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Flashcards in Inflammation Deck (69):
1


2 key mechanisms of cellular injury

  • hypoxia
  • ischemia

2


4 cellular adaptations to injury

  1. hyperplasia
  2. hypertrophy
  3. atrophy
  4. metaplasia

3


hyperplasia

  • increase in # of cells in organ or tissue
  • often related to increase in demand for fxn
  • may be associated with increase in cell size
    • normal- uterus
    • compensatory - liver repair
    • pathalogic-graves

4

Autoimmune antibodies associated with Graves

HLAB8, HLADR3

5

Graves Pathogenesis

ab bind to TSH receptor --> increase TH hormone --> hyperplasia --> hyperthyroidism

6

Hypertrophy

  • increase in cell size due to increased protein synthesis (not cell swelling)
  • increased demand for function
     

7

Atrophy

  • decrease in cell size
  • decreased workload, decreased blood supply, inadequate nutrition, loss of endocrin, denervation

8


Spinal Muscular Atrophy (SMA) Pathogenesis

mutation in SMN1 gene --> LOF -->neuronal death --> atrophy of muscle

9


Metaplasia

  • reversible change in differentiation program of tissue stem cells to different cell type
  • e.g. columnar to squamous metaplasia of respiratory tract in response to cigarettes

10

Why is ischemia more rapidly injurious than hypoxia?

loss of both oxygen and nutrients

 

11


Factors of irreversible cell injur

  • severe mitochondrial swelling --> free radical production and release
  • extensive membrane damage --> Ca influx --> enzyme activation --> digestion of cell

12

Anti-oxidant mediators

  1. superoxide dismutase
  2. catalase
  3. glutathione peroxidase

13


Free radical effects on cell

  1. DNA --> breaks, modifications
  2. proteins --> misfolding, cross-linking
  3. lipid peroxidation --> unstable, chain-reactive

14


CCL4 mediated cellular injury - MOA

CCL4 --> converted to CCL3 radical by P450 --> lipid peroxidation --> diminished protein synthesis in ER --> reduced export from ER --> fat retention --> autocatalyzed peroxidation --> Ca influx --> death

15

Necrosis

morphologic changes due to degradative actions of enzymes on lethally inured cell

  1. coagulative
  2. liquefactive
  3. caseous

16

Coagulative necrosis-features

  • acidophilic (pink) cytoplasm
  • nuclei disappearance
  • preservation of cell architecture
  • hyperemic border

17

Coagulative necrosis is indicative of what process?

Irreversible ischemic injury

18


Liquefactive necrosis-features

  • hydrolytic enzymes predominate
  • rapid softening
  • loss of architecture
  • abscess formation
  • brain and pus

19


Abscess

focal localized collection of bacteria and pus with fibrotic border w/liquefactive necrosis

20

Caseous necrosis-features

  • incomplete liquefication of celular architecture
  • cheesy
  • granulomatous inflammatory wall
  • mycobacteria

21


Apoptosis

regulated programmed cell death to eliminate unwanted cells

22


Apoptosis-features

  • cells shrink
  • chromatin condenses
  • blebs form
  • phagocytosis
  • plasma membrane remains intact
  • no inflammation

23


Apoptosis triggers

  1. withdrawal of growth factors
  2. receptor-ligand interactions (FAS)
  3. CTL mediated

24

25


2 main features of acute inflammation

  1. fluid exudation
  2. neutrophil emigration

26


2 main features of chronic inflammation

  1. scarring/fibrosis
  2. macrophages and lymphocytes

27

Vascular effects in acute inflammation

  1. vasodilation
  2. incrased permeability
  3. stasis
  4. leukocyte margination

28

Four key mediators that induce endothelial cell contraction in blood vessels to increase permeability

  1. histamine
  2. bradykinin
  3. leukotrienes
  4. VEGF

29

Edema

accumulation of fluid extravascular compartment or interstitial tissues (stains pink)

30

Exudates have a higher _______ than transudates

specific gravity due to protein/cell content

31


Serous inflammation-morphology

  • watery, protein poor fluid
  • bright pink
  • few cells

32


Fibrinous inflmmation-morphology

  • fibroblasts and vessels
  • linings of body cavities

33


Suppurative inflammation-morphology

  • neutrophils
  • edema fluid
  • necrotic cells
  • central necrosis with scarring

34

Ulcer


site of inflammation where epithelial surface has become necrotic and eroded/sloughed

35


3 Key cellular events in inflammation

  1. leukocyte emigration
  2. chemotaxis
  3. leukocyte activation

36

Leukocyte rolling and activation

  • rolling mediated by selectins --> bind w/low affinity to leukocytes
  • integrins finally bind strongly
  • leukocytes spread out on endothelial surface
  • trnasmigration via PECAM-1/CD31

37

Key mediator of leukocyte transmigration

PECAM-1/CD31

38

Ways leukocytes kill ingested pathogens

  1. HOCL- myeloperoxidase radical
  2. bactericidal permeability increasing protein
  3. lysozyme
  4. major basic protein - parasites

39

Which complement molecules are anaphylatoxins?

C3a and C5a

40

Which complement molecule activates leukocytes via chemotaxis?

C5a

41

Which complement molecule is an opsonin?

C3b

42


Histamine

  • found in mast, basophils, platelets
  • released by truama, heat, IgE, C3a, C5a
  • vasodilation and venular endothelial contraction

43


Roles of TNFalpha and IL1 in inflammation

  1. endothelial activation
  2. systemic acute phase reactions
  3. hypotension
  4. aggregation and activation of neutrophils, protease release, tissue damage

44

NO

  • produced by macrophages and endothelial cells in inflammation
  • vasodilator, antagonizes platelets, microcidal
  •  

45


Neutral proteases

  • contained in neutrophil/monocyte lysosomal granules
  • e.g. elastase, collagenase
  • antiproteases like a-1 antitrypsin reduce tissue damage --> deficiency =  emphysema
  •  

46

Chronic inflammation

  • can coexist with acute
  • can be caused by acute or start off chronic
  • accumulation of APCs (macrophages, lymphocytes, plasma cells) --> lymphocytic infiltrate
  • angiogenesis and feibrosis

47


Granulomatous inflammation

  • characterized by epithelioid histiocyte cells -activated macrophages that are squamous (abundant pink cytoplasm)
  • multinucleated giant cells (langhans)
  • wall off injury
  1. tb
  2. leprosy
  3. syphilis
  4. cat scratch
  5. parasitic
  6. fungal
  7. silicosis
  8. foreign bodies (sutures
  9. sarcoidosis
  10. crohn's

48

Granulation tissue

49


Fever generation in acute inflammation

  • pyrogens
    • exogenous: lps
    • endogenous: IL1, TNF

50

ESR

acute phase proteins (fibrinogen and Ig) in plasma neutralize neg. charges on RBCs--> no more repulsion --> staacking --> sinking in test tube

51


A normal ESR rules out

inflammatory conditions.

52


Wound healing


repair of damaged tissue by replacement and/or regeneration

53

Regeneration


restoration of lost tissue structures via cell division

  1. division of parnchymal cells in normal stroma (post-CCL4 exposure)
  2. compensatory division of parenchymal cells (after hepatectomy)
  3. stem cell division

54

Replacement

filling of wound with less specialized connective tissue

55

Which tissues regenerate readily?

GI epithelium, epidermis, bone marrow

56


Which tissues regnerate on a normally limited but inducible basis?

liver, kidney, vascular endothelia

57

Healing by primary union

straight wound, well apposed edges, clean --> minimal scar

58

Healing by secondary union

Irregular wound, unapposed edges, dirty --> significant scarring

59

______ cells release PDGF, resulting in ______.

  • activated platelets and macrophages
  • proliferation of fibroblasts and vascular endothelial cells

60

______ cells release FGF, resulting in ______.

  • macrophages and fibroblasts
  • angiogenesis

61

______ cells release KGF, resulting in ______.

  • fibroblasts
  • growth of keratinocytes

62


______ cells release VEGF, resulting in ______.

  • endothelial cells, fibroblasts, macrophages in hypoxic environment
  • endothelial cell proliferation, angiogenesis, vessel permeability

63

______ cells release TGF beta, resulting in ______.

  • platelets, macrophages, fibroblasts, keratinocytes
  • A LOT

64

Wound healing day 0

  • Clot
  • entry of acute inflammatory cells
  • chemokine and growth factor release

65


Wound healing day 2

epithelialization

66


Wound healing day 7

granulation tissue
 

67

Wound healing day 14

disordered collagenization (type 3)

68


Wound healing 1 year

organized scar-type 1 collagen

69

What cell cycle inhibitor may limit full wound healing and is a key mediator of proliferative arrest in senescent cells?

p21