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104 Cards in this Set
- Front
- Back
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What eicosanoids are responsible for vasodialation?
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PGl2 (prostacyclin), PGE 1 &2, PGD2
Prostaglandins |
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What eicosanoids are responsible for vasoconstriction?
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Thromboxane A2
Leukotrienes C,D,E |
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What eicosanoids are responsible for increased vascular permeability?
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Leukotrienes C,D,E
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What eicosanoids are responsible for Chemotaxis and leukocyte adhesion?
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Leukotriebe B
HETE |
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Histamine role in inflammation...
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vasodialation
increased vascular permeability endothelial activation Source: Mast Cells |
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Serotonin role in inflammation...
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Vasodialation
increased vascular permeability |
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Prostaglandin role in inflammation....
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Vasodialation
Pain Fever |
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Leukotriene tole in inflammation...
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increased vascular permeability
chemotaxis leukocyte adhesion and activation |
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Platelet activating factors roles in inflammation...
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Vasodilation
increased vascular permiability leukocyte adhesion chemotaxis degranulation oxidative burst |
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ROS role in inflammation
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Tissue damage due to killing microbes
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NO role in inflammation
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vascualr smooth muscle changes
killing of microbes |
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Cytokine TNF-a and IL-1 role in inflammation
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Local endothelial activation of adhesion molecules
fever, pain, aneorexia, hypotension decreased vascualr resistance (shock) |
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Chemokines role in inflammation...
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Chemotaxis and leukocyte activation
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What is the role of Compliment proteins C5a, C3a, & C4a in inflammation?
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They are responsible for leukocyte chemotaxis amd activation and vasodialation my mast cell stimulation
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What is the role of (brady) Kinin in inflammation?
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Increased vascular permiablity
smooth muscle contraction vasodialation Pain |
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What are the roles of proteases activated during coagulation?
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Endothelial activation
leukocyte recruitment |
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What cell signaling transduction pathway tends to be more associated with pathological hypertrophy?
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G- protein coupled
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What cell signaling transduction pathway tends to be more associated with physiologicall hypertrophy?
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phosphoinositide 3‐kinase/Akt pathway appears
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What agonists cause Cardiomyocyte Hypertrophy?
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a- adrenergic hormones
angiotensin |
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What is the morphology of myocardial hypertrophy?
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Genes are induced: nucleus of cardiomyocyte is enlarged, boxy, hyperchromatic
Lipofusion may be visible |
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What is the DD for cardiac hypertrophy?
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Systemic HTN
Ischemic heart disease aortic stenosis mitral regurgitation Dialated cardio myopathy |
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What substances can cause ER hypertophy?
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phenobarbital
ETOH Anything that uses CYP/P450 for metabolism will enduce further synthesis of enzymes |
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What is polycythemia?
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the proportion of blood volume that is occupied by red blood cells increases. Blood volume proportions can be measured as hematocrit level.
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What cells produce keloids?
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(excess collagen) produced by fibroblasts
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What cells produce hypertrophic scars?
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myofibroblasts
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How is the HPV virus able to proliferate/ produce warts?
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It promotes the growth squamous epithelium via cell cycle inhibitors – viral E6, E7
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What is psoriasis?
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Proliferation of epidermal squamous cells by inflammatory cytokines
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What are the 6 causes of atrophy
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• Decreased workload‐disuse atrophy
• Loss of endocrine stimulation Loss of endocrine stimulation • Denervation atrophy • Pressure atrophy • Diminished blood supply • Inadequate nutrition |
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Myocytes that vary in size and shape
that are angulated and grouped are caused by what pathology? |
atrophy from denervation
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What clinical dernvation atrophys did we discusss?
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Charcot Marie Tooth
SMA Polio West Nume |
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What is severe protein calorie malnutrition called?
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Marasmus
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What are some causes of cachexia
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HIV
TB Chronic Inflammation Cancer |
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What is the mechanism of atrophy?
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Net loss of intracellular protein: decreased
synthesis / increased degradation via the ubiquitin‐proteosome pathway. Also seen in conjunction with autophagy |
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What is the purpose of autophagy?
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to yeild energy or recycle damaged structures
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How might autophagy look morphologically?
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Residual bodies/lipofucsin accumulation =
“ brown atrophy” of long‐lived surviving cells Phagolysosomes mayhave organelle parts in them |
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What is myositis ossificans?
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myositis ossificans means that bone forms within the muscle
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What is the morphology of dysplasia?
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‐ Disordered growth of cells ‐Enlarged, hyperchromatic, pleomorphic (atypical) nuclei
‐ Increased mitoses ‐ Basement membrane is intact |
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Which form of cell death is always pathologic?
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necrosis
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Describe the pathogenesis of Autophagy. How is it regulated?
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‐ autophagocytic vacuole formed of membrane
bound sequestered cytosol/organelle autophagolysosome formed when vacuole fuses with lysosome, contents degraded; nutrients released Regulated by autophagy genes, Atgs |
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What is the Morphology of Reversibly Injured Cells
by light microscopy? |
• Changes visible w/in hours
• Hydropic change/swelling • Fatty change: |
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What is the Electron Microscopic Morphology
of Reversible Cell Injury? |
Plasma membrane blebs,
blunting, loss of microvilli Mitochondrial swelling; Amorphous densities Dilation of ER with detachment of polysomes Chromatin clumpping |
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When is cell injury irreversible?
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Mitochondrial dysfunction Membranes lost ‐ function and integrity
Nuclear dissolution |
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What is the morphology (EM) of necrosis?
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Large myelin figures
Mitochondria swollen with amorphous, flocculent (fluffy) densities |
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What is the morphology light microscope of necrosis?
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Cytoplasm has:
Increased red‐staining‐‐eosinophilia Homogenous, moth‐eaten appearance |
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Fading of nuclei is called?
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karyolysis
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Shrinkage and increased basophilia of nuclei called? When is it seen?
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Nuclear pyknosis:
Necrosis and apoptosis |
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What is fragmentation of pyknotic
nucleus called? |
Karyorrhexis
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When do you see Liquefactive Necrosis?
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Stroke/hypoxic death in CNS can turn to LN
Abcesses |
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What type of necrosis is described:
granular amorphous fragmented cells; often cavitates border of giant cells, lymphs, epithelioid, macrophages (granuloma) |
caseous
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What is fibrinoid necrosis?
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• Used to describe appearance of immune
mediated blood vessel damage mediated blood vessel damage • Micro: smudgy, eosinophilic deposit in wall of blood vessel obscures cellular detail |
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With the depletion of ATP, what ions are moving into/out of the cell?
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Na+ and Ca2+ both move in
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Name a toxin/drug that damages mtochondira...
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Cyanide poisons cytochrome oxidase
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What is the result of cytochrome c being released into the cytosol?
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It triggers apoptosis
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What are caspases?
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The caspases are a family of proteins that are one of the main executors of the apoptotic process.
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How does increased Ca2+ cause cell death?
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It can make mitochondria more permeable and make them cpill cytochrome c
it can directly act on signaling pathways in the cell and activate caspases |
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What is CYP2E1?
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a protein coding gene for Cytochrome P450 2E1.
Detoxifies ETOH |
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Which free radical is the most damaging and why?
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Hydroyly -OH* ions because they can act systemically
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What are some antioxidants/removal mechanisms of free radicals?
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Vitamens A, E, C sulfhydryl compounds cysteine, glutathione
ceruloplasmin and Fe binding compounds |
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What breaks down breaks down H2O2?
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Catalase in peroxisomes
Glutathione peroxidase in mitochondria |
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What converts the superoxide radical?
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Superoxide dismutatase (SOD)
in mitochondria; cytosol |
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What are the 3 main Pathologic Effects of ROS?
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Lipid peroxidation in membranes
Oxidation modification of proteins DNA Lesions |
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What is an exudate?
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•Extracellular fluid with high protein
content, cell debris and high specific gravity (greater than 3) |
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What are the 4 principal mechanisms of increased vascular permiability?
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1) Retraction of endo cells
2) Endo Injury 3) Leukocyte mediated vascualr injury 4) Increased transocytosis |
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Describe the mechanism, features, underlying cause of retraction of endothelial cells....
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Occurs in venules
Induced by histamine and NO Rapid (minutes) |
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Describe the mechanism, features, underlying cause of endothelial injury...
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arteriols, capillaris and venules
caused by burns and some microbial toxins Rapid, but may last hours to days |
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Describe the mechanism, features, underlying cause of leukocyte mediated vascualr injury
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venules. pulmonary capillaries
associated with late sighns of inflammation long lived (hours) |
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Describe the mechanism, features, underlying cause of incrased transocytosis
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occcurs in venules
induced by VEGF |
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What are the names of the Adhesion molecules in intercellular
junctions of endothelial cells that help leukocytes |
PECAM 1 CD 31
aka Platelet endothelial cell adhesion molecule |
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Endothelial cells have what adhesion molecules?
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Think selectins!
P & E Selectins Glycam CD34 ICAM1 VCAM1 |
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Leukocytes have what adhesion molecules?
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Sialyl-Lewis
L- Selectins CD11/18 B2 Integrins VLA4 B1 Integrins |
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What famous opsonins would a scavenger receptor see?
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IgG, C3b
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G Coupled Protein receptors have what role in inflammation response?
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The stimulate increased integrin activit and chemotaxis
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Toll Like receptors have what role in inflammation response?
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They amplify the inflammatory reaction by producing mediators like AA, cytokines, etc
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What is myeloperoxidase (MPO)?
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A compound that mixes with peroxide and a halide can kill bacteria in neutrophils
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What is a LAD deficiency?
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Leukocyte adhesion deficiency (LAD), is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections;
Type 1 -Mutation with integtins Type 2- Mutation with selections causes defects in neutrophil adhesion |
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What is chronic granulomatous disease?
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n inherited disorder of phagocytic cells, results from an inability of phagocytes to produce bactericidal superoxide anions (O2-) leading to recurrent bacterial and fungal infections
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What is MPO deficiency?
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Decreased microbial killing due to ineffective MPO-H2O2 system
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What is Chediak-Higashi syndrome
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decreased leukocyte function because of mutations involved with lysosomal membrane trafficking.
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What are the acute inflammation cytokines?
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TNF-a
IL-1 IL-6 Chemokines |
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What are the chronic inflammation cytokines?
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IL-12
IFN-y IL-17 |
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What is the role of Alpha1‐antitrypsin?
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It protects tissues from enzymes of inflammatory cells, especially neutrophil elastase.
(its absence leads to too much NE as seen in COPD, emphysems and cirrosis) |
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What neuoropeptides are secreted by sensory nerves and various leukocytes?
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Substance P& neurokinin A
Substance P transmits pain signals, powerful mediator of increased vascular permeability |
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What is the role of compliment in inflammation?
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C5a and C3a lead to inflammation
C3b leads to phagocytosis in interity can lead to MAC |
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What is Hageman Factor?
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Clotting factor XII that when activated, activates:
1) the kinen system->bradykinin 2)The clotting system->thrombin 3)the fibrinolytic system 4) the compliment system |
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What is the role of compliment in inflammation?
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C5a and C3a lead to inflammation
C3b leads to phagocytosis in interity can lead to MAC |
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What is Hageman Factor?
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Clotting factor XII that when activated, activates:
1) the kinen system->bradykinin 2)The clotting system->thrombin 3)the fibrinolytic system 4) the compliment system |
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What organisms tend to cause purulent inflammation?
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Staphalococci
"The Grapes of Staph" |
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What is lympangitis?
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Lymphangitis is an infection of the lymph vessels (channels)
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What is lymphadenitis?
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Lymphadenitis is an infection of the lymph nodes (also called lymph glands)
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Name endogenous pyrogens...Exogenous...
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Endogenous TNF & IL-1
Exogenous: bacteria |
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What are the main acute phase proteins?
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C reactive protein (CRP)
fibrinogen and serum amyloid A (SAA) protein |
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What are the clinical manifestations of Acute phase response?
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– Increased heart rate and blood pressure
– Decreased sweating – Rigors – Chills – Anorexia – Somnolence-"drowsiness" – Malaise-generalized feeling of discomfort, illness, or lack of well-being |
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What are the pro-inflammatory cytokines?
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TNF-a
IL-1 IL8 Il12 IFN-y |
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What are the anti-inflammatory cytokines?
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IL4/13
IL1 TGF-B IL-10 |
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What pathway Eliminates self reactive lymphs&
certain other cells? |
Fas‐L : membrane protein of T‐lymphs
‐ Binds to Fas on target cell which triggers apoptosis via caspsase cascade |
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What is the result of TNF binding to a cell domain?
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Promotes cell survival by proliferation via activation of transcription factor NF‐ KB.
NF-KB stimulates synthesis of anti‐apoptotic members of Bcl‐2 familyy |
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What blocks NF-Kappa-B from reaching the nucleus for transcription?
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Blocked by Bortezomib
This BCL-2 and anti-apoptotic can't be made |
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How does cytochrom c cause apoptosis of a cell?
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It binds to activating
factor 1 (Apaf‐1) which stimulates caspase 9 activation |
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What is the role of p53?
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it sccumulates whene there is DNA damage that needs repaired and halts the cell cycle so that repair can take place. If it CANNOT, it triggers BAX which is pro-apoptotoic
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What are the ANTI apoptotic members of the Bcl-2 family?
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Bcl‐2, Bcl‐x, Mcl‐1
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What are the PRO apoptotic members of the Bcl-2 family?
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Bax, Bak
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How are Bax and Bak activated? What is the result?
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BH3‐only proteins (Bim, Bid, Bad) are sensors
‐ activate Bax, Bak to open channel; release cytochrome c; other mitochondrial proteins |
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Besides the BCL family, what are Other Inhibitors of Apoptosis?
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Growth factors, sex hormones
Cytoplasmic inhibitors of apoptosis, FLIP : inhibitor of caspase 8 NF-kB |
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How does Hemosiderin stain?
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prussian blue
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