Question | Answer |
PO2 | driving force for diffusion of O2 into tissue |
SaO2 | percent heme groups occupied by O2 |
Cyanosis | decreased O2 saturation (SaO2); O2 content |
Oxygen | electron acceptor in oxidative pathway |
Hypoxia | inadequate O2 leads to ATP depletion |
Ischemia | decreased arterial (or venous) blood flow |
Respiratory acidosis | retention of CO, always decreases PaO2 |
Ventilation defect | impaired delivery of O2 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 | O2 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis) |
Methemoglobin | ↓ SaO2; heme Fe+3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue |
Clinical methemoglobinemia | cyanosis not corrected by O2; chocolate colored blood |
Carbon monoxide | ↓ SaO2; left-shift O2 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 | inhibits cytochrome oxidase; systemic asphyxiant |
Carbon monoxide + cyanide poisoning | house fires |
Left-shifted O2 curve | ↓ 2, 3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia |
Right-shifted O2 curve | ↑ 2, 3 BPG, high altitude, acidosis, fever |
High altitude | respiratory alkalosis enhances glycolysis; ↑ 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 | hyperthermia |
Decreased ATP | impaired Na+/K+ ATPase pump (cellular swelling); reversible |
Anaerobic glycolysis | ATP synthesis in hypoxia; lactate ↓ intracellular pH, denatures proteins |
Irreversible injury hypoxia | membrane/mitochondrial damage |
Mitochondrial damage | release cytochrome c activates apoptosis |
Irreversible injury hypoxia | ↑ cytosolic Ca2+ activates phospholipase, proteases, endonuclease |
Free radicals | unpaired electron in outer orbit; damage cell membranes and DNA |
Free radicals | superoxide, hydroxyl, peroxide, drugs (acetaminophen) |
Superoxide dismutase | neutralizes superoxide |
Glutathione | neutralizes peroxide, drug FRs |
Catalase | neutralizes peroxide |
Lipofuscin | indigestible lipid of lipid peroxidation; brown pigment increased in atrophy and FR damage |
Reperfusion injury in heart | superoxide FRs + calcium |
Mitochondrial injury | cytochrome c in cytosol initiates apoptosis |
SER hyperplasia | alcohol, barbiturates, phenytoin |
Complications SER hyperplasia | increases drug metabolism (e.g., oral contraceptives); low vitamin D |
Chediak-Higashi | membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles |
Chediak-Higashi | AR; 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 alcohol (increase in NADH); DHAP → G3P → TG |
Fatty change in liver | VLDL pushes nucleus to side |
Causes fatty change | ↑ synthesis TG/FAs, beta-oxidation of FAs, synthesis apoproteins/release VLDL |
Fatty change in kwashiorkor | ↓ synthesis of apoproteins |
Ferritin | primary iron storage protein; soluble in blood; serum level reflects marrow storage iron |
Hemosiderin | insoluble ferritin degradation product visible with Prussian blue stain |
Atrophy | 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 G0 phase (smooth muscle, hepatocytes); can enter cell cycle (growth factors, hormones) |
Permanent cells | cannot replicate; cardiac/striated muscle; neurons |
Hypertrophy | increase in cell size (structural components, DNA) |
LVH | increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis) |
RVH | pulmonary hypertension |
Bladder smooth muscle hypertrophy | prostate hyperplasia constricts urethra |
Removal of kidney | hypertrophy of remaining kidney |
Hyperplasia | 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 (DHEA) |
Gynecomastia | hyperplasia male breast tissue; normal in newborn, adolescent, elderly |
Metaplasia | one adult cell type replaces another cell type |
Squamous metaplasia in bronchus | smoking |
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 |
Dysplasia | atypical hyperplasia and metaplasia are precursors for cancer |
Squamous dysplasia in cervix | human papilloma virus |
Squamous dysplasia in bronchus | smoking |
Necrosis | death of groups of cells |
Coagulation necrosis | preservation of structural outline (due to ↑ lactic acid) |
Infarction | 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 |
Granulomas | activated macrophages (epithelioid cells); multinucleated giant cells; CD4 TH1 cells |
Epithelioid cells | γ-interferon released by CD4 T cells activates macrophages |
Multinucleated giant cells | fusion of epithelioid cells |
Granulomas | 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 |
Nephrocalcinosis | metastatic calcification of collecting tubule basement membranes |
S/S nephrocalcinosis | polyuria due to nephrogenic diabetes insipidus; renal failure |
Apoptosis | 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 |
Caspases | responsible for enzymatic cell death in apoptosis; proteases and endonucleases |
Markers of apoptosis | eosinophilic cytoplasm, pyknotic (ink dot) nucleus |
Apoptosis | loss Mullerian epithelium in male fetus; thymus involution; killing cancer cells |
Histamine | key chemical in acute inflammation; mast cell; arteriole vasodilation; ↑ venular permeability |
Rubor acute inflammation | redness; arteriole vasodilation (histamine) |
Calor acute inflammation | heat; arteriole vasodilation (histamine) |
Tumor acute inflammation | swelling; ↑ vessel permeability (histamine) |
Dolor acute inflammation | pain; bradykinin, PGE |
Acute inflammation | neutrophil dominant; ↑ IgM |
Initial vessel events | transient vasoconstriction → arteriolar vasodilation → ↑ venular permeability |
Neutrophil rolling acute inflammation | due to selectins |
Integrins | neutrophil adhesion molecules; C5a and leukotriene B, activate; neutrophil margination |
CD11/CD18 | markers for integrins |
Endothelial cell adhesion molecules | activated by IL-1 and TNF |
ICAM | intercellular adhesion molecule |
VCAM | vascular cell adhesion molecule Leukocyte adhesion molecule defect |
Activation neutrophil adhesion molecules | neutrophilic leukocytosis; corticosteroids |
Activation neutrophil adhesion molecules | neutropenia; endotoxins |
Chemotaxis | directed movement; C5a and LTB4 |
Opsonizing agents | IgG, C3b; enhance phagocytosis |
Neutrophils, monocytes, macrophages | receptors for IgG, C3b |
O2-dependent MPO system | most potent microbicidal system; neutrophils, monocytes |
ProductionofsuperoxidefromO2 | NADPH oxidase with NADPH cofactor; produces respiratory burst |
Nitro blue tetrazolium (NBT) | test for respiratory burst |
Superoxide dismutase | converts superoxide to peroxide |
Myeloperoxidase | lysosomal enzyme that combines peroxide + Cl to form bleach (HOCl) |
Microbicidal defects | chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR) |
Chronic granulomatous disease | absent NADPH oxidase; no respiratory burst |
Chronic granulomatous disease | Staphylococcus aureus not killed (catalase positive) |
Chronic granulomatous disease | 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 (see cell injury); also has defect in microtubule polymerization |
COX inhibitors | non-steroidals (non-selective), selective COX-2 inhibitors |
PGE2 | vasodilation, fever |
PGI2 | 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 |
IL-6 | stimulated by IL-1; stimulates synthesis of acute phase reactants |
Acute phase reactants | fibrinogen, ferritin, C-reactive protein |
Bradykinin | kinin produced in conversion of factor XII to factor XI |
Bradykinin | pain, vasodilator, vessel permeability; cough/angioedema, ACE inhibitors |
Anaphylatoxins | C3a and C5a; directly stimulate mast cell release of histamine |
Prostaglandin I2 | synthesized by endothelial cells; vasodilator, inhibits platelet aggregation |
Lipoxygenase | hydroxylation of arachidonic acid |
Zileuton | inhibits lipoxygenase |
Zafirlukast, montelukast | block lipoxygenase receptor |
LTC4, -D4, -E4 | bronchoconstrictors |
TXA2 | synthesized by platelets; platelet aggregation, vasoconstriction, bronchoconstriction |
Dipyridamole | inhibits thromboxane synthase |
Corticosteroids | inhibits phospholipase A2, activation neutrophil adhesion molecules |
Corticosteroids | neutrophilic leukocytosis, lymphopenia, eosinopenia |
Fever | right shift OBC; hostile to bacterial/viral replication |
Chronic inflammation | monocyte/macrophage; ↑ IgG; repair by fibrosis |
Granuloma | cellular immunity; macrophages interact with TH1 class cells (memory cells) |
Positive PPD | Langerhan’s cells process PPD and interact with TH1 class cells |
Suppurative inflammation | abscess; Staphylococcus aureus (coagulase) |
Cellulitis | subcutaneous inflammation; Streptococcus pyogenes (hyaluronidase) |
Pseudomembranous inflammation | toxins from Corynebacterium diphtheriae, Clostridium difficile |
Cell cycle | key checkpoint G1 to S phase |
TP53 and RB suppressor genes | arrests cell in G1 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 | cell must be capable of duplication, no damage to basement membrane |
Scar tissue | end-product of repair by connective tissue |
Collagen | triple helix of cross-linked α chains |
Collagen | cross-links at points of hydroxylation (lysyl oxidase) increase tensile strength |
Type I collagen | bones, tendons |
Type II collagen | early wound repair |
Type IV collagen | basement membrane |
Type X collagen | epiphyseal plate |
Laminin | key basement membrane glycoprotein |
Fibronectin | 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 | becomes scar tissue |
Collagenases | zinc cofactor (metalloprotease); type III collagen replaced by type I collagen |
Tensile strength of healed wound | 80% original strength |
Inhibition wound healing | infection (MCC S. aureus), zinc deficiency, DM |
Ehlers-Danlos syndrome | defects in collagen synthesis and structure; hyperelasticity |
Scurvy | ↓ collagen tensile strength by decreasing cross-links at points of hydroxylation |
Keloid | excessive type III collagen; common in blacks |
Pyogenic granuloma | exuberant granulation tissue; bleeds when touched |
Healing by primary intention | clean wound; appose wound margins with suture |
Healing by secondary intention | infected wound; leave wound open; myofibroblasts important |
Liver injury | regenerative nodules; abnormal cytoarchitecture |
Lung injury | type II pneumocyte repair cell |
CNS injury | astrocyte and microglial cell repair cells; gliosis |
WBC alterations in acute inflammation | neutrophilic leukocytosis, left shift, toxic granulation |
Erythrocyte sedimentation rate | increased fibrinogen enhances rouleaux |
C-reactive protein | indicator of acute inflammation and inflammatory atheromatous plaque |
Polyclonal gammopathy | diffuse ↑ of γ-globulins; ↑ IgG; chronic inflammation |
Total body water | ECF (plasma, interstitial fluid) + ICF (cytosol) |
Osmosis | H20 shift between ECF and ICF; controlled by serum Na+ and glucose |
Edema | increased fluid in interstitial space or body cavities; transudate, exudate, lymph |
Transudate | 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 |
↑ Hydrostatic pressure | pulmonary edema in LHF; pitting edema of legs in RHF; portal hypertension |
Renal retention sodium and water | ↑ hydrostatic pressure and ↓ oncotic pressure |
Causes of renal retention of sodium/water | ↓ cardiac output (activation RAA system), primary renal disease |
↓ Oncotic pressure (hypoalbuminemia) | kwashiorkor; nephrotic syndrome; cirrhosis |
Ascites in cirrhosis | ↓ oncotic pressure, ↑ hydrostatic pressure |
Exudate | protein and cell rich (pus); acute inflammation with ↑ vessel permeability |
Lymphedema | radical mastectomy; filariasis; inflammatory carcinoma (lymphatics plugged by tumor) |
Thrombus | endothelial injury, stasis, hypercoagulability |
Venous thrombus | fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis) |
Heparin/warfarin | anticoagulants that prevent venous clot formation |
Arterial thrombus | endothelial injury; platelets held together by fibrin |
Aspirin | 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 |
Diving | 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) | ↓ CO and LVEDP; ↑ PVR |
Cardiogenic shock | ↓ CO; ↑ LVEDP and PVR |
Septic shock | ↑ CO (↑ venous return); ↓ PVR (vasodilation) |
Kidneys | most susceptible organ in shock; straight portion proximal tubule most susceptible |
Shock complications | ischemic ATN, multiorgan failure, ↑ AG metabolic acidosis |
Tumors | parenchyma neoplastic component |
Benign tumors | epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma) |
Carcinoma | epithelial origin; squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma |
Basal cell carcinoma | invades but does not metastasize |
Squamous cell carcinoma | lower lip, oral pharynx, larynx, lung, esophagus, skin, cervix |
Adenocarcinoma | distal esophagus → colon, kidney, liver, pancreas, prostate, breast, lung, endometrium |
Transitional cell carcinoma | renal pelvis, ureter, bladder |
Sarcoma | malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone) |
Liposarcoma | MC sarcoma in adults |
Embryonal rhabdomyosarcoma | MC sarcoma in children |
Teratoma | ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray |
Hamartoma | normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp |
Choristoma | normal tissue aberrant tissue location; pancreatic tissue stomach wall |
Mixed tumor | different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid |
Leukemia | malignancy of stem cells in bone marrow |
Lymphoma | 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 |
Monoclonality | key finding in neoplastic vs. normal cells |
E-Cadherin | intercellular adhesion; lose adhesion in malignant cells |
Malignant cells | receptors for laminin (basement membrane), fibronectin (ECM) |
Invasion enzyme | type IV collagenase (basement membrane) |
Angiogenesis | basic fibroblast growth factor, vascular endothelium growth factor |
Metastasis | lymphatic, hematogenous, seeding; often more common than primary cancer |
Carcinoma | lymph node -> hematogenous |
Vessel invading carcinomas | renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma |
Sarcoma | hematogenous |
Seeding | 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 |
Osteolytic metastasis | breast cancer |
EM neurosecretory granules | carcinoid tumors, small cell carcinoma, neuroblastoma |
EM thin and thick myofilaments | rhabdomyosarcoma |
EM Birbeck granules | histocytic neoplasms (Langerhan’s histiocytosis) |
Primary prevention | 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 | decreased incidence of cervical cancer; detects cervical dysplasia |
Malignant melanoma | fastest increasing in world |
Southeast China | nasopharyngeal carcinoma (EBV) |
Southeast Asia | hepatocellular carcinoma (HBV + aflatoxin) |
Japan | stomach cancer |
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) | risk factor for adenocarcinoma |
Endometrial hyperplasia | risk factor for adenocarcinoma |
Glandular (intestinal) metaplasia of stomach (Helicobacter) | risk factor for adenocarcinoma |
Chronic ulcerative colitis | risk factor for adenocarcinoma |
Villous adenoma of rectum | risk factor for adenocarcinoma |
Tubular adenoma of colon | risk factor for adenocarcinoma |
Scar tissue in lung | risk factor for adenocarcinoma |
Regenerative nodules in cirrhosis | risk factor for hepatocellular carcinoma |
Complete hydatidiform mole | risk factor for choriocarcinoma |
Dysplastic mole | MC risk factor for malignant melanoma |
UVB light | MC risk factor for BCC, SCC, melanoma |
HHV-8 | MC risk factor for Kaposi’s sarcoma |
EBV | MC risk factor for nasopharyngeal carcinoma |
Polycyclic hydrocarbons | MC risk factor for larynx (SCC), lung cancers |
Asbestos | MC risk factor for mesothelioma |
Polycyclic hydrocarbons | MC risk factor for oral cavity, mid-esophagus SCC |
Barrett’s esophagus | MC risk factor for distal esophagus adenocarcinoma |
H. pylori | MC risk factor for stomach adenocarcinoma and lymphoma |
Tubular adenoma, villous adenoma | MC risk factors for colon adenocarcinoma |
HBV and HCV | MC risk factors for hepatocellular carcinoma |
Vinyl chloride | MC risk factor for liver angiosarcoma |
Gallstones, porcelain gallbladder | MC risk factor for gallbladder adenocarcinoma |
Polycyclic hydrocarbons | MC risk factor for pancreas adenocarcinoma |
Polycyclic hydrocarbons | MC risk factor for renal cell carcinoma |
Polycyclic hydrocarbons | MC risk factor for urinary bladder |
HPV + lack of circumcision | MC risk factor for penis SCC |
Age | MC risk factor for prostate adenocarcinoma |
Cryptorchid testis | MC risk factor for seminoma |
Age >50 with excess estrogen exposure | MC risk factor for breast and endometrial carcinoma |
HPV 16/18 | MC risk factor for vulva, vagina, cervix SCC |
DES | MC risk factor for vagina/cervix clear cell carcinoma |
Nulliparity | MC risk factor for surface derived ovarian cancer |
Complete mole | MC risk factor for choriocarcinoma |
Turner syndrome (XO) | MC risk factor for dysgerminoma of ovary |
Turner syndrome (XO/XY) | gonadoblastoma of ovary |
Ionizing radiation | MC risk factor for papillary cancer of thyroid |
Family history (MEN IIa/IIb) | MC risk factor for medullary carcinoma thyroid |
Hashimoto’s thyroiditis | MC risk factor for malignant lymphoma thyroid |
Ionizing radiation | MC risk factor for osteogenic sarcoma |
EBV | MC risk factor for primary CNS lymphoma in AIDS and Burkitt’s lymphoma |
Ionizing radiation | MC risk factor for acute/chronic myelogenous leukemia |
EBV | MC risk factor for Burkitt’s lymphoma |
HTLV-1 | 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) |
Carcinogenesis | mutations involving regulatory genes |
Regulatory genes | proto-oncogenes, suppressor genes, anti-apoptosis genes |
Types mutations | point mutation MC, translocation, amplification (↑ copies), overexpression (↑ activity) |
Translocations | Burkitt’s t(8;14); CML t(9;22); follicular lymphoma t( 14;18); APL leukemia t( 15;17) |
Key cancer genes | TP53 suppressor gene, RAS protooncogene |
Point mutation | inactivates suppressor genes (e.g., TP53), activates proto-oncogenes (e.g., RAS) |
Amplification | activates ERB-B2 |
Overexpression | enhances activity of BCL-2 |
S/S POC | function-growth factor synthesis; mutation-overexpression |
ERB-B2 POC | function growth factor receptor; activation bad prognostic sign for breast carcinoma |
RAS POC | function-GTP signal transduction; point mutation; 30% of all human cancer |
ABL POC | function-non-receptor tyrosine kinase activity; translocation (9;22) causing CML |
MYC POC | 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 |
AD retinoblastoma | one hit theory; one already inactivated in germ cells |
TP53 suppressor gene functions | G,-S phase inhibition, DNA repair, activation BAX apoptosis gene |
Inactivation TP 53 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 (FAP) |
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 [think t(14;18) = t(l4;lB) for foLLicular B] |
Xeroderma pigmentosum | AR; defect in DNA repair enzymes; ↑ risk for UVB light cancers |
Hereditary non-polyposis syndrome (HNPCC) | AD; inactivation DNA mismatch genes; colorectal cancer |
Chromosome instability syndromes | AR; susceptibility to DNA damage; leukemias, lymphomas |
Examples chromosome instability | Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome |
Carcinogens | chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in bum scar) |
Polycyclic hydrocarbons | key chemical carcinogen (cigarette smoke) |
Aflatoxins | produced from Aspergillus; hepatocellular carcinoma |
Asbestos | lung cancer, mesothelioma |
Thorium dioxide | hepatocellular carcinoma, cholangiocarcinoma |
Aniline dyes | transitional cell carcinoma |
Vinyl chloride | angiosarcoma of liver |
Benzene | leukemia |
Cyclophosphamide | transitional cell carcinoma of bladder |
EBV | Burkitt’s; CNS lymphoma (AIDS); Hodgkin’s mixed cellularity; nasopharyngeal carcinoma |
HBV and HCV | hepatocellular carcinoma |
HPV | cervical, penis, and anorectal squamous cancers |
HHV-8 | Kaposi sarcoma |
UVB cancers | basal cell carcinoma, squamous cell carcinoma, malignant melanoma |
Key host defense | cytotoxic CD8 T cells (type IV hypersensitivity) |
Cachexia | due to tumor necrosis factor-α |
Most common anemia | anemia chronic disease |
Most common coagulopathy | hypercoagulability |
Most common COD in cancer | gram negative infection |
Acanthosis nigricans, seborrheic keratoses; possible markers for gastric adenocarcinoma | |
Clubbing | possible marker for lung cancer |
Non-bacterial thrombotic endocarditis mitral valve | possible marker for pancreatic cancer |
TNM staging | metastasis more important than nodal involvement |
AFP | hepatocellular carcinoma, yolk sac tumors |
PSA | prostate cancer |
CEA | recurrence colorectal cancer |
BJ (Bence-Jones) protein | multiple myeloma |
β-human chorionic gonadotropin | choriocarcinoma |
Calcitonin | medullary carcinoma thyroid; hypocalcemia |
Small cell carcinoma lung | ADH (hyponatremia), ACTH (ectopic Cushing’s) |
Renal cell carcinoma | EPO (polycythemia), PTH-related peptide (hypercalcemia) |
Hepatocellular carcinoma | EPO (polycythemia), insulin-like factor (hypoglycemia) |
Medullary carcinoma of thyroid | calcitonin (hypocalcemia), ACTH (ectopic Cushing’s) |
Squamous cell carcinoma of lung | PTH-related peptide (hypercalcemia) |