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107 Cards in this Set
- Front
- Back
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Intinsic pathway of apoptosis
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occurs during embrogenesis, homone induction (menstruation), and atrophy, and as a result of injurious stimuli like radiation, toxins, hypoxia. Changes in the levels of anti and pro-apoptotic factors leads to increased mitochondrial permeability and release of cytochrome c
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Extrinsic pathway of apoptosis
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occurs w. ligand receptor interactions (Fas-FasL) or NK cell release of granzyme B and perforin.
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Apoptosis
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Programmed cell death. ATP required. Characterized by cell shrinkage, nuclear shrinkage and basophila/pyknosis, membrane blebbing, pyknotic nuclear fragmentation (karyorrhexis), nuclear fading (karyolysis), and formation of apoptotic bodies, which are then phagocytosed. No significant inflammation.
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Necrosis
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Enzymatic degradation of a cell resulting from exogenous injury. Characterized by enzymatic digestion and protein denaturation, with release of intracellular components. Inflammatory. Morphologies: Coagulative- heart, liver, kidney. Liquefactive-brain. Caseous-tuberculosis. Fat- pancreas. Fibrinoid- blood vessels. Limbs and GI tract: Dry gangrene-ischemic coagulative. Wet gangrene-bacterial.
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Reversible cell injury
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Cellular swelling, nuclear chromatin clumping, decreased ATP synthesis, decreased glycogen, fatty change, ribosomal detachment
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Irreversible cell injury
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Nuclear pyknosis, karyolysis, karyorrhexis. Calcium influx leads to caspase activation. Plasma membrane damage. Lysosomal rupture. Mitochondrial permeability.
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Red infarct
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Hemorrhagic, follows reperfusion, occur in loose tissues w/ collaterals like liver, lungs, or intestine. Injury due to damage by free radicals.
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Pale infart
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Occurs in solid tissues w/ single blood supply like heart, kidney, spleen
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Inflammation
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Characterized by rubor, calor, dolor, and tumor, and functio laesa
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Fluid exudation
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increased vascular permeability, vasodilation, endothelial injury
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Neutrophil chemotactics
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CILK- C5a, IL-8, Leukotriene B4, Kallikrein
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Leukocyte activation
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Emigration (rolling, tight binding, diapedesis), Chemotaxis (bacterial products, chemokines, complement), Phagocytosis and killing
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Fibrosis
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Fibroblast emigration and proliferation, deposition of ECM
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Acute inflammation
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Mediated by neutrophils, eos, and ab
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Chronic inflammation
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Mononuclear cell mediated. Characterized by persistent destruction and repair. Associated w/ blood vessel proliferation, fibrosis.
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Granuloma
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nodular collection of epithelioid machrophages and giant cells
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Resolution of inflammation
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Restoration of normal structure, Granulation tissue (highly vascularized, fibrotic. Abscess (fibrosis surrounding pus). Fistula (abnormal communication). Scarring (collagen deposition resulting in altered structure and function.
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Transudate
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Hypocellular, Protein poor, specific gravity<1.012. Due to increased hydrostatic pressure, decreased oncotic pressure, Na+ retention
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Exudate
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Cellular, Protein rich, Specific gravity >1.020. Due to- lymphatic obstruction, inflammation
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Leukocyte rolling mediated by
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Vasculature/Stroma- E-selectin, P-selectin. Leukocyte- Siayll-Lewis X
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Leokocyte tight binding mediated by
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Vasculature/Stroma- ICAM-1. Leukocyte- LFA-1 (integrin)
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Leukocyte Diapedesis mediated by
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Vasculature/Stroma- PECAM-1. Leukocyte- PECAM-1
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Leukocyte migration mediated by
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Vasculature/Stroma- bacterial products, CILK=C5a, IL-8, LTB4, Kallikrein. Leukocyte- Various
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Free radical injury
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Initiated by radiation exposure, metabolism of drugs, redox rxn, NO, transition metals, oxidative burst. Induces cell injury by membran lipid peroxidation, protein modification, DNA breakage. Free radical degradation done by catalase, superoxide dismutase, glutathione reductase, spotaneous decay, antioxidants (Vit A, C, E). Reperfusion after anoxia induces free radical production (superoxide) and is a major cause of injury after thrombolytic therapy.
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Primary amyloidosis
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Protein- AL derived from Ig light chains (multiple myeloma)
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Secondary amyloidosis
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Protein AA from Serum amyloid associated protein (SAA), chronic inflammatory dz, AA is an acute phase reactant
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Senile cardiac amyloidosis
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Transthyretin from AF
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Diabetes mellitus type 2 amyloidosis
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Amylin from AE
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Medullary carcinoma of the thyroid
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A-CAL, Calcitonin
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Alzheimer's amyloidosis
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beta-amyloid from amyloid precursor protein (APP)
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Dialysis associated amyloidosis
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beta2-microglobulin from MHC class I proteins
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Hypovolemic/cardiogenic shock
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Low CO, high total peripheral resistance, Cold, clammy pt
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Septic shock
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Decreased total peripheral resistance, dilated arterioles, high mixed venous pressure, hot pt
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Hallmarks of cancer
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evading apoptosis, self-sufficiency in growth signals, insensitive to anti-growth signals, sustained angiogenesis, limitless replicative potential, tissue invasion and metastasis
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Reversible -plasia
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Hyperplasia- increase in number of cells. Metaplasia- 1 adult cell type is replaced by another. Often secondary to irritation or environmental exposure. Dysplasia-abnormal growth w/ loss of cellular orientation, shape, and size in comparison to normal tissue maturation, commonly preneoplastic.
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Irreversible -plasia
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Anaplasia-abnormal cells lacking differentiation, like primitive cells of same tissue, often equated with undifferentiated malignant neoplasms. Little or no resemblance to tissue of origin. Neoplasia- a clonal proliferation of cells that is uncontrolled and excessive. Desmoplasia- fibrous tissue formation in response to neoplasm
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Down syndrome associated with
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ALL, AML
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Xeroderma pigmentosum and albinism associated with
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Melanoma, basal cell carcinoma, esp squamous cell carcinoma of skin
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Chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants associated with
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Gastric adenocarcinoma
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Tuberous sclerosis, facial angiofibroma, seizures, mental retardation associated with
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Astrocytoma, angiomyolipoma, and cardiac rhabdomyoma
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Actinic keratosis associated with
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Squamous cell carcinoma of skin
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Barrett's esophagus associated with
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Esophageal adenocarcinoma
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Plummer-Vinson syndrome associated with
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Squamous cell carcinoma of esophagus
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Cirrhosis associated with
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Hepatocellular carcinoma
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Ulcerative colitis associated with
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colonic adenocarcinoma
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Paget's disease of bone associated with
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secondary osteosarcoma and fibrosarcoma
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Immunodeficiency states associated with
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Malignant lymphomas
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AIDS associated with
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Aggressive malignant lymphomas (non-Hodgkin's), Kaposi's sarcoma
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Autoimmune dz (Hashimoto's, myasthenia gravis) associated with
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Lymphoma
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Acanthosis nigricans associated with
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visceral malignancy (stomach, lung, breast, uterus)
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Dysplastic nevus associated with
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Malignant melanoma
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Radiation exposure associated with
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Sarcoma, papillary thyroid cancer
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oncogene abl
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CML, tyrosine kinase
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oncogene c-myc
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Burkitt's lymphoma, transcription factor
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oncogene bcl-2
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Follicular and undifferentiated lymphomas, inhibits apoptosis
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oncogene erb-B2
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epidermal growth factor receptor, breast, ovarian, and gastric carcinomas
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oncogene ras
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Colon carcinoma, signal transduction protein involved in MAP kinase pathway
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oncogene L-myc
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Lung cancer, transcription factor
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oncogene, N-myc
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Neuroblastoma, transcription factor
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oncogene ret
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MEN 2 and 3, part of TGF-beta signaling
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oncogene c-kit
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Gastrointestinal stromal tumor (GIST), stem cell growth factor receptor
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Oncogene
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gain of function leads to cancer. Need damage to only 1 allele.
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Tumor suppressor
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loss of function leads to cancer. Need damage to both alleles.
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tumor suppressor Rb
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Ch13q, Retinoblastoma, osteosarcoma
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tumor suppressor BRCA1
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ch17q, breast and ovarian cancer
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tumor suppressor BRCA2
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ch13q, breast cancer
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tumor suppressor p53
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ch17p, most human cancers, Li-Fraumeni syndrome
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tumor suppressor p16
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ch9p, melanoma
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tumor suppressor APC
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ch5q, colorectal cancer (associated w/ FAP)
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tumor suppressor WT1
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ch11p, Wilm's tumor
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tumor suppressor NF1
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ch17q, Neurofibromatosis type 1
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tumor suppressor NF2
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ch22q, Neurofibromatosis type 2
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tumor suppressor DPC
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ch18q, pancreatic cancer, DPC=Deleted in Pancreatic Cancer
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tumor suppressor DCC
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ch18q, colon cancer, DCC=Deleted in Colon Cancer
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CEA tumor marker
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Carcinoembryonic antigen. Very nonspecific, produced by ~70% of colorectal and pancreatic cancers, also produced by breast and gastric cancers
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alpha-fetoprotein
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normally made by fetus. Marker for hepatocellular carcinoma. Nonseminomatous germ cell tumors of the testis (e.g. yolk sac tumor)
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CA-125 tumor marker
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Ovarian, malignant epithelial tumors
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S-100 tumor marker
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Melanoma, neural tumors, astrocytomas
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Alkaline phosphatase tumor marker
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Metastases to bone, obstructive biliary disease, Paget's disease of bone
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Bombesin tumor marker
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Neuroblastoma, lung and gastric cancer
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TRAP tumor marker
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Tartrate-resistant Acid Phosphatase- Hairy cell leukemia, a B cell neoplasm
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CA-19-9 tumor marker
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pancreatic adenocarcinoma
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Toxin- Aflatoxin
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Hepatocellular carcinoma
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Toxin- Vinyl chloride
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Angiosarcoma, liver
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Toxin-CCl4
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Liver- centrolobular necrosis, fatty change
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Toxin- nitrosamines in smoked foods
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Esophagus, stomach
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Toxin-Cigarette smoke
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Larynx (squamous cell carcinoma), Lung (squamous cell carcinoma and small cell carcinoma), Kidney (renal cell carcinoma), Bladder (transitional cell carcinoma)
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Toxin-Asbestos
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Lung (mesothelioma, bronchogenic carcinoma)
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Toxin-arsenic
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Skin (squamous cell carcinoma), Liver (angiosarcoma)
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Toxin-Naphthalene (aniline) dyes
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Bladder (transitional cell carcinoma)
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Toxin- Alkylating agents
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Blood (leukemia)
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Psammoma bodies
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Laminated, concentric, calcific spherules seen in: 1. Papillary adenocarcinoma of thyroid, 2. Serous papillary cystadenocarcinoma of ovary, 3. Meningioma, 4. Malignant mesothelioma
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Increased ESR
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infections, inflammation, cancer, pregnancy, SLE
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Decreased ESR
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sickle cell, polycythemia, CHF
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Metastasis to brain
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Lung, Breast, Skin (melanoma), Kidney (RCC), GI. 50% of brain cancers are mets. "Lots of Bad Stuff Kills Glia"
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Metastasis to liver
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Colon>Stomach>Pancreas>Breast>Lung, metastases more common than primary liver tumors. Cancer Sometimes Penetrates Benign Liver.
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Metastasis to bone
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Prostate, Thyroid, Testes, Breast, Lung, Kidney. Breast and prostate most common. "P.T. Barnum Loves Kids." Lung=lytic, Prostate=blastic, Breast=both lytic and blastic
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Male cancer incidence
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Prostate 32%, Lung 16%, Colon and rectum 12%
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Female cancer incidence
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Breast 32%, Lung 13%, Colon and rectum 13%
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Male cancer mortality
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Lung 33%, Prostate 13%
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Female cancer mortality
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Lung 23%, Breast 18%
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Paraneoplastic small cell lung carcinoma
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ACTH, ACTH-like peptide leads to Cushing's syndrome
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Paraneoplastic small cell lung cancer and intracranial neoplasms
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ADH leads to SIADH
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Paraneoplastic Squamous cell lung carcinoma, RCC, breast cancer
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PTH-related peptide, TGF-beta, TNF, IL-1 leads to Hypercalcemia
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Paraneoplastic RCC, hemangioblastoma
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Erythropoietin leads to polycythemia
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Paraneoplastic Thymoma, small cell lung carcinoma
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Ab against presynaptic Ca2+ channels at NMJxn leads to Lambert-Eaton syndrome (muscle weakness)
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Paraneoplastic Leukemia and lymphomas
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Hyperuricemia due to excess nucleic acid turnover (cytotoxic tx) leads to Gout and urate nephropathy
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