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Goljan HY General

Goljan HY General Pathology

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)
Created by: megankirch