Goljan 1 - Goljan Flashcards Preview

USMLE > Goljan 1 - Goljan > Flashcards

Flashcards in Goljan 1 - Goljan Deck (499)
1

PO2

driving force for diffusion of O2 into tissue

2

SaO2

percent heme groups occupied by O2

3

Cyanosis

decreased O2 saturation (SaO2); O2 content

4

Oxygen

electron acceptor in oxidative pathway

5

Hypoxia

inadequate O2 leads to ATP depletion

6

Ischemia

decreased arterial (or venous) blood flow

7

Respiratory acidosis

retention of CO, always decreases PaO2

8

Ventilation defect

impaired delivery of O2 to alveoli; intrapulmonary shunting of blood (e.g., RDS)

9

Perfusion defect

absent blood flow to alveoli; increased alveolar dead space (e.g., pulmonary embolus)

10

Diffusion defect

O2 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis)

11

Methemoglobin

? SaO2; heme Fe+3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue

12

Clinical methemoglobinemia

cyanosis not corrected by O2; chocolate colored blood

13

Carbon monoxide

? SaO2; left-shift O2 binding curve; inhibits cytochrome oxidase

14

Causes carbon monoxide poisoning

car exhaust, space heaters, smoke inhalation

15

S/S carbon monoxide poisoning

headache; cherry red color skin

16

Cyanide

inhibits cytochrome oxidase; systemic asphyxiant

17

Carbon monoxide + cyanide poisoning

house fires

18

Left-shifted O2 curve

? 2, 3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia

19

Right-shifted O2 curve

? 2, 3 BPG, high altitude, acidosis, fever

20

High altitude

respiratory alkalosis enhances glycolysis; ? synthesis 2,3 BPG

21

Mitochondrial poisons

damages membrane and drains off protons; alcohol, salicylates

22

Uncoupling agents in mitochondria

drain off protons; dinitrophenol, thermogenin (brown fat)

23

Complication mitochondrial poisons/uncoupling agents

hyperthermia

24

Decreased ATP

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