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57 Cards in this Set
- Front
- Back
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What is a functional disease?
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A state that lacks lacks altered anatomy or measurable biochemistry. (not covered in path)
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Name four causes of hyperplasia/hypertrophy.
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Increased demand (weight lifting), nutrition (adipose tissue), growth/mechanical factors (skin callous) and hormonal stimulation (uterus in pregnancy).
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Define hypertrophy and name a physiologic and pathologic example of hypertrophy.
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Increase in cell size: muscle hypertrophy (insulin-like growth factor) and LVH (aortic stenosis and HTN), also defective myostatin gene (anti-GF) <--muscular cow
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Define hyperplasia and name a physiologic and pathologic example of hyperplasia.
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Increase in cell number: BPH = benign prostatic hyperplasia, uterine myometrium in pregnancy,alveoli of lactating breast from prolactin and TSH hyperplasia
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Define subcellular adapatation.
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Change in cellular organelles; liver increases SER with exposure to drugs
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What are the causes of atrophy?
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Ischemia (loss of blood supply), loss of endocrine support (thymus involution - mostly fat), denervation, decreased workload (broken limb), decreased nutrition, aging (fewer trabeculae in osteoporosis), pressure (i.e. adjacent cells to a tumor), toxins or drugs, X rays, and immunologic mechanisms. (Atrophy is potentially reversible but later is replaced by CT).
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What are the 2 mechanisms of subcellular atrophy?
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Ubiquitin-proteosome pathway: ubiquitin recognizes and targets proteins for destruction by proteosome; Autophagy: catabolism of cytoplasm and cell organelles in autophagic vacuoles, undigested lipid material appears as lipofuscin pigment in residual bodies (termed "brown atrophy" if grossly apparent)
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Define metaplasia.
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Change in cell type in response to a chronic stimulus; common in epithelia, can occur in CT; often irreversible
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What kinds of metaplasia are the following: physiologic metaplasia of uterine cervix at puberty, Barret's espohagus, bronchical mucosa to smoking, bladder mucosa to inflammation, Helicobacter pylori, Schistosoma hematobium, myeloid metaplasia
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Squamous (uterine cervix), columnar in response to acid; squamous (bronchus), squamous (bladder), columnar intestinal metaplasia (H pylori), squamous metaplasia of bladder (Schistosoma), proliferation of hematopoietic tissue in sites other than bone marrow (i.e. liver, spleen)
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What is cellular regeneration?
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The replacement of lost cells by cells of the same type.
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What are the three cell types (for regeneration? Give examples.
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Labile: regenerate t/o life (epithelia (basal cells), crypts in GI, stem cells in bone marrow; Stabile: normally quiescent, can regenerate (liver, smooth muscle, fibroblasts, endothelium, kidney); Permanent: don't regenerate (neurons, cardiac and skeletal muscle, kidney glomeruli)
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What is the Hayflick number?
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50-60 divisions: "cellular aging" that limits regeneration
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What factors affect regeneration? What must be present for epithelia to regenerate?
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Growth factors (paracrine) are multi-functional, age, electric currents, neuronal stimuli, cell-to-cell interactions. A scaffolding or basement membrane must be present.
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What happens in regeneration from acute tubular necrosis and what are freeze branded cattle?
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Acute tubular necrosis: low urine output initially, BM intact so cells regenerate but take time to function normally; Cattle: death of melanoytes = depigmentation
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What is dysplasia?
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Development of abnormal cells (often precursor for cancer)
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What are some causes of cellular injury?
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(cells stressed beyond adaptation) Hypoxia, ischemia, physical agents (trauma, heat), chemical agents, drugs, infection, immune injury, genetics, nutrition
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What is hypoxia and how is it different from ischemia (list MCC)?
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Hypoxia: low O2 in tissue (less ATP synthesis). Ischemia: lack of blood flow or obstruction of venous outflow; deprive oxygen and nutrients so more damaging (atherosclerosis)
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Give examples of non-ischemic hypoxias and define hypoxemia and anemia.
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Anemia, CO poisoning (blocks O2 binding site on Hb), methemoglobinemia (higher affinity), pulmonary failure; histotoxic hypoxia - cyanide poisoning (block use of O2 by cell). Hypoxemia: lack of O2 in blood; Anemia: decreased Hb
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What 2 things lead to the failure of the cytochrome oxidase system?
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CO or CN poisoning (Cytochrome oxidase = 3 C's), causes ATP depletion
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What tissues are susceptible to hypoxia?
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"Watershed areas" (b/w 2 blood supplies): splenic flexure bw sup and inf mesenteric a's, CNS bw ACA and MCA. Also subendocardial tissue and kidney regions with most ATP (straight portion of prox tubule, NKCC in TAL)
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What are reversible and irreversible events in cellular injury?
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REV: cellular swelling (impaired Na/K ATPase), nuclear chromatin clumping (pyknosis), decrease in ATP synthesis, ribosomal detachment (decreased protein synt), glycogen usage (inc in anaerobic metab, lactic acid decreases pH, denatures proteins), steatosis. IRREV: influx of Ca and calcification (oxid phos to phospholipases, proteases, endonucleases), membrane damage, lysosomal rupture, mitoc permeability
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What is steatosis?
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Fatty change = abnormal accumulation of triglycerides in parenchymal cells (usu liver, sometimes heart)
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What are common causes of steatosis?
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MCC = ethanol -> acetaldehyde (by ADH) -> acetate (by ALDH), gives 2 NADH for fatty acid synthesis, inhibits gluconeogenesis. Diabetes: inability to use glucose -> increased ffa. NASH = nonalcoholic steatohepatitis. Malnutrition, toxins, hypoxia
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How does Kwashiorkor lead to steatosis?
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Protein deficiency -> reduced apolipoproteins -> impaired transport of triglycerides. Presents with enlarged abdomen bc of fatty liver vs. Marasmus: overall caloric deficiency, muscle wasting
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Calcium influx in cellular injury leads to activation of phospholipases. What do these to do the cellular membranes?
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Insert lysolecithim instead of lecithin which alters shape of membranes and creates pores.
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What are the common sources of free radical generation? What are the types of free radicals and what is free radical injury?
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Inflammation MC generator (neutrophils), also X rays, UV light, toxins, chemicals, also reperfusion injury. Superoxide reduces iron, hydrogen peroxide, hydroxyl most highly reactive, acetaminophen (APAP is active cmpd), carbon tetrachloride (assoc with liver cancer). Bend, break, cross-link macromolecules, damage to DNA, cross-link sulfhydryl groups, oxidize fatty acids in membranes.
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What substances neutralize free radicals?
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Enzymes: catalase (staph), superoxide dismutase, glutathione peroxidase. Vitamin antioxidants: A, C, E (hydroxyl radical)
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Contrast necrosis and apoptosis (how many cells, swell/shrink, inflamm, ATP dependence)
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Necrosis: gps of cells, swelling, pathologic, inflamm present, does not require ATP, stimulus usu direct cause of death. Apoptosis: ind cells, shrinkage, physiologic or pathologic, no inflamm, ATP dependent, stimulus activates cascade
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What is the time course of morphologic changes in necrosis and how do they appear?
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Gross changes (white, opaque, softened, sometimes hemorrhagic) lag behind LM changes lag behind ultrastructural changes (eosinophilia = red means dead) lag behind death.
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Define pyknosis, karyorrhexis and karyolysis.
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Pyknosis: shrink, dark nucleus. Karyorrhexis: fragmented into "dust." Karyolysis: dissolution of swollen nucleus.
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How does hypoxia present clinically? How does cell sensitivity to hypoxia differ from neurons to heart muscle to the leg?
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Cyanosis, confusion, cognitive impairment. Neurons: 3-5 min; Heart: 30-60 min; Leg: several hours.
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What is an infarction?
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An infarction is the formation of an infarct, that is, an area of tissue death (necrosis) due to a local lack of oxygen caused by obstruction of the tissue's blood supply as in a thrombus or embolus.
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What are the seven types of necrosis?
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Coagulation, Liquefactive, Hemorrhagic, Caseous, Enzymatic fat Gangrenous, and Fibrinoid
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Describe coagulation necrosis.
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Tissue architecture is preserved, Pink staining area surrounded by inflammatory edges. Usual type in infarcts (dense tissue like heart, liver, kidney, spleen), MC MI. If reperfused, can leak blood into necrotic area -> hemorrhagic necrosis.
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Describe hemorrhagic necrosis.
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Venous obstruction (blood cannot go in because pressure too high, leads to ischemia), reperfused infarcts, infarcts in loose tissue (lungs, small intestine)
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Describe liquefactive necrosis.
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Tissue is hydrolyzed by enzymes (from tissue or neutrophils). 2 types: abscess (skin, lungs); CNS/cerebral infarct: neurons and glia killed, brain liquefies
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Describe caseous necrosis.
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Granulomatous inflammation, tissue turns into crumbly cheesy powder. Formed by release of lipids. (macrophages, CD4 T cells/lymphocytes, giant cells, fibroblasts, CT). TB and histoplasmosis (noncaseating: sarcoidosis, Crohn disease - granulomatous enteritis and colitis)
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Define enzymatic fat necrosis.
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Pancreatic enzymes (lipases, proteases) into tissue, saponification (fatty acids plus calcium). MC pancreatitis, traumatic fat necrosis in fatty tissue
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Define gangrenous necrosis.
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Grossly visible necrosis, usually with secondary or primary infection. Wet: liquefactive (infection can spread); Dry: coagulation
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Define fibrinoid necrosis.
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Damage to vascular wall (arterioles, venules, glomerular capillaries), allows seepage of plasma proteins (fibrin-clotting factor) that stain pink. Immune-mediated vasculitis and malignant HTN
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Name some common examples of apoptosis.
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Embryogenesis (fingers), hormone-dependent involution (menses), epithelia, neutrophils (1 week) and lymphocytes (autoreactive clones), death induced by cytotoxic T cells, proximal cells to duct obstruction, virally infected cells (T cells), radiation, hypoxia
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What are the pathways to apoptosis?
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Intrinsic: BCL2 is pro-survival gene, prevents release of cytochrome c from mitochondria; p53 suppressor gene detects DNA damage, activates BAX/BAK gene which inactivates BCL-2. Extrinsic: TNF (macrophages) or Fas-L (cytotoxic T cells) to receptors. Both activate caspases.
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What is contagious apoptosis?
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When caspases leak into surrounding tissue, can damage neighbor (edges of strokes)
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What happens to protein synthesis in response to cellular stress?
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It shuts down temporarily and there is an increase in synthesis of heat-shock proteins. These include unfoldases or chaperones that repair damaged proteins and the ubiquitin-proteosome pathway is activated.
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Name the five cellular pigments.
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Lipochrome (lipofuscin), hemosiderin, melanin, bilirubin and carbon.
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What is lipochrome?
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A brown, granular pigment from normal "wear and tear." (brown atrophy) In liver, heart, brain (long-lived cells), not pathologic, lipid pigments, oxidation of fatty acid
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What is hemosiderin?
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Iron bound to ferritin (storage protein) shows up as brown, granular pigment in bone marrow, liver, spleen (normal), and sites of hemorrhage (abnormal). Prussian blue stain and context to dx.
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What is hemachromatosis and generalized hemosiderosis?
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Increased absorption of dietary iron, can lead to generalized excess of hemosiderin causing organ damage by generation of free radical
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What is melanin?
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A granular, brown pigment that protects against UV damage; found in skin and CNS (substantia nigra) (hypervitaminosis D vs. rickets)
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What is bilirubin?
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A bile pigment from breakdown of heme/porphyrin rings that is yellow grossly and nongranular greenish-brown microscopically. Causes jaundice (skin) and icterus (eyes). Found in canaliculi (liver, bile system)
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What is carbon?
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Black pigment, granular, innocuous, stored in macrophages, found in lungs and lymph nodes (anthracosis = coal miner's lung)
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What are soluble pigments?
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Carotene and urochrome (end prod of Hb breakdown), do not appear in tissue sections
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Name 4 clear accumulations and what they are associated with.
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Triglycerides (well demarcated) - fatty change, aplastic anemia; glycogen (fuzzy) - diabetes, glycogen storage diseases (lack lysosomal enzymes), cholesterol (in macrophages = foam cells, cholesterol clefts in tissues, needle-shaped cholesterol esters) - atherosclerosis, hydropic change - membrane pumps disorder
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What is calcification and what are some physiologic examples? How does it appear grossly and microscopically?
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Deposition of calcium salts in cells or extracellular space, first in mitochondria. Pineal gland, cartilages of ribs and trachea and mitral valve. White or gray, gritty grossly; blue-purple, pale, hard-edged microscopically
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What are the 2 types of calcification?
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1) Dystrophic: localized in necrotic tissue, normal Ca/phosphate, secondary to pathology (pancreatitis, breast ca, heart valves, atherosclerosis, scars) 2) Metastatic: serum Ca/phosphate high, healthy tissues calcify (hyperparathyroidism, destruction of bone tissue, vit D disorders)
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What is autolysis?
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Cell death after removal from or death of body, due to liberation of hydrolytic enzymes, first in pancreas/gastric mucosa, preserve in fixative
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What are some cellular aging theories? How can you live longer?
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Telomere shortening, wear and tear, mutations/repair defects, genetic activity changes. (cancer cells have telomerase) Increase HDL, decrease caloric intake (increases Sirtuin - stablizes DNA), decrease insulin
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