Section 1
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Hypertrophy
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Last updated
6 years ago
Date created
Mar 14, 2020
Cards (125)
Section 1
(50 cards)
Hypertrophy
increase in cell size increase in structure proteins and organelles cells in G0, dont divide much so grow
amyloidosis
aggregates of proteins into beta pleated sheets that make insoluble fibrils and cause cell damage seen via congo red stain or H and E Cardiac, GI, renal, hematologic, neurologic, msk
Reversible Cell injury
Loss ATP, less pumps, SWELLING (mitochondrial and cell) Fatty change> lipid accumulation in vacuoles Ribosome/polysome detachment (clump) plasma membrane blebbing nuclear changes (chromatin clump) rapid loss of function (no contraction)
Lipofuscin
wear and tear normal aging oxidation and polymerization of autophagocytized organelles product of lipid peroxidation heart, colon, liver, kidney, eyes
Causes of cell injury
Exceed capacity of adaptation exposure to toxin deprived of nutrients mutation disrupts metabolism
Leukocyte extraversion
Occurs at postcapillary venules 1.) Rolling: E selectin (TNF and IL1) and P selectin on endothelial cell bind sialyl lewis on leukocyte (dficient in LAD) 2.) Adhesion: ICAM on endothelial cell bind integrin (LFA) on PMN 3.) transmigration: PECAM 4.) migration: C5a, IL8, LTB4, kallikreinin and PAF guide neutrophils to where they should go
Calciphylaxis
hyperphosphatemia smooth muscle osteogenesis vascular wall calcification small vessel thrombosis
Leukocytosis
increase WBC type dependts on inciting agetn
Gangere necrosis
distal extremity after chronic ischemia dry: coag wet: both coag and liq
Cardinal signs of inflammation
rubor, calor: histamine, PG, brady, NO (vasodilate) tumor: leukotrienes, histamine, serotonin(permeability, postcapillary venules) dolor: brady, PGE2, histamine Loss of function
Hyperplasia
controlled prolfoeration of stem cells and differentiated cells... increase in number of cells excess stimulation could lead to pathologic hyperplasia which could be dysplasia or cancer (more cell divisons is dangerous) epithelial cells, constantly divinding
Necrosis
Loss cell membrane, cell contents leak, inflammation! exogenous injury
metaplasia
reprogramming stem cells replace one type by another usually bc expsure to an irritant ex: barrets esophagus (acid) or smoke (PCCE to strat squam) can become malignant if persistent metaplasia of connective tissue can also occur (myositis ossificans... muscle to bone following trauma)
Inflammasome
Cytoplasmic protien complex that recognizes dead cells, microbial products, crystal> IL 1 and indlammatory response
Cell injury
can become irreversible if persistent
fibrinoid necrosis
immune vasulcar reactions, HTN type III HS or plasma protein (fibrin) leak into damage vessel vessel walls are thick and pink
dialysis related amyloidosis
beta 2 microglobulin pt wtih ESRD
Transudate
hypocellular, low protein high hydrostatic pressure or low oncotic pressure
Intrinsic (mitochondrial) apoptosis
Tissue remodeling in embyogenesis When a regulating factor is withdrawn (ex low IL2) OR after exposure to injurous stimuli BCL2 family: BAX and BAK= proapotosis (a's); Bcl2 and BclxL are antiapoptosis (l=live) BAK and BAX form pores in the mitochondrial membrane> rlease of cytochrome c to activate caspase Bcl2 keeps the membrane impermeable... overactivity= tumor proliferation
Fat necrosis
enzymatic: pancreatitis nonenz: traumatic (breast) damaged pancrease releases lipase and breaks down TG, FA bind calcium and cause saponificaiton outline dead fat cells without peripheral nuclei saponifcation of fat is dark blue
Free radical injury
Damage cells by lipid peroxidation (damage membrane), protein modification (enz damage), DNA breakage (Crosslink). Radiation, drug metabolism, redox, NO, metals, ox burst are causes Eliminated by: scavenging enzymes, decay, antioxidants, metal carrier proteins
Light criteria
Pleural fluid protein : serum protein >0.5, Pleural fluid LDH : serum LDH >0.6, Pleural fluid LDH >2/3 upper limit of normal serum LDH
Acute phase reactants
IL 6 induces made by liver
Examples of localized amyloid
Alzhemiers: Beta (from APP) T2D: islet amyloid polypeptide medulary thyoid cancer: calcitonin isolated atrial amyloidosis: ANP, nromal aging senile amyloidosis: wild type transthyretin, cardiac
Mitochondrial permeability transition pore
Lack O2 or ROS Ca2+ comes in and caues loss of membrane potential
Familial amyloid polyneuropathies
Mutated transthyretin (ATTR) Due to transthyretin gene mutation
Exrinisic
Ligand receptor interactions (FasL to CD95 or TNFa to its receptor) Immune Cell (cytotoxic T cell release of perforin and granzyme B-MHC1) Fas-FasL needed in thymic medullary negative selection Defective Fas-FasL causes autoimmune lymphoproliferative sydrome (T cells bind self Ag)
Inflammation
Response to eliminated the cause of cell injury, remove necrotic cells, or repair tissue Can be harmful if excessive or inappropriate
Primary amyloidosis
AL light chains plasma cell disorders
Metastatic calcification
nromal tissues, widespread kidney, lung, gastic mucosa higher pH favors impairs concentrating ability of kidney caused by hypercalcemia or high calcium phosphate levels abnormal serum levels metastatic, kidney disease, multiple myeloma
Fever
pyrogens (LPS) induce macro to release IL 1 and TNF to increase COX in hypothalamus...increase PGE2 to increase temperature set point
Ischemic brain stroke timeline
Pale infarct
solid organs with a single blood supple
Examples of free radical injury
oxygen toxicity: repurfusion, retinopathy of prematurity drug toxicity: acetominphin overdose, carbon tetrachloriad makes fatty liver and centrilobular necrosis metal storage disease: wilson or hemochromatosis
Caseous necrosis
TB, systemic fungi macro wall off infecting organism fragmented cells and debris surrounded by lymphocytes and macro, granuloma mycolic acids and lipids give cheese appearance
Dysplasia
precancerous growth loss of uniformity of cell shape and size> pleomorphism nuclear changes (increase nuclear: cytoplasm ratio) may regress or may become carcionoma
Dystophic calcification
In abnormal tissues localized TB, granulomaous infections, liq necrosis of absesses, far necrosis, infarct, CMV, toxo, psmamomma bodies, atherosclerotic plaques caused by injury or necrosis normal serum calcium
Apoptosis
ATP depdent programmed cell death Involve caspase activation> cell shrink, chrom condense, membrane blebbing then phagocytosis membrane INTACT (no inflammation) Eosinphilic cytoplasm and basophilic nucleus, pyknosis DNA laddering= 180 bp indicates Causes: embyrogenesis, hormone withdrawal, DNA damage, immune cells, viral infected
Cellular adaptation
Reversible changes Can progress to injury if overwhleming stress
atrophy
decrease in tissue mass because decrease size cytoskeleton degredation bc ubiquitin proteasome pathway and autophagy, less protein synthesis apoptosis can cause less number of cells caused by denervation, loss blood supply, loss hormone stimulation, loss nutrition
Red infarct
venous occlusions or reperfusion repurfision injury is bc increase O2 supply, damaged mito cannot use so free radicals
Exudate
cellular, high protein caused by lymphatic obstruction, inflammation, malignanct, infection
Chronic inflammation
Prolonged inflammation in which active inflammation, tissue injury, and healing proceed simultaneously. Persistent infection: stimuli Mediators: macrophages are main cell -Th1: IFNg (proinflammatory) -Th2: IL4 and IL13 (repair and antiinflammatory) Outcomes: scarring, amyloidosis, neoplastic transformation
Secondary amyloidosis
AA serum amyloid chronic inflammatory conditions
Familial amyloid cardiomyopathy
Mutated serum transthyretin deposits in the heart, leading to resrictive cardiomyopathy
Irreversible Cell injury
plasma membrane breakdown (cytosolic enzymes leak into serum, influx of Ca2+ and degradative enzymes are activated.. phospholipid breakdown) mitochondrial damage (loss ETC, no ATP) rupture of lysosomes (autolysis) nuclear degredation -pyknosis (shrink) -karryohexis (frgamentation by endonuclease) -karryolysis (nuclear dissolution/fade)
Liquefactive necrosis
bacterial absess, brain infarct neutrophils release lysosomal enzumes that digest tissue cell debris and macrophages, cavitation neutrophils**
Coagulative necrosis
Ischemia/ infarcts (not brain) injury denatures enzymes.. tissue architecture remains intact and proteolysis is blocked nuclei disappear (eosinophlic, WBC)
Acute Inflammtion
Early, neutrophils, edeam, rapid onset, short duration, innate edeama first, neutrophils second, macro last caused by infection, trauma, necrosis, foreign body TLR, AA, neutrophils, eosinophils, mast cells, complement Vasodilation, increase permeability, leukocyte extravasion Outcomes: Heal (IL10, TGFB), persistent inflammation (IL8), absess, chronic inflammation (APC), scarring
ESR
RBCs seperated normally by - charge inflammation products coat RBC and decrease charge so cause aggregation High ESR: anemia, infections, inflammation, cancer, renal diseasse, pregnancy low ESR: sickel cell, polychthemia (more dilute aggregation factors), HF, microcytosis, low fibrinogen
Section 2
(50 cards)
Growth signal self-suffienciency
Hallmark of cancer mutations in genes encoding... protooncogenes: increase growth factors> autocrine loop GF receptors> constant signalling Signaling molecules (Ras) Trans factors (myc) cell cycle regulators
Tumor stage
Degree of localization/spread based on site and size of 1' lesion, spread to regional LNs, presence of metastases; spread of tumor in a specific pt. S tage = S pread TMN T: tumor size/ invasiveness M: mets N: node involvement
BRCA1 and BRCA2
Tumor Suppressor (2 hit) Breast and ovarian cancer DNA repair protein
Most common cancers (incidence and mortality) Adults
Skin cancer is most common (B>S>>M) Incidence: 1. Prostate/Breast 2. Lung 3. colon/ rectum Mortality: 1. Lung 2. Prostate/ breast 3. colon/ rectume
BCR-ABL
Oncogene - fusion protein Tyrosine kinase, t(9;22), signal transducer CML and ALL (poor) Tx: imatinib
Bone metastases
Prostate, breast> kidnye, thyroid, kung PB KTL
Healing by first and second intention
first: epithelial regeneration, minimal scar (surgical incision, staples, stitches) second: large, cannot approximate edges (pressure ulcer_ (more inflammation, granulaiton tissue and scar)
Sustained angiogenesis
Hallmark of cancer more proangiogenic facros, or less inhibitory vessels sprout from existing capillaries may be leaky or dilated
mycl1
Oncogene Transcription factor Lung tumor
Keloid scar
increase type 1 and 3 collagen disorganized, extends beyond borders or original wound claw like projections typically on ear lobes, face, upper extremities recurs if removed more in ethnic groups with darker skin
Tumor grade
Degree of cellular differentiation based on histologic appearance of tumor. Usually graded I-IV based on degree of differentiation and number of mitoses per high-power field; character of tumor itself. Need biopsy to determine
Tissue invasion
Hallmark of cancer loss of e cadherin> lose intercellular junctions > metalloproteinases degrade BM and ECM> cells attach to ECM> migrate through ECM> vacular disemmination
Tumor suppressor genes
loss of function, need two hits deactivating mutation
Dysplasia types
low grade: less than 1/3 epithelium involved and can regress spontaneously high grade: greater risk for progression
Scar formation
When repair cannot be done by cell regeneration alone, instead they are replaced by connective tissue 80% of tensile strength regained after 3 months TGFbeta excess
Evasion of apoptosis
Hallmark of cancer mutations in gene that regulation apoptosis p53, Bcl2
Limitless replicative potential
Hallmark of cancer reactivation of telomerase> prevent cell aging immortal
Metastasis
Hallmark of cancer tumor cells or emboli in blood or lymphatics adhesion to endothelium> extravasion and homing
Most common cancers (incidence and mortality) Kids
Incidence + mortality: 1. leukemia 2. CNS 3. neuroblastoma
RET
Oncogene - Tyrosine kinase MEN 2A and 2B, medullary thyroid cancer
BRAF
Oncogene Serine/threonine kinase Melanoma, Non-HL
Wound healing mediators
FGF: angiogensis and ECM TGFB: angiogenesis, fibrosis VEGF: angiogensis (venules) PDGF: secreted by plt and macro, vascular remodeling and smooth muscle cell migration. fibroblast growth for collagen synthesis Metalloproteinases: tissue remodeling, myofibroblast accumulation EGF: stimulates growth via tyrosin kinases
Immune checkpoint interactions
Signals that modulate T cell activation and function> decrease immune response against tumor cells -interactions between PD-1 (on t cell) and PDL1 on tumor cells > T cell dysfunction > some therapies inhibit PD1 or PDL1 -CTLA1 on T cells outcompetes CD28 for B7 on APCS> loss of T cell costimulatory signal (ipilumumab blocks)
Liver metastases
Colon >> stomach, pancreas
Neoplasia
uncontrolled, monoclonal proliferaion of cells parenchyma: neoplastic cell supporting stroma: non neoplastic, blood vessels and CT
Neoantigen
Haptens become immunogenic when they bind to host proteins Antigens from proteins that aren't fonud in healthy cells T cells see a foreign
Oncogenes
Gain of function mutation that converts proto onco to onco increase cancer risk only needs one mutation, gain of function (activating)
Differentiation
degree to which a tumor resembles its cells of origin well dif: close resemble poor dif: do not resemble anaplasia: Complete lack of differentiation of cells in a malignant neoplasm
c-myc
Oncogene Transcription factor for growth proteins, t(8;14) (myc from 8 is put on IgH 14 locus) Burkitt Lymphoma
Choristoma
normal tissue in a foreign location (meckels diverticulum)
hypertrophic scar
Excess production of scar tissue that is localized to the wound type III collagen increased parallel organization doesnt recur if removed
Warburg effect
Shift of glucose metabolism to glycolysis and away from mito ox phos anaerobic LOTS of glucose used and less ATP made basis for pet scan
Hamartoma
disorganized growth of normal tissues in their native location (puetz jager)
Immune evasion in cancer
immune cells see and attack cancer cells tumor cells must evade to grow -MHC class 1 down rgulated> cytotoxic T cells cannot recognize -Tumor cells secrete immunosppressive factors (TGFbeta) and recruit Treg cells to downregulate immune response -tumor cells up regulate immune checkpoint molecules, which inhibit immune response
JAK2
Oncogene Tyrosine kinase Chronic myeloproliferative disorders
Neoplastic progression
Normal cells: have basal apical polarity Dysplasia: lose unifromity of size/ shape (pleomorphism), lose orientation, nucelar changes (increase nuclear:cytoplasm) Carcinoma in situ: Irreversible and involves entire thickness of epithelium but NOT involve basement membrane Invasive carcinoma: invaded BM with collagenases and hydrolases, cell to cell contact lost by inactivation of E cadherin Metastasis: spread by lymph or blood
Carcinoma spread
usually lymph EXCEPT: -choriocarcinoma -RCC -HCC -follicular thyroid Four Carcinomas Route Hematogenously
BCL2
oncogene inhibits apoptosis follocular and DLBC
Granulomatous inflammation
"wall off" a resistant stimulus without erradicating it> persistent inflammation> fibrosis/ damage Epithelioid cells (Activated macro with pink cytoplasm) surrounded by lymphocytes Caseating: central necrosis (TB) noncaseating: autoimmune diseases Mechanism: 1. APCs to CD4 cells and IL12 to make CD4 Th1 cells 2. TH1 make IFNg> macro 3. macro release cytokines (TNF) to form giant cells and epithelioid macros Anti TNF therapy: granuloma breakdown and diseeminated disease associated with hypercalemia due to increase in 1alpha hydroxylase and vitamin D activation
ALK
Oncogene Receptor tyrosine kinase Lung adenocarcinoma
APC
Tumor Suppressor (2 hit) Colorectal cancer (associated with FAP) beta catenin/ wnt pathway
Wound healing
Inflammatory: platelets, neutrophils, macro. Clot formed, increase permeability, cell debris celarance. 3 days Proliferative: weeks after. fibroblasts, endothelial cells, macrophages. granulation tissue and type III collage, angiogenesis, epithelial cell prolif, clot dissolution, contractin **delayed phase 2 if low copper or vitamin c remodeling: months. fibroblasts. type 1 collage replaces type III to icnrease strength; collagenases remove type 3 (zinc def is delayed wound healing bc cofactor for metallopreases)
HER2/neu
Oncogene Breast, ovarian, and gastric carcinoma Tyrosine kinase
c-kit
oncogene cytokine receptor gastrointestinal stromal tumor (GIST)
Brain metastases
Lung> breast> melanoma, kidney, colon
n-myc
TF oncogene neuroblastoma
Anti-growth signal insensitivy
Hallmark of cancer mutation in tumor suppressor genes Rb loss of e cadherin (loss contact inhibition)
Common metastases
sarcomas: hematogenously carcinomas: lymphatics
KRAS
oncogene GTPase colon cancer, lung cancer, pancreatic cancer
Tumor nomenclature
Carcinoma: epithelial, malig Sarcoma: mesenchyme, malig Benign: well differentiated and demrcated, low mitotic activity, no mets or necrosis malignant: poor differentiation, erratic growth, local invasion, less apoptosis, more metastasis
Section 3
(25 cards)