Goljan 1 - Goljan Flashcards
(499 cards)
1
Q
PO2
A
driving force for diffusion of O2 into tissue
2
Q
SaO2
A
percent heme groups occupied by O2
3
Q
Cyanosis
A
decreased O2 saturation (SaO2); O2 content
4
Q
Oxygen
A
electron acceptor in oxidative pathway
5
Q
Hypoxia
A
inadequate O2 leads to ATP depletion
6
Q
Ischemia
A
decreased arterial (or venous) blood flow
7
Q
Respiratory acidosis
A
retention of CO, always decreases PaO2
8
Q
Ventilation defect
A
impaired delivery of O2 to alveoli; intrapulmonary shunting of blood (e.g., RDS)
9
Q
Perfusion defect
A
absent blood flow to alveoli; increased alveolar dead space (e.g., pulmonary embolus)
10
Q
Diffusion defect
A
O2 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis)
11
Q
Methemoglobin
A
? SaO2; heme Fe+3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue
12
Q
Clinical methemoglobinemia
A
cyanosis not corrected by O2; chocolate colored blood
13
Q
Carbon monoxide
A
? SaO2; left-shift O2 binding curve; inhibits cytochrome oxidase
14
Q
Causes carbon monoxide poisoning
A
car exhaust, space heaters, smoke inhalation
15
Q
S/S carbon monoxide poisoning
A
headache; cherry red color skin
16
Q
Cyanide
A
inhibits cytochrome oxidase; systemic asphyxiant
17
Q
Carbon monoxide + cyanide poisoning
A
house fires
18
Q
Left-shifted O2 curve
A
? 2, 3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia
19
Q
Right-shifted O2 curve
A
? 2, 3 BPG, high altitude, acidosis, fever
20
Q
High altitude
A
respiratory alkalosis enhances glycolysis; ? synthesis 2,3 BPG
21
Q
Mitochondrial poisons
A
damages membrane and drains off protons; alcohol, salicylates
22
Q
Uncoupling agents in mitochondria
A
drain off protons; dinitrophenol, thermogenin (brown fat)
23
Q
Complication mitochondrial poisons/uncoupling agents
A
hyperthermia
24
Q
Decreased ATP
A
impaired Na+/K+ ATPase pump (cellular swelling); reversible
25
Anaerobic glycolysis
ATP synthesis in hypoxia; lactate ? intracellular pH, denatures proteins
26
Irreversible injury hypoxia
membrane/mitochondrial damage
27
Mitochondrial damage
release cytochrome c activates apoptosis
28
Irreversible injury hypoxia
? cytosolic Ca2+ activates phospholipase, proteases, endonuclease
29
Free radicals
unpaired electron in outer orbit; damage cell membranes and DNA
30
Free radicals
superoxide, hydroxyl, peroxide, drugs (acetaminophen)
31
Superoxide dismutase
neutralizes superoxide
32
Glutathione
neutralizes peroxide, drug FRs
33
Catalase
neutralizes peroxide
34
Lipofuscin
indigestible lipid of lipid peroxidation; brown pigment increased in atrophy and FR damage
35
Reperfusion injury in heart
superoxide FRs + calcium
36
Mitochondrial injury
cytochrome c in cytosol initiates apoptosis
37
SER hyperplasia
alcohol, barbiturates, phenytoin
38
Complications SER hyperplasia
increases drug metabolism (e.g., oral contraceptives); low vitamin D
39
Chediak-Higashi
membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles
40
Chediak-Higashi
AR; giant lysosomes
41
I cell disease
absent enzyme marker in Golgi apparatus (mannose 6-phosphate); empty lysosomes
42
Rigor mortis
stiff muscles after death due to ATP depletion
43
Fatty change in liver
MCC alcohol (increase in NADH); DHAP ? G3P ? TG
44
Fatty change in liver
VLDL pushes nucleus to side
45
Causes fatty change
? synthesis TG/FAs, beta-oxidation of FAs, synthesis apoproteins/release VLDL
46
Fatty change in kwashiorkor
? synthesis of apoproteins
47
Ferritin
primary iron storage protein; soluble in blood; serum level reflects marrow storage iron
48
Hemosiderin
insoluble ferritin degradation product visible with Prussian blue stain
49
Atrophy
reduction in cell/tissue mass by either loss or cell shrinkage
50
Brain atrophy
ischemia; AlzheimerÕs
51
Exocrine gland atrophy in CF
duct obstruction by thick secretions
52
Labile cells
stem cells (skin, marrow, GI tract) ?????
53
Stable cells
in G0 phase (smooth muscle, hepatocytes); can enter cell cycle (growth factors, hormones)
54
Permanent cells
cannot replicate; cardiac/striated muscle; neurons
55
Hypertrophy
increase in cell size (structural components, DNA)
56
LVH
increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis)
57
RVH
pulmonary hypertension
58
Bladder smooth muscle hypertrophy
prostate hyperplasia constricts urethra
59
Removal of kidney
hypertrophy of remaining kidney
60
Hyperplasia
increase in number of cells
61
Endometrial hyperplasia
unopposed estrogen (obesity, taking estrogen)
62
RBC hyperplasia
increased EPO (blood loss, ectopic secretion, high altitude)
63
Prostate hyperplasia
increased dihydrotestosterone (DHEA)
64
Gynecomastia
hyperplasia male breast tissue; normal in newborn, adolescent, elderly
65
Metaplasia
one adult cell type replaces another cell type
66
Squamous metaplasia in bronchus
smoking
67
Intestinal metaplasia in stomach
Paneth cells, goblet cells; H pylori chronic atrophic gastritis
68
Squamous metaplasia bladder
Schistosoma hematobium infection
69
BarrettÕs esophagus
glandular metaplasia of distal esophagus; due to GERD
70
Dysplasia
atypical hyperplasia and metaplasia are precursors for cancer
71
Squamous dysplasia in cervix
human papilloma virus
72
Squamous dysplasia in bronchus
smoking
73
Necrosis
death of groups of cells
74
Coagulation necrosis
preservation of structural outline (due to ? lactic acid)
75
Infarction
pale (e.g., heart, kidney); hemorrhagic (e.g., lung, small bowel); dry gangrene
76
Liquefactive necrosis
brain infarct, bacterial infections; wet gangrene
77
Caseous necrosis
variant coagulation necrosis; granulomas due to TB/systemic fungi
78
Granulomas
activated macrophages (epithelioid cells); multinucleated giant cells; CD4 TH1 cells
79
Epithelioid cells
?-interferon released by CD4 T cells activates macrophages
80
Multinucleated giant cells
fusion of epithelioid cells
81
Granulomas
type IV hypersensitivity
82
Enzymatic fat necrosis
associated with pancreatitis; soap formation (Ca2+ + fatty acids)
83
Fibrinoid necrosis
necrosis of immune reactions (immune vasculitis/endocarditis)
84
Postmortem necrosis
autolysis; no inflammatory reaction
85
Dystrophic calcification
calcification of damaged tissue; normal serum calcium
86
Dystrophic calcification
pancreatitis; atherosclerotic plaque
87
Metastatic calcification
calcification of normal tissue; increased serum calcium or phosphorus
88
Nephrocalcinosis
metastatic calcification of collecting tubule basement membranes
89
S/S nephrocalcinosis
polyuria due to nephrogenic diabetes insipidus; renal failure
90
Apoptosis
gene regulated individual cell death
91
Signals activating apoptosis
mullerian inhibitory factor, tumor necrosis factor, hormone withdrawal
92
Signal modulators of apoptosis
TP53 suppressor gene, BCL-2 genes
93
BCL-2 genes
anti-apoptosis gene; prevents cytochrome c from leaving mitochondria
94
Caspases
responsible for enzymatic cell death in apoptosis; proteases and endonucleases
95
Markers of apoptosis
eosinophilic cytoplasm, pyknotic (ink dot) nucleus
96
Apoptosis
loss Mullerian epithelium in male fetus; thymus involution; killing cancer cells
97
Histamine
key chemical in acute inflammation; mast cell; arteriole vasodilation; ? venular permeability
98
Rubor acute inflammation
redness; arteriole vasodilation (histamine)
99
Calor acute inflammation
heat; arteriole vasodilation (histamine)
100
Tumor acute inflammation
swelling; ? vessel permeability (histamine)
101
Dolor acute inflammation
pain; bradykinin, PGE
102
Acute inflammation
neutrophil dominant; ? IgM
103
Initial vessel events
transient vasoconstriction ? arteriolar vasodilation ? ? venular permeability
104
Neutrophil rolling acute inflammation
due to selectins
105
Integrins
neutrophil adhesion molecules; C5a and leukotriene B, activate; neutrophil margination
106
CD11/CD18
markers for integrins
107
Endothelial cell adhesion molecules
activated by IL-1 and TNF
108
ICAM
intercellular adhesion molecule
109
VCAM
vascular cell adhesion molecule Leukocyte adhesion molecule defect
110
Activation neutrophil adhesion molecules
neutrophilic leukocytosis; corticosteroids
111
Activation neutrophil adhesion molecules
neutropenia; endotoxins
112
Chemotaxis
directed movement; C5a and LTB4
113
Opsonizing agents
IgG, C3b; enhance phagocytosis
114
Neutrophils, monocytes, macrophages
receptors for IgG, C3b
115
O2-dependent MPO system
most potent microbicidal system; neutrophils, monocytes
116
ProductionofsuperoxidefromO2
NADPH oxidase with NADPH cofactor; produces respiratory burst
117
Nitro blue tetrazolium (NBT)
test for respiratory burst
118
Superoxide dismutase
converts superoxide to peroxide
119
Myeloperoxidase
lysosomal enzyme that combines peroxide + Cl to form bleach (HOCl)
120
Microbicidal defects
chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR)
121
Chronic granulomatous disease
absent NADPH oxidase; no respiratory burst
122
Chronic granulomatous disease
Staphylococcus aureus not killed (catalase positive)
123
Chronic granulomatous disease
Streptococcus killed (catalase negative)
124
Myeloperoxidase deficiency
AR; respiratory burst present; no bleach produced
125
Opsonization defect
BrutonÕs agammaglobulinemia (XR, decreased IgG)
126
Phagocytosis defect
Chediak-Higashi (see cell injury); also has defect in microtubule polymerization
127
COX inhibitors
non-steroidals (non-selective), selective COX-2 inhibitors
128
PGE2
vasodilation, fever
129
PGI2
vasodilator; prevent platelet aggregation
130
Nitric oxide
vasodilator; FR gas from conversion arginine to citrulline
131
IL-1 and TNF
fever, synthesis acute phase reactants in liver, leukocytosis
132
IL-6
stimulated by IL-1; stimulates synthesis of acute phase reactants
133
Acute phase reactants
fibrinogen, ferritin, C-reactive protein
134
Bradykinin
kinin produced in conversion of factor XII to factor XI
135
Bradykinin
pain, vasodilator, vessel permeability; cough/angioedema, ACE inhibitors
136
Anaphylatoxins
C3a and C5a; directly stimulate mast cell release of histamine
137
Prostaglandin I2
synthesized by endothelial cells; vasodilator, inhibits platelet aggregation
138
Lipoxygenase
hydroxylation of arachidonic acid
139
Zileuton
inhibits lipoxygenase
140
Zafirlukast, montelukast
block lipoxygenase receptor
141
LTC4, -D4, -E4
bronchoconstrictors
142
TXA2
synthesized by platelets; platelet aggregation, vasoconstriction, bronchoconstriction
143
Dipyridamole
inhibits thromboxane synthase
144
Corticosteroids
inhibits phospholipase A2, activation neutrophil adhesion molecules
145
Corticosteroids
neutrophilic leukocytosis, lymphopenia, eosinopenia
146
Fever
right shift OBC; hostile to bacterial/viral replication
147
Chronic inflammation
monocyte/macrophage; ? IgG; repair by fibrosis
148
Granuloma
cellular immunity; macrophages interact with TH1 class cells (memory cells)
149
Positive PPD
LangerhanÕs cells process PPD and interact with TH1 class cells
150
Suppurative inflammation
abscess; Staphylococcus aureus (coagulase)
151
Cellulitis
subcutaneous inflammation; Streptococcus pyogenes (hyaluronidase)
152
Pseudomembranous inflammation
toxins from Corynebacterium diphtheriae, Clostridium difficile
153
Cell cycle
key checkpoint G1 to S phase
154
TP53 and RB suppressor genes
arrests cell in G1 phase for DNA repair or apoptosis
155
BAX gene
stimulates apoptosis; activated by TP53 suppressor gene if too much DNA damage
156
Extracellular matrix
basement membrane, interstitial matrix
157
Complete restoration
cell must be capable of duplication, no damage to basement membrane
158
Scar tissue
end-product of repair by connective tissue
159
Collagen
triple helix of cross-linked ? chains
160
Collagen
cross-links at points of hydroxylation (lysyl oxidase) increase tensile strength
161
Type I collagen
bones, tendons
162
Type II collagen
early wound repair
163
Type IV collagen
basement membrane
164
Type X collagen
epiphyseal plate
165
Laminin
key basement membrane glycoprotein
166
Fibronectin
key interstitial matrix glycoprotein
167
Angiogenesis in repair
basic fibroblast growth factor, vascular endothelial growth factor
168
Key event in wound repair
granulation tissue formation; fibronectin responsible
169
Granulation tissue
becomes scar tissue
170
Collagenases
zinc cofactor (metalloprotease); type III collagen replaced by type I collagen
171
Tensile strength of healed wound
80% original strength
172
Inhibition wound healing
infection (MCC S. aureus), zinc deficiency, DM
173
Ehlers-Danlos syndrome
defects in collagen synthesis and structure; hyperelasticity
174
Scurvy
? collagen tensile strength by decreasing cross-links at points of hydroxylation
175
Keloid
excessive type III collagen; common in blacks
176
Pyogenic granuloma
exuberant granulation tissue; bleeds when touched
177
Healing by primary intention
clean wound; appose wound margins with suture
178
Healing by secondary intention
infected wound; leave wound open; myofibroblasts important
179
Liver injury
regenerative nodules; abnormal cytoarchitecture
180
Lung injury
type II pneumocyte repair cell
181
CNS injury
astrocyte and microglial cell repair cells; gliosis
182
WBC alterations in acute inflammation
neutrophilic leukocytosis, left shift, toxic granulation
183
Erythrocyte sedimentation rate
increased fibrinogen enhances rouleaux
184
C-reactive protein
indicator of acute inflammation and inflammatory atheromatous plaque
185
Polyclonal gammopathy
diffuse ? of ?-globulins; ? IgG; chronic inflammation
186
Total body water
ECF (plasma, interstitial fluid) + ICF (cytosol)
187
Osmosis
H20 shift between ECF and ICF; controlled by serum Na+ and glucose
188
Edema
increased fluid in interstitial space or body cavities; transudate, exudate, lymph
189
Transudate
protein and cell-poor fluid in interstitial space/body cavity; alteration StarlingÕs forces
190
StarlingÕs forces
oncotic pressure (albumin) keeps fluid in vessels, hydrostatic pressure pushes fluid out
191
Pitting edema
decreased oncotic pressure and/or increased hydrostatic pressure
192
? Hydrostatic pressure
pulmonary edema in LHF; pitting edema of legs in RHF; portal hypertension
193
Renal retention sodium and water
? hydrostatic pressure and ? oncotic pressure
194
Causes of renal retention of sodium/water
? cardiac output (activation RAA system), primary renal disease
195
? Oncotic pressure (hypoalbuminemia)
kwashiorkor; nephrotic syndrome; cirrhosis
196
Ascites in cirrhosis
? oncotic pressure, ? hydrostatic pressure
197
Exudate
protein and cell rich (pus); acute inflammation with ? vessel permeability
198
Lymphedema
radical mastectomy; filariasis; inflammatory carcinoma (lymphatics plugged by tumor)
199
Thrombus
endothelial injury, stasis, hypercoagulability
200
Venous thrombus
fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis)
201
Heparin/warfarin
anticoagulants that prevent venous clot formation
202
Arterial thrombus
endothelial injury; platelets held together by fibrin
203
Aspirin
prevents platelet thrombus in arteries
204
Pulmonary thromboembolism
femoral vein site of origin
205
Systemic thromboembolism
majority from left heart
206
Fat embolus
long bone fractures; delayed symptoms (48 hrs); thrombocytopenia, hypoxemia
207
Amniotic fluid embolism
DIC; lanugo hair in maternal pulmonary arteries
208
Diving
1 atmosphere pressure increase with 33 foot descent into water; N2 gas dissolved in tissue
209
Decompression sickness
release of N2 gas from tissue with rapid ascent; ischemic damage
210
Dyspnea, chest pain underwater
pulmonary embolus
211
Dyspnea, chest pain rising to surface
spontaneous pneumothorax
212
Hypovolemic shock (blood loss)
? CO and LVEDP; ? PVR
213
Cardiogenic shock
? CO; ? LVEDP and PVR
214
Septic shock
? CO (? venous return); ? PVR (vasodilation)
215
Kidneys
most susceptible organ in shock; straight portion proximal tubule most susceptible
216
Shock complications
ischemic ATN, multiorgan failure, ? AG metabolic acidosis
217
Tumors
parenchyma neoplastic component
218
Benign tumors
epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma)
219
Carcinoma
epithelial origin; squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma
220
Basal cell carcinoma
invades but does not metastasize
221
Squamous cell carcinoma
lower lip, oral pharynx, larynx, lung, esophagus, skin, cervix
222
Adenocarcinoma
distal esophagus ? colon, kidney, liver, pancreas, prostate, breast, lung, endometrium
223
Transitional cell carcinoma
renal pelvis, ureter, bladder
224
Sarcoma
malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone)
225
Liposarcoma
MC sarcoma in adults
226
Embryonal rhabdomyosarcoma
MC sarcoma in children
227
Teratoma
ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray
228
Hamartoma
normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp
229
Choristoma
normal tissue aberrant tissue location; pancreatic tissue stomach wall
230
Mixed tumor
different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid
231
Leukemia
malignancy of stem cells in bone marrow
232
Lymphoma
malignancy of lymph nodes
233
Extranodal lymphoma sites
stomach (MC), PeyerÕs patches
234
Malignant tumors
invade and metastasize; benign tumors do not
235
Upregulate telomerase
increases telomere length; found in all neoplastic cells
236
Monoclonality
key finding in neoplastic vs. normal cells
237
E-Cadherin
intercellular adhesion; lose adhesion in malignant cells
238
Malignant cells
receptors for laminin (basement membrane), fibronectin (ECM)
239
Invasion enzyme
type IV collagenase (basement membrane)
240
Angiogenesis
basic fibroblast growth factor, vascular endothelium growth factor
241
Metastasis
lymphatic, hematogenous, seeding; often more common than primary cancer
242
Carcinoma
lymph node -> hematogenous
243
Vessel invading carcinomas
renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma
244
Sarcoma
hematogenous
245
Seeding
ovarian cancer, periphery lung, CNS via spinal fluid
246
Sites where metastasis more common primary cancer
lung, bone, brain, liver, adrenal
247
Sites where primary cancer more common than metastasis
GI tract, kidney, urogenital
248
Bone metastasis
osteoblastic (radiodense); osteolytic (radiolucent)
249
Bone sites metastasis
vertebra MC (Batson venous plexus)
250
Osteoblastic metastasis
prostate cancer; increased serum AP, hypercalcemia
251
Osteolytic metastasis
breast cancer
252
EM neurosecretory granules
carcinoid tumors, small cell carcinoma, neuroblastoma
253
EM thin and thick myofilaments
rhabdomyosarcoma
254
EM Birbeck granules
histocytic neoplasms (LangerhanÕs histiocytosis)
255
Primary prevention
stop smoking; sun screen; high fiber diet
256
Cancers in children
leukemia (MC), CNS tumors, BurkittÕs, EwingÕs, neuroblastoma
257
Cancer vaccine
hepatitis B vaccine; prevents hepatocellular carcinoma
258
Cancer incidence men
prostate ? lung ? colorectal
259
Cancer incidence women
breast ? lung ? colorectal
260
Cancer mortality men
lung ? prostate ? colorectal
261
Cancer mortality women
lung ? breast ? colorectal
262
Gynecologic cancers
endometrium ? ovary ? cervix
263
Cervical Pap smear
decreased incidence of cervical cancer; detects cervical dysplasia
264
Malignant melanoma
fastest increasing in world
265
Southeast China
nasopharyngeal carcinoma (EBV)
266
Southeast Asia
hepatocellular carcinoma (HBV + aflatoxin)
267
Japan
stomach cancer
268
Africa
BurkittÕs lymphoma, Kaposi sarcoma (HHV-8)
269
Squamous dysplasia oropharynx, larynx, bronchus, cervix
risk for squamous cell carcinoma (SCC)
270
Chronic irritation sinus orifices, third degree burn scars
risk for SCC
271
Actinic (solar) keratosis
risk factor for SCC
272
Glandular metaplasia of esophagus (BarrettÕs)
risk factor for adenocarcinoma
273
Endometrial hyperplasia
risk factor for adenocarcinoma
274
Glandular (intestinal) metaplasia of stomach (Helicobacter)
risk factor for adenocarcinoma
275
Chronic ulcerative colitis
risk factor for adenocarcinoma
276
Villous adenoma of rectum
risk factor for adenocarcinoma
277
Tubular adenoma of colon
risk factor for adenocarcinoma
278
Scar tissue in lung
risk factor for adenocarcinoma
279
Regenerative nodules in cirrhosis
risk factor for hepatocellular carcinoma
280
Complete hydatidiform mole
risk factor for choriocarcinoma
281
Dysplastic mole
MC risk factor for malignant melanoma
282
UVB light
MC risk factor for BCC, SCC, melanoma
283
HHV-8
MC risk factor for KaposiÕs sarcoma
284
EBV
MC risk factor for nasopharyngeal carcinoma
285
Polycyclic hydrocarbons
MC risk factor for larynx (SCC), lung cancers
286
Asbestos
MC risk factor for mesothelioma
287
Polycyclic hydrocarbons
MC risk factor for oral cavity, mid-esophagus SCC
288
BarrettÕs esophagus
MC risk factor for distal esophagus adenocarcinoma
289
H. pylori
MC risk factor for stomach adenocarcinoma and lymphoma
290
Tubular adenoma, villous adenoma
MC risk factors for colon adenocarcinoma
291
HBV and HCV
MC risk factors for hepatocellular carcinoma
292
Vinyl chloride
MC risk factor for liver angiosarcoma
293
Gallstones, porcelain gallbladder
MC risk factor for gallbladder adenocarcinoma
294
Polycyclic hydrocarbons
MC risk factor for pancreas adenocarcinoma
295
Polycyclic hydrocarbons
MC risk factor for renal cell carcinoma
296
Polycyclic hydrocarbons
MC risk factor for urinary bladder
297
HPV + lack of circumcision
MC risk factor for penis SCC
298
Age
MC risk factor for prostate adenocarcinoma
299
Cryptorchid testis
MC risk factor for seminoma
300
Age >50 with excess estrogen exposure
MC risk factor for breast and endometrial carcinoma
301
HPV 16/18
MC risk factor for vulva, vagina, cervix SCC
302
DES
MC risk factor for vagina/cervix clear cell carcinoma
303
Nulliparity
MC risk factor for surface derived ovarian cancer
304
Complete mole
MC risk factor for choriocarcinoma
305
Turner syndrome (XO)
MC risk factor for dysgerminoma of ovary
306
Turner syndrome (XO/XY)
gonadoblastoma of ovary
307
Ionizing radiation
MC risk factor for papillary cancer of thyroid
308
Family history (MEN IIa/IIb)
MC risk factor for medullary carcinoma thyroid
309
HashimotoÕs thyroiditis
MC risk factor for malignant lymphoma thyroid
310
Ionizing radiation
MC risk factor for osteogenic sarcoma
311
EBV
MC risk factor for primary CNS lymphoma in AIDS and BurkittÕs lymphoma
312
Ionizing radiation
MC risk factor for acute/chronic myelogenous leukemia
313
EBV
MC risk factor for BurkittÕs lymphoma
314
HTLV-1
MC risk factor for T cell leukemia/lymphoma
315
Bacterial causes of cancer
H. pylori (stomach adenocarcinoma and lymphoma)
316
Parasitic causes of cancer
S. hematobium (SCC bladder), C. sinensis (cholangiocarcinoma)
317
Carcinogenesis
mutations involving regulatory genes
318
Regulatory genes
proto-oncogenes, suppressor genes, anti-apoptosis genes
319
Types mutations
point mutation MC, translocation, amplification (? copies), overexpression (? activity)
320
Translocations
BurkittÕs t(8;14); CML t(9;22); follicular lymphoma t( 14;18); APL leukemia t( 15;17)
321
Key cancer genes
TP53 suppressor gene, RAS protooncogene
322
Point mutation
inactivates suppressor genes (e.g., TP53), activates proto-oncogenes (e.g., RAS)
323
Amplification
activates ERB-B2
324
Overexpression
enhances activity of BCL-2
325
S/S POC
function-growth factor synthesis; mutation-overexpression
326
ERB-B2 POC
function growth factor receptor; activation bad prognostic sign for breast carcinoma
327
RAS POC
function-GTP signal transduction; point mutation; 30% of all human cancer
328
ABL POC
function-non-receptor tyrosine kinase activity; translocation (9;22) causing CML
329
MYC POC
function nuclear transcription; translocation (8; 14) causing BurkittÕs lymphoma
330
Inactivation suppressor genes
majority are point mutations; loss of suppression
331
Sporadic retinoblastoma
two hit theory; two separate point mutations of RB suppressor gene on
332
AD retinoblastoma
one hit theory; one already inactivated in germ cells
333
TP53 suppressor gene functions
G,-S phase inhibition, DNA repair, activation BAX apoptosis gene
334
Inactivation TP 53 suppressor gene
inactivation causes majority of human cancers
335
RB suppressor gene function
G1-S phase inhibition
336
Inactivation RB suppressor gene
retinoblastoma, osteogenic sarcoma
337
APC suppressor gene function
prevents nuclear transcription by catenin
338
Inactivation APC suppressor gene
familial polyposis (FAP)
339
BRCA1/2 suppressor genes function
DNA repair Inactivation
340
BRCA 1/2 suppressor genes
breast, ovarian cancers
341
BCL-2 function
anti apoptosis gene (keeps cytochrome c in mitochondria)
342
BCL-2 gene
t(14;18) translocation of heavy chain causes overexpression; follicular B cell lymphoma [think t(14;18) = t(l4;lB) for foLLicular B]
343
Xeroderma pigmentosum
AR; defect in DNA repair enzymes; ? risk for UVB light cancers
344
Hereditary non-polyposis syndrome (HNPCC)
AD; inactivation DNA mismatch genes; colorectal cancer
345
Chromosome instability syndromes
AR; susceptibility to DNA damage; leukemias, lymphomas
346
Examples chromosome instability
Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome
347
Carcinogens
chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in bum scar)
348
Polycyclic hydrocarbons
key chemical carcinogen (cigarette smoke)
349
Aflatoxins
produced from Aspergillus; hepatocellular carcinoma
350
Asbestos
lung cancer, mesothelioma
351
Thorium dioxide
hepatocellular carcinoma, cholangiocarcinoma
352
Aniline dyes
transitional cell carcinoma
353
Vinyl chloride
angiosarcoma of liver
354
Benzene
leukemia
355
Cyclophosphamide
transitional cell carcinoma of bladder
356
EBV
BurkittÕs; CNS lymphoma (AIDS); HodgkinÕs mixed cellularity; nasopharyngeal carcinoma
357
HBV and HCV
hepatocellular carcinoma
358
HPV
cervical, penis, and anorectal squamous cancers
359
HHV-8
Kaposi sarcoma
360
UVB cancers
basal cell carcinoma, squamous cell carcinoma, malignant melanoma
361
Key host defense
cytotoxic CD8 T cells (type IV hypersensitivity)
362
Cachexia
due to tumor necrosis factor-?
363
Most common anemia
anemia chronic disease
364
Most common coagulopathy
hypercoagulability
365
Most common COD in cancer
gram negative infection
366
Clubbing
possible marker for lung cancer
367
Non-bacterial thrombotic endocarditis mitral valve
possible marker for pancreatic cancer
368
TNM staging
metastasis more important than nodal involvement
369
AFP
hepatocellular carcinoma, yolk sac tumors
370
PSA
prostate cancer
371
CEA
recurrence colorectal cancer
372
BJ (Bence-Jones) protein
multiple myeloma
373
?-human chorionic gonadotropin
choriocarcinoma
374
Calcitonin
medullary carcinoma thyroid; hypocalcemia
375
Small cell carcinoma lung
ADH (hyponatremia), ACTH (ectopic CushingÕs)
376
Renal cell carcinoma
EPO (polycythemia), PTH-related peptide (hypercalcemia)
377
Hepatocellular carcinoma
EPO (polycythemia), insulin-like factor (hypoglycemia)
378
Medullary carcinoma of thyroid
calcitonin (hypocalcemia), ACTH (ectopic CushingÕs)
379
Squamous cell carcinoma of lung
PTH-related peptide (hypercalcemia)
380
Erythropoietin
synthesized in peritubular capillaries
381
Reticulocyte count
measure of effective erythropoiesis; correct for degree of anemia
382
Extramedullary hematopoiesis
hematopoiesis outside bone marrow (e.g., spleen)
383
Newborn physiologic anemia
drop in Hb due to replacement of HbF RBCs with HbA
384
Pregnancy
Hb and Hct decreased; greater increase in plasma volume than RBC mass
385
Anemia
normal O2 saturation and arterial PO2
386
MCV
average volume of RBCs; useful for anemia classification
387
MCHC
average Hb concentration in RBCs
388
MCHC
? in microcytic anemias; ? in spherocytosis
389
Thalassemias
? MCV, ? RBC count
390
RDW
RBC size variation; ? iron deficiency; normal in other microcytic anemias
391
Mature RBC
anaerobic glycolysis; no mitochondria or HLA antigens
392
Total iron binding capacity
? iron deficiency; ? anemia chronic disease, sideroblastic anemia
393
% Saturation
? iron deficiency, anemia chronic disease; ? sideroblastic anemia
394
Serum ferritin
? iron deficiency; ? anemia chronic disease, sideroblastic anemia; normal thalassemia
395
Microcytic anemias
iron deficiency MC, anemic chronic disease, thalassemia, sideroblastic anemia
396
Iron deficiency child
MCC MeckelÕs diverticulum
397
Iron deficiency woman < 50
MCC menorrhagia
398
Iron deficiency man < 50
MCC peptic ulcer disease
399
Iron deficiency men/woman > 50
MCC colon cancer
400
Stages iron deficiency
? ferritin; ? Fe and % saturation, ? TIBC; normocytic then microcytic anemia
401
Anemia chronic disease
MC anemia in malignancy and alcoholics
402
?-Thalassemia trait
AR; two ?-globin gene deletions; normal Hb electrophoresis
403
HbH disease
three ?-globin gene deletions; hemolytic anemia; four ?-globin chains
404
Hb BartÕs disease
four ?-globin gene deletions; four ?-globin chains
405
?-Thalassemia minor
AR; DNA splicing defect; ? HbA2 and F; ? HbA
406
?-Thalassemia major
nonsense mutation with stop codon; hemolytic anemia; ?? HbF, ? HbA2
407
Sideroblastic anemia
defect in mitochondrial heme synthesis producing ringed sideroblasts
408
Causes sideroblastic anemia
alcohol, pyridoxine deficiency (isoniazid Rx of TB), Pb poisoning
409
Pb poisoning
inhibition ferrochelatase, d-aminolevulinic acid dehydrase, ribonuclease
410
S/S Pb poisoning children
growth retardation; Pb in epiphyses (lead lines); abdominal colic; encephalopathy
411
S/S Pb poisoning adult
peripheral neuropathy; proximal renal tubule damage (FanconiÕs syndrome)
412
Lab Pb poisoning
coarse basophilic stippling RBCs; ? MCV; ? blood Pb; ? d-aminolevulinic acid
413
Vitamin B12
animal products; requires intrinsic factor for reabsorption in terminal ileum
414
Vitamin B12
transfers methyl group to homocysteine
415
R factor
binds with B12 in mouth, removed by pancreatic enzymes in small intestine
416
Vitamin B12
involved in propionate metabolism; end-product succinyl CoA
417
Causes B12 deficiency
vegan, pernicious anemia MC, fish tapeworm, pancreatitis, bacterial overgrowth, CrohnÕs disease
418
Pernicious anemia
autoimmune destruction parietal cells; chronic gastritis body/fundus; achlorhydria; ? gastrin
419
Causes folate deficiency
alcohol MCC, poor diet, drugs, malabsorption, pregnancy, goat milk
420
Drugs and folate deficiency
alcohol, OC, phenytoin, methotrexate, trimethoprim, 5-fluorouracil
421
Intestinal conjugase in folate metabolism
inhibited by phenytoin
422
Jejunal uptake of monoglutamate form of folate
inhibited by alcohol and OC
423
Dihydrofolate reductase
inhibited by methotrexate, trimethoprim
424
Thymidylate synthetase
inhibited by 5-fluorouracil
425
Folate deficiency
MCC of increased serum homocysteine
426
Lab in B12/folate deficiency
pancytopenia; hypersegmented neutrophils; ? homocysteine
427
Lab findings unique to B12 deficiency
? gastrin (pernicious anemia), ? methylmalonic acid
428
B12 reabsorbed absorbed after administration of intrinsic factor
PA
429
B12 reabsorbed absorbed after administration of antibiotics
bacterial overgrowth
430
B12 reabsorbed absorbed after administration of pancreatic extract
chronic pancreatitis
431
Acute blood loss
initially normal Hb and Hct; 0.9% saline uncovers RBC deficit
432
Aplastic anemia
drugs (e.g., phenylbutazone); infection (e.g., parvovirus); benzene
433
Lab findings aplastic anemia
pancytopenia; hypocellular bone marrow
434
Anemia in renal disease
normocytic; decreased EPO
435
Extravascular hemolysis
macrophage phagocytosis of RBCs; ? unconjugated bilirubin and urine UBG
436
Intravascular hemolysis
? serum haptoglobin; hemoglobinuria; hemosiderinuria
437
Congenital spherocytosis
AD; defect in spectrin; extravascular hemolysis; splenomegaly
438
Blood findings in spherocytosis
normocytic anemia; dense RBCs, ? MCHC, ? osmotic fragility
439
PNH
missing decay accelerating factor; complement destruction RBCs, neutrophils, platelets
440
S/S PNH
pancytopenia; hemoglobinuria; positive sugar water test and acidified serum test
441
HbSS
AR; missense mutation (valine for glutamic acid 6th positive ?-globin chain)
442
Causes of sickling
? deoxyhemoglobin (hypoxemia, acidosis); HbS > 60%
443
HbF
inhibits sickling; hydroxyurea ? HbF
444
Pathophysiology HbSS
vasoocclusive crises, hemolytic anemia (extravascular)
445
HbSS children
dactylitis (6-9 months); Streptococcus pneumoniae sepsis (dysfunctional spleen)
446
HbSS osteomyelitis
Salmonella paratyphi
447
HbSS complications
aplastic crisis (parvovirus B-19), acute chest syndrome, autosplenectomy, calcium bilirubinate gallstones, priapism, aseptic necrosis
448
HbAS
microhematuria from sickling in renal medulla; renal papillary necrosis
449
Hb electrophoresis
HbAS-HbA 55-60%, HbS 40-45%; HbSS-HbS 90-95%, HbF 5-10%
450
Blood findings in HbSS
sickle cells; target cells; Howell-Jolly bodies (nuclear remnants)
451
G6PD deficiency
XR; oxidant damage (peroxide) to Hb (e.g., primaquine; dapsone; fava beans)
452
Blood findings G6PD deficiency
Heinz bodies (denatured Hb; special stain); bite cells
453
Pyruvate kinase deficiency
? ATP; RBCs dehydrated; ? 2,3-BPG (right-shifted OBC)
454
Warm type AIHA
IgG; extravascular hemolysis; e.g., SLE, drugs
455
Cold type AIHA
IgM intravascular hemolysis; e.g., CLL, Mycoplasma
456
Penicillin
IgG antibody against penicillin attached to RBC (type II hypersensitivity)
457
Methyldopa
drug alters Rh antigens; IgG antibody against Rh antigens (type II hypersensitivity)
458
Quinidine
drug-IgM IC; intravascular hemolysis; type III hypersensitivity
459
Lab findings AIHA
positive direct CoombsÕ; spherocytes
460
Micro-macroangiopathic hemolysis
mechanical damage causing intravascular hemolysis
461
Causes of micro/macro hemolysis
aortic stenosis (MCC), DIC, TIP, HUS
462
Peripheral blood findings micro/macro hemolysis
schistocytes; iron deficiency from hemoglobinuria
463
Malaria
intravascular hemolysis correlates with fever; falciparum-ring forms and gametocytes
464
Leukemoid reaction
exaggerated WBC response to infection; usually due to infection
465
Leukoerythroblastic reaction
marrow infiltrative disease peripheralizes myeloblasts/nucleated RBCs
466
Causes of leukoerythroblastic reaction
bone metastasis MCC, myelofibrosis
467
Eosinophilia
type I hypersensitivity (e.g., penicillin reaction); invasive helminthic infection
468
Helminthes not producing eosinophilia
pinworms, adult worms in ascariasis
469
Atypical lymphocytes
mononucleosis; CMV; toxoplasmosis; viral hepatitis; phenytoin
470
Mononucleosis
due to EBV; EBV attaches to CD21 receptors on B cells
471
Clinical findings mono
exudative tonsillitis, generalized lymphadenopathy, hepatosplenomegaly
472
Lab findings mono
atypical lymphocytosis; IgM heterophile antibodies against horse RBCs
473
Lymphopenia
T cell deficiencies (HIV); combined B/T deficiency (adenine deaminase deficiency)
474
Lymphocytosis
viral infections, whooping cough
475
Corticosteroids
lymphopenia, eosinopenia, neutrophilia
476
Chronic MPD
neoplastic stem cell disorder; splenomegaly; marrow fibrosis; risk for leukemia
477
Examples of MPD
polycythemia vera, myelofibrosis and myeloid metaplasia
478
Relative polycythemia
? plasma volume; ? RBC count; normal RBC mass
479
Absolute polycythemia
? RBC count and RBC mass
480
Appropriate polycythemia
hypoxic stimulus for EPO to generate RBCs
481
Causes of appropriate absolute polycythemia
lung disease, cyanotic heart disease, high altitude
482
Appropriate absolute polycythemia
normal plasma volume; ? RBC mass; ? SaO2; ? EPO
483
Inappropriate absolute polycythemia
no hypoxic stimulus for EPO
484
Causes of inappropriate polycythemia
ectopic secretion EPO, polycythemia vera
485
Polycythemia vera
? plasma volume and RBC mass; normal SaO2; ? EPO
486
Ectopic EPO (renal cell carcinoma)
normal plasma volume; ? RBC mass; normal SaO2; ? EPO
487
Myelofibrosis myeloid metaplasia
marrow fibrosis; extramedullary hematopoiesis; splenomegaly
488
Lab findings in myelofibrosis
tear drop RBCs; dry bone marrow aspirate (marrow fibrosis)
489
Essential thrombocythemia
MPO with increase in abnormal appearing platelets
490
Myelodysplastic syndrome
severe anemia in elderly; 30% develop leukemia; ringed sideroblasts
491
Benzene
aplastic anemia; acute leukemia
492
Leukemia by age
ALL, newborn-14; AML, 15-60; CML, 40-60; CLL, >60
493
Acute vs. chronic leukemia
acute, blasts >30% in bone marrow; chronic, blasts <10% in bone marrow
494
AML
Auer rods in myeloblasts
495
Acute promyelocytic leukemia
t(15;17); defect in retinoic acid; Rx retinoic acid (? maturation); DIC
496
Acute monocytic leukemia
gum infiltration
497
CML
t(9;22) of ABL POC; Philadelphia chromosome 22; ? alkaline phosphatase score
498
ALL
early pre-B (80%); CALLA (CD10) and TdT positive; CNS and testicle involvement
499
ALL
t(12;21) offers good prognosis
