PHRD5015 Lecture 11 - Inflammation in Disease: Acute Processes

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PHRD5015 Lecture 11 - Inflammation in Disease: Acute Processes
2013-10-29 22:04:41
PHRD5015 inflammation

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  1. infection that has moved into the system circulation
  2. important cytokines associated with sepsis
    TNF, IL-1
  3. SIRS
    • systemic inflammatory response syndrome
    • early in disease - focus is on fighting infection
  4. cause of deaths during SIRS
    toxic shock
  5. CARS
    • compensatory anti-inflammatory response syndrome
    • occurs as disease progresses past SIRS - immunosuppression
  6. cause of death during CARS
    secondary infections/reactivation of viral infections
  7. therapies against sepsis (3)
    • 1) endotoxin removal (polymixin)
    • 2) TLR4 inhibition (Eritoran)
    • 3) block immune suppression (GM-CSF administration)
  8. occurs when blood flow has been cut off and then restored
    ischemia reperfusion injury
  9. cause of primary damage (ischemia induced damage)
    ATP depletion leading to cellular necrosis
  10. cause of secondary damage (caused by reperfusion)
    acute inflammatory response
  11. events during myocardial ischemia
    increased H+ due to anaerobic glycolysis/ATP breakdown -> increased Na+ to correct pH -> increased Ca2+ extrusion from SR -> contraction/constriction
  12. major contributor to mitochondria undergoing permeability transition
    ROS from ETC due to breakdown in antioxidant circuits
  13. during reperfusion, this hydrolyzes proteins from the sarcolemma and cytoskeleton
  14. no-reflow phenomena
    microembolisms, platelet aggregation, endothelial swelling, neutrophil plugging, & interstitial edema contribute to lack of blood flow after inflammatory mediators have been released
  15. how is the integrity of the blood brain barrier compromised after head trauma?
    secretion of matrix metalloproteinases allow extravasation of inflammatory cells to the area
  16. inflammatory mediator playing an important role in CNS injury by directly inducing apoptosis of neurons
  17. 2 sources of IL-1
    • 1) inflammasome activation
    • 2) macrophages release IL-1 through TLR activation
  18. involved in both inflammation and resolution of inflammation during CNS injury
  19. DAMPs
    • danger associated molecular patterns
    • endogenous signals that can activate TLRs
  20. TLRs associated with CNS injury
    TLR2 and TLR4
  21. ARDS
    • acute respiratory distress syndrome
    • caused by injury to the lung
  22. cause of fluid in lungs in ARDS
    inflammation causes leaky vasculature/increased permeability leading to alveolar flooding
  23. cause of fluid in lungs in cardiac pulmonary edema
    thicker lymphatics create increased hydrostatic pressure causing alveolar flooding by bulk flow
  24. primary contributor to damage in ARDS
    secreting neutrophils adhere to CAMs expressed by the lung vasculature or migrate into the inner surface of the alveoli
  25. Tunnel staining
    stains DNA ends brown
  26. Caspase-3 staining
    stains cleaved casp3
  27. proposed mechanism for migraine headaches
    initial vasospasm in the cerebral vasculature followed by a reflex vasodilation
  28. effects of vasospasm in migraine
    creates ischemia leading to release of inflammatory mediators
  29. neurogenic inflammation
    rebound vasodilation (in relation to migraines)
  30. associated with initial pain of migraine
    • edema¬†
    • release of neuropeptides (tachykinins, substance P, calcitonin gene related peptide CGRP)
  31. shown to end migraine pain
    vasoconstriction after initial vasoconstriction/dilation
  32. origin/location of pain in migraines
    trigeminal nociceptive neurons - cause classic throbbing pain
  33. metabolic disease involving uric acid metabolism
  34. Podogra
    gout affecting the joint of the big toe
  35. chalky deposits of uric acid under the skin near affected joints
  36. increased uric acid content in the blood
  37. cause of hyperuricemia
    diet rich in purines
  38. 4 stages of gout
    • 1) asymptomatic hyperuricemia
    • 2) acute gout (acute pain)
    • 3) interval gout (aymptomatic)
    • 4) chronic tophaceous gout (disabling, permanent damage)
  39. causes of gout
    lead exposure, renal insufficiency, high BP, hypothyroidism