00 - path-review again crds
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- 2 common chronic injury cell type changes
- smoker:ciliated epithelium - stratified squamous. Cervix - glandular to squamous epithelium
- 4 systems in cell vulnerable to injury
- membrane pump, genetic apparatus, aerobic respiration, structural-enzymatic proteins
- 4 mediators - cell death
- 02 and 02 free radicals, intracellular Ca+, ATP depletion, membrane permeability defects
- 2 energy mechs affected in cell injury
- aerobic respiration (oxydative phosphorylation), glycolysis (anaerobic respiration)
- result when each energy mech. injured
- aerobic - ATP production lost. glycolysis - depletion of glucogen, byproducts and acidity
- byproducts - glycolysis
- lactic acid, reduces intercellular pH
- 4 mechanisms free radical injury
- peroxidation of membrane lipids, DNA breaks, X-linking of proteins destroys function, damage to mitochondria.
- 6 free radical injuries
- reperfusion/hypoxia, aging, radiation, 02 toxicity, chemical injury, INFLAMMATION
- 2 mechanisms chemical injury
- direct (chemotherapy), toxic reactive metabolite reaction (in liver)
- 2 methods necrotic cell removal
- denaturation, enzymatic digestion
- nuclear shrinkage
- pyknosis
- many cytoplasmic proteins denature - result?
- cytoplasmic eosinophilia (incr. staining)
- markers of infarct in brain
- cyst, tissue debris, fluid, inflamm. cells, bacteria
- normally seen in caseous necrosis
- granulomatous inflammatory border with giant cells, epitheloid histiocytes
- 2 conditions assoc. w apoptosis
- viral infections, radiation injury
- fast necrosis dev. in organs with?
- high met. rate (int. mucosa), cytolytic enzymes(pancreas), vital organs - high O2 (brain, heart, lungs)
- physiologic hyperplasia 2 types, examples
- compensatory (liver regen) hormonal (breast/uterus - pregnancy)
- inflammation mediators
- chemicals derived from host
- inflammatory changes occur where
- terminal vascular bed, blood, conn. tissue
- main cells involved in inflammation
- monocytes, neutrophils, macrophages
- purpose of inflammation
- eliminate injurious agent and initiate repair, restoring continuity if not function
- characteristics acute inflam.
- short duration, fluid exudate, plasma proteins (edema), neutrophil and leukocytes to tissue, then macrophages.
- chronic inflam. char.
- long duration, lymphocytes, plasma cells, macrophages, vascularization, fibroblasts.
- following vascular chgs
- blood tissue barrier chgs - widen endothelial gaps - histamine reaction - edema
- swelling of inflammation bc of
- capillary leakage - blood plasma and leukocytes to tissue
- inflammatory exudate
- cellular debris, plasma proteins, fluid
- cellular events of inflamm
- margination, pavementing w/in vessel wall, emigration from vessel to interstitium, chemotaxis-site, phagocytosis
- inflamm cell types
- Neutrophils first 24 hrs, then monocytes 24-48 hrs
- 5 host derived main mediators inflammation
- vasoactive amines, plasma proteases, cytokines, adhesion molecules, arachiodonic acid metabolites
- 2 vasoactive amines
- histamine, seratonin
- purpose, origin vasoactive amines
- vascular chgs inflammation
- what produces vasoactive amines
- mast cells, platelets
- 3 systems of plasma proteases
- kinin, clotting, complement systems
- cytokine, peptide source
- macrophages
- cytokine purposes
- inflammatory mediators (IL1, TNF), activate polymorphs, macrophages to incr. killing, incr. vasc. permeability
- ICAM1 def
- cytokine - initiated production by endothelium
- ICAM1 purpose
- facilitates inflam cell binding to vessel endothelium
- AA metabolites are?
- arachiodonic acid - degraded phospholipids of cell membranes
- AA’s cause?
- inflammation - vasodilation, chemotaxis, increase vasc. permeability
- aspirin function
- blocks prostaglandin synthesis
- prostaglandin function
- pathogenesis of pain and fever - hyperalgesic
- steroid function
- blocks prostaglandin, leukotrines
- leukotrines
- chemotactic, activate neutrophil aggregation, adhesion
- chronic inflam cells
- MNL, lymphocytes, plasma cells
- main processes, chronic inflam
- healing and repair and tissue destruction cycle
- define granuloma
- form of chronic inflam w/ lots of histiocytes, giant cells, LANGHANS cells
- granuloma forms bc
- bacterial or fungal infection, foreign materials
- 3 examples persistent infections causing chronic inflam
- tuberculosis, syphilis, fungi
- 2 autoimmune disorders assoc w chronic nflamm
- rheumatoid arthritis, thyroiditis
- chronic inflammation: granuloma histology
- activated macrophages, large squamous cell epitheloid appearance
- pyogenic organism example
- staphlococcus
- 3 systemic effects inflam
- fever, elevated WBC count, neutrophylia, lymphocytosis
- exudate with RBCs
- hemorrhagic
- inflammation is
- response of VASCULARIZED tissue to injury
- inflammation designed to
- bring plasma proteins to site of injury in fastest poss.time
- main chgs in inflammation
- blood flow changes, formation of fluid and cellular exudates
- 3 functions fluid exudate
- bring plasma proteins, dilute toxins, loosen conn. tissue to allow diffus-migration of cells to injury site
- cell type assoc w/ parasitic infection
- EOSINOPHILS
- PMN
- polymorphonuclear leukocytes: NEUTROPHILS
- chemical attractants at injury site
- host factors - plasma proteins, and infectious agents
- protein expressed on infectious agent
- OPSONIN - labels agent for phagocytic destruction
- 3 conditions lysosomal enzymes released inadvert. during inflamm.
- during phagocytosis, trying to digest on flat surface (frustrated phagocytosis), cytotoxic release
- system: removes AgAb complexes in spleen, liver, bone marrow
- reticulo-endothelial system
- tissue destruction from cytotoxic release
- GOUT
- 4 agents of chronic inflammation
- microorganisms, foreign bodies, toxins, auto-immune reactions
- chronic inflam main events
- cellular infiltrate, tissue destruction, repair by scar
- granuloma
- chronic infection, macrophages differentiate - epitheloid cells, cluster
- 4 disorders assoc w granulomatous inflam
- tuberculosis, syphilis, leprosy, crohns
- 2 modes of destruction AbAg complex
- direct lysis, complement activation
- cells with FC receptors
- macrophages, NK cells, eosinophils, neutrophils
- direct lysis of AgAb complexes how
- cell with FC receptor engages FC fragment, releases lysosomes - destroys complex
- 2 basics of complement system
- hydrolytic enzymes directly lyse infectious agents or chemical mediators initiate acute inflammation, attract neutrophils to phagocytose
- 2 main classes Tlymphocytes
- CD4s assist others, CD8s kill directly
- 3 types of antigen presenting cells
- dendritic(skin), macrophages, langerhans
- distinguish self from non-self
- major histocompatibility protein (MHP)
- two types of MHP & locations
- Class I - all cells, Class II - ONLY antigen-pres. cells
- MHC protein recognition
- CD4s recognize class II, CD8s only class I
- cytokine, source activates Bcells
- interleukin produced by Type2 CD4s
- cytokine source - activates macrophages
- Interferon Gamma, produced by Type1 CD4s
- macrophage activation results
- increased size, lysosomal enzymes, ability to digest/kill, secretion of growth factors(endothelial cells, fibroblasts), hydrolytic enzymes
- macrophages kill what and how
- TB, parasites, fungi, tumour cells, organ trans. direct lysis or phagocytosis
- CD8s kill antigens how
- proteolytic enzymes -- osmotic lysis
- CD8s mostly kill
- virus infected cells, tumour cells, organ trans (non-self)
- stimulates scar repair in chronic inflam
- activated macrophages secrete growth factors
- Type I hypersensitivity mediated by Ig?
- IgE
- 2 cell types central to Type I hypersensitivity
- mast cells and basophils
- mast cells - what and where
- from marrow, wide dist. in body, esp. around nerves, vessels, subepithelial where Type I reacts occur
- Mast cells/basophils activated how?
- crosslinking IgE receptors
- diff btwn mast cells and basophils
- basophils in blood, small numbers
- type of helper cell assoc. w Type I hypersens
- Type 2 CD4s
- What is produced by Type 2 CD4s
- Interleukins 4 and 5
- genetic predisposition to type 1 hypersensitivity called
- atopic disease (allergy) IgE diseases
- other IgE mediated diseases
- asthma, dermatitis, gastrointestinal food allergy
- released upon exposure to allergen?
- histamines, leukotrines
- SRS-A
- slow-reacting substance of anaphylaxis
- ECF-A
- eosinophil chemotactic factor of anaphylaxis
- type 1 mediators act on what?
- vessels, sm. musc, secretory glands
- Type 1 mediators cause what?
- edema, cellular infiltrate, clinical features of allergy
- IL4 is what
- IgE switch factor, produced by Th2, activates Bcells
- HDN example of what type hypersensitivity
- Type II
- produced in mother in HDN following second child?
- IgG antibodies, which cross placenta
- problem with IgG crossing placenta?
- attack fetal erythrocytes - hemolytic anemia
- natural antibodies reactive with AB blood groups
- IgM - can’t cross placenta
- 2 examples of Type II hypersensitivity
- organ rejection, myasthenia gravis
- define RA (rheumatoid arthritis)
- chronic systemic inflamm.autoimmune disease - joints
- what histocompatibility complex assoc. with rheum arth
- HLA-D4, and HLA- DR4
- what are rheumatoid factors
- immunoglobulins specific for FC fragment of IgG - an antibody against ones own antibody Immunoglobulin
- 2 examples Type III hypersensitivity
- serum sickness, arthus phenomenon
- inflammatory factors associated with rheumatoid arthritis
- histamine release, cytokine production (neutrophils, monocytes), white cells to synovial space
- define pannus
- vascular mass of lymphocytes around area of necrosis where bone and cartilage have degraded
- cause of tuberculosis
- mycobacterium tuberculosis (or mycobac.T.bovine)
- TB inflammation type
- focal granulomatous with central caseous necrosis
- tuberculosis vaccine
- BCG - bacille Camette Geurin
- Test for TB
- PPD purified protein derivative
- endogenous infection
- from interior - ones own flora attacking system
- how well an organism can produce symptoms
- pathogenicity
- how severe symptoms are that are prod. by organism
- virulence
- poisons secreted by bacteria
- exotoxins
- examples of 3 exotoxins
- diptheria, tetanus, enterotoxin
- diptheria pathology
- sore throat - death. destroys epithelium and mucous memb, leaving fibrous necrotic tissue, esp. in throat.
- tetanus pathology
- neurotoxin, interrupts motor nerve signals, causes spasm
- enterotoxin
- food poisoning - staphylococcus
- endotoxins released when
- when bacteria destroyed
- 3 bacterial metabolic examples - contrib. to disease
- hyaluronidase, streptokinase, coagulase
- metabolite - dissolves conn. tissue
- hyaluronidase
- metabolite - demineralizes tooth enamel
- plaque acid
- metabolite - breaks down fibrin
- streptokinase
- metabolite, breaks down DNA
- streptoadornase
- 3 examples where foreign organisms multiply - prod. inflammation
- shigellosis(dysentry), Salmonella Typhi (Typhoid Fever), Spirochete(necrotizing ulcerative gingivitis)
- organism in bloodstream from infection called
- bacteremia
- another name for blood poisoning
- sepsis
- 3 main factors - infection resistance
- patient factors(immunity, nutrition, biochem, secretions), organism virulence, site of infection, level of blood supp.
- atrophy caused by plasma protein deposition in tissue
- amyloidosis
- autoimmune disease where antibodies clog acetylcholine receptors
- myasthenia gravis - causes generalized muscular weakness
- chronic rheumatic fever can lead to risk of
- infective endocarditis - heart valve deformity, incompetency
- asthma
- mast cell histamine release-mucous hypersecretion-more goblet cells - bsmt. memb. thickening-sm. vessel constriction
- 5 HIV related infections
- fungus in meninges, cytomegalovirus - gigantic langhans cell, lung yeast infection, carposis sarcoma, lymphoma
- proteins that regulate cell cycle
- cyclins
- continuously regenerating cells
- labile, from stem cells, eg: marrow, epithelia
- cells which can but don’t normally divide
- stable- divide if injured, eg: liver, fibroblasts, sm. musc
- cycle stage cells at
- G0 - resting(quiescent)
- matrix btwn cells - origin, composition
- interstitial matrix:fibroblasts-amorphous gel, collagen, elastin, proteoglycan, glycoproteins
- bsmt membrane composition
- platelike mesh, type IV collagen, glycoproteins
- extracellular matrix active in tissue repair how
- mech support, determine orientation, control regulate growth and differentiation, pres: regulatory molecules
- collagen - describe
- fibrous structure proteins from fibroblasts Xlink by VitC in triple helix
- source of cell growth factors
- activated macrophages
- 3 examples growth factors
- epidermal, fibroblast, cytokines
- basic substrate extracell. matrix forms on and timing
- granulation tissue at abt. 3 days
- char. of first intention healing
- more epithelial regen than fibrosis
- 1st intention - process
- neutrophils, mitosis; epithelial migration, new bsmt memb.; macrophages, granulation tissue, collagen fibres; epidermis - collagen fibre bridge
- char. of 2nd intention healing
- fibrosis rather than epithelial regen
- example 2nd intention
- ulcer (eg Diabetes)
- process 2nd intention
- big inflamm. reaction, lots of granulation tissue, wound CONTRACTS
- 3RD intention
- delayed closure to allow some natural disinfection
- exuberant collagen production in 1st intention wound
- keloid
- types of factors effecting healing
- local(infection, foreign body, blood supp, temp.) Systemic(immunosup.,vasc.disease, nutrition, alcohol)
- key characteristics neoplasia
- autonomous cell division persisting post cessation of initiating stimuli
- 2 components of tumours
- parenchyma (prolif. neoplastic cells) stroma (conn. tiss & vessels)
- benign tumour of epithelial origin
- papilloma (eg squamous or transitional)
- malignant tumour of epithelium
- carcinoma
- benign tumour of glandular origin
- adenoma
- malignant tumour of glandular origin
- adenocarcinoma
- age effected carcinoma versus sarcoma
- carcinoma 55+, sarcoma usually children
- 3 categories of hereditary cancers
- mutant gene inheritance (autosomal dominant - eg:retinoblastoma), familial (uncommon CA type, prevolent in family), autosomal recessive (need both parental alleles)
- well differentiated versus poorly differentiated
- Grade I (less agress) - Grade III(v.aggress)
- highly UNDIFFERENTIATED tumour cells called
- ANAPLASIA
- variation in size and shape of tumour cells called
- pleomorphism
- tumour cell nuclei with lots of DNA - dark staining
- hyperchromasia
- 6 morphologic chgs in anaplasia
- pleomorphism, hyperchromasia, lg nuclei, incr. mitosis, giant cells, disturbed orientation
- disorderly growth type that doesn’t nec. lead to CA
- dysplasia
- type of benign tumour not well defined
- hemangioma (tum. of blood vessels)
- spread through blood
- hematogenous - usually sarcomas
- tumour (benign or malig) effects depend on what 6?
- location, impingement; functional activity; bleeding; 2ndary infections; ulcerations; initiation of acute symptoms: rupture or infarct
- example of local effect of benign tumour
- adenoma of pituitary destroying pit. function, causing endocrinopathy
- hormonal effect example - benign tumour
- pancreatic islet tumour, overproduction of insulin, causes deadly hypoglycemia
- wasting syndrome associated with cancer
- cachexia - usually a result of cytokines
- example of substance imbalance assoc. w cancer
- cushings syndrome - lung or pancreatic CA producing ACTH
- histologic features, squam. cell CA
- sheets or solid nests “mosaic†pattern, intercellular bridges, sometimes keratinized
- term: sm. muscle
- leiomyo
- examples of acquired pre-neoplastic disorders
- chronic wound - cell regeneration, so potential for cancer; smokers - chronic bronchial dysplasia; chronic gastritis (pernicious enemia) - all can become malignant
- risk factor for oral CA
- leukoplakia - incr. risk squamous cell CA
- risk for colorectal CA
- villous adenoma (glandular)
- basis of carcinogenesis
- non-lethal genetic damage (chem, radiation, viral)
- targets of genetic dmg in cells
- genes: promote or inhibit growth, or apop.regulators
- growth promoting gene
- proto-oncogene
- oncogene is what
- a mutant allele of a proto-oncogene
- oncogene does what
- promotes autonomous cell growth
- example tumour supressor gene
- Rb gene - usually prevents cell cycle which otherwise causes retinoblastoma
- Most common genetic disorder in cancer
- TP53 gene - regulates apoptosis, senses DNA damage and initiates repair
- HER2 gene does what
- protooncogene - produces growth factor. commonly damaged in 20 - 30% of breast cancer cases.
- Type I hypersensitivity
- mast cells, basophiles release vasoactive amines, provoke an immediate (anaphylactic) response - eg food allergy, hay fever - IgE antibodies
- Type II hypersensitivity
- mediated by humoral antibodies which predispose cells to phagocytosis, lysis - complement mediated cytotoxicity - (hemolytic disease of newborn, transfusion reactions) - IgG antibodies
- Type III hypersensitivity
- Immune complex mediated (rheumatoid arthritis, serum sickness) --acute inflammatory response initiated, causing cell injury (in Rheum - fc fragment of IgG antibody)
- type IV hypersensitivity
- cell mediated (delayed hypersensitivity reaction) TCells rather than antibodies. eg tuberculosis.
- what might accompany a type II transfusion reaction
- hemolysis
- what is the last stage in wound healing?
- remodelling
- what type of cancer is xeroderma pigmentosum
- autosomal recessive CA-probs w genetic repair mechs
- in what vessels does the exudate occur
- post-capillary venules
- what percentage of patients have paraneoplastic syndromes associated with cancer
- 10%