Goljan 1 - Goljan Flashcards

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1
Q

PO2

A

driving force for diffusion of O2 into tissue

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2
Q

SaO2

A

percent heme groups occupied by O2

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3
Q

Cyanosis

A

decreased O2 saturation (SaO2); O2 content

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4
Q

Oxygen

A

electron acceptor in oxidative pathway

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5
Q

Hypoxia

A

inadequate O2 leads to ATP depletion

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6
Q

Ischemia

A

decreased arterial (or venous) blood flow

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7
Q

Respiratory acidosis

A

retention of CO, always decreases PaO2

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8
Q

Ventilation defect

A

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

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9
Q

Perfusion defect

A

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

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10
Q

Diffusion defect

A

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

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11
Q

Methemoglobin

A

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

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12
Q

Clinical methemoglobinemia

A

cyanosis not corrected by O2; chocolate colored blood

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13
Q

Carbon monoxide

A

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

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14
Q

Causes carbon monoxide poisoning

A

car exhaust, space heaters, smoke inhalation

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15
Q

S/S carbon monoxide poisoning

A

headache; cherry red color skin

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16
Q

Cyanide

A

inhibits cytochrome oxidase; systemic asphyxiant

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17
Q

Carbon monoxide + cyanide poisoning

A

house fires

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18
Q

Left-shifted O2 curve

A

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

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19
Q

Right-shifted O2 curve

A

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

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20
Q

High altitude

A

respiratory alkalosis enhances glycolysis; ? synthesis 2,3 BPG

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21
Q

Mitochondrial poisons

A

damages membrane and drains off protons; alcohol, salicylates

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22
Q

Uncoupling agents in mitochondria

A

drain off protons; dinitrophenol, thermogenin (brown fat)

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23
Q

Complication mitochondrial poisons/uncoupling agents

A

hyperthermia

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24
Q

Decreased ATP

A

impaired Na+/K+ ATPase pump (cellular swelling); reversible

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25
Q

Anaerobic glycolysis

A

ATP synthesis in hypoxia; lactate ? intracellular pH, denatures proteins

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26
Q

Irreversible injury hypoxia

A

membrane/mitochondrial damage

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27
Q

Mitochondrial damage

A

release cytochrome c activates apoptosis

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28
Q

Irreversible injury hypoxia

A

? cytosolic Ca2+ activates phospholipase, proteases, endonuclease

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29
Q

Free radicals

A

unpaired electron in outer orbit; damage cell membranes and DNA

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30
Q

Free radicals

A

superoxide, hydroxyl, peroxide, drugs (acetaminophen)

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31
Q

Superoxide dismutase

A

neutralizes superoxide

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32
Q

Glutathione

A

neutralizes peroxide, drug FRs

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33
Q

Catalase

A

neutralizes peroxide

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34
Q

Lipofuscin

A

indigestible lipid of lipid peroxidation; brown pigment increased in atrophy and FR damage

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35
Q

Reperfusion injury in heart

A

superoxide FRs + calcium

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36
Q

Mitochondrial injury

A

cytochrome c in cytosol initiates apoptosis

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37
Q

SER hyperplasia

A

alcohol, barbiturates, phenytoin

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38
Q

Complications SER hyperplasia

A

increases drug metabolism (e.g., oral contraceptives); low vitamin D

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39
Q

Chediak-Higashi

A

membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles

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40
Q

Chediak-Higashi

A

AR; giant lysosomes

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41
Q

I cell disease

A

absent enzyme marker in Golgi apparatus (mannose 6-phosphate); empty lysosomes

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42
Q

Rigor mortis

A

stiff muscles after death due to ATP depletion

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43
Q

Fatty change in liver

A

MCC alcohol (increase in NADH); DHAP ? G3P ? TG

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44
Q

Fatty change in liver

A

VLDL pushes nucleus to side

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45
Q

Causes fatty change

A

? synthesis TG/FAs, beta-oxidation of FAs, synthesis apoproteins/release VLDL

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46
Q

Fatty change in kwashiorkor

A

? synthesis of apoproteins

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47
Q

Ferritin

A

primary iron storage protein; soluble in blood; serum level reflects marrow storage iron

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48
Q

Hemosiderin

A

insoluble ferritin degradation product visible with Prussian blue stain

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49
Q

Atrophy

A

reduction in cell/tissue mass by either loss or cell shrinkage

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50
Q

Brain atrophy

A

ischemia; AlzheimerÕs

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51
Q

Exocrine gland atrophy in CF

A

duct obstruction by thick secretions

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52
Q

Labile cells

A

stem cells (skin, marrow, GI tract) ?????

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53
Q

Stable cells

A

in G0 phase (smooth muscle, hepatocytes); can enter cell cycle (growth factors, hormones)

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54
Q

Permanent cells

A

cannot replicate; cardiac/striated muscle; neurons

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55
Q

Hypertrophy

A

increase in cell size (structural components, DNA)

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56
Q

LVH

A

increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis)

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57
Q

RVH

A

pulmonary hypertension

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58
Q

Bladder smooth muscle hypertrophy

A

prostate hyperplasia constricts urethra

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59
Q

Removal of kidney

A

hypertrophy of remaining kidney

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60
Q

Hyperplasia

A

increase in number of cells

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61
Q

Endometrial hyperplasia

A

unopposed estrogen (obesity, taking estrogen)

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62
Q

RBC hyperplasia

A

increased EPO (blood loss, ectopic secretion, high altitude)

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63
Q

Prostate hyperplasia

A

increased dihydrotestosterone (DHEA)

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64
Q

Gynecomastia

A

hyperplasia male breast tissue; normal in newborn, adolescent, elderly

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65
Q

Metaplasia

A

one adult cell type replaces another cell type

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66
Q

Squamous metaplasia in bronchus

A

smoking

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67
Q

Intestinal metaplasia in stomach

A

Paneth cells, goblet cells; H pylori chronic atrophic gastritis

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68
Q

Squamous metaplasia bladder

A

Schistosoma hematobium infection

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69
Q

BarrettÕs esophagus

A

glandular metaplasia of distal esophagus; due to GERD

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70
Q

Dysplasia

A

atypical hyperplasia and metaplasia are precursors for cancer

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71
Q

Squamous dysplasia in cervix

A

human papilloma virus

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72
Q

Squamous dysplasia in bronchus

A

smoking

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73
Q

Necrosis

A

death of groups of cells

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74
Q

Coagulation necrosis

A

preservation of structural outline (due to ? lactic acid)

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75
Q

Infarction

A

pale (e.g., heart, kidney); hemorrhagic (e.g., lung, small bowel); dry gangrene

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76
Q

Liquefactive necrosis

A

brain infarct, bacterial infections; wet gangrene

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77
Q

Caseous necrosis

A

variant coagulation necrosis; granulomas due to TB/systemic fungi

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78
Q

Granulomas

A

activated macrophages (epithelioid cells); multinucleated giant cells; CD4 TH1 cells

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79
Q

Epithelioid cells

A

?-interferon released by CD4 T cells activates macrophages

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80
Q

Multinucleated giant cells

A

fusion of epithelioid cells

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81
Q

Granulomas

A

type IV hypersensitivity

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82
Q

Enzymatic fat necrosis

A

associated with pancreatitis; soap formation (Ca2+ + fatty acids)

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83
Q

Fibrinoid necrosis

A

necrosis of immune reactions (immune vasculitis/endocarditis)

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84
Q

Postmortem necrosis

A

autolysis; no inflammatory reaction

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85
Q

Dystrophic calcification

A

calcification of damaged tissue; normal serum calcium

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86
Q

Dystrophic calcification

A

pancreatitis; atherosclerotic plaque

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87
Q

Metastatic calcification

A

calcification of normal tissue; increased serum calcium or phosphorus

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88
Q

Nephrocalcinosis

A

metastatic calcification of collecting tubule basement membranes

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89
Q

S/S nephrocalcinosis

A

polyuria due to nephrogenic diabetes insipidus; renal failure

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90
Q

Apoptosis

A

gene regulated individual cell death

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91
Q

Signals activating apoptosis

A

mullerian inhibitory factor, tumor necrosis factor, hormone withdrawal

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92
Q

Signal modulators of apoptosis

A

TP53 suppressor gene, BCL-2 genes

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93
Q

BCL-2 genes

A

anti-apoptosis gene; prevents cytochrome c from leaving mitochondria

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94
Q

Caspases

A

responsible for enzymatic cell death in apoptosis; proteases and endonucleases

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95
Q

Markers of apoptosis

A

eosinophilic cytoplasm, pyknotic (ink dot) nucleus

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96
Q

Apoptosis

A

loss Mullerian epithelium in male fetus; thymus involution; killing cancer cells

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97
Q

Histamine

A

key chemical in acute inflammation; mast cell; arteriole vasodilation; ? venular permeability

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98
Q

Rubor acute inflammation

A

redness; arteriole vasodilation (histamine)

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99
Q

Calor acute inflammation

A

heat; arteriole vasodilation (histamine)

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100
Q

Tumor acute inflammation

A

swelling; ? vessel permeability (histamine)

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101
Q

Dolor acute inflammation

A

pain; bradykinin, PGE

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102
Q

Acute inflammation

A

neutrophil dominant; ? IgM

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103
Q

Initial vessel events

A

transient vasoconstriction ? arteriolar vasodilation ? ? venular permeability

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104
Q

Neutrophil rolling acute inflammation

A

due to selectins

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105
Q

Integrins

A

neutrophil adhesion molecules; C5a and leukotriene B, activate; neutrophil margination

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106
Q

CD11/CD18

A

markers for integrins

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107
Q

Endothelial cell adhesion molecules

A

activated by IL-1 and TNF

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108
Q

ICAM

A

intercellular adhesion molecule

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109
Q

VCAM

A

vascular cell adhesion molecule Leukocyte adhesion molecule defect

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110
Q

Activation neutrophil adhesion molecules

A

neutrophilic leukocytosis; corticosteroids

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111
Q

Activation neutrophil adhesion molecules

A

neutropenia; endotoxins

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112
Q

Chemotaxis

A

directed movement; C5a and LTB4

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113
Q

Opsonizing agents

A

IgG, C3b; enhance phagocytosis

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114
Q

Neutrophils, monocytes, macrophages

A

receptors for IgG, C3b

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115
Q

O2-dependent MPO system

A

most potent microbicidal system; neutrophils, monocytes

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116
Q

ProductionofsuperoxidefromO2

A

NADPH oxidase with NADPH cofactor; produces respiratory burst

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117
Q

Nitro blue tetrazolium (NBT)

A

test for respiratory burst

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118
Q

Superoxide dismutase

A

converts superoxide to peroxide

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119
Q

Myeloperoxidase

A

lysosomal enzyme that combines peroxide + Cl to form bleach (HOCl)

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120
Q

Microbicidal defects

A

chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR)

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121
Q

Chronic granulomatous disease

A

absent NADPH oxidase; no respiratory burst

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122
Q

Chronic granulomatous disease

A

Staphylococcus aureus not killed (catalase positive)

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123
Q

Chronic granulomatous disease

A

Streptococcus killed (catalase negative)

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124
Q

Myeloperoxidase deficiency

A

AR; respiratory burst present; no bleach produced

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125
Q

Opsonization defect

A

BrutonÕs agammaglobulinemia (XR, decreased IgG)

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126
Q

Phagocytosis defect

A

Chediak-Higashi (see cell injury); also has defect in microtubule polymerization

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127
Q

COX inhibitors

A

non-steroidals (non-selective), selective COX-2 inhibitors

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128
Q

PGE2

A

vasodilation, fever

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129
Q

PGI2

A

vasodilator; prevent platelet aggregation

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130
Q

Nitric oxide

A

vasodilator; FR gas from conversion arginine to citrulline

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131
Q

IL-1 and TNF

A

fever, synthesis acute phase reactants in liver, leukocytosis

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132
Q

IL-6

A

stimulated by IL-1; stimulates synthesis of acute phase reactants

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133
Q

Acute phase reactants

A

fibrinogen, ferritin, C-reactive protein

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134
Q

Bradykinin

A

kinin produced in conversion of factor XII to factor XI

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135
Q

Bradykinin

A

pain, vasodilator, vessel permeability; cough/angioedema, ACE inhibitors

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136
Q

Anaphylatoxins

A

C3a and C5a; directly stimulate mast cell release of histamine

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137
Q

Prostaglandin I2

A

synthesized by endothelial cells; vasodilator, inhibits platelet aggregation

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138
Q

Lipoxygenase

A

hydroxylation of arachidonic acid

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139
Q

Zileuton

A

inhibits lipoxygenase

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140
Q

Zafirlukast, montelukast

A

block lipoxygenase receptor

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141
Q

LTC4, -D4, -E4

A

bronchoconstrictors

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142
Q

TXA2

A

synthesized by platelets; platelet aggregation, vasoconstriction, bronchoconstriction

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143
Q

Dipyridamole

A

inhibits thromboxane synthase

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144
Q

Corticosteroids

A

inhibits phospholipase A2, activation neutrophil adhesion molecules

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145
Q

Corticosteroids

A

neutrophilic leukocytosis, lymphopenia, eosinopenia

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146
Q

Fever

A

right shift OBC; hostile to bacterial/viral replication

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147
Q

Chronic inflammation

A

monocyte/macrophage; ? IgG; repair by fibrosis

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148
Q

Granuloma

A

cellular immunity; macrophages interact with TH1 class cells (memory cells)

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149
Q

Positive PPD

A

LangerhanÕs cells process PPD and interact with TH1 class cells

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150
Q

Suppurative inflammation

A

abscess; Staphylococcus aureus (coagulase)

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151
Q

Cellulitis

A

subcutaneous inflammation; Streptococcus pyogenes (hyaluronidase)

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152
Q

Pseudomembranous inflammation

A

toxins from Corynebacterium diphtheriae, Clostridium difficile

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153
Q

Cell cycle

A

key checkpoint G1 to S phase

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154
Q

TP53 and RB suppressor genes

A

arrests cell in G1 phase for DNA repair or apoptosis

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155
Q

BAX gene

A

stimulates apoptosis; activated by TP53 suppressor gene if too much DNA damage

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156
Q

Extracellular matrix

A

basement membrane, interstitial matrix

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157
Q

Complete restoration

A

cell must be capable of duplication, no damage to basement membrane

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158
Q

Scar tissue

A

end-product of repair by connective tissue

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159
Q

Collagen

A

triple helix of cross-linked ? chains

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160
Q

Collagen

A

cross-links at points of hydroxylation (lysyl oxidase) increase tensile strength

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161
Q

Type I collagen

A

bones, tendons

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162
Q

Type II collagen

A

early wound repair

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163
Q

Type IV collagen

A

basement membrane

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164
Q

Type X collagen

A

epiphyseal plate

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165
Q

Laminin

A

key basement membrane glycoprotein

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166
Q

Fibronectin

A

key interstitial matrix glycoprotein

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167
Q

Angiogenesis in repair

A

basic fibroblast growth factor, vascular endothelial growth factor

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168
Q

Key event in wound repair

A

granulation tissue formation; fibronectin responsible

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169
Q

Granulation tissue

A

becomes scar tissue

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170
Q

Collagenases

A

zinc cofactor (metalloprotease); type III collagen replaced by type I collagen

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171
Q

Tensile strength of healed wound

A

80% original strength

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172
Q

Inhibition wound healing

A

infection (MCC S. aureus), zinc deficiency, DM

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173
Q

Ehlers-Danlos syndrome

A

defects in collagen synthesis and structure; hyperelasticity

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174
Q

Scurvy

A

? collagen tensile strength by decreasing cross-links at points of hydroxylation

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175
Q

Keloid

A

excessive type III collagen; common in blacks

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176
Q

Pyogenic granuloma

A

exuberant granulation tissue; bleeds when touched

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177
Q

Healing by primary intention

A

clean wound; appose wound margins with suture

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178
Q

Healing by secondary intention

A

infected wound; leave wound open; myofibroblasts important

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179
Q

Liver injury

A

regenerative nodules; abnormal cytoarchitecture

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180
Q

Lung injury

A

type II pneumocyte repair cell

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181
Q

CNS injury

A

astrocyte and microglial cell repair cells; gliosis

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182
Q

WBC alterations in acute inflammation

A

neutrophilic leukocytosis, left shift, toxic granulation

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183
Q

Erythrocyte sedimentation rate

A

increased fibrinogen enhances rouleaux

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184
Q

C-reactive protein

A

indicator of acute inflammation and inflammatory atheromatous plaque

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185
Q

Polyclonal gammopathy

A

diffuse ? of ?-globulins; ? IgG; chronic inflammation

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186
Q

Total body water

A

ECF (plasma, interstitial fluid) + ICF (cytosol)

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187
Q

Osmosis

A

H20 shift between ECF and ICF; controlled by serum Na+ and glucose

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188
Q

Edema

A

increased fluid in interstitial space or body cavities; transudate, exudate, lymph

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189
Q

Transudate

A

protein and cell-poor fluid in interstitial space/body cavity; alteration StarlingÕs forces

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190
Q

StarlingÕs forces

A

oncotic pressure (albumin) keeps fluid in vessels, hydrostatic pressure pushes fluid out

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191
Q

Pitting edema

A

decreased oncotic pressure and/or increased hydrostatic pressure

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192
Q

? Hydrostatic pressure

A

pulmonary edema in LHF; pitting edema of legs in RHF; portal hypertension

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193
Q

Renal retention sodium and water

A

? hydrostatic pressure and ? oncotic pressure

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194
Q

Causes of renal retention of sodium/water

A

? cardiac output (activation RAA system), primary renal disease

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195
Q

? Oncotic pressure (hypoalbuminemia)

A

kwashiorkor; nephrotic syndrome; cirrhosis

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196
Q

Ascites in cirrhosis

A

? oncotic pressure, ? hydrostatic pressure

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197
Q

Exudate

A

protein and cell rich (pus); acute inflammation with ? vessel permeability

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198
Q

Lymphedema

A

radical mastectomy; filariasis; inflammatory carcinoma (lymphatics plugged by tumor)

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199
Q

Thrombus

A

endothelial injury, stasis, hypercoagulability

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200
Q

Venous thrombus

A

fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis)

201
Q

Heparin/warfarin

A

anticoagulants that prevent venous clot formation

202
Q

Arterial thrombus

A

endothelial injury; platelets held together by fibrin

203
Q

Aspirin

A

prevents platelet thrombus in arteries

204
Q

Pulmonary thromboembolism

A

femoral vein site of origin

205
Q

Systemic thromboembolism

A

majority from left heart

206
Q

Fat embolus

A

long bone fractures; delayed symptoms (48 hrs); thrombocytopenia, hypoxemia

207
Q

Amniotic fluid embolism

A

DIC; lanugo hair in maternal pulmonary arteries

208
Q

Diving

A

1 atmosphere pressure increase with 33 foot descent into water; N2 gas dissolved in tissue

209
Q

Decompression sickness

A

release of N2 gas from tissue with rapid ascent; ischemic damage

210
Q

Dyspnea, chest pain underwater

A

pulmonary embolus

211
Q

Dyspnea, chest pain rising to surface

A

spontaneous pneumothorax

212
Q

Hypovolemic shock (blood loss)

A

? CO and LVEDP; ? PVR

213
Q

Cardiogenic shock

A

? CO; ? LVEDP and PVR

214
Q

Septic shock

A

? CO (? venous return); ? PVR (vasodilation)

215
Q

Kidneys

A

most susceptible organ in shock; straight portion proximal tubule most susceptible

216
Q

Shock complications

A

ischemic ATN, multiorgan failure, ? AG metabolic acidosis

217
Q

Tumors

A

parenchyma neoplastic component

218
Q

Benign tumors

A

epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma)

219
Q

Carcinoma

A

epithelial origin; squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma

220
Q

Basal cell carcinoma

A

invades but does not metastasize

221
Q

Squamous cell carcinoma

A

lower lip, oral pharynx, larynx, lung, esophagus, skin, cervix

222
Q

Adenocarcinoma

A

distal esophagus ? colon, kidney, liver, pancreas, prostate, breast, lung, endometrium

223
Q

Transitional cell carcinoma

A

renal pelvis, ureter, bladder

224
Q

Sarcoma

A

malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone)

225
Q

Liposarcoma

A

MC sarcoma in adults

226
Q

Embryonal rhabdomyosarcoma

A

MC sarcoma in children

227
Q

Teratoma

A

ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray

228
Q

Hamartoma

A

normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp

229
Q

Choristoma

A

normal tissue aberrant tissue location; pancreatic tissue stomach wall

230
Q

Mixed tumor

A

different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid

231
Q

Leukemia

A

malignancy of stem cells in bone marrow

232
Q

Lymphoma

A

malignancy of lymph nodes

233
Q

Extranodal lymphoma sites

A

stomach (MC), PeyerÕs patches

234
Q

Malignant tumors

A

invade and metastasize; benign tumors do not

235
Q

Upregulate telomerase

A

increases telomere length; found in all neoplastic cells

236
Q

Monoclonality

A

key finding in neoplastic vs. normal cells

237
Q

E-Cadherin

A

intercellular adhesion; lose adhesion in malignant cells

238
Q

Malignant cells

A

receptors for laminin (basement membrane), fibronectin (ECM)

239
Q

Invasion enzyme

A

type IV collagenase (basement membrane)

240
Q

Angiogenesis

A

basic fibroblast growth factor, vascular endothelium growth factor

241
Q

Metastasis

A

lymphatic, hematogenous, seeding; often more common than primary cancer

242
Q

Carcinoma

A

lymph node -> hematogenous

243
Q

Vessel invading carcinomas

A

renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma

244
Q

Sarcoma

A

hematogenous

245
Q

Seeding

A

ovarian cancer, periphery lung, CNS via spinal fluid

246
Q

Sites where metastasis more common primary cancer

A

lung, bone, brain, liver, adrenal

247
Q

Sites where primary cancer more common than metastasis

A

GI tract, kidney, urogenital

248
Q

Bone metastasis

A

osteoblastic (radiodense); osteolytic (radiolucent)

249
Q

Bone sites metastasis

A

vertebra MC (Batson venous plexus)

250
Q

Osteoblastic metastasis

A

prostate cancer; increased serum AP, hypercalcemia

251
Q

Osteolytic metastasis

A

breast cancer

252
Q

EM neurosecretory granules

A

carcinoid tumors, small cell carcinoma, neuroblastoma

253
Q

EM thin and thick myofilaments

A

rhabdomyosarcoma

254
Q

EM Birbeck granules

A

histocytic neoplasms (LangerhanÕs histiocytosis)

255
Q

Primary prevention

A

stop smoking; sun screen; high fiber diet

256
Q

Cancers in children

A

leukemia (MC), CNS tumors, BurkittÕs, EwingÕs, neuroblastoma

257
Q

Cancer vaccine

A

hepatitis B vaccine; prevents hepatocellular carcinoma

258
Q

Cancer incidence men

A

prostate ? lung ? colorectal

259
Q

Cancer incidence women

A

breast ? lung ? colorectal

260
Q

Cancer mortality men

A

lung ? prostate ? colorectal

261
Q

Cancer mortality women

A

lung ? breast ? colorectal

262
Q

Gynecologic cancers

A

endometrium ? ovary ? cervix

263
Q

Cervical Pap smear

A

decreased incidence of cervical cancer; detects cervical dysplasia

264
Q

Malignant melanoma

A

fastest increasing in world

265
Q

Southeast China

A

nasopharyngeal carcinoma (EBV)

266
Q

Southeast Asia

A

hepatocellular carcinoma (HBV + aflatoxin)

267
Q

Japan

A

stomach cancer

268
Q

Africa

A

BurkittÕs lymphoma, Kaposi sarcoma (HHV-8)

269
Q

Squamous dysplasia oropharynx, larynx, bronchus, cervix

A

risk for squamous cell carcinoma (SCC)

270
Q

Chronic irritation sinus orifices, third degree burn scars

A

risk for SCC

271
Q

Actinic (solar) keratosis

A

risk factor for SCC

272
Q

Glandular metaplasia of esophagus (BarrettÕs)

A

risk factor for adenocarcinoma

273
Q

Endometrial hyperplasia

A

risk factor for adenocarcinoma

274
Q

Glandular (intestinal) metaplasia of stomach (Helicobacter)

A

risk factor for adenocarcinoma

275
Q

Chronic ulcerative colitis

A

risk factor for adenocarcinoma

276
Q

Villous adenoma of rectum

A

risk factor for adenocarcinoma

277
Q

Tubular adenoma of colon

A

risk factor for adenocarcinoma

278
Q

Scar tissue in lung

A

risk factor for adenocarcinoma

279
Q

Regenerative nodules in cirrhosis

A

risk factor for hepatocellular carcinoma

280
Q

Complete hydatidiform mole

A

risk factor for choriocarcinoma

281
Q

Dysplastic mole

A

MC risk factor for malignant melanoma

282
Q

UVB light

A

MC risk factor for BCC, SCC, melanoma

283
Q

HHV-8

A

MC risk factor for KaposiÕs sarcoma

284
Q

EBV

A

MC risk factor for nasopharyngeal carcinoma

285
Q

Polycyclic hydrocarbons

A

MC risk factor for larynx (SCC), lung cancers

286
Q

Asbestos

A

MC risk factor for mesothelioma

287
Q

Polycyclic hydrocarbons

A

MC risk factor for oral cavity, mid-esophagus SCC

288
Q

BarrettÕs esophagus

A

MC risk factor for distal esophagus adenocarcinoma

289
Q

H. pylori

A

MC risk factor for stomach adenocarcinoma and lymphoma

290
Q

Tubular adenoma, villous adenoma

A

MC risk factors for colon adenocarcinoma

291
Q

HBV and HCV

A

MC risk factors for hepatocellular carcinoma

292
Q

Vinyl chloride

A

MC risk factor for liver angiosarcoma

293
Q

Gallstones, porcelain gallbladder

A

MC risk factor for gallbladder adenocarcinoma

294
Q

Polycyclic hydrocarbons

A

MC risk factor for pancreas adenocarcinoma

295
Q

Polycyclic hydrocarbons

A

MC risk factor for renal cell carcinoma

296
Q

Polycyclic hydrocarbons

A

MC risk factor for urinary bladder

297
Q

HPV + lack of circumcision

A

MC risk factor for penis SCC

298
Q

Age

A

MC risk factor for prostate adenocarcinoma

299
Q

Cryptorchid testis

A

MC risk factor for seminoma

300
Q

Age >50 with excess estrogen exposure

A

MC risk factor for breast and endometrial carcinoma

301
Q

HPV 16/18

A

MC risk factor for vulva, vagina, cervix SCC

302
Q

DES

A

MC risk factor for vagina/cervix clear cell carcinoma

303
Q

Nulliparity

A

MC risk factor for surface derived ovarian cancer

304
Q

Complete mole

A

MC risk factor for choriocarcinoma

305
Q

Turner syndrome (XO)

A

MC risk factor for dysgerminoma of ovary

306
Q

Turner syndrome (XO/XY)

A

gonadoblastoma of ovary

307
Q

Ionizing radiation

A

MC risk factor for papillary cancer of thyroid

308
Q

Family history (MEN IIa/IIb)

A

MC risk factor for medullary carcinoma thyroid

309
Q

HashimotoÕs thyroiditis

A

MC risk factor for malignant lymphoma thyroid

310
Q

Ionizing radiation

A

MC risk factor for osteogenic sarcoma

311
Q

EBV

A

MC risk factor for primary CNS lymphoma in AIDS and BurkittÕs lymphoma

312
Q

Ionizing radiation

A

MC risk factor for acute/chronic myelogenous leukemia

313
Q

EBV

A

MC risk factor for BurkittÕs lymphoma

314
Q

HTLV-1

A

MC risk factor for T cell leukemia/lymphoma

315
Q

Bacterial causes of cancer

A

H. pylori (stomach adenocarcinoma and lymphoma)

316
Q

Parasitic causes of cancer

A

S. hematobium (SCC bladder), C. sinensis (cholangiocarcinoma)

317
Q

Carcinogenesis

A

mutations involving regulatory genes

318
Q

Regulatory genes

A

proto-oncogenes, suppressor genes, anti-apoptosis genes

319
Q

Types mutations

A

point mutation MC, translocation, amplification (? copies), overexpression (? activity)

320
Q

Translocations

A

BurkittÕs t(8;14); CML t(9;22); follicular lymphoma t( 14;18); APL leukemia t( 15;17)

321
Q

Key cancer genes

A

TP53 suppressor gene, RAS protooncogene

322
Q

Point mutation

A

inactivates suppressor genes (e.g., TP53), activates proto-oncogenes (e.g., RAS)

323
Q

Amplification

A

activates ERB-B2

324
Q

Overexpression

A

enhances activity of BCL-2

325
Q

S/S POC

A

function-growth factor synthesis; mutation-overexpression

326
Q

ERB-B2 POC

A

function growth factor receptor; activation bad prognostic sign for breast carcinoma

327
Q

RAS POC

A

function-GTP signal transduction; point mutation; 30% of all human cancer

328
Q

ABL POC

A

function-non-receptor tyrosine kinase activity; translocation (9;22) causing CML

329
Q

MYC POC

A

function nuclear transcription; translocation (8; 14) causing BurkittÕs lymphoma

330
Q

Inactivation suppressor genes

A

majority are point mutations; loss of suppression

331
Q

Sporadic retinoblastoma

A

two hit theory; two separate point mutations of RB suppressor gene on

332
Q

AD retinoblastoma

A

one hit theory; one already inactivated in germ cells

333
Q

TP53 suppressor gene functions

A

G,-S phase inhibition, DNA repair, activation BAX apoptosis gene

334
Q

Inactivation TP 53 suppressor gene

A

inactivation causes majority of human cancers

335
Q

RB suppressor gene function

A

G1-S phase inhibition

336
Q

Inactivation RB suppressor gene

A

retinoblastoma, osteogenic sarcoma

337
Q

APC suppressor gene function

A

prevents nuclear transcription by catenin

338
Q

Inactivation APC suppressor gene

A

familial polyposis (FAP)

339
Q

BRCA1/2 suppressor genes function

A

DNA repair Inactivation

340
Q

BRCA 1/2 suppressor genes

A

breast, ovarian cancers

341
Q

BCL-2 function

A

anti apoptosis gene (keeps cytochrome c in mitochondria)

342
Q

BCL-2 gene

A

t(14;18) translocation of heavy chain causes overexpression; follicular B cell lymphoma [think t(14;18) = t(l4;lB) for foLLicular B]

343
Q

Xeroderma pigmentosum

A

AR; defect in DNA repair enzymes; ? risk for UVB light cancers

344
Q

Hereditary non-polyposis syndrome (HNPCC)

A

AD; inactivation DNA mismatch genes; colorectal cancer

345
Q

Chromosome instability syndromes

A

AR; susceptibility to DNA damage; leukemias, lymphomas

346
Q

Examples chromosome instability

A

Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome

347
Q

Carcinogens

A

chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in bum scar)

348
Q

Polycyclic hydrocarbons

A

key chemical carcinogen (cigarette smoke)

349
Q

Aflatoxins

A

produced from Aspergillus; hepatocellular carcinoma

350
Q

Asbestos

A

lung cancer, mesothelioma

351
Q

Thorium dioxide

A

hepatocellular carcinoma, cholangiocarcinoma

352
Q

Aniline dyes

A

transitional cell carcinoma

353
Q

Vinyl chloride

A

angiosarcoma of liver

354
Q

Benzene

A

leukemia

355
Q

Cyclophosphamide

A

transitional cell carcinoma of bladder

356
Q

EBV

A

BurkittÕs; CNS lymphoma (AIDS); HodgkinÕs mixed cellularity; nasopharyngeal carcinoma

357
Q

HBV and HCV

A

hepatocellular carcinoma

358
Q

HPV

A

cervical, penis, and anorectal squamous cancers

359
Q

HHV-8

A

Kaposi sarcoma

360
Q

UVB cancers

A

basal cell carcinoma, squamous cell carcinoma, malignant melanoma

361
Q

Key host defense

A

cytotoxic CD8 T cells (type IV hypersensitivity)

362
Q

Cachexia

A

due to tumor necrosis factor-?

363
Q

Most common anemia

A

anemia chronic disease

364
Q

Most common coagulopathy

A

hypercoagulability

365
Q

Most common COD in cancer

A

gram negative infection

366
Q

Clubbing

A

possible marker for lung cancer

367
Q

Non-bacterial thrombotic endocarditis mitral valve

A

possible marker for pancreatic cancer

368
Q

TNM staging

A

metastasis more important than nodal involvement

369
Q

AFP

A

hepatocellular carcinoma, yolk sac tumors

370
Q

PSA

A

prostate cancer

371
Q

CEA

A

recurrence colorectal cancer

372
Q

BJ (Bence-Jones) protein

A

multiple myeloma

373
Q

?-human chorionic gonadotropin

A

choriocarcinoma

374
Q

Calcitonin

A

medullary carcinoma thyroid; hypocalcemia

375
Q

Small cell carcinoma lung

A

ADH (hyponatremia), ACTH (ectopic CushingÕs)

376
Q

Renal cell carcinoma

A

EPO (polycythemia), PTH-related peptide (hypercalcemia)

377
Q

Hepatocellular carcinoma

A

EPO (polycythemia), insulin-like factor (hypoglycemia)

378
Q

Medullary carcinoma of thyroid

A

calcitonin (hypocalcemia), ACTH (ectopic CushingÕs)

379
Q

Squamous cell carcinoma of lung

A

PTH-related peptide (hypercalcemia)

380
Q

Erythropoietin

A

synthesized in peritubular capillaries

381
Q

Reticulocyte count

A

measure of effective erythropoiesis; correct for degree of anemia

382
Q

Extramedullary hematopoiesis

A

hematopoiesis outside bone marrow (e.g., spleen)

383
Q

Newborn physiologic anemia

A

drop in Hb due to replacement of HbF RBCs with HbA

384
Q

Pregnancy

A

Hb and Hct decreased; greater increase in plasma volume than RBC mass

385
Q

Anemia

A

normal O2 saturation and arterial PO2

386
Q

MCV

A

average volume of RBCs; useful for anemia classification

387
Q

MCHC

A

average Hb concentration in RBCs

388
Q

MCHC

A

? in microcytic anemias; ? in spherocytosis

389
Q

Thalassemias

A

? MCV, ? RBC count

390
Q

RDW

A

RBC size variation; ? iron deficiency; normal in other microcytic anemias

391
Q

Mature RBC

A

anaerobic glycolysis; no mitochondria or HLA antigens

392
Q

Total iron binding capacity

A

? iron deficiency; ? anemia chronic disease, sideroblastic anemia

393
Q

% Saturation

A

? iron deficiency, anemia chronic disease; ? sideroblastic anemia

394
Q

Serum ferritin

A

? iron deficiency; ? anemia chronic disease, sideroblastic anemia; normal thalassemia

395
Q

Microcytic anemias

A

iron deficiency MC, anemic chronic disease, thalassemia, sideroblastic anemia

396
Q

Iron deficiency child

A

MCC MeckelÕs diverticulum

397
Q

Iron deficiency woman < 50

A

MCC menorrhagia

398
Q

Iron deficiency man < 50

A

MCC peptic ulcer disease

399
Q

Iron deficiency men/woman > 50

A

MCC colon cancer

400
Q

Stages iron deficiency

A

? ferritin; ? Fe and % saturation, ? TIBC; normocytic then microcytic anemia

401
Q

Anemia chronic disease

A

MC anemia in malignancy and alcoholics

402
Q

?-Thalassemia trait

A

AR; two ?-globin gene deletions; normal Hb electrophoresis

403
Q

HbH disease

A

three ?-globin gene deletions; hemolytic anemia; four ?-globin chains

404
Q

Hb BartÕs disease

A

four ?-globin gene deletions; four ?-globin chains

405
Q

?-Thalassemia minor

A

AR; DNA splicing defect; ? HbA2 and F; ? HbA

406
Q

?-Thalassemia major

A

nonsense mutation with stop codon; hemolytic anemia; ?? HbF, ? HbA2

407
Q

Sideroblastic anemia

A

defect in mitochondrial heme synthesis producing ringed sideroblasts

408
Q

Causes sideroblastic anemia

A

alcohol, pyridoxine deficiency (isoniazid Rx of TB), Pb poisoning

409
Q

Pb poisoning

A

inhibition ferrochelatase, d-aminolevulinic acid dehydrase, ribonuclease

410
Q

S/S Pb poisoning children

A

growth retardation; Pb in epiphyses (lead lines); abdominal colic; encephalopathy

411
Q

S/S Pb poisoning adult

A

peripheral neuropathy; proximal renal tubule damage (FanconiÕs syndrome)

412
Q

Lab Pb poisoning

A

coarse basophilic stippling RBCs; ? MCV; ? blood Pb; ? d-aminolevulinic acid

413
Q

Vitamin B12

A

animal products; requires intrinsic factor for reabsorption in terminal ileum

414
Q

Vitamin B12

A

transfers methyl group to homocysteine

415
Q

R factor

A

binds with B12 in mouth, removed by pancreatic enzymes in small intestine

416
Q

Vitamin B12

A

involved in propionate metabolism; end-product succinyl CoA

417
Q

Causes B12 deficiency

A

vegan, pernicious anemia MC, fish tapeworm, pancreatitis, bacterial overgrowth, CrohnÕs disease

418
Q

Pernicious anemia

A

autoimmune destruction parietal cells; chronic gastritis body/fundus; achlorhydria; ? gastrin

419
Q

Causes folate deficiency

A

alcohol MCC, poor diet, drugs, malabsorption, pregnancy, goat milk

420
Q

Drugs and folate deficiency

A

alcohol, OC, phenytoin, methotrexate, trimethoprim, 5-fluorouracil

421
Q

Intestinal conjugase in folate metabolism

A

inhibited by phenytoin

422
Q

Jejunal uptake of monoglutamate form of folate

A

inhibited by alcohol and OC

423
Q

Dihydrofolate reductase

A

inhibited by methotrexate, trimethoprim

424
Q

Thymidylate synthetase

A

inhibited by 5-fluorouracil

425
Q

Folate deficiency

A

MCC of increased serum homocysteine

426
Q

Lab in B12/folate deficiency

A

pancytopenia; hypersegmented neutrophils; ? homocysteine

427
Q

Lab findings unique to B12 deficiency

A

? gastrin (pernicious anemia), ? methylmalonic acid

428
Q

B12 reabsorbed absorbed after administration of intrinsic factor

A

PA

429
Q

B12 reabsorbed absorbed after administration of antibiotics

A

bacterial overgrowth

430
Q

B12 reabsorbed absorbed after administration of pancreatic extract

A

chronic pancreatitis

431
Q

Acute blood loss

A

initially normal Hb and Hct; 0.9% saline uncovers RBC deficit

432
Q

Aplastic anemia

A

drugs (e.g., phenylbutazone); infection (e.g., parvovirus); benzene

433
Q

Lab findings aplastic anemia

A

pancytopenia; hypocellular bone marrow

434
Q

Anemia in renal disease

A

normocytic; decreased EPO

435
Q

Extravascular hemolysis

A

macrophage phagocytosis of RBCs; ? unconjugated bilirubin and urine UBG

436
Q

Intravascular hemolysis

A

? serum haptoglobin; hemoglobinuria; hemosiderinuria

437
Q

Congenital spherocytosis

A

AD; defect in spectrin; extravascular hemolysis; splenomegaly

438
Q

Blood findings in spherocytosis

A

normocytic anemia; dense RBCs, ? MCHC, ? osmotic fragility

439
Q

PNH

A

missing decay accelerating factor; complement destruction RBCs, neutrophils, platelets

440
Q

S/S PNH

A

pancytopenia; hemoglobinuria; positive sugar water test and acidified serum test

441
Q

HbSS

A

AR; missense mutation (valine for glutamic acid 6th positive ?-globin chain)

442
Q

Causes of sickling

A

? deoxyhemoglobin (hypoxemia, acidosis); HbS > 60%

443
Q

HbF

A

inhibits sickling; hydroxyurea ? HbF

444
Q

Pathophysiology HbSS

A

vasoocclusive crises, hemolytic anemia (extravascular)

445
Q

HbSS children

A

dactylitis (6-9 months); Streptococcus pneumoniae sepsis (dysfunctional spleen)

446
Q

HbSS osteomyelitis

A

Salmonella paratyphi

447
Q

HbSS complications

A

aplastic crisis (parvovirus B-19), acute chest syndrome, autosplenectomy, calcium bilirubinate gallstones, priapism, aseptic necrosis

448
Q

HbAS

A

microhematuria from sickling in renal medulla; renal papillary necrosis

449
Q

Hb electrophoresis

A

HbAS-HbA 55-60%, HbS 40-45%; HbSS-HbS 90-95%, HbF 5-10%

450
Q

Blood findings in HbSS

A

sickle cells; target cells; Howell-Jolly bodies (nuclear remnants)

451
Q

G6PD deficiency

A

XR; oxidant damage (peroxide) to Hb (e.g., primaquine; dapsone; fava beans)

452
Q

Blood findings G6PD deficiency

A

Heinz bodies (denatured Hb; special stain); bite cells

453
Q

Pyruvate kinase deficiency

A

? ATP; RBCs dehydrated; ? 2,3-BPG (right-shifted OBC)

454
Q

Warm type AIHA

A

IgG; extravascular hemolysis; e.g., SLE, drugs

455
Q

Cold type AIHA

A

IgM intravascular hemolysis; e.g., CLL, Mycoplasma

456
Q

Penicillin

A

IgG antibody against penicillin attached to RBC (type II hypersensitivity)

457
Q

Methyldopa

A

drug alters Rh antigens; IgG antibody against Rh antigens (type II hypersensitivity)

458
Q

Quinidine

A

drug-IgM IC; intravascular hemolysis; type III hypersensitivity

459
Q

Lab findings AIHA

A

positive direct CoombsÕ; spherocytes

460
Q

Micro-macroangiopathic hemolysis

A

mechanical damage causing intravascular hemolysis

461
Q

Causes of micro/macro hemolysis

A

aortic stenosis (MCC), DIC, TIP, HUS

462
Q

Peripheral blood findings micro/macro hemolysis

A

schistocytes; iron deficiency from hemoglobinuria

463
Q

Malaria

A

intravascular hemolysis correlates with fever; falciparum-ring forms and gametocytes

464
Q

Leukemoid reaction

A

exaggerated WBC response to infection; usually due to infection

465
Q

Leukoerythroblastic reaction

A

marrow infiltrative disease peripheralizes myeloblasts/nucleated RBCs

466
Q

Causes of leukoerythroblastic reaction

A

bone metastasis MCC, myelofibrosis

467
Q

Eosinophilia

A

type I hypersensitivity (e.g., penicillin reaction); invasive helminthic infection

468
Q

Helminthes not producing eosinophilia

A

pinworms, adult worms in ascariasis

469
Q

Atypical lymphocytes

A

mononucleosis; CMV; toxoplasmosis; viral hepatitis; phenytoin

470
Q

Mononucleosis

A

due to EBV; EBV attaches to CD21 receptors on B cells

471
Q

Clinical findings mono

A

exudative tonsillitis, generalized lymphadenopathy, hepatosplenomegaly

472
Q

Lab findings mono

A

atypical lymphocytosis; IgM heterophile antibodies against horse RBCs

473
Q

Lymphopenia

A

T cell deficiencies (HIV); combined B/T deficiency (adenine deaminase deficiency)

474
Q

Lymphocytosis

A

viral infections, whooping cough

475
Q

Corticosteroids

A

lymphopenia, eosinopenia, neutrophilia

476
Q

Chronic MPD

A

neoplastic stem cell disorder; splenomegaly; marrow fibrosis; risk for leukemia

477
Q

Examples of MPD

A

polycythemia vera, myelofibrosis and myeloid metaplasia

478
Q

Relative polycythemia

A

? plasma volume; ? RBC count; normal RBC mass

479
Q

Absolute polycythemia

A

? RBC count and RBC mass

480
Q

Appropriate polycythemia

A

hypoxic stimulus for EPO to generate RBCs

481
Q

Causes of appropriate absolute polycythemia

A

lung disease, cyanotic heart disease, high altitude

482
Q

Appropriate absolute polycythemia

A

normal plasma volume; ? RBC mass; ? SaO2; ? EPO

483
Q

Inappropriate absolute polycythemia

A

no hypoxic stimulus for EPO

484
Q

Causes of inappropriate polycythemia

A

ectopic secretion EPO, polycythemia vera

485
Q

Polycythemia vera

A

? plasma volume and RBC mass; normal SaO2; ? EPO

486
Q

Ectopic EPO (renal cell carcinoma)

A

normal plasma volume; ? RBC mass; normal SaO2; ? EPO

487
Q

Myelofibrosis myeloid metaplasia

A

marrow fibrosis; extramedullary hematopoiesis; splenomegaly

488
Q

Lab findings in myelofibrosis

A

tear drop RBCs; dry bone marrow aspirate (marrow fibrosis)

489
Q

Essential thrombocythemia

A

MPO with increase in abnormal appearing platelets

490
Q

Myelodysplastic syndrome

A

severe anemia in elderly; 30% develop leukemia; ringed sideroblasts

491
Q

Benzene

A

aplastic anemia; acute leukemia

492
Q

Leukemia by age

A

ALL, newborn-14; AML, 15-60; CML, 40-60; CLL, >60

493
Q

Acute vs. chronic leukemia

A

acute, blasts >30% in bone marrow; chronic, blasts <10% in bone marrow

494
Q

AML

A

Auer rods in myeloblasts

495
Q

Acute promyelocytic leukemia

A

t(15;17); defect in retinoic acid; Rx retinoic acid (? maturation); DIC

496
Q

Acute monocytic leukemia

A

gum infiltration

497
Q

CML

A

t(9;22) of ABL POC; Philadelphia chromosome 22; ? alkaline phosphatase score

498
Q

ALL

A

early pre-B (80%); CALLA (CD10) and TdT positive; CNS and testicle involvement

499
Q

ALL

A

t(12;21) offers good prognosis