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Fundamentals Block 1 > Inflammation and Repair > Flashcards

Inflammation and Repair Flashcards

1
Q

Define inflammation.

A

It is the body’s response to injury and functions to defend the host against infectious agents and repair damaged tissues

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2
Q

How do acute and chronic inflammation differ in onset?

A

Acute has rapid onset and persists for minutes-hours.

Chronic has a slow onset that may take days

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3
Q

How does the cellular infiltrate differ between chronic and acute inflammation>?

A

Acute- a lot of neutrophils and a vascular response

Chronic- monocytes, lymphocytes`

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4
Q

How does tissue injury differ from acute and chronic inflammation?

A

Acute- tissue damage tends to be mild and self-limiting

Chronic- tissue damage is severe and progressive

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5
Q

Acute inflammation refers to the _______ present and not the _______ of the infection.

A

types of cells (neutrophils) and not the time course

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6
Q

What are the five cardinal symptoms of inflammation?

A
  1. Rubor (red)
  2. Calor (hot)
  3. Loss of function
  4. Tumor (Swelling)
  5. Dolor (pain)
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7
Q

What produces the five cardinal symptoms of inflammation?

A

vascular changes and recruitment of inflammatory cells

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8
Q

How do pathologists define a chronic inflammation?

A
  1. macrophages
  2. lymphocytes
  3. angioblasts
  4. fibrosis
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9
Q

What are the two mechanisms by which acute inflammatory responses begin?

A
  1. Pattern Recognition Receptors (TLR)

2. Inflammosome

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10
Q

How do Pattern recognition receptors begin an acute inflammatory response?

A

Pattern recognition receptors on the plasma membrane or endosomes of epithelial cells, phagocytes and dendritic cells see signals on microbes or dead cells. When they bind the receptor, they activate transcription factors for:

  1. mediators of inflammation
  2. cytokines
  3. lymphocyte activators
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11
Q

How do inflammasomes initiate an acute inflammatory response?

A

Inflammasomes are cytoplasmic and bind microbial products, dead cells and URATE CRYSTALS (gout). Once, bound the inflammasome is activated and can cleave/activate caspase-1. Caspase-1 activates IL-1 which recruits inflammatory cells.

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12
Q

What is the job of IL-1? How is it activated?

A

It recruits inflammatory cells to the disrupted tissue.

It is activated by caspase-1 (which was activated by inflammasome)

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13
Q

What are the two major vascular responses you see in acute inflammation?

A
  1. Vasodilation

2. Increased vascular permeability

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14
Q

Vasodilation in acute inflammation causes the emergence of what 3 “cardinal symptoms”

A

Heat, Redness and swelling

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15
Q

What is hyperemia?

A

After activation of acute inflammation, the smooth muscle of arterioles relaxes opening previously closed capillary beds and increasing blood flow to the tissue. Hyperemia is excess blood flow to an injured area

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16
Q

What causes edema in acute inflammation?

A

The increased blood flow will increase hydrostatic pressure forcing fluid into the surrounding tissue

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17
Q

What is the difference between a transudate and an exudate?

A

Transudate- there is less protein in the capillary reducing oncotic pressure. This forces fluid into the surrounding tissue. It has a low specific gravity.
Exudate- Due to increased vascular permeability, protein rich plasma is forced out into the injured tissue. This increases osmotic pressure

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18
Q

What proteins are typically found in an exudate?

A

albumin from the plasma, fibrinogen, Ig

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19
Q

Why are vessels leaky to proteins in acute inflammation?

A

Inflammatory mediators will cause contraction of endothelial cells in venules widening intercellular spaces so fluid/proteins can move into the tissue

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20
Q

What are the three roles of the lymphatic system in acute inflammation?

A
  1. Remove fluid exudate, leukocytes, cell debris, plasma proteins, fibrin
  2. Allow dendritic cells to carry antigens to lymph nodes to meet T-cells
  3. Carry mediators away from the inflammation site so that it can be controlled
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21
Q

What cells are the source of histamine in the acute inflammatory response?

A

MAST CELLs
(basophils and platelets)

have histamine in prepackaged granules that get released when the cell is activated

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22
Q

What are the two major functions of histamine?

A
  1. Vasodilation by relaxing smooth muscle in vessel walls

2. Contract endothelial cells creating space

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23
Q

What three things can cause the release of histamine?

A
  1. C3a and C5a complement
  2. IgE crosslinking
  3. trauma or exposure to heat
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24
Q

What cells are the source of serotonin?

A

Platelets secrete it when stimulated by PAF

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25
Q

What is the function of serotonin?

A

Vasoconstriction

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26
Q

What are the three major plasma protease system?

A
  1. Kinin
  2. Fibrinolytic
  3. Complement systems
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27
Q

What triggers the Kinin and Fibrinolytic systems?

A

Hageman Factor (12) is activated by HMWK and a negative surface (collagen, BM, activated platelets)

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28
Q

Activated Hageman cleaves _______ to ________ in the kinin pathway/

A

prekallikrein to kallikrein

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29
Q

In the kinin pathway, kallikrein cleaves____________ which was circulating in the blood to make __________________.

A

HMWK (high molecular weight kininogen) to make bradykinin

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30
Q

What is the end product of the kinin system?

What is the function of this vasoactive protein?

A

Bradykinin:

  1. increases vascular permeability
  2. causes vasodilation
  3. Causes pain
  4. Contracts non-vascular smooth muscle
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31
Q

In the fibrinolytic cascade, Hageman factor (12) generates__________________ from the inactive precursor ________________.

A

Plasmin is generated from plasminogen

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32
Q

What is the function of plasmin in the acute immune response?

A
  1. digests fibrin in clots to increase vascular permeability
  2. cleave kininogens to make bradykinin
  3. activate complement system by cleaving C3
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33
Q

What are the four ways the complement system helps acute inflammation?

A
  1. Increases vasodilation by stimulating mast cells (C3a and C5a)
  2. Chemotaxis for neutrophils (C5a)
  3. Opsonization of microbes (C3b)
  4. MAC complex to damage/kill target cells (C5b)
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34
Q

What are the three pathways of complement and what are the activators of each pathway?1

A
  1. Classic- microbes
  2. Mannose binding lectin
  3. Alternative- Antibodies
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35
Q

What intermediate do the three pathways of complement activation converge on?

A

C3 convertase which cleaves into C3a and C3b

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36
Q

What is the major function of C3a?

A

To stimulate mast cells to release histamine

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37
Q

What is the major role of C5a?

A

Chemotaxis and activator of neutrophils, degranulation of mast cells

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38
Q

What is the major role of C3b?

A

C3b remains on the cell surface to opsonize (help phagocytose neutrophils

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39
Q

What is the function of C5b?

A

Continue the cascade by adding 6-9 to form the MAC that lyses cells

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40
Q

How do arachadonic acid derivatives differ from histamine in the way it is produced?

A

Histamine is stored as granulations in mast cells, basophils and platelets and is released upon activation.
Arachadonic acid derivatives are synthesized when they are needed within neutrophils and macrophages

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41
Q

What are the two relevant pathways that arachodonic acid can be metabolized by?

A
  1. Cycooxygenase to prostaglandin and thromboxane

2. 5-Lipooxygenase to leukotrienes

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42
Q

What is the main function of PGD2, PGE2 and PGF2?

Which is responsible for fever and pain?

A

vasodilation and increased vascular permeability.

PGE2 is responsible for pain and fever

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43
Q

What are the two fates of leukotriene A4?

A
  1. Hydrolyzed to B4

2. conjugated with glutathione to C4

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44
Q

What is the role of leukotriene B4?

A
  1. Attract neutrophils, macrophages and inflammatory agents

2. Induce chemokinesis and attachment

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45
Q

What are the four chemotactant factors for neutrophils?

A
  1. leuko B4
  2. C5a
  3. bacterial factors
  4. IL-8
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46
Q

Which leukotrienes are the cysteinyl leukotrienes and why?

A

C4, D4 and E4 because they have a cysteine that binds to CysLT1 and CysLT2 on leukocytes, epithelial cells, smooth muscle and endothelial cells

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47
Q

What is the function of leukotrienes C4 D4 and E4?

A
  1. Increase vascular permeability by contracting endothelial cells
  2. bronchoconstriction
  3. vasoconstriction
  4. stimulate mucus secretion
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48
Q

In addition to the mediators (histamine, serotonin, PGs, leukotriene, etc) what other three aspects of the inflammatory response affect vascular permeability?

A
  1. Neutrophils marginate and roll along the vessel walls secreting toxins to damage endothelial lining
  2. VEGF forms channels through endothelial cells by fusing intracellular vesicles
  3. New vessels formed during repair are leaky because they have not established tight junctions
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49
Q

What is the roll of VEGF in inflammation?

A

VEGF forms channels between endothelial cells to allow for the trancytosis of fluid from vessel lumen to the interstitium

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50
Q

Why are new vessels formed during repair leaky?

A

They lack mature tight junctions

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51
Q

Describe the steps in lekocyte recruitment and activation.

*8L

A
  1. Vessel dilates and blood flow slows
  2. Leukocyte “marginates” and moves toward the vessel wall
  3. Histamine, IL-1 TNFa and PAF stimulate E and P selectin on the surface of endothelial cells
  4. L selectin on neutrophils is upregulated
  5. Selectins bind Sailyl-Lewis X modified proteins allowing the neutrophil to “roll”
  6. Integrins on the neutrophil bind tightly to ICAM and VCAM (upregulated by IL-1 and TNF) on endothelial cells
  7. Chemotaxis attracts the neutrophil to the inflamed tissue
  8. The cell passes through intact endothelial lining (diapedesis)
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52
Q

What chemokines are involved in “rolling”?

A

IL-1, histamines, PAF, TNFa increase expression of E and P selectins on the endothelial cells

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53
Q

What leukocyte molecule do the selectins bind to?

A

Sailyl- Lewis X modified proteins

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54
Q

What ensures that neutrophils only roll in vessel with enflamed tissue?

A

The selective expression of selectins in response to inflammatory signals

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55
Q

What are the most important chemotactic factors for leukocytes?

A
  1. Bacterial products
  2. C5a
  3. leukotreine B
  4. IL-8 (chemokines)
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56
Q

Which leukocytes migrate through the vessel walls depends of what two factors?

A
  1. the age of the lesion (6-24 hr=neutrophil, 24-48= macrophage)
  2. the chemotactic stimuli
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57
Q

What are two exceptions to the “neutrophil is the first responder” rule?

A
  1. Viral infections have monocytes as the first responder

2. Asthma- IgE to mast cells activates eosinophils

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58
Q

What are the two major opsinins that facilitate phagocytosis of microbes?

A

C3b and IgG

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59
Q

What are the four ways phagolysosomes kill bacteria?

A
  1. ROS from oxidizing NADPH to superoxide to H2O2
  2. myeloperoxidase-> with Cl reacts to H2O2 to make HOCl radical (bleach)
  3. Reactive nitrogen species
  4. Defensins and lysozymes
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60
Q

How does the neutrophil amplify the inflammatory response?

A

It produces mediators for arachadonic acid and cytokines which attract more neutrophils to the site of action

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61
Q

What are the three most common causes of leukocyte disfunction?

A
  1. Chemo/radiation have a depressed leukocyte number thus are prone to infections
  2. Chronic renal failure have low integrins so the neutrophils have a hard time adhering and moving into the tissue
  3. Diabetes have poor functioning neutrophils
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62
Q

What are the 4 rare inherited diseases caused by neutrophil dysfunction?

A
  1. LAD-1 (Defective synthesis of CD18b of leukocyte integrin)
  2. LAD-2 (defect in fucose metabolism-> no Sailyl LEwis-X-> no rolling)
  3. chronic granulomatous disease-> defect in ROS generation so can’t oxidize pathogens
  4. Chediak-Higashi (do not form phagolysosomes and ctotoxic lymphocytes are impaired)
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63
Q

What is the hallmark of LAD-1?

A

There is failure to make CD18b part of the leukocyte integrin so it cannot adhere

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64
Q

What is the problem in LAD-2?

A

Errors in fucose metabolism-> no Sailyl Lewis X->no rolling

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65
Q

What is the problem with chronic granulomatous disesase?

A

The lysosome doesn’t make ROS (error with oxidation) so pathogens cannot be killed

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66
Q

What is Chediak-Higashi?

A

Movement disorder of organelles so they cant form phagolysosomes.
Secretory efforts of cytotoxic T-cells is impaired too

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67
Q

What are the three most common causes of leukocyte disfunction?

A
  1. Chemo/radiation have a depressed leukocyte number thus are prone to infections
  2. Chronic renal failure have low integrins so the neutrophils have a hard time adhering and moving into the tissue
  3. Diabetes have poor functioning neutrophils
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68
Q

What are the 4 rare inherited diseases caused by neutrophil dysfunction?

A
  1. LAD-1 (Defective synthesis of CD18b of leukocyte integrin)
  2. LAD-2 (defect in fucose metabolism-> no Sailyl LEwis-X-> no rolling)
  3. chronic granulomatous disease-> defect in ROS generation so can’t oxidize pathogens
  4. Chediak-Higashi (do not form phagolysosomes and ctotoxic lymphocytes are impaired)
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69
Q

What is the hallmark of LAD-1?

A

There is failure to make CD18b part of the leukocyte integrin so it cannot adhere

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70
Q

What is the problem in LAD-2?

A

Errors in fucose metabolism-> no Sailyl Lewis X->no rolling

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71
Q

What is the problem with chronic granulomatous disesase?

A

The lysosome doesn’t make ROS (error with oxidation) so pathogens cannot be killed

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72
Q

What is Chediak-Higashi?

A

Movement disorder of organelles so they cant form phagolysosomes.
Secretory efforts of cytotoxic T-cells is impaired too

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73
Q

What is the difference between cytokines and chemokines?

A

Cytokines are proteins that mediate inflammatory or anti-inflammatory effects.
Chemokines are a subset of cytokines that have a cysteine-cysteine bond that can induce movement of leukocytes

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74
Q

What are the two most important cytokines in acute inflammation?

A

IL-1 and TNFa because they regulate adhesion molecules (selectins) that attract leukocytes to infection

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75
Q

What cell produces IL-1 and TNFa? What are their local and systemic effects?

A

Macrophages make IL1 and TNFa and they work locally to attract neutrophils.
Systemically they circulate to cause fever, cachexia and lethargy

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76
Q

What would cause an acute inflammation to progress to scarring and fibrosis?

A
  1. there is extensive damage to tissue
  2. the tissue damage incites inflammation
  3. the inflammation had extensive fibrin exudate that couldnt be cleared by plasmin or macrophages
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77
Q

What happens if lysosomal enzymes are released into tissue?

A

Cathepsin, collagenase and elastase will destroy the basic structure of the ECM

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78
Q

What is a major problem that can arise if lysosomal enzymes are released in low grade chronic inflammation of the lung?

A

Elastase will destroy the elastic recoil of the lung and cause emphyseyma

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79
Q

What are the three possible outcomes for acute inflammation?

A
  1. Complete resolution
  2. progression to chronic inflammation
  3. scarring and fibrosis
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80
Q

What would allow for complete resolution of acute inflammation?

A
  1. removal of stimulus
  2. return of normal vascular permeability
  3. inflammatory mediators drained by lymphatics
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81
Q

What would cause an acute inflammation to progress to chronic?

A
  1. the stimulus is NOT removed
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82
Q

What would cause an acute inflammation to progress to scarring and fibrosis?

A
  1. there is extensive damage to tissue
  2. the tissue damage incites inflammation
    3.
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83
Q

How does fibrin facilitate fibrosis?

A

It binds to MAC-1 on the macrophage which produces TGF-b that binds to fibroblasts and stimulates collagen production

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84
Q

What are the four major patterns of acute inflammation?

A
  1. Serous
  2. Fibrinous
  3. Hemolytic
  4. Purulent (supporative)
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85
Q

Where is serous inflammation typically seen?

What is the histology/morphology?

A

Body cavities and blisters (between dermis and epidermis)

You will see a transudate instead of an exudate (low amount of protein, mostly fluid)

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86
Q

What proliferate to cause granulation tissue to form at the base of the ulcer?

A

angioblasts and fibroblasts (loose connective tissue and proliferating capillaries) to replace damaged tissue

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87
Q

How is fibrinous exudate resolved?

What if there is too much?

A

Enzymatic degradation by plasmin and macrophages.
If there is too much fibrin to be digested, it becomes organized by fibroblasts and vessels and leads to permanent collagen scarring

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88
Q

What tends to cause purulent inflammation?

A

bacteria (pyogenic organisms) like staph and pseudomonas

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89
Q

What is in the exudate of a purulent inflammation? What does this inflammation typically cause?

A

Neutrophils.

It produces necrosis and proceeds to an absess

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90
Q

What is it called if purulent exudate is released in the lung and causes suppurative pleuritis?

A

empyema

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91
Q

What is an ulcer?
What will the tissue under the ulcer look like?
What will the tissue over the ulcer look like?

A

Destruction of the epithelium due to inflammation.

The tissue under the ulcer will have neutrophils and the surface of the ulcer will be fibrinopurulent

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92
Q

What proliferate to cause granulation tissue to form at the base of the ulcer?

A

angioblasts and fibroblasts (loose connective tissue and proliferating capillaries) to replace damaged tissue

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93
Q

How does the histology of acute inflammation differ from chronic?

A

Acute- edema, vascular congestion, neutrophils, exudate

Chronic- fibroblasts, angioblasts, macrophages, lymphocytes

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94
Q

What is an example of a chronic infection that occurs on a clinically acute time frame?

A

Poison ivy or contact dermatitis (they are considered chronic because of the lymphocytes and macrophages)

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5
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95
Q

What are the four major causes of chronic inflammation?

A
  1. Infectious agents (mycobacterium, fungal, leprosy, syphilis)
  2. Foreign bodies
  3. Products of metabolism (urate crystals)
  4. Immune reactions
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1
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96
Q

What are foreign bodies that are particularly difficult for a macrophage to digest (leading to chronic inflammation)?

A

hair, talc, sutures, silicone, wood splinters

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2
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97
Q

What inflammatory response is seen with hypercholesterolemia?

A

Cholesterol moves into the tissue and forms a xanthoma on the eyelids, elbows, joints or tendons

How well did you know this?
1
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98
Q

What is the structure called when macrophages, lymphocytes and fibrosis surround urate crystals in the joints?

A

tophus which is characteristic of gout

How well did you know this?
1
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99
Q

What happens in rheumatoid arthritis?

A

autoantibodies form and cause inflammation which swells synovial joints with macrophages, plasma cells, B and T cells

How well did you know this?
1
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2
3
4
5
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100
Q

When an infection becomes chronic, what changes are made by the macrophage?

A

They become activated (epithelioid cells with eosinophilic cytoplasm).
Epitheloid cells fuse to become giant syncitial cells

How well did you know this?
1
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101
Q

What is a nodular region composed of epitheloid and giant cells called?

A

Granuloma

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102
Q

What is meant by granulomatous?

A

It is an adjective to describe chronic inflammation with epitheloid macrophages and giant cells

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103
Q

What is a granuloma?

A

It is a compact, centrally located area of macrophages, epitheliod cells, giant cells surrounded by lymphocytes and loose connective tissue

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104
Q

What would you notice that would help you determine if the granuloma was new or old?

A

Mature granulomas are ensheathed by fibroblasts and collagen

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105
Q

What is granulation tissue?

A

Tissue in healing that consists of loose connective tissue of fibroblasts and angioblasts to make new cells (found under a scab)

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106
Q

In granulation tissue, how are fibroblasts and angioblasts oriented?

A

Fibroblasts are parallel to the surface of the wound and angioblasts are perpendicular

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107
Q

What is a granulocyte?

A

a synonym for neutrophil

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108
Q

Describe the classic pathway of macrophage activation.

A

LPS, IFNgamma from lymphocyes or foreign bodies will activate the macrophages which will kill by secreting ROS and NO from lysosomes

How well did you know this?
1
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2
3
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5
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109
Q

Describe the alternative pathway of macrophage activation.

A

IL4 and IL13 stimulate the macrophage which will help healing by secreting growth factors that encourage fibroblasts and angioblasts

How well did you know this?
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110
Q

What term is used to describe the systemic responses that occur during chronic inflammation?

A

acute phase response

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111
Q

What are acute phase proteins?

Name 3 + and 3 - acute phase proteins.

A

They are proteins whose plasma concentrations change during inflammation.
+ serum amyloid A, fibrinogen and c-reactive protein
- albumin, transferrin, insulin growth factor 1

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112
Q

What organ plays a large role in the acute phase response?

A

liver because it synthesizes acute phase proteins in response to TNF, IL1 and IL6

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113
Q

What is the function of c-reactive protein?

A

It is a positive acute phase protein that eliminates infecting organisms

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114
Q

What lab test is done to see if the level of fibrinogen has risen?

A

the sedimentation test- excess fibrinogen binds to erythrocytes and forms rouleaux making then sedimentary faster

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115
Q

What are the major pyrogens that change set point to cause fever?

A

IL1, IL6, TNF, or bacterial LPS

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116
Q

What prostaglandin increased the set point of temperature in the hypothalamus?

A

PGE2

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117
Q

In addition to the hypothalamus raising set point, how else does the body achieve a temperature increase?

A
  1. shivering

2. vasoconstriction of extremities

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118
Q

How does fever aid the healing process?

A
  1. increased leukocyte mobility
  2. enhance phagocytosis
  3. T-cell proliferation
  4. compromise survival temp of pathogens
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119
Q

What is leukocytosis?

What stimulates this?

A

increased white blood cell count stimulated by TNF and IL1 which releases neutrophils from bone marrow

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120
Q

What is it called when neutrophils are released from the bone marrow before they are mature?

A

Leukocytosis with a left shift

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121
Q

What is a leukemoid response?

A

Extremely elevated WBC count (40,000-100,000 instead of 4000 to 10,000)

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122
Q

If you notice a patient has a leukemoid response (elevated WBC), which WBC would you expect to be in excess in:

  1. bacterial infection
  2. viral infection
  3. parasitic infection
A
  1. neutrophilia
  2. lymphocytosis
  3. eosinophilia
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123
Q

What are the three steps of wound repair?

A
  1. inflammation
  2. epithelialization and formation of granulation tissue
  3. Tissue remodeling (maturation/scar contraction)
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124
Q

What cells are involved in the inflammation portion of wound repair?

A

Platelet-derived growth factor is released from platelets which recruits macrophages and fibroblasts to the site of injury

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1
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2
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125
Q

After neutrophils infiltrate lesions and digest bacteria and necrotic debris, what happens?

A

TGFb recruits monocytes to infiltrate the wound.

M2 macrophages use integrin to attach to the ECM to become reparative macrophages

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126
Q

What are the three major things expressed by M2 macrophages and what are the roles?

A
  1. Colony-stimulating factor-1 to promote longevity
  2. TNFa to augment inflammation
  3. PDGF to recruit fibroblasts
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127
Q

Describe the process of epithelialization.

A

Epithelial cells at the would margin lose their attachments and migrate into the wound.
The movement is directed by integrins that secrete collagenase which eats up the fibrin clot to make a path.
They secrete components of a basement membrane then revert to their prior phenotype to attach to the BM and each other

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128
Q

What cells migrate into a wound when forming granulation tissue?

A

macrophages, fibroblasts and angioblasts

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129
Q

When does granulation tissue reach its peak in an uncomplicated wound repair?

A

5 days after injury

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130
Q

In granulation tissue, fibroblasts form a new matrix of _________ and _______ to support _________ while the angioblast provide _________ and ______.

A

collagen and elastin to support cell migration while the angioblasts make vessels to provide oxygen and nutrients

How well did you know this?
1
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5
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131
Q

During tissue remodeling and contraction of scar, fibroblasts change to become what?

A

myofibroblasts that have characteristics of smooth muscle cells and fibroblasts to contract the wound

132
Q

What happens to the majority of fibroblasts and capillaries that were in granulation tissue when remodeling begins?

A

They undergo apoptosis and leave an acellular scar

133
Q

What controls collagen degradation during remodeling?

A

proteolytic enzymes called metalloproteinases

134
Q

What cells secrete metalloproteinases?

A

macrophages, endothelial cells, keratinocytes, fibroblasts

135
Q

What is healing by first intention?

A

the resolution and repair of a wound that has apposed edges (sutured or glued) and was uninfected

136
Q

What is exuberant wound healing?

A

When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across

137
Q

What type of cell is CRUCIAL for second intention healing of a wound?

A

Myofibroblasts because the smooth muscle properties are necessary to contract the scar

138
Q

What are the six common things that can compromise wound healing?

A
  1. septic- healing is delayed bc inflammatory phase is extended
  2. Vit C deficiency- impaired collagen synth
  3. Steroids- delay fibrosis and dampen inflammation
  4. mechanical stress
  5. Foreign bodies
  6. malnutrition
139
Q

Why does sepsis compromise wound healing?

A

Because inflammation is extended

140
Q

Why does vit C deficiency compromise wound healing?

A

It impairs collagen synthesis

141
Q

What are the two proposed reasons for poor healing of diabetic ulcers?

A
  1. vascular disease narrows vessels so reduces O2 and nutrients to the granulation bed
  2. Ulcers get infected bc neutrophil function is impaired
142
Q

What is exuberant wound healing?

A

When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across

143
Q

What are permanent cells? Give examples.

A

Permanent cells have no capacity to divide postnatally.
Ex. neurons and cardiac myocytes
If permanent tissue gets injured, the cells can’t regenerate so it is replaced by a fibrous scar.

144
Q

What is an example of a chronic infection that occurs on a clinically acute time frame?

A

Poison ivy or contact dermatitis (they are considered chronic because of the lymphocytes and macrophages)

145
Q

What are the four major causes of chronic inflammation?

A
  1. Infectious agents (mycobacterium, fungal, leprosy, syphilis)
  2. Foreign bodies
  3. Products of metabolism (urate crystals)
  4. Immune reactions
146
Q

What are foreign bodies that are particularly difficult for a macrophage to digest (leading to chronic inflammation)?

A

hair, talc, sutures, silicone, wood splinters

147
Q

What inflammatory response is seen with hypercholesterolemia?

A

Cholesterol moves into the tissue and forms a xanthoma on the eyelids, elbows, joints or tendons

148
Q

What is the structure called when macrophages, lymphocytes and fibrosis surround urate crystals in the joints?

A

tophus which is characteristic of gout

149
Q

What happens in rheumatoid arthritis?

A

autoantibodies form and cause inflammation which swells synovial joints with macrophages, plasma cells, B and T cells

150
Q

When an infection becomes chronic, what changes are made by the macrophage?

A

They become activated (epithelioid cells with eosinophilic cytoplasm).
Epitheloid cells fuse to become giant syncitial cells

151
Q

What is a nodular region composed of epitheloid and giant cells called?

A

Granuloma

152
Q

What is meant by granulomatous?

A

It is an adjective to describe chronic inflammation with epitheloid macrophages and giant cells

153
Q

What is a granuloma?

A

It is a compact, centrally located area of macrophages, epitheliod cells, giant cells surrounded by lymphocytes and loose connective tissue

154
Q

What would you notice that would help you determine if the granuloma was new or old?

A

Mature granulomas are ensheathed by fibroblasts and collagen

155
Q

What is granulation tissue?

A

Tissue in healing that consists of loose connective tissue of fibroblasts and angioblasts to make new cells (found under a scab)

156
Q

In granulation tissue, how are fibroblasts and angioblasts oriented?

A

Fibroblasts are parallel to the surface of the wound and angioblasts are perpendicular

157
Q

What is a granulocyte?

A

a synonym for neutrophil

158
Q

Describe the classic pathway of macrophage activation.

A

LPS, IFNgamma from lymphocyes or foreign bodies will activate the macrophages which will kill by secreting ROS and NO from lysosomes

159
Q

Describe the alternative pathway of macrophage activation.

A

IL4 and IL13 stimulate the macrophage which will help healing by secreting growth factors that encourage fibroblasts and angioblasts

160
Q

What term is used to describe the systemic responses that occur during chronic inflammation?

A

acute phase response

161
Q

What are acute phase proteins?

Name 3 + and 3 - acute phase proteins.

A

They are proteins whose plasma concentrations change during inflammation.
+ serum amyloid A, fibrinogen and c-reactive protein
- albumin, transferrin, insulin growth factor 1

162
Q

What organ plays a large role in the acute phase response?

A

liver because it synthesizes acute phase proteins in response to TNF, IL1 and IL6

163
Q

What is the function of c-reactive protein?

A

It is a positive acute phase protein that eliminates infecting organisms

164
Q

What lab test is done to see if the level of fibrinogen has risen?

A

the sedimentation test- excess fibrinogen binds to erythrocytes and forms rouleaux making then sedimentary faster

165
Q

What are the major pyrogens that change set point to cause fever?

A

IL1, IL6, TNF, or bacterial LPS

166
Q

What prostaglandin increased the set point of temperature in the hypothalamus?

A

PGE2

167
Q

In addition to the hypothalamus raising set point, how else does the body achieve a temperature increase?

A
  1. shivering

2. vasoconstriction of extremities

168
Q

How does fever aid the healing process?

A
  1. increased leukocyte mobility
  2. enhance phagocytosis
  3. T-cell proliferation
  4. compromise survival temp of pathogens
169
Q

What is leukocytosis?

What stimulates this?

A

increased white blood cell count stimulated by TNF and IL1 which releases neutrophils from bone marrow

170
Q

What is it called when neutrophils are released from the bone marrow before they are mature?

A

Leukocytosis with a left shift

171
Q

What is a leukemoid response?

A

Extremely elevated WBC count (40,000-100,000 instead of 4000 to 10,000)

172
Q

If you notice a patient has a leukemoid response (elevated WBC), which WBC would you expect to be in excess in:

  1. bacterial infection
  2. viral infection
  3. parasitic infection
A
  1. neutrophilia
  2. lymphocytosis
  3. eosinophilia
173
Q

What are the three steps of wound repair?

A
  1. inflammation
  2. epithelialization and formation of granulation tissue
  3. Tissue remodeling (maturation/scar contraction)
174
Q

What cells are involved in the inflammation portion of wound repair?

A

Platelet-derived growth factor is released from platelets which recruits macrophages and fibroblasts to the site of injury

175
Q

After neutrophils infiltrate lesions and digest bacteria and necrotic debris, what happens?

A

TGFb recruits monocytes to infiltrate the wound.

M2 macrophages use integrin to attach to the ECM to become reparative macrophages

176
Q

What are the three major things expressed by M2 macrophages and what are the roles?

A
  1. Colony-stimulating factor-1 to promote longevity
  2. TNFa to augment inflammation
  3. PDGF to recruit fibroblasts
177
Q

Describe the process of epithelialization.

A

Epithelial cells at the would margin lose their attachments and migrate into the wound.
The movement is directed by integrins that secrete collagenase which eats up the fibrin clot to make a path.
They secrete components of a basement membrane then revert to their prior phenotype to attach to the BM and each other

178
Q

What cells migrate into a wound when forming granulation tissue?

A

macrophages, fibroblasts and angioblasts

179
Q

When does granulation tissue reach its peak in an uncomplicated wound repair?

A

5 days after injury

180
Q

In granulation tissue, fibroblasts form a new matrix of _________ and _______ to support _________ while the angioblast provide _________ and ______.

A

collagen and elastin to support cell migration while the angioblasts make vessels to provide oxygen and nutrients

181
Q

During tissue remodeling and contraction of scar, fibroblasts change to become what?

A

myofibroblasts that have characteristics of smooth muscle cells and fibroblasts to contract the wound

182
Q

What happens to the majority of fibroblasts and capillaries that were in granulation tissue when remodeling begins?

A

They undergo apoptosis and leave an acellular scar

183
Q

What controls collagen degradation during remodeling?

A

proteolytic enzymes called metalloproteinases

184
Q

What cells secrete metalloproteinases?

A

macrophages, endothelial cells, keratinocytes, fibroblasts

185
Q

What is healing by first intention?

A

the resolution and repair of a wound that has apposed edges (sutured or glued) and was uninfected

186
Q

What is healing by second intention?

A

There is a gaping would like an ulcer or burn and the edges are not closely apposed.

187
Q

What type of cell is CRUCIAL for second intention healing of a wound?

A

Myofibroblasts because the smooth muscle properties are necessary to contract the scar

188
Q

What are the six common things that can compromise wound healing?

A
  1. septic- healing is delayed bc inflammatory phase is extended
  2. Vit C deficiency- impaired collagen synth
  3. Steroids- delay fibrosis and dampen inflammation
  4. mechanical stress
  5. Foreign bodies
  6. malnutrition
189
Q

Why does sepsis compromise wound healing?

A

Because inflammation is extended

190
Q

Why does vit C deficiency compromise wound healing?

A

It impairs collagen synthesis

191
Q

What are the two proposed reasons for poor healing of diabetic ulcers?

A
  1. vascular disease narrows vessels so reduces O2 and nutrients to the granulation bed
  2. Ulcers get infected bc neutrophil function is impaired
192
Q

What is exuberant wound healing?

A

When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across

193
Q

How does the histology of acute inflammation differ from chronic?

A

Acute- edema, vascular congestion, neutrophils, exudate

Chronic- fibroblasts, angioblasts, macrophages, lymphocytes

194
Q

What is an example of a chronic infection that occurs on a clinically acute time frame?

A

Poison ivy or contact dermatitis (they are considered chronic because of the lymphocytes and macrophages)

195
Q

What are the four major causes of chronic inflammation?

A
  1. Infectious agents (mycobacterium, fungal, leprosy, syphilis)
  2. Foreign bodies
  3. Products of metabolism (urate crystals)
  4. Immune reactions
196
Q

What are foreign bodies that are particularly difficult for a macrophage to digest (leading to chronic inflammation)?

A

hair, talc, sutures, silicone, wood splinters

197
Q

What inflammatory response is seen with hypercholesterolemia?

A

Cholesterol moves into the tissue and forms a xanthoma on the eyelids, elbows, joints or tendons

198
Q

What is the structure called when macrophages, lymphocytes and fibrosis surround urate crystals in the joints?

A

tophus which is characteristic of gout

199
Q

What happens in rheumatoid arthritis?

A

autoantibodies form and cause inflammation which swells synovial joints with macrophages, plasma cells, B and T cells

200
Q

When an infection becomes chronic, what changes are made by the macrophage?

A

They become activated (epithelioid cells with eosinophilic cytoplasm).
Epitheloid cells fuse to become giant syncitial cells

201
Q

What is a nodular region composed of epitheloid and giant cells called?

A

Granuloma

202
Q

What is meant by granulomatous?

A

It is an adjective to describe chronic inflammation with epitheloid macrophages and giant cells

203
Q

What is a granuloma?

A

It is a compact, centrally located area of macrophages, epitheliod cells, giant cells surrounded by lymphocytes and loose connective tissue

204
Q

What would you notice that would help you determine if the granuloma was new or old?

A

Mature granulomas are ensheathed by fibroblasts and collagen

205
Q

What is granulation tissue?

A

Tissue in healing that consists of loose connective tissue of fibroblasts and angioblasts to make new cells (found under a scab)

206
Q

In granulation tissue, how are fibroblasts and angioblasts oriented?

A

Fibroblasts are parallel to the surface of the wound and angioblasts are perpendicular

207
Q

What is a granulocyte?

A

a synonym for neutrophil

208
Q

Describe the classic pathway of macrophage activation.

A

LPS, IFNgamma from lymphocyes or foreign bodies will activate the macrophages which will kill by secreting ROS and NO from lysosomes

209
Q

Describe the alternative pathway of macrophage activation.

A

IL4 and IL13 stimulate the macrophage which will help healing by secreting growth factors that encourage fibroblasts and angioblasts

210
Q

What term is used to describe the systemic responses that occur during chronic inflammation?

A

acute phase response

211
Q

What are acute phase proteins?

Name 3 + and 3 - acute phase proteins.

A

They are proteins whose plasma concentrations change during inflammation.
+ serum amyloid A, fibrinogen and c-reactive protein
- albumin, transferrin, insulin growth factor 1

212
Q

What organ plays a large role in the acute phase response?

A

liver because it synthesizes acute phase proteins in response to TNF, IL1 and IL6

213
Q

What is the function of c-reactive protein?

A

It is a positive acute phase protein that eliminates infecting organisms

214
Q

What lab test is done to see if the level of fibrinogen has risen?

A

the sedimentation test- excess fibrinogen binds to erythrocytes and forms rouleaux making then sedimentary faster

215
Q

What are the major pyrogens that change set point to cause fever?

A

IL1, IL6, TNF, or bacterial LPS

216
Q

What prostaglandin increased the set point of temperature in the hypothalamus?

A

PGE2

217
Q

In addition to the hypothalamus raising set point, how else does the body achieve a temperature increase?

A
  1. shivering

2. vasoconstriction of extremities

218
Q

How does fever aid the healing process?

A
  1. increased leukocyte mobility
  2. enhance phagocytosis
  3. T-cell proliferation
  4. compromise survival temp of pathogens
219
Q

What is leukocytosis?

What stimulates this?

A

increased white blood cell count stimulated by TNF and IL1 which releases neutrophils from bone marrow

220
Q

What is it called when neutrophils are released from the bone marrow before they are mature?

A

Leukocytosis with a left shift

221
Q

What is a leukemoid response?

A

Extremely elevated WBC count (40,000-100,000 instead of 4000 to 10,000)

222
Q

If you notice a patient has a leukemoid response (elevated WBC), which WBC would you expect to be in excess in:

  1. bacterial infection
  2. viral infection
  3. parasitic infection
A
  1. neutrophilia
  2. lymphocytosis
  3. eosinophilia
223
Q

What are the three steps of wound repair?

A
  1. inflammation
  2. epithelialization and formation of granulation tissue
  3. Tissue remodeling (maturation/scar contraction)
224
Q

What cells are involved in the inflammation portion of wound repair?

A

Platelet-derived growth factor is released from platelets which recruits macrophages and fibroblasts to the site of injury

225
Q

After neutrophils infiltrate lesions and digest bacteria and necrotic debris, what happens?

A

TGFb recruits monocytes to infiltrate the wound.

M2 macrophages use integrin to attach to the ECM to become reparative macrophages

226
Q

What are the three major things expressed by M2 macrophages and what are the roles?

A
  1. Colony-stimulating factor-1 to promote longevity
  2. TNFa to augment inflammation
  3. PDGF to recruit fibroblasts
227
Q

Describe the process of epithelialization.

A

Epithelial cells at the would margin lose their attachments and migrate into the wound.
The movement is directed by integrins that secrete collagenase which eats up the fibrin clot to make a path.
They secrete components of a basement membrane then revert to their prior phenotype to attach to the BM and each other

228
Q

What cells migrate into a wound when forming granulation tissue?

A

macrophages, fibroblasts and angioblasts

229
Q

When does granulation tissue reach its peak in an uncomplicated wound repair?

A

5 days after injury

230
Q

In granulation tissue, fibroblasts form a new matrix of _________ and _______ to support _________ while the angioblast provide _________ and ______.

A

collagen and elastin to support cell migration while the angioblasts make vessels to provide oxygen and nutrients

231
Q

During tissue remodeling and contraction of scar, fibroblasts change to become what?

A

myofibroblasts that have characteristics of smooth muscle cells and fibroblasts to contract the wound

232
Q

What happens to the majority of fibroblasts and capillaries that were in granulation tissue when remodeling begins?

A

They undergo apoptosis and leave an acellular scar

233
Q

What controls collagen degradation during remodeling?

A

proteolytic enzymes called metalloproteinases

234
Q

What cells secrete metalloproteinases?

A

macrophages, endothelial cells, keratinocytes, fibroblasts

235
Q

What is healing by first intention?

A

the resolution and repair of a wound that has apposed edges (sutured or glued) and was uninfected

236
Q

What is healing by second intention?

A

There is a gaping would like an ulcer or burn and the edges are not closely apposed.

237
Q

What type of cell is CRUCIAL for second intention healing of a wound?

A

Myofibroblasts because the smooth muscle properties are necessary to contract the scar

238
Q

What are the six common things that can compromise wound healing?

A
  1. septic- healing is delayed bc inflammatory phase is extended
  2. Vit C deficiency- impaired collagen synth
  3. Steroids- delay fibrosis and dampen inflammation
  4. mechanical stress
  5. Foreign bodies
  6. malnutrition
239
Q

Why does sepsis compromise wound healing?

A

Because inflammation is extended

240
Q

Why does vit C deficiency compromise wound healing?

A

It impairs collagen synthesis

241
Q

What are the two proposed reasons for poor healing of diabetic ulcers?

A
  1. vascular disease narrows vessels so reduces O2 and nutrients to the granulation bed
  2. Ulcers get infected bc neutrophil function is impaired
242
Q

What is exuberant wound healing?

A

When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across

243
Q

How does the histology of acute inflammation differ from chronic?

A

Acute- edema, vascular congestion, neutrophils, exudate

Chronic- fibroblasts, angioblasts, macrophages, lymphocytes

244
Q

What is an example of a chronic infection that occurs on a clinically acute time frame?

A

Poison ivy or contact dermatitis (they are considered chronic because of the lymphocytes and macrophages)

245
Q

What are the four major causes of chronic inflammation?

A
  1. Infectious agents (mycobacterium, fungal, leprosy, syphilis)
  2. Foreign bodies
  3. Products of metabolism (urate crystals)
  4. Immune reactions
246
Q

What are foreign bodies that are particularly difficult for a macrophage to digest (leading to chronic inflammation)?

A

hair, talc, sutures, silicone, wood splinters

247
Q

What inflammatory response is seen with hypercholesterolemia?

A

Cholesterol moves into the tissue and forms a xanthoma on the eyelids, elbows, joints or tendons

248
Q

What is the structure called when macrophages, lymphocytes and fibrosis surround urate crystals in the joints?

A

tophus which is characteristic of gout

249
Q

What happens in rheumatoid arthritis?

A

autoantibodies form and cause inflammation which swells synovial joints with macrophages, plasma cells, B and T cells

250
Q

When an infection becomes chronic, what changes are made by the macrophage?

A

They become activated (epithelioid cells with eosinophilic cytoplasm).
Epitheloid cells fuse to become giant syncitial cells

251
Q

What is a nodular region composed of epitheloid and giant cells called?

A

Granuloma

252
Q

What is meant by granulomatous?

A

It is an adjective to describe chronic inflammation with epitheloid macrophages and giant cells

253
Q

What is a granuloma?

A

It is a compact, centrally located area of macrophages, epitheliod cells, giant cells surrounded by lymphocytes and loose connective tissue

254
Q

What would you notice that would help you determine if the granuloma was new or old?

A

Mature granulomas are ensheathed by fibroblasts and collagen

255
Q

What is granulation tissue?

A

Tissue in healing that consists of loose connective tissue of fibroblasts and angioblasts to make new cells (found under a scab)

256
Q

In granulation tissue, how are fibroblasts and angioblasts oriented?

A

Fibroblasts are parallel to the surface of the wound and angioblasts are perpendicular

257
Q

What is a granulocyte?

A

a synonym for neutrophil

258
Q

Describe the classic pathway of macrophage activation.

A

LPS, IFNgamma from lymphocyes or foreign bodies will activate the macrophages which will kill by secreting ROS and NO from lysosomes

259
Q

Describe the alternative pathway of macrophage activation.

A

IL4 and IL13 stimulate the macrophage which will help healing by secreting growth factors that encourage fibroblasts and angioblasts

260
Q

What term is used to describe the systemic responses that occur during chronic inflammation?

A

acute phase response

261
Q

What are acute phase proteins?

Name 3 + and 3 - acute phase proteins.

A

They are proteins whose plasma concentrations change during inflammation.
+ serum amyloid A, fibrinogen and c-reactive protein
- albumin, transferrin, insulin growth factor 1

262
Q

What organ plays a large role in the acute phase response?

A

liver because it synthesizes acute phase proteins in response to TNF, IL1 and IL6

263
Q

What is the function of c-reactive protein?

A

It is a positive acute phase protein that eliminates infecting organisms

264
Q

What lab test is done to see if the level of fibrinogen has risen?

A

the sedimentation test- excess fibrinogen binds to erythrocytes and forms rouleaux making then sedimentary faster

265
Q

What are the major pyrogens that change set point to cause fever?

A

IL1, IL6, TNF, or bacterial LPS

266
Q

What prostaglandin increased the set point of temperature in the hypothalamus?

A

PGE2

267
Q

In addition to the hypothalamus raising set point, how else does the body achieve a temperature increase?

A
  1. shivering

2. vasoconstriction of extremities

268
Q

How does fever aid the healing process?

A
  1. increased leukocyte mobility
  2. enhance phagocytosis
  3. T-cell proliferation
  4. compromise survival temp of pathogens
269
Q

What is leukocytosis?

What stimulates this?

A

increased white blood cell count stimulated by TNF and IL1 which releases neutrophils from bone marrow

270
Q

What is it called when neutrophils are released from the bone marrow before they are mature?

A

Leukocytosis with a left shift

271
Q

What is a leukemoid response?

A

Extremely elevated WBC count (40,000-100,000 instead of 4000 to 10,000)

272
Q

If you notice a patient has a leukemoid response (elevated WBC), which WBC would you expect to be in excess in:

  1. bacterial infection
  2. viral infection
  3. parasitic infection
A
  1. neutrophilia
  2. lymphocytosis
  3. eosinophilia
273
Q

What are the three steps of wound repair?

A
  1. inflammation
  2. epithelialization and formation of granulation tissue
  3. Tissue remodeling (maturation/scar contraction)
274
Q

What cells are involved in the inflammation portion of wound repair?

A

Platelet-derived growth factor is released from platelets which recruits macrophages and fibroblasts to the site of injury

275
Q

After neutrophils infiltrate lesions and digest bacteria and necrotic debris, what happens?

A

TGFb recruits monocytes to infiltrate the wound.

M2 macrophages use integrin to attach to the ECM to become reparative macrophages

276
Q

What are the three major things expressed by M2 macrophages and what are the roles?

A
  1. Colony-stimulating factor-1 to promote longevity
  2. TNFa to augment inflammation
  3. PDGF to recruit fibroblasts
277
Q

Describe the process of epithelialization.

A

Epithelial cells at the would margin lose their attachments and migrate into the wound.
The movement is directed by integrins that secrete collagenase which eats up the fibrin clot to make a path.
They secrete components of a basement membrane then revert to their prior phenotype to attach to the BM and each other

278
Q

What cells migrate into a wound when forming granulation tissue?

A

macrophages, fibroblasts and angioblasts

279
Q

When does granulation tissue reach its peak in an uncomplicated wound repair?

A

5 days after injury

280
Q

In granulation tissue, fibroblasts form a new matrix of _________ and _______ to support _________ while the angioblast provide _________ and ______.

A

collagen and elastin to support cell migration while the angioblasts make vessels to provide oxygen and nutrients

281
Q

During tissue remodeling and contraction of scar, fibroblasts change to become what?

A

myofibroblasts that have characteristics of smooth muscle cells and fibroblasts to contract the wound

282
Q

What happens to the majority of fibroblasts and capillaries that were in granulation tissue when remodeling begins?

A

They undergo apoptosis and leave an acellular scar

283
Q

What controls collagen degradation during remodeling?

A

proteolytic enzymes called metalloproteinases

284
Q

What cells secrete metalloproteinases?

A

macrophages, endothelial cells, keratinocytes, fibroblasts

285
Q

What is healing by first intention?

A

the resolution and repair of a wound that has apposed edges (sutured or glued) and was uninfected

286
Q

What is healing by second intention?

A

There is a gaping would like an ulcer or burn and the edges are not closely apposed.

287
Q

What type of cell is CRUCIAL for second intention healing of a wound?

A

Myofibroblasts because the smooth muscle properties are necessary to contract the scar

288
Q

What are the six common things that can compromise wound healing?

A
  1. septic- healing is delayed bc inflammatory phase is extended
  2. Vit C deficiency- impaired collagen synth
  3. Steroids- delay fibrosis and dampen inflammation
  4. mechanical stress
  5. Foreign bodies
  6. malnutrition
289
Q

Why does sepsis compromise wound healing?

A

Because inflammation is extended

290
Q

Why does vit C deficiency compromise wound healing?

A

It impairs collagen synthesis

291
Q

What are the two proposed reasons for poor healing of diabetic ulcers?

A
  1. vascular disease narrows vessels so reduces O2 and nutrients to the granulation bed
  2. Ulcers get infected bc neutrophil function is impaired
292
Q

What is exuberant wound healing?

A

When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across

293
Q

What is a keloid?

A

Keloid is a raised scar from overproduction of collagen due to atypical fibroblasts that deposit too much collagen, elastin, proteoglycans and fibronectin

294
Q

Whether or not regeneration of tissue occurs depends on what three factors?

A
  1. the regeneration ability of the tissue type
  2. The number of viable cells left
  3. if there is a connective tissue framework to support growth (ECM, BM)
295
Q

When scientists analyzed C14 DNA in cardiac myocytes, what were they able to determine?

A

The turnover rate for cardiac myocytes is 1% annually (so essentially it is permanent tissue)

296
Q

Stem cells are what replace injured cells or replenish labile tissue. What are the three major divisions of stem cells?

A

Pluripotent- any of the three germ layers
Multipotent- related heritage (ex. hematopoetic stem cells replace RBC, WBC, platelets)
Unipotent- only replace one specific cell type

297
Q

What are labile cells? Give examples.

A

Labile cells are cells that are constantly dividing to replace cells lost from the body.

  1. cells lining the gut, uterus, skin
  2. hematopoeitic cells
298
Q

What are stable cells? Give examples.

A

Stable cells form the parenchyma of organs and spend most time in G0 but upon injury they are able to go to G1 to replenish lost tissue.
Ex. Liver cells, renal tubular epithelium, fibroblasts, smooth muscle, endothelial cells

299
Q

What are permanent cells? Give examples.

A

Permanent cells have no capacity to divide postnatally.
Ex. neurons and cardiac myocytes
If permanent tissue gets injured, the cells can’t regenerate so it is replaced by a fibrous scar.

300
Q

What is a keloid?

A

Keloid is a raised scar from overproduction of collagen due to atypical fibroblasts that deposit too much collagen, elastin, proteoglycans and fibronectin

301
Q

Whether or not regeneration of tissue occurs depends on what three factors?

A
  1. the regeneration ability of the tissue type
  2. The number of viable cells left
  3. if there is a connective tissue framework to support growth (ECM, BM)
302
Q

When scientists analyzed C14 DNA in cardiac myocytes, what were they able to determine?

A

The turnover rate for cardiac myocytes is 1% annually (so essentially it is permanent tissue)

303
Q

Stem cells are what replace injured cells or replenish labile tissue. What are the three major divisions of stem cells?

A

Pluripotent- any of the three germ layers
Multipotent- related heritage (ex. hematopoetic stem cells replace RBC, WBC, platelets)
Unipotent- only replace one specific cell type

304
Q

What are labile cells? Give examples.

A

Labile cells are cells that are constantly dividing to replace cells lost from the body.

  1. cells lining the gut, uterus, skin
  2. hematopoeitic cells
305
Q

What are stable cells? Give examples.

A

Stable cells form the parenchyma of organs and spend most time in G0 but upon injury they are able to go to G1 to replenish lost tissue.
Ex. Liver cells, renal tubular epithelium, fibroblasts, smooth muscle, endothelial cells

306
Q

What are permanent cells? Give examples.

A

Permanent cells have no capacity to divide postnatally.
Ex. neurons and cardiac myocytes
If permanent tissue gets injured, the cells can’t regenerate so it is replaced by a fibrous scar.

307
Q

What are the three growth factors most important for wound repair?
What are the major functions of these growth factors?

A

Platelet Derived Growth Factor (PDGF)
Transforming Growth Factor b (TGFb)
Fibroblast Growth Factor (FGF)

These growth factors: prevent apoptosis, increase cell size and increase mitotic capability of cells

308
Q

What is the ECM?

Where is it located and what does it help regulate?

A

It is a locally synthesized network surrounding cells that provides a framework for cell proliferation, migration, and differentiation.
It is located between the BM and layer of cells

309
Q

Where do the macromolecules that make up the ECM come from?

What are the two main macromolecules?

A

Fibroblasts secrete Glycosaminoglycan (GAG) and fibrous proteins

310
Q

What are GAGs usually covalently bound to? What does this form?
What is the GAG that is an exception?

A

Proteins to make proteoglycans
Hyluronic acid is an unusual GAG that does not bind to proteins but rather is a sequence of disaccharides that are hydrophilic and form a gel.

311
Q

What is the function of proteoglycans and hyluronic acid on the ECM?

A

They allow diffusion of nutrients and signalling molecules

312
Q

What are the four major fibrous proteins in the ECM?

A
  1. collagen
  2. laminin
  3. elastin
  4. Fibronectin
313
Q

What do the fibrous proteins in the ECM do?

A

provide strength and elasticity to the newly forming tissue

314
Q

Proteoglycans can affect chemical signaling between cells by binding growth factors etc and depending on context can ______ or _______ their signaling.

A

enhance or inhibit

315
Q

What are the 5 ways by which proteoglycans can enhance or inhibit signaling from growth factors and inflammatory molecules?

A
  1. immobilize the mediator to keep inflammation local
  2. block the activity
  3. hold the mediator for controlled/delayed release
  4. protect the mediator from degradation
  5. alter the mediator so it can be presented to cell receptors
316
Q

When proteoglycans in the ECM bind fibroblast growth factor (FGF), what happens?

A

It allows oligomerization so that the FGF can cross link and activate cell-surface receptors

317
Q

What is decorin?

A

It is a proteoglycan associated collagen bundle that will inhibit TGFB.
TGFb is an inhibitor of cell proliferation so this will allow cells to grow and repair tissue

318
Q

Disturbances to ECM will release ______ which was bound to proteoglycan in the matrix. This growth factor will then recruit ______, ______, and ______/

A

FGF2 which will promote fibroblasts, angiogenesis and neutrophil recruitment

319
Q

Patients with Marfan’s syndrome have a mutation in _________ which is a glycoprotein associated with ECM that is critical for __________ formation.

A

Fibrillin-1 which is important for making elastin

320
Q

In addition to making elastin, Fibrillin-1 also binds ______ sequestering it in the ECM until the ECM is disrupted (wound).
What problem does this cause for patients with Marfan’s syndrome?

A

TGFB

In Marfan’s, Fibrillin-1 can’t bind TGFB well so it causes low grade inflammation due to TGFB release which eventually degenerates the aortic wall

321
Q

What is typically used to treat Marfan’s patients?

A

B-blockers so the blood pressure is reduced in the weakened aorta
Now that we know TGF-B plays a large role in the pathogenesis, we give patients Losartan which blocks AngII receptors reducing TGFB levels

322
Q

What pathway makes TGF-B? How does this knowledge allow us to better treat Marfan’s?

A

Ang II- now we can use losartan to reduce TGFB levels to reduce the low grade inflammation associated with weakened aorta (aortic dissection)

323
Q

What is the major function of fibronectin?

A

It is an ECM glycoprotein that helps cells bind to the matrix via integrins.
It also helps cell migration.

324
Q

Cells that are forced to spread out _______ and ___________ than cells that are not spread out/

A

PRoliferate faster and survivebetter

325
Q

Where is laminin found?

A

Basal lamina of the ECM. It it survives the wounding event, they provide a scaffold for cells to regenerate and migrate

Fundamentals Block 1 (7 decks)

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