pro-apoptotic protease activating factor (Apaf-1)
- p53 (which stimulates apoptosis) is elevated by DNA injury and arrests cell cycle. If DNA repair is impossible, p53 stimulates apoptosis
- oncogenic viruses can inactivate p53 (i.e. Hep B, HIV, EBV, HPV)
- in viral hepatits see councilman body (pathologic examples of apoptosis will have inflammation; physiologic apoptosis have NO inflammation)
35
execution of apoptosis
mediated by cascade of caspases that digest nuclear and cytoskeletal proteins and activate endonucleases
36
graft vs host disease
- example of pathogenic apoptosis (will see inflammation)
- occurs in allogenic bone marrow transplant recipients
- the transplanted marrow has cytotoxic T cells that recognize the new host proteins (usually HLA) as foreign
- signals cell to undergo apoptosis while releasing their TNF-α and interferon-γ
- organs typically involved = skin, mucosa, liver, GI
- path: see single-cell apoptosis occurring in affected organs and adjacent T cells
37
cells unable to undergo hyperplasia
- hyperplasia = increase in # of cells
| - nerve, cardiac, skeletal muscle cells
38
secondary polycythemia
- living at high altitudes (where O2 content of air is relatively low) --> compensatory hyperplasia of RBC precursors in BM --> increase in # of circulating RBC
39
HPV
- high risk strains
- E6 does
- E7 does
- high risk: 16, 18, 31, 33
- E6 knocks out p53
- E7 knocks out RB
- low risk: 6, 11: genital wart. condolyoma lata "go to heaven"
- 1-4: get from floor = plantar wart
40
black liver
- durbin-johnson
- melanin binds bilirubin
- asymptomatic
41
lysozymes containing peroxided free-radical injured lipid
lipofuscin
42
melanin is derived from
- tyrosine
- found in melanocytes (neural crest cell derivatives) and substantial nigra
- S100+
43
dystrophic calcification
ppt of calcium phosphate in dying or necrotic tissues. dying tissues expose phosphates --> calcium is attracted.
- Ex: fat necrosis (saponification) psammoma bodies (laminated calcifications that occur in meningiomas) papillary carcinomas of thyroid and ovary
44
when the substantial nigra is pale think
parkinsons
45
mullerian duct derivatives
- fallopian tube, uterus, cervix, upper portion of vagina
46
wolffian duct derivatives
epididymis, vas deferens, seminal vesicles, ejaculatory ducts
47
AR inheritance
- onset
- penetrance
- mutation
- requires
AR inheritance
- onset: early uniform onset (infancy/childhood)
- penetrance: complete penetrance
- mutation: usually an enzyme protein
- requires: mutation of both alleles
48
AD inheritance
- onset
- penetrance
- mutation
- requires
AD inheritance
- onset: variable; may be delayed into adulthood
- penetrance: incomplete with variable expression
- mutation: usually a structural protein or receptor
- requires: mutation of one allele
49
what causes fat accumulation in kwashiorker
decreased synthesis of apolipoproteins, can't get VLDL out of liver, lipoproteins make VLDL soluble in fluid
50
Russell body
pink; accumulation of Ig in RER of plasma cells
51
mallory body
- masses of keratin intermediate filaments (alcohol hyaline) within hepatocytes
- seen in pts with alcoholic liver disease
52
alkaptonuria
- enzyme def: homogentisate oxidase
- ochronosis: accumulation of black homogentisate pigments in joints, cartilage, urine (turns black on exposure to sunlight)
53
melanosis coli (black bowel syndrome)
- refers to deposition of black anthracene pigments in macrophages within lamina propria of large intestine
- associated w/ laxative abuse from which pigment is derived
54
causes of melanin excess
- increases in ACTH (ie pit adenoma, ectopic ACTH, addison's dz, adrenogenital syndrome)
55
albinism
- lack of tyrosinase
| - melanocytes present, but don't contain melanin in melanosomes
56
PKU
- missing enzyme: phenylalanine hydrolyzes (normally converts phenylalanine into tyrosine)
- deficiency of Tyr --> blonde hair
57
Things that cause an increase in unconjugated bilirubin
- bilirubin is derived from the breakdown of Hb by macrophages in the spleen and BM, released from Macrophages as lipid soluble, UCB
- hemolytic anemia (hereditary spherocytosis - spectrin)
- problem w uptake and conjugation of bilirubin (physiologic jaundice of newborn)
- newborns w Rh disease of newborns (may develop kernicterus due to entry of dissolution of UCB in brain tissue)
58
things that cause an increase in conjugated bilirubin
- bilirubin is derived from the breakdown of Hb by macrophages in the spleen and BM, released from Macrophages as lipid soluble, UCB, bound to plasma in albumin
- bound to albumin in plasma, delivered to hepatocytes for conjugation into CB
- hepatitis
- obstructive jaundice (gallstones in CBD)
