Step 1 - Patho

denniskwinn's version from 2015-04-25 16:12


Question Answer
Apoptosis Intrinsic pathwayChanges in the level of anti- and pro-apoptotic factors lead to ↑ mitochondrial permeability and release of cytochrome c leads to activation of cytosolic caspases that mediate cell breakdown - embryogenesis, hormone induced (menstruation), and atrophy (endometrium in menopause) and injurious stimuli (radiation, toxins, hypoxia)
Apoptosis Extrinsic pathway ligand-receptor interactions (Pas ligand to Fas [CD95]) or immune cell (Tkliler) release of perforin and granzyme B - leads to activation of cytosolic caspases that mediate cell breakdown
Apoptosis microcell shrinkage, nuclear shrinkage and basophilia (pyknosis ), membrane blebbing, pyknotic nuclear fragmentation (karyorrhexis), nuclear fading (karyolysis), formation of apoptotic bodies, which are phagocytosed. No significant inflammation.
Necrosis characterizationenzymatic cell degradation from exogenous injury. digestion and protein denaturation w/ release of intracellular components, Inflammation
Necrosis histo typescoagulative (heart, liver, kidney), liquefactive (brain ),caseous (tuberculosis), Fat (pancreas), or fi brinoid (blood vessels). Gangrenous necrosis can be dry (ischemic coagulative) Wet Gangrene (with Bacteria) and is common in limbs and GI tract.
Reversible cell injuryCell swelling, chromatin clumping, ↓ ATP synthesis, ↓ glycogen, Fatty change, Ribosomal detachment
Irreversible cell injuryNuclear pyknosis , karyolysis, karyorrhexis, Ca2+ influx →caspase activation, Plasma membrane damage, Lysosomal rupture, Mitochondrial permeability
Pale infarctin solid tissues with single blood supply = heart, kidney, and spleen
Red infarct (hemorrhagic)in loose tissues with collaterals = liver, lungs, or intestine or following reperfusion.
Reperfusion injurydue to damage by free radicals
Inflammation characterrubor (redness), dolor (pain), calor (heat), tumor ( swelling), and loss of function
Fluid exudation in inflammation ↑ vascular permeability, vasodilation, endothelial injury.
Leukocyte activation in inflammationEmigration (rolling, tight binding, diapedesis); chemotaxis (bacterial products, complement, chemokines); phagocytosis and killing.
Neutrophil chemokinesC5a, IL-8, Leukotrlene B4, and Kallikrein
Fibrosis in inflammationFibroblast emigration and proliferation; deposition of ECM.
Mediators of Acute InflammationNeutrophil, eosinophil, and antibodies - rapid onset (seconds to minutes) last minutes to days
Mediators of Chronic InflammationMononuclear cells - characterized by persistent destruction and repair - assoc w/ blood vessel proliferation, fibrosis
Granulomanodular collections of epitheliod macros and giant cells
Granulomatous diseasesTB (caseating), syphilis, Listeria monocytogenes, Wegener’s, leprosy, bartonella, some fungal pneumonias, sarcoidosis, Crohn’s (this stupid loser won't let baby frankenstein steal cars)
Granuloma formation mediationIL-2, IFN- gamma
Possible resolutions of inflammationRestoration to normal, Granulation tissue, Abscess, Fistula, Scarring
Granulation tissueresolution of inflammation - highly vascularized, fibrotic.
Abscessresolution of inflammation - fibrosis surrounding pus.
Fistularesolution of inflammation - abnormal communication.
Scarringresolution of inflammation - collagen deposition resulting in altered structure and function
TransudateHypocellular, Protein poor, Specific gravity < 1.012, Due to: ↑ hydrostatic pressure, ↓ oncotic pressure, Na+ retention
ExudateCellular, Protein Rich, Specific gravity>1.020, Due to: lymphatic obstruction, inflammation
Free radical injury can be initiated byradiation, metabolism of drugs (phase I), redox reaction, nitric oxide, transition metals, leukocyte oxidative burst.
Free radical injuryInduces injury through membrane lipid peroxidation, protein modification, DNA breakage - degradation through enzymes (catalase, superoxlde dismutase, glutathione peroxidase), spontancous decay, antioxIdants (vitamins A, C, E) - Reperfusion after anoxia induces free radical production (e.g., superoxide) = major cause of injury after thrombolytic therapy.
AmyloidosisBeta-pleated sheet demonstrable by apple-green birefringence of Congo red stain under polarized light; affected tissue has waxy appearance
Primary amyloidAL - from Ig light chains (multiple myeloma)
Secondary amyloidAA - serum amyloid associated protein (SAA) (chronic inflammatory disease) - Acute phase reactant
Senile cardiac amyloidTransthyretin - from AF- F for fogies
Dm2 amyloidAmylin - from AE - E for endocrine
Medullary carcinoma of thyroid amyloidA-CAL - from calcitonin - CAL
Alz amyloidBeta-amyloid - from APP (amyloid precursor protein)
Dialysis associated amyloidBeta-microglobulin - from MHC class I proteins
Hypovolemic/cardiogenic shockLow output failure, ↑TPR, Low CO, Cold, clammy patient
Septic shockHigh-output failure, ↓TPR, Dilated arterioles, high MVP, Hot patient


Question Answer
Hallmarks of cancerevading apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signal , sustained angiogenesIs, limitless replicative potential, tissue invasion , and metastasis
Hyperplasiaincreased number of cells
Dysplasiaabnormal prolif of cells with loss of size, shape and orientation
In situ carcinomaNeoplastic cells have not invaded basement membrane, High nuclear/cytoplasmic ratio and clumped chromatin, Neoplastic cells encompass entire thickness, Tumor cells are monoclonal
Requirement to transition to invasive carcinomainvading basement membrane using collagenases and hydrolases, can metastasize if they reach a blood or lymphatic vessel
Requirements to Metastasisspread to distant organ, “Seed and soil” theory of metastasis, Seed=tumor embolus, Soil=target organ -liver, lungs, bone, brain, angiogenesis allows for tumor survival, ↓ cadherin, ↑ laminin, integrin receptors
Metaplasia1 adult cell type replaced by another - often secondary to irritation and/or environmental exposure
Anaplasiaabnormal cells lacking differentiation - like primitive cells of same tissue - often equated with undifferentiated malignant neoplasms - littler or no resemblance to tissue of origin.
Tumor gradeDegree of differentiation based on histologic appearance. Usually graded I-IV on degree of differentiation and number of mitoses per high-power field; character of tumor itself.
Tumor stageDegree of localization Is based on site and size of lesion, spread to regional lymph nodes, presence of metastases; spread of tumor in a specific patient.
TNM tumor stagingT= size of Tumor, N= node of involvement, M=metastases
Epithelial tumorsBenign = Adenoma, papilloma . . Malignant=Adenocarcinoma, papillary carcinoma
Malignant blood cell tumorsLeukemia, Lymphomas
Blood vessel tumorsBenign = Hemangioma, Malignant = Angiosarcoma
Smooth muscle tumorsBenign = Leiomyoma, Malignant = Leiomyosarcoma
Skeletal muscle tumorsBenign = Rhabdomyoma, Malignant = Rhabdomyosarcoma
Bone tumorsBenign = Osteoma Malignant = Osteosarcoma
Fat tumorsBenign = Lipoma, Malignant = Liposarcoma
Tumors with >1 cell typeMature teratoma (women), Immature teratoma and mature teratoma in men
Benign tumor characteristicsUsually well differentiated, slow growing, well demarcated. no metastasis.
Malignant tumor characteristicsMay be poorly differentia ted, erratic growth, locally invasive/diffuse, may metastasize


Question Answer
Neoplasms assoc w/ Down SyndromeALL, AML
Neoplasms assoc w/ Xeroderma pigmentosum, albinismMelanoma, basal cell carcinoma and especially squamous cell carcinoma of skin
Neoplasms assoc w/ chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnantsgastric adenocarcinomas
Neoplasms assoc w/ Tuberous sclerosis (facial angiofibroma, seizures, MR)Astrocytoma, angiomyolipoma, cardiac rhabdomyoma
Neoplasms assoc w/ Actinic keratosissquamous cell carcinoma of skin
Neoplasms assoc w/ Barrett’s esophagus (chronic GI reflux)Esophageal adenocarcinoma
Neoplasms assoc w/ Plummer-Vinson syndrome (Atrophic glossitis, esophageal webs, anemia, all due to iron deficiency) Squamous cell carcinoma of esophagus
Neoplasms assoc w/ Cirrhosis (EtOH, HBV, HCV)Hepatocellular carcinoma
Neoplasms assoc w/ Ulcerative colitisColonic adenocarcinoma
Neoplasms assoc w/ Paget’s disease of bonesecondary osteosarcoma and fibrosarcoma
Neoplasms assoc w/ Immunodeficiency statesMalignant lymphomas
Neoplasms assoc w/ AIDSAggressive malignant lymphomas (non-Hodgkins) and Kaposi’s sarcoma
Neoplasms assoc w/ Autoimmune diseases (Hashimoto’s, Myasthenia gravis)Lymphoma
Neoplasms assoc w/ Acanthosis nigricans (hyperpigmentation and epidermal thickening)Visceral malignancy (stomach, lung, breast, uterus)
Neoplasms assoc w/ dysplastic nevusMalignant melanoma
Neoplasms assoc w/ radiation exposureSarcoma, papillary thyroid cancer
Oncogenesgain of function genes - only need one allele
Abloncogene assoc w/ CML
C-myconcogene assoc w/ Burkitt’s lymphoma
Bcl-2oncogene assoc w/ Follicular and undifferentiated lymphomas (inhibits apoptosis)
Erb-B2oncogene assoc w/ breast, ovarian, gastric carcinomas
Rasoncogene assoc w/ colon carcinoma
L-myconcogene assoc w/ lung tumor
N-myconcogene assoc w/ neuroblastoma
Retoncogene assoc w/ multiple endocrine neoplasia (MEN) types II
C-kitoncogene assoc w/ Gastrointestinal stromal tumor (GIST)
Tumor suppressor genesLoss of function→cancer’ both alleles must be lost for expression of disease
Rbtumor suppressor assoc w/ Retinoblastoma, osteosarcoma - 13q
BRCA1tumor suppressor assoc w/ breast and ovarian cancer - 17q
BRCA2tumor suppressor assoc w/ breast cancer only - 13q
P53tumor suppressor assoc w/ most human cancers, Li-fraumeni syndrome - 17p
P16tumor suppressor assoc w/ melanoma - 9p
APCtumor suppressor assoc w/ colorectal cancer (assoc w/ FAP) - 5q
Wt1tumor suppressor assoc w/ Wilms’ tumor - 11p
Nf1tumor suppressor assoc w/ Neurofibromatosis 1 - 17q
Nf2tumor suppressor assoc w/ Neurofibromatosis 2 - 22q
DPCtumor suppressor assoc w/ pancreatic cancer - 18q
DCCtumor suppressor assoc w/ colon cancer - 18q
Tumor markersnot to be used as the primary tool for cancer diagnosis. may be used to confirm diagnosis,monitor recurrence, and monitor response
PSAProstate-specific antigen. Used to screen for prostate carcinoma. Also elevated in BPH and prostatitis.
Prostatic acid phosphataseTumor marker for Prostate carcinoma.
CEATumor marker, Carcinoembryonic antigen. Very nonspecific but produced by - 70% of colorectal and pancreatic cancers; also produced by gastric and breast carcinomas .
Alpha fetoproteinNormally made by fetus. Marker for Hepatocellular carcinomas. Nonseminomatous germ cell tumors of the testis (yolk sac tumor).
Beta-hCGTumor marker for Hydatidiform moles, Choriocarcinomas, and Gestational trophoblastic tumors.
CA-125Tumor marker for ovarian, malignant epithelial tumors
S-100Tumor marker for melanoma, neural tumors, astrocytomas
Alkaline phosphataseTumor marker for Mets to bone, obstructive biliary disease, Paget’s disease
BombesinTumor marker for Neuroblastoma, lung and gastric cancer
TRAPTumor marker for Tartrate-resistant acid phosphatase - Hairy cell leukemia - a B cell neoplasm
CA-19-9tumor marker for Pancreatic adenocarcinoma
HTLV-1Oncogenic virus assoc w/ Adult T-cell leukemia/lymphoma
HBV,HCVOncogenic virus assoc w/ Hepatocellular carcinoma
EBVOncogenic virus assoc w/ Burkitt’s lymphoma, nasopharyngeal carcinoma
HPVOncogenic virus assoc w/ cervical carcinoma (16,18), penile/anal carcinoma
HHV-8Oncogenic virus assoc w/ Kaposi’s sarcoma, body cavity fluid B-cell lymphoma
Aflatoxinschemical carcinogen produced by aspergillus affecting liver (hepatocellular carcinoma)
Vinyl chloridechemical carcinogen affecting liver (angiosarcoma)
CCL4chemical carcinogen affecting liver (centrolobular necrosis, fatty change)
Nitrosamineschemical carcinogen in smoked foods affecting Esophagus, stomach
Cigarette smokechemical carcinogen affecting Larynx (squamous), lung (squamous and small cell), kidney (renal cell), bladder( transitional cell)
Asbestoschemical carcinogen affecting lung (mesothelioma, bronchogenic carcinoma)
Arsenicchemical carcinogen affecting skin (squamous), liver (angiosarcoma)
Naphthalene (aniline) dyeschemical carcinogen affecting bladder (transitional cell carcinoma)
Alkylating agentschemical carcinogen affecting blood (leukemia)
ACTH or ACTH like peptide paraneoplastic assoc w/Small cell lung carcinoma →Cushing’s
ADH paraneoplastic assocs w/Small lung cell carcinoma, intracranial neoplasms →SIADH
PTH-related peptide, TGF-Beta, TNF, IL-1 paraneoplastic assocs w/Squamous cell lung carcinoma, renal cell carcinoma, breast carcinoma → Hypercalcemia
EPO paraneoplastic assocsRenal cell carcinoma, Pheo, Hepatocellular carcinoma, hemangioblastoma →Polycythemia
paraneoplastic assocs w/ Ab against presynaptic Ca2+ channels at NM junctionThymoma, small cell lung carcinoma → Lambert-eaton syndrome (muscle weakness0
paraneoplastic assocs w/ hyperuricemia due to excess nucleic acid turnoverleukemias and lymphomas → gout, urate nephropathy
Psammoma bodies inLaminated, concentric, calcific spherules seen in: 1. Papillary adenocarcinoma of thyroid 2. Serous papillary cystadenocarcinoma of ovary 3. Meningioma 4. Malignant mesothelioma
ESRaggregated RBCs fall at a faster rate in test tube
↑ESR ininfections, inflammation (e.g. Temporal arteritis), cancer, pregnancy, SLE
↓ESR inSickle cell (altered shape), Polycythemia (too many), CHF
Primary tumors that metastasize to brainLung, Breast, Skin (melanoma), Kidney (renal cell carcinoma), Gl. Overall , approximately 50% of brain tumors are from metastases.. . . Lots of Bad Stuff Kills Glia
Primary tumors that metastasize to the liverColon >Stomach > Pancreas> Breast> Lung. . . Cancer Sometimes Penetrates Benign Liver
Primary tumor mets to bone Prostate, Thyroid, Testes, Breast, Lung, Kidney - from breast and prostate most common - PT Barnum Loves Kids
Male cancer incidenceProstate (32%), Lung (16%), Colon and rectum (12%)
Male cancer mortalityLung (33%), Prostate (13%)
Female cancer incidenceBreast (32%), Lung (13%)-continues to increase, Colon and rectum (13%)
Female cancer mortalityLung (23%), Breast 18%)


Leukocyte extravasation
StepNphil partVasculature part
RollingSialyl Lewis x E-and P-selectin on endo cells
Tight bindingLFA-1 on nphilICAM-3
Diapedesis: leukocyte travels b/w endo cells and exits blood vessel PECAM1PECAM1
Migration - leukocyte travels through interstitium to site of injury or infection by chemotactic signals none C5a, IL8, LTB4, Kallikrein