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391 Cards in this Set

  • Front
  • Back
driving force for diffusion of 02 into tissue
percent heme groups occupied by 02
decreased 02 saturation (Sa02)
02 content equation
1.34 x Hb x Sa02 + Pa02
electron acceptor in oxidative pathway
inadequate 02 leads to ATP depletion
decreased arterial (or venous) blood flow
PaO2 of respiratory acidosis
retention of CO2 always decreases Pa02
Ventilation defect
impaired delivery of 02 to alveoli; intrapulmonary shunting of blood (e.g., RDS)
Perfusion defect
absent blood flow to alveoli; increased alveolar dead space (e.g., pulmonary embolus)
Diffusion defect
02 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis)
Sa02; heme iron +3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue
Clinical methemoglobinemia
cyanosis not corrected by 02; chocolate colored blood
Carbon monoxide
L Sa02; left-shift 02 binding curve; inhibits cytochrome oxidase
Causes carbon monoxide poisoning
car exhaust, space heaters, smoke inhalation
S/S carbon monoxide poisoning
headache; cherry red color skin
Cyanide mechanisms of toxicity
inhibits cytochrome oxidase; systemic asphyxiant
Carbon monoxide + cyanide poisoning
house fires
house fires
2,3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia
Right-shifted 02 curve
T 2,3 BPG, high altitude, acidosis, fever
Diffusion defect
02 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis)
Sa02; heme iron +3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue
Clinical methemoglobinemia
cyanosis not corrected by 02; chocolate colored blood
Carbon monoxide
L Sa02; left-shift 02 binding curve; inhibits cytochrome oxidase
Causes carbon monoxide poisoning
car exhaust, space heaters, smoke inhalation
S/S carbon monoxide poisoning
headache; cherry red color skin
Cyanide mechanisms of toxicity
inhibits cytochrome oxidase; systemic asphyxiant
Carbon monoxide + cyanide poisoning
house fires
house fires
2,3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia
Right-shifted 02 curve
T 2,3 BPG, high altitude, acidosis, fever
High altitude
respiratory alkalosis enhances glycolysis; T synthesis 2,3 BPG
Mitochondrial poisons
damages membrane and drains off protons; alcohol, salicylates
Uncoupling agents in mitochondria
drain off protons; dinitrophenol, thermogenin (brown fat)
Complication mitochondrial poisons/uncoupling agents
Anaerobic glycolysis
ATP synthesis in hypoxia; lactate, dec intracellular pH, denatures proteins
Decreased ATP
impaired Na+/K+ ATPase pump (cellular swelling); reversible
Irreversible injury hypoxia
membrane/mitochondrial damage
Mitochondrial damage causes release of:
cytochrome c activates apoptosis
Irreversible injury hypoxia leads to the cascade in which:
inc cytosolic Ca2+ activates phospholipase, proteases, endonuclease
Free radicals
unpaired electron in outer orbit; damage cell membranes and DNA
Free radicals examples
superoxide, hydroxyl, peroxide, drugs (acetaminophen)
Superoxide dismutase
neutralizes superoxide
neutralizes peroxide, drug FRs
neutralizes peroxide
lipid of lipid peroxidation; brown pigment increased in atrophy and FR damage
Reperfusion injury in heart
superoxide FRs + calcium
Mitochondrial injury leads to:
cytochrome c in cytosol initiates apoptosis
SER hyperplasia
alcohol, barbiturates, phenytoin
Complications SER hyperplasia
increases drug metabolism (e.g., oral contraceptives); dec vitamin D
cause of Chediak-Higashi
microtubule polymerization defect resulting in decreased phagocytosis
Chediak-Higashi details
autosomal recessive, giant lysosomes
I cell disease
absent enzyme marker in Golgi apparatus (mannose 6-phosphate); empty lysosomes
Rigor mortis
stiff muscles after death due to ATP depletion
Fatty change in liver MCC
MCC alcohol (increase in NADH); DHAP--> G3P-> TG
Fatty change in liver cellular appearance
inc VLDL pushes nucleus to side
Cause of fatty change in liver
inc synthesis TG/FAs, dec beta-oxid FAs/synthesis apoproteins/release VLDL
Fatty change in kwashiorkor
dec synthesis of apoproteins
primary iron storage protein; soluble in blood; serum level reflects marrow storage iron
insoluble ferritin degradation product visible with Prussian blue stain
reduction in cell/tissue mass by either loss or cell shrinkage
Brain atrophy
ischemia; Alzheimer's
Exocrine gland atrophy in CF
duct obstruction by thick secretions
Labile cells
stem cells (skin, marrow, GI tract)
Stable cells: in Go phase
(smooth muscle, hepatocytes); can enter cell cycle (growth factors, hormones)
Permanent cells
cannot replicate; cardiac/striated muscle; neurons
increase in cell size (structural components, DNA)
increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis)
pulmonary hypertension
Bladder smooth muscle hypertrophy
prostate hyperplasia constricts urethra
Removal of kidney
hypertrophy of remaining kidney
increase in number of cells
Endometrial hyperplasia
unopposed estrogen (obesity, taking estrogen)
RBC hyperplasia
increased EPO (blood loss, ectopic secretion, high altitude)
Prostate hyperplasia
increased dihydrotestosterone
hyperplasia male breast tissue; normal in newborn, adolescent, elderly
one adult cell type replaces another cell type
Squamous metaplasia in bronchus
Intestinal metaplasia in stomach
Paneth cells, goblet cells; H. pylori chronic atrophic gastritis
Squamous metaplasia bladder
Schistosoma hematobium infection
Barrett's esophagus
glandular metaplasia of distal esophagus; due to GERD
atypical hyperplasia or metaplasia are precursors for cancer
Squamous dysplasia in cervix
Squamous dysplasia in bronchus
death of groups of cells
Coagulation necrosis
preservation of structural outline (due to inc lactic acid)
pale (e.g., heart, kidney); hemorrhagic (e.g., lung, small bowel); dry gangrene
Liquefactive necrosis
brain infarct, bacterial infections; wet gangrene
Caseous necrosis
variant coagulation necrosis; granulomas due to TB/systemic fungi
activated macrophages (epithelioid cells); multinucleated giant cells; CD4 T cells
Epithelioid cells
y-interferon released by CD4 T cells activates macrophages
type IV hypersensitivity
Enzymatic fat necrosis
associated with pancreatitis; soap formation (Ca2+ + fatty acids)
Fibrinoid necrosis:
necrosis of immune reactions (immune vasculitis/endocarditis)
Postmortem necrosis
autolysis; no inflammatory reaction
Dystrophic calcification
calcification of damaged tissue; normal serum calcium
Dystrophic calcification
pancreatitis; atherosclerotic plaque
Metastatic calcification
calcification of normal tissue; increased serum calcium or phosphorus
metastatic calcification of collecting tubule basement membranes
S/S nephrocalcinosis
polyuria due to nephrogenic diabetes insipidus; renal failure
gene regulated individual cell death
Signals activating apoptosis
mullerian inhibitory factor, tumor necrosis factor, hormone withdrawal
Signal modulators of apoptosis
TP53 suppressor gene, BCL-2 genes
BCL-2 genes
anti-apoptosis gene; prevents cytochrome c from leaving mitochondria
responsible for enzymatic cell death in apoptosis; proteases and endonucleases
Markers of apoptosis
eosinophilic cytoplasm, pyknotic (ink dot) nucleus
Apoptosis in the healthy body
loss Mullerian epithelium in male fetus; thymus involution; killing cancer cells
key chemical in acute inflammation; mast cell; arteriole vasodilation; T venular permeability
Rubor acute inflammation
redness; arteriole vasodilation (histamine)
Calor acute inflammation
heat; arteriole vasodilation (histamine)
Tumor acute inflammation
swelling; inc vessel permeability (histamine)
Dolor acute inflammation
pain; bradykinin, PGE
Acute inflammation
neutrophil dominant; inc IgM
Initial vessel events in inflammation
transient vasoconstriction -> arteriolar vasodilation -> inc venular permeability
Neutrophil rolling acute inflammation
due to selectin
neutrophil adhesion molecules; C5a and leukotriene B4 activate; neutrophil margination
markers for integrins
Endothelial cell adhesion molecules activated by:
IL-1 and TNF
intercellular adhesion molecule
vascular cell adhesion molecule
Leukocyte adhesion molecule defect clinical presentation
failure of umbilical cord to separate; poor wound healing
dec Activation neutrophil adhesion molecules by
neutrophilic leukocytosis; corticosteroids
inc Activation neutrophil adhesion molecules by
neutropenia; endotoxins
directed movement; C5a and LTB4
Opsonizing agents
IgG, C3b; enhance phagocytosis
Neutrophils, monocytes, macrophages
receptors for IgG, C3b
02-dependent MPO system
most potent microbicidal system; neutrophils, monocytes
Production of superoxide from 02
NADPH oxidase with NADPH cofactor; produces respiratory burst
Nitroblue tetrazolium (NBT):
test for respiratory burst
Superoxide dismutase
converts superoxide to peroxide
lysosomal enzyme that combines peroxide + Cl to form bleach (HOC1)
genetic Microbicidal defects
chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR)
Chronic granulomatous disease etiology
absent NADPH oxidase; no respiratory burst
Chronic granulomatous disease organism
Staphylococcus aureus not killed (catalase positive)
Chronic granulomatous disease, organisms NOT involved
Streptococcus killed (catalase negative)
Myeloperoxidase deficiency
AR; respiratory burst present; no bleach produced
Opsonization defect
Bruton's agammaglobulinemia (XR, decreased IgG)
Phagocytosis defect
Chediak-Higashi; also has defect in microtubule polymerization
COX inhibitors
non-steroidals (non-selective), selective COX-2 inhibitors
vasodilation, fever
vasodilator; prevent platelet aggregation
Nitric oxide
vasodilator; FR gas from conversion arginine to citrulline
IL-1 and TNF
fever, synthesis acute phase reactants in liver, leukocytosis
stimulated by IL-1; stimulates synthesis of acute phase reactants
Acute phase reactants
fibrinogen, ferritin, C-reactive protein
bradykinin produced:
in conversion of factor XII to factor XI
Bradykinin effects
pain, vasodilator, inc vessel permeability; cough/angioedema ACE inhibitors
C3a and C5a; directly stimulate mast cell release of histamine
Prostaglandin I2
synthesized by endothelial cells; vasodilator, inhibits platelet aggregation
hydroxylation of arachidonic acid
inhibits lipoxygenase
Zafirlukast, montelukast
block lipoxygenase receptor
LTC4, -D4, -E4:
synthesized by platelets; platelet aggregation, vasoconstriction, bronchoconstriction
inhibits thromboxane synthase
Corticosteroids biochemical effect
inhibits phospholipase A2, activation neutrophil adhesion molecules
Corticosteroids peripheral blod smear effect:
neutrophilic leukocytosis, lymphopenia, eosinopenia
right shift OBC; hostile to bacterial/viral replication
Chronic inflammation
monocyte/macrophage; inc IgG; repair by fibrosis
cellular immunity; macrophages interact with THl class cells (memory cells)
Positive PPD
Langerhan's cells process PPD and interact with TH1 class cells
Suppurative inflammation
abscess; Staphylococcus aureus (coagulase)
subcutaneous inflammation; Streptococcus pyogenes (hyaluronidase)
Pseudomembranous inflammation
toxins from Corynebacterium diphtheriae, Clostridium d ffcile Cell cycle: key checkpoint Gt to S phase
TP53 and RB suppressor genes
arrests cell in G, phase for DNA repair or apoptosis
BAX gene
stimulates apoptosis; activated by TP53 suppressor gene if too much DNA damage
Extracellular matrix
basement membrane, interstitial matrix
Complete restoration of a cell
cell must be capable of duplication, no damage to basement membrane
Scar tissue:
end-product of repair by connective tissue
triple helix of cross-linked a chains
cross-links at points of hydroxylation (lysyl oxidase) increase tensile strength
Type I collagen
bones, tendons
Type III collagen
early wound repair
Type IV collagen
basement membrane
Type X collagen
epiphyseal plate
key basement membrane glycoprotein
key interstitial matrix glycoprotein
Angiogenesis in repair
basic fibroblast growth factor, vascular endothelial growth factor
Key event in wound repair
granulation tissue formation; fibronectin responsible
Granulation tissue eventually...
becomes scar tissue
zinc cofactor (metalloprotease); type III collagen replaced by type I collagen
Tensile strength of healed wound
80% original strength
Inhibition of wound healing
infection (MCC; S. aureus), zinc deficiency, DM
Ehlers-Danlos syndrome
defects in collagen synthesis and structure; hyperelasticity
collagen tensile strength by decreasing cross-links at points of hydroxylation
excessive type III collagen; common in blacks
Pyogenic granuloma
exuberant granulation tissue; bleeds when touched
Healing primary intention
clean wound; appose wound margins with suture
Healing secondary intention
infected wound; leave wound open; myofibroblasts important
Liver injury and repair
regenerative nodules; abnormal cytoarchitecture
Lung injury
type II pneumocyte repair cell
CNS injury and repair
astrocyte and microglial cell repair cells; gliosis
WBC alterations acute inflammation
neutrophilic leukocytosis, left shift, toxic granulation
Erythrocyte sedimentation rate
increased fibrinogen enhances rouleau
C-reactive protein
indicator acute inflammation and inflammatory atheromatous plaque
Polyclonal gammopathy
diffuse elevation y-globulins; T IgG; chronic inflammation
Total body water
ECF (plasma, interstitial fluid), ICF (cytosol)
H2O shift between ECF and ICF; controlled by serum Na and glucose
increased fluid in interstitial space or body cavities; transudate, exudate, lymph
protein and cell-poor fluid in interstitial space/body cavity; alteration Starling's forces
Starling's forces
oncotic pressure (albumin) keeps fluid in vessels, hydrostatic pressure pushes fluid out
Pitting edema
decreased oncotic pressure and/or increased hydrostatic pressure
inc Hydrostatic pressure
pulmonary edema in LHF; pitting edema of legs in RHF; portal hypertension
Renal retention sodium and water
inc hydrostatic pressure and dec oncotic pressure
Causes renal retention sodium/water
Dec cardiac output (activation RAA system), primary renal disease
Dec Oncotic pressure (hypoalbuminemia):
kwashiorkor; nephrotic syndrome; cirrhosis
Ascites in cirrhosis
dec oncotic pressure, inc hydrostatic pressure
protein and cell rich (pus); acute inflammation with inc vessel permeability
radical mastectomy; filariasis; inflammatory carcinoma (lymphatics plugged by tumor)
endothelial injury, stasis, hypercoagulability
Venous thrombus
fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis)
anticoagulants that prevent venous clot formation
Arterial thrombus
endothelial injury; platelets held together by fibrin
prevents platelet thrombus in arteries
Pulmonary thromboembolism
femoral vein site of origin
Systemic thromboembolism
majority from left heart
Fat embolus
long bone fractures; delayed symptoms (48 hrs); thrombocytopenia, hypoxemia
Amniotic fluid embolism
DIC; lanugo hair in maternal pulmonary arteries
1 atmosphere pressure increase with 33 foot descent into water; N2 gas dissolved in tissue
Decompression sickness
release of N2 gas from tissue with rapid ascent; ischemic damage
Dyspnea, chest pain underwater
pulmonary embolus
Dyspnea, chest pain rising to surface
spontaneous pneumothorax
Hypovolemic shock (blood loss)
dec CO and LVEDP; inc PVR
Cardiogenic shock
dec CO; inc LVEDP and PVR
Septic shock
inc CO (inc venous return); dec PVR (vasodilation)
Kidneys and shock
most susceptible organ in shock; straight portion proximal tubule most susceptible
Shock complications
ischemic ATN, multiorgan failure, inc AG metabolic acidosis
parenchyma neoplastic component
Benign tumors
epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma)
epithelial origin; squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma
Basal cell carcinoma
invades but does not metastasize
Squamous cell carcinoma location
lower lip, oral pharynx, larynx, lung, esophagus, skin, cervix
distal esophagus--> colon, kidney, liver, pancreas, prostate, breast, lung, endometrium
Transitional cell carcinoma
renal pelvis, ureter, bladder
malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone)
MC sarcoma in adults
MC sarcoma in children
Embryonal rhabdomyosarcoma
Teratoma appearance
ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray
Hamartoma appearance
normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp
normal tissue aberrant tissue location; pancreatic tissue stomach wall
Mixed tumor
different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid
Leukemia definition
malignancy of stem cells in bone marrow
malignancy of lymph nodes
Extranodal lymphoma sites:
stomach (MC), Peyer's patches
Malignant tumors
invade and metastasize; benign tumors do not
Upregulate telomerase
increases telomere length; found in all neoplastic cells
key finding in neoplastic vs normal cells
intercellular adhesion; lose adhesion in malignant cells
Malignant cells have receptors for:
laminin (basement membrane), fibronectin (ECM)
Invasion enzyme
type IV collagenase (basement membrane)
basic fibroblast growth factor, vascular endothelium growth factor
lymphatic, hematogenous, seeding; often more common than primary cancer
Carcinoma metastasis
lymph node--> hematogenous
Vessel invading carcinomas
renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma
Sarcoma metastasis
Seedind of a tumor
ovarian cancer, periphery lung, CNS via spinal fluid
Sites where metastasis more common primary cancer
lung, bone, brain, liver, adrenal
Sites where primary cancer more common than metastasis
GI tract, kidney, urogenital
Bone metastasis
osteoblastic (radiodense); osteolytic (radiolucent)
Bone sites metastasis
vertebra MC (Batson venous plexus)
Osteoblastic metastasis
prostate cancer; increased serum AP, hypercalcemia
EM neurosecretory granules and cancer
carcinoid tumors, small cell carcinoma, neuroblastoma
EM thin and thick myofilaments
EM Birbeck granules
histocytic neoplasms (Langerhan's histiocytosis)
Primary prevention of cancer
stop smoking; sun screen; high fiber diet
Cancers in children
leukemia (MC), CNS tumors, Burkitt's, Ewing's, neuroblastoma
Cancer vaccine:
hepatitis B vaccine; prevents hepatocellular carcinoma
Cancer incidence men
prostate > lung > colorectal
Cancer incidence women
breast > lung > colorectal
Cancer mortality men
lung > prostate > colorectal
Cancer mortality women
lung > breast > colorectal
Gynecologic cancers
endometrium > ovary > cervix
Cervical Pap smear has resulted in
decreased incidence of cervical cancer; detects cervical dysplasia
Malignant melanoma
fastest increasing in world
cancer in person from Southeast China
nasopharyngeal carcinoma (EBV)
cancer in person from Southeast Asia
hepatocellular carcinoma (HBV + aflatoxin)
cancer in person from Japan
stomach cancer
cancer in person from Africa
Burkitt's lymphoma, Kaposi sarcoma (HHV-8)
Squamous dysplasia oropharynx, larynx, bronchus, cervix
risk for squamous cell carcinoma (SCC)
Chronic irritation sinus orifices, third degree burn scars
risk for SCC
Actinic (solar) keratosis
risk factor for SCC
Glandular metaplasia of esophagus (Barrett's) as a risk factor for
risk factor for adenocarcinoma
Endometrial hyperplasia as a risk factor for
risk factor for adenocarcinoma
Glandular (intestinal) metaplasia of stomach (Helicobacter) as a risk factor for
risk factor for adenocarcinoma
Chronic ulcerative colitis as a risk factor for
risk factor for adenocarcinoma
Villous adenoma of rectum as a risk factor for
risk factor for adenocarcinoma
Tubular adenoma of colon as a risk factor for
risk factor for adenocarcinoma
Scar tissue in lung as a risk factor for
risk factor for adenocarcinoma
Regenerative nodules in as a risk factor forcirrhosis
risk factor for hepatocellular carcinoma
Complete hydatidiform mole as a risk factor for
risk factor for choriocarcinoma
Dysplastic mole as a risk factor for
MC risk factor for malignant melanoma
UVB light as a risk factor for
MC risk factor for BCC, SCC, melanoma HHV-8: MC risk factor for Kaposi's sarcoma
EBV as a risk factor for
MC risk factor for nasopharyngeal carcinoma
Polycyclic hydrocarbons as a risk factor for
MC risk factor for larynx (SCC), lung cancers
Asbestos as a risk factor for
MC risk factor for mesothelioma
Polycyclic hydrocarbons as a risk factor for
MC risk factor for oral cavity, mid-esophagus SCC
Barrett's esophagus as a risk factor for
MC risk factor for distal esophagus adenocarcinoma
H. pylori as a risk factor for
MC risk factor for stomach adenocarcinoma and lymphoma
Tubular adenoma, villous adenoma as a risk factor for
MC risk factors for colon adenocarcinoma
HBV and HCV as a risk factor for
MC risk factors for hepatocellular carcinoma
Vinyl chloride as a risk factor for
MC risk factor for liver angiosarcoma
MC risk factor for gallbladder adenocarcinoma
Gallstones, porcelain gallbladder
MC risk factor for pancreas adenocarcinoma
Polycyclic hydrocarbons
MC risk factor for renal cell carcinoma
Polycyclic hydrocarbons
MC risk factor for urinary bladder
Polycyclic hydrocarbons
MC risk factor for penis SCC
HPV + lack of circumcision
MC risk factor for prostate adenocarcinoma
MC risk factor for seminoma
Cryptorchid testis
MC risk factor for breast and endometrial carcinoma
Age > 50 with excess estrogen exposure
MC risk factor for vulva, vagina, cervix SCC
HPV 16/18
MC risk factor for vagina/cervix clear cell carcinoma
MC risk factor for surface derived ovarian cancer
MC risk factor for choriocarcinoma
Complete mole
MC risk factor for dysgerminoma of ovary
Turner syndrome (XO)
Turner syndrome (XO/XY) as a risk factor for
gonadoblastoma of ovary
MC risk factor for papillary cancer of thyroid
Ionizing radiation
MC risk factor for medullary carcinoma thyroid
Family history (MEN IIa/IIb)
MC risk factor for malignant lymphoma thyroid
Hashimoto's Thyroiditis
MC risk factor for osteogenic sarcoma
ionizing radiation
MC risk factor for primary CNS lymphoma in AIDS and Burkitt's lymphoma
MC risk factor for acute/chronic myelogenous leukemia
Ionizing radiation
MC risk factor for Burkitt's lymphoma
MC risk factor for T cell leukemia/lymphoma
Bacterial causes of cancer
H. pylori (stomach adenocarcinoma and lymphoma)
Parasitic causes of cancer
S. hematobium (SCC bladder), C. sinensis (cholangiocarcinoma)
mutations involving regulatory genes
Regulatory genes, general types
protooncogenes, suppressor genes, anti-apoptosis genes
Types of mutations
point mutation MC, translocation, amplification (inc copies), overexpression (inc activity)
Burkitt's translocation
CML translocation
follicular lymphoma translocation
APL leukemia translocation
2 Key cancer genes:
TP53 suppressor gene, RAS protooncogene
Point mutation
inactivates suppressor genes (e.g., TP53), activates protooncogenes (e.g., RAS)
Amplification mutation
activates ERB-B2
Overexpression mutation
enhances activity of BCL-2
SIS Proto-oncogene
function- growth factor synthesis; mutation- overexpression
ERB-B2 Proto-oncogene
function- growth factor receptor; activation bad prognostic sign for breast carcinoma
RAS Proto-oncogene
function- GTP signal transduction; point mutation; 30% of all human cancer
ABL Proto-oncogene
function- non-receptor tyrosine kinase activity; translocation (9;22) causing CML
MYC Proto-oncogene
function- nuclear transcription; translocation (8; 14) causing Burkitt's lymphoma
Inactivation suppressor genes
majority are point mutations; loss of suppression
Sporadic retinoblastoma
two hit theory; two separate point mutations of RB suppressor gene on # 13
AD retinoblastoma
one hit theory; one already inactivated in germ cells
TP53 suppressor gene functions
G1-S phase inhibition, DNA repair, activation BAX apoptosis gene
Inactivation TP53 suppressor gene:
inactivation causes majority of human cancers
RB suppressor gene function
G1-S phase inhibition
Inactivation RB suppressor gene
retinoblastoma, osteogenic sarcoma
APC suppressor gene function
prevents nuclear transcription by catenin
Inactivation APC suppressor gene
familial polyposis
BRCA1-2 suppressor genes function
DNA repair
Inactivation BRCA 1/2 suppressor genes
breast, ovarian cancers
BCL-2 function
anti apoptosis gene (keeps cytochrome c in mitochondria)
BCL-2 gene
t(14;18) translocation of heavy chain causes overexpression; follicular B cell lymphoma
Xeroderma pigmentosum
AR; defect in DNA repair enzymes; inc risk for UVB light cancers
Hereditary non-polyposis syndrome
AD; inactivation DNA mismatch genes; colorectal cancer
Chromosome instability syndromes
AR; susceptibility to DNA damage; leukemias, lymphomas
Examples of chromosome instability
Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome
chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in burn scar)
Polycyclic hydrocarbons
key chemical carcinogen (cigarette smoke)
produced from Aspergillus; hepatocellular carcinoma
lung cancer, mesothelioma
Thorium dioxide causes
hepatocellular carcinoma, cholangiocarcinoma
Aniline dyes causes
transitional cell carcinoma
Vinyl chloride causes
angiosarcoma of liver
Benzene causes
Cyclophosphamide causes (neoplasm)
transitional cell carcinoma of bladder
EBV causes which neoplasms:
Burkitt's; CNS lymphoma (AIDS); Hodgkins mixed cellularity; nasopharyngeal carcinoma
HBV and HCV cause which neoplasm
hepatocellular carcinoma
HPV causes which neoplasms
cervical, penis, and anorectal squamous cancers
HHV-8 causes which neoplasm
Kaposi sarcoma
basal cell carcinoma, squamous cell carcinoma, malignant melanoma
Key host defense to neoplasms
cytotoxic CD8 T cells (type N hypersensitivity)
cachexia in cancer
due to tumor necrosis factor-alpha
Most common anemia in cancer
anemia chronic disease
Most common coagulopathy in cancer
Most common COD in cancer
gram negative infection
Acanthosis nigricans, seborrheic keratoses and cancer
possible markers for gastric adenocarcinoma
clubbing and cancer
possible marker for lung cancer
Non-bacterial thrombotic endocarditis mitral valve and cancer
possible marker for pancreatic cancer
TNM staging
metastasis more important than nodal involvement
AFP found with
hepatocellular carcinoma, yolk sac tumors
PSA found with
prostate cancer
CEA found with
recurrence colorectal cancer
(any GI cancer)
BJ protein found with
multiple myeloma
beta hCG found with
Calcitonin elevated with
medullary carcinoma thyroid, hypocalcemia
Small cell carcinoma lung associated hormones
ADH (hyponatremia), ACTH (ectopic Cushing's)
Renal cell carcinoma associated hormones
EPO (polycythemia), PTH-related peptide (hypercalcemia)
Hepatocellular carcinoma associated hormones
EPO (polycythemia), insulin-like factor (hypoglycemia)
Medullary carcinoma of thyroid associated hormones
calcitonin (hypocalcemia), ACTH (ectopic Cushing's)
Squamous cell carcinoma of lung associated hormones
PTH-related peptide (hypercalcemia)