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
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
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`
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
5
Q
Acute inflammation refers to the _______ present and not the _______ of the infection.
A
types of cells (neutrophils) and not the time course
6
Q
What are the five cardinal symptoms of inflammation?
A
- Rubor (red)
- Calor (hot)
- Loss of function
- Tumor (Swelling)
- Dolor (pain)
7
Q
What produces the five cardinal symptoms of inflammation?
A
vascular changes and recruitment of inflammatory cells
8
Q
How do pathologists define a chronic inflammation?
A
- macrophages
- lymphocytes
- angioblasts
- fibrosis
9
Q
What are the two mechanisms by which acute inflammatory responses begin?
A
- Pattern Recognition Receptors (TLR)
2. Inflammosome
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:
- mediators of inflammation
- cytokines
- lymphocyte activators
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.
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)
13
Q
What are the two major vascular responses you see in acute inflammation?
A
- Vasodilation
2. Increased vascular permeability
14
Q
Vasodilation in acute inflammation causes the emergence of what 3 “cardinal symptoms”
A
Heat, Redness and swelling
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
16
Q
What causes edema in acute inflammation?
A
The increased blood flow will increase hydrostatic pressure forcing fluid into the surrounding tissue
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
18
Q
What proteins are typically found in an exudate?
A
albumin from the plasma, fibrinogen, Ig
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
20
Q
What are the three roles of the lymphatic system in acute inflammation?
A
- Remove fluid exudate, leukocytes, cell debris, plasma proteins, fibrin
- Allow dendritic cells to carry antigens to lymph nodes to meet T-cells
- Carry mediators away from the inflammation site so that it can be controlled
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
22
Q
What are the two major functions of histamine?
A
- Vasodilation by relaxing smooth muscle in vessel walls
2. Contract endothelial cells creating space
23
Q
What three things can cause the release of histamine?
A
- C3a and C5a complement
- IgE crosslinking
- trauma or exposure to heat
24
Q
What cells are the source of serotonin?
A
Platelets secrete it when stimulated by PAF
25
What is the function of serotonin?
Vasoconstriction
26
What are the three major plasma protease system?
1. Kinin
2. Fibrinolytic
3. Complement systems
27
What triggers the Kinin and Fibrinolytic systems?
Hageman Factor (12) is activated by HMWK and a negative surface (collagen, BM, activated platelets)
28
Activated Hageman cleaves _______ to ________ in the kinin pathway/
prekallikrein to kallikrein
29
In the kinin pathway, kallikrein cleaves____________ which was circulating in the blood to make __________________.
HMWK (high molecular weight kininogen) to make bradykinin
30
What is the end product of the kinin system?
| What is the function of this vasoactive protein?
Bradykinin:
1. increases vascular permeability
2. causes vasodilation
3. Causes pain
4. Contracts non-vascular smooth muscle
31
In the fibrinolytic cascade, Hageman factor (12) generates__________________ from the inactive precursor ________________.
Plasmin is generated from plasminogen
32
What is the function of plasmin in the acute immune response?
1. digests fibrin in clots to increase vascular permeability
2. cleave kininogens to make bradykinin
3. activate complement system by cleaving C3
33
What are the four ways the complement system helps acute inflammation?
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)
34
What are the three pathways of complement and what are the activators of each pathway?1
1. Classic- microbes
2. Mannose binding lectin
3. Alternative- Antibodies
35
What intermediate do the three pathways of complement activation converge on?
C3 convertase which cleaves into C3a and C3b
36
What is the major function of C3a?
To stimulate mast cells to release histamine
37
What is the major role of C5a?
Chemotaxis and activator of neutrophils, degranulation of mast cells
38
What is the major role of C3b?
C3b remains on the cell surface to opsonize (help phagocytose neutrophils
39
What is the function of C5b?
Continue the cascade by adding 6-9 to form the MAC that lyses cells
40
How do arachadonic acid derivatives differ from histamine in the way it is produced?
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
41
What are the two relevant pathways that arachodonic acid can be metabolized by?
1. Cycooxygenase to prostaglandin and thromboxane
| 2. 5-Lipooxygenase to leukotrienes
42
What is the main function of PGD2, PGE2 and PGF2?
| Which is responsible for fever and pain?
vasodilation and increased vascular permeability.
| PGE2 is responsible for pain and fever
43
What are the two fates of leukotriene A4?
1. Hydrolyzed to B4
| 2. conjugated with glutathione to C4
44
What is the role of leukotriene B4?
1. Attract neutrophils, macrophages and inflammatory agents
| 2. Induce chemokinesis and attachment
45
What are the four chemotactant factors for neutrophils?
1. leuko B4
2. C5a
3. bacterial factors
4. IL-8
46
Which leukotrienes are the cysteinyl leukotrienes and why?
C4, D4 and E4 because they have a cysteine that binds to CysLT1 and CysLT2 on leukocytes, epithelial cells, smooth muscle and endothelial cells
47
What is the function of leukotrienes C4 D4 and E4?
1. Increase vascular permeability by contracting endothelial cells
2. bronchoconstriction
3. vasoconstriction
4. stimulate mucus secretion
48
In addition to the mediators (histamine, serotonin, PGs, leukotriene, etc) what other three aspects of the inflammatory response affect vascular permeability?
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
49
What is the roll of VEGF in inflammation?
VEGF forms channels between endothelial cells to allow for the trancytosis of fluid from vessel lumen to the interstitium
50
Why are new vessels formed during repair leaky?
They lack mature tight junctions
51
Describe the steps in lekocyte recruitment and activation.
| *8L
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)
52
What chemokines are involved in "rolling"?
IL-1, histamines, PAF, TNFa increase expression of E and P selectins on the endothelial cells
53
What leukocyte molecule do the selectins bind to?
Sailyl- Lewis X modified proteins
54
What ensures that neutrophils only roll in vessel with enflamed tissue?
The selective expression of selectins in response to inflammatory signals
55
What are the most important chemotactic factors for leukocytes?
1. Bacterial products
2. C5a
3. leukotreine B
4. IL-8 (chemokines)
56
Which leukocytes migrate through the vessel walls depends of what two factors?
1. the age of the lesion (6-24 hr=neutrophil, 24-48= macrophage)
2. the chemotactic stimuli
57
What are two exceptions to the "neutrophil is the first responder" rule?
1. Viral infections have monocytes as the first responder
| 2. Asthma- IgE to mast cells activates eosinophils
58
What are the two major opsinins that facilitate phagocytosis of microbes?
C3b and IgG
59
What are the four ways phagolysosomes kill bacteria?
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
60
How does the neutrophil amplify the inflammatory response?
It produces mediators for arachadonic acid and cytokines which attract more neutrophils to the site of action
61
What are the three most common causes of leukocyte disfunction?
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
62
What are the 4 rare inherited diseases caused by neutrophil dysfunction?
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)
63
What is the hallmark of LAD-1?
There is failure to make CD18b part of the leukocyte integrin so it cannot adhere
64
What is the problem in LAD-2?
Errors in fucose metabolism-> no Sailyl Lewis X->no rolling
65
What is the problem with chronic granulomatous disesase?
The lysosome doesn't make ROS (error with oxidation) so pathogens cannot be killed
66
What is Chediak-Higashi?
Movement disorder of organelles so they cant form phagolysosomes.
Secretory efforts of cytotoxic T-cells is impaired too
67
What are the three most common causes of leukocyte disfunction?
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
68
What are the 4 rare inherited diseases caused by neutrophil dysfunction?
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)
69
What is the hallmark of LAD-1?
There is failure to make CD18b part of the leukocyte integrin so it cannot adhere
70
What is the problem in LAD-2?
Errors in fucose metabolism-> no Sailyl Lewis X->no rolling
71
What is the problem with chronic granulomatous disesase?
The lysosome doesn't make ROS (error with oxidation) so pathogens cannot be killed
72
What is Chediak-Higashi?
Movement disorder of organelles so they cant form phagolysosomes.
Secretory efforts of cytotoxic T-cells is impaired too
73
What is the difference between cytokines and chemokines?
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
74
What are the two most important cytokines in acute inflammation?
IL-1 and TNFa because they regulate adhesion molecules (selectins) that attract leukocytes to infection
75
What cell produces IL-1 and TNFa? What are their local and systemic effects?
Macrophages make IL1 and TNFa and they work locally to attract neutrophils.
Systemically they circulate to cause fever, cachexia and lethargy
76
What would cause an acute inflammation to progress to scarring and fibrosis?
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
77
What happens if lysosomal enzymes are released into tissue?
Cathepsin, collagenase and elastase will destroy the basic structure of the ECM
78
What is a major problem that can arise if lysosomal enzymes are released in low grade chronic inflammation of the lung?
Elastase will destroy the elastic recoil of the lung and cause emphyseyma
79
What are the three possible outcomes for acute inflammation?
1. Complete resolution
2. progression to chronic inflammation
3. scarring and fibrosis
80
What would allow for complete resolution of acute inflammation?
1. removal of stimulus
2. return of normal vascular permeability
3. inflammatory mediators drained by lymphatics
81
What would cause an acute inflammation to progress to chronic?
1. the stimulus is NOT removed
82
What would cause an acute inflammation to progress to scarring and fibrosis?
1. there is extensive damage to tissue
2. the tissue damage incites inflammation
3.
83
How does fibrin facilitate fibrosis?
It binds to MAC-1 on the macrophage which produces TGF-b that binds to fibroblasts and stimulates collagen production
84
What are the four major patterns of acute inflammation?
1. Serous
2. Fibrinous
3. Hemolytic
4. Purulent (supporative)
85
Where is serous inflammation typically seen?
| What is the histology/morphology?
Body cavities and blisters (between dermis and epidermis)
| You will see a transudate instead of an exudate (low amount of protein, mostly fluid)
86
What proliferate to cause granulation tissue to form at the base of the ulcer?
angioblasts and fibroblasts (loose connective tissue and proliferating capillaries) to replace damaged tissue
87
How is fibrinous exudate resolved?
| What if there is too much?
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
88
What tends to cause purulent inflammation?
bacteria (pyogenic organisms) like staph and pseudomonas
89
What is in the exudate of a purulent inflammation? What does this inflammation typically cause?
Neutrophils.
| It produces necrosis and proceeds to an absess
90
What is it called if purulent exudate is released in the lung and causes suppurative pleuritis?
empyema
91
What is an ulcer?
What will the tissue under the ulcer look like?
What will the tissue over the ulcer look like?
Destruction of the epithelium due to inflammation.
| The tissue under the ulcer will have neutrophils and the surface of the ulcer will be fibrinopurulent
92
What proliferate to cause granulation tissue to form at the base of the ulcer?
angioblasts and fibroblasts (loose connective tissue and proliferating capillaries) to replace damaged tissue
93
How does the histology of acute inflammation differ from chronic?
Acute- edema, vascular congestion, neutrophils, exudate
| Chronic- fibroblasts, angioblasts, macrophages, lymphocytes
94
What is an example of a chronic infection that occurs on a clinically acute time frame?
Poison ivy or contact dermatitis (they are considered chronic because of the lymphocytes and macrophages)
95
What are the four major causes of chronic inflammation?
1. Infectious agents (mycobacterium, fungal, leprosy, syphilis)
2. Foreign bodies
3. Products of metabolism (urate crystals)
4. Immune reactions
96
What are foreign bodies that are particularly difficult for a macrophage to digest (leading to chronic inflammation)?
hair, talc, sutures, silicone, wood splinters
97
What inflammatory response is seen with hypercholesterolemia?
Cholesterol moves into the tissue and forms a xanthoma on the eyelids, elbows, joints or tendons
98
What is the structure called when macrophages, lymphocytes and fibrosis surround urate crystals in the joints?
tophus which is characteristic of gout
99
What happens in rheumatoid arthritis?
autoantibodies form and cause inflammation which swells synovial joints with macrophages, plasma cells, B and T cells
100
When an infection becomes chronic, what changes are made by the macrophage?
They become activated (epithelioid cells with eosinophilic cytoplasm).
Epitheloid cells fuse to become giant syncitial cells
101
What is a nodular region composed of epitheloid and giant cells called?
Granuloma
102
What is meant by granulomatous?
It is an adjective to describe chronic inflammation with epitheloid macrophages and giant cells
103
What is a granuloma?
It is a compact, centrally located area of macrophages, epitheliod cells, giant cells surrounded by lymphocytes and loose connective tissue
104
What would you notice that would help you determine if the granuloma was new or old?
Mature granulomas are ensheathed by fibroblasts and collagen
105
What is granulation tissue?
Tissue in healing that consists of loose connective tissue of fibroblasts and angioblasts to make new cells (found under a scab)
106
In granulation tissue, how are fibroblasts and angioblasts oriented?
Fibroblasts are parallel to the surface of the wound and angioblasts are perpendicular
107
What is a granulocyte?
a synonym for neutrophil
108
Describe the classic pathway of macrophage activation.
LPS, IFNgamma from lymphocyes or foreign bodies will activate the macrophages which will kill by secreting ROS and NO from lysosomes
109
Describe the alternative pathway of macrophage activation.
IL4 and IL13 stimulate the macrophage which will help healing by secreting growth factors that encourage fibroblasts and angioblasts
110
What term is used to describe the systemic responses that occur during chronic inflammation?
acute phase response
111
What are acute phase proteins?
| Name 3 + and 3 - acute phase proteins.
They are proteins whose plasma concentrations change during inflammation.
+ serum amyloid A, fibrinogen and c-reactive protein
- albumin, transferrin, insulin growth factor 1
112
What organ plays a large role in the acute phase response?
liver because it synthesizes acute phase proteins in response to TNF, IL1 and IL6
113
What is the function of c-reactive protein?
It is a positive acute phase protein that eliminates infecting organisms
114
What lab test is done to see if the level of fibrinogen has risen?
the sedimentation test- excess fibrinogen binds to erythrocytes and forms rouleaux making then sedimentary faster
115
What are the major pyrogens that change set point to cause fever?
IL1, IL6, TNF, or bacterial LPS
116
What prostaglandin increased the set point of temperature in the hypothalamus?
PGE2
117
In addition to the hypothalamus raising set point, how else does the body achieve a temperature increase?
1. shivering
| 2. vasoconstriction of extremities
118
How does fever aid the healing process?
1. increased leukocyte mobility
2. enhance phagocytosis
3. T-cell proliferation
4. compromise survival temp of pathogens
119
What is leukocytosis?
| What stimulates this?
increased white blood cell count stimulated by TNF and IL1 which releases neutrophils from bone marrow
120
What is it called when neutrophils are released from the bone marrow before they are mature?
Leukocytosis with a left shift
121
What is a leukemoid response?
Extremely elevated WBC count (40,000-100,000 instead of 4000 to 10,000)
122
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
1. neutrophilia
2. lymphocytosis
3. eosinophilia
123
What are the three steps of wound repair?
1. inflammation
2. epithelialization and formation of granulation tissue
3. Tissue remodeling (maturation/scar contraction)
124
What cells are involved in the inflammation portion of wound repair?
Platelet-derived growth factor is released from platelets which recruits macrophages and fibroblasts to the site of injury
125
After neutrophils infiltrate lesions and digest bacteria and necrotic debris, what happens?
TGFb recruits monocytes to infiltrate the wound.
| M2 macrophages use integrin to attach to the ECM to become reparative macrophages
126
What are the three major things expressed by M2 macrophages and what are the roles?
1. Colony-stimulating factor-1 to promote longevity
2. TNFa to augment inflammation
3. PDGF to recruit fibroblasts
127
Describe the process of epithelialization.
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
128
What cells migrate into a wound when forming granulation tissue?
macrophages, fibroblasts and angioblasts
129
When does granulation tissue reach its peak in an uncomplicated wound repair?
5 days after injury
130
In granulation tissue, fibroblasts form a new matrix of _________ and _______ to support _________ while the angioblast provide _________ and ______.
collagen and elastin to support cell migration while the angioblasts make vessels to provide oxygen and nutrients
131
During tissue remodeling and contraction of scar, fibroblasts change to become what?
myofibroblasts that have characteristics of smooth muscle cells and fibroblasts to contract the wound
132
What happens to the majority of fibroblasts and capillaries that were in granulation tissue when remodeling begins?
They undergo apoptosis and leave an acellular scar
133
What controls collagen degradation during remodeling?
proteolytic enzymes called metalloproteinases
134
What cells secrete metalloproteinases?
macrophages, endothelial cells, keratinocytes, fibroblasts
135
What is healing by first intention?
the resolution and repair of a wound that has apposed edges (sutured or glued) and was uninfected
136
What is exuberant wound healing?
When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across
137
What type of cell is CRUCIAL for second intention healing of a wound?
Myofibroblasts because the smooth muscle properties are necessary to contract the scar
138
What are the six common things that can compromise wound healing?
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
Why does sepsis compromise wound healing?
Because inflammation is extended
140
Why does vit C deficiency compromise wound healing?
It impairs collagen synthesis
141
What are the two proposed reasons for poor healing of diabetic ulcers?
1. vascular disease narrows vessels so reduces O2 and nutrients to the granulation bed
2. Ulcers get infected bc neutrophil function is impaired
142
What is exuberant wound healing?
When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across
143
What are permanent cells? Give examples.
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
What is an example of a chronic infection that occurs on a clinically acute time frame?
Poison ivy or contact dermatitis (they are considered chronic because of the lymphocytes and macrophages)
145
What are the four major causes of chronic inflammation?
1. Infectious agents (mycobacterium, fungal, leprosy, syphilis)
2. Foreign bodies
3. Products of metabolism (urate crystals)
4. Immune reactions
146
What are foreign bodies that are particularly difficult for a macrophage to digest (leading to chronic inflammation)?
hair, talc, sutures, silicone, wood splinters
147
What inflammatory response is seen with hypercholesterolemia?
Cholesterol moves into the tissue and forms a xanthoma on the eyelids, elbows, joints or tendons
148
What is the structure called when macrophages, lymphocytes and fibrosis surround urate crystals in the joints?
tophus which is characteristic of gout
149
What happens in rheumatoid arthritis?
autoantibodies form and cause inflammation which swells synovial joints with macrophages, plasma cells, B and T cells
150
When an infection becomes chronic, what changes are made by the macrophage?
They become activated (epithelioid cells with eosinophilic cytoplasm).
Epitheloid cells fuse to become giant syncitial cells
151
What is a nodular region composed of epitheloid and giant cells called?
Granuloma
152
What is meant by granulomatous?
It is an adjective to describe chronic inflammation with epitheloid macrophages and giant cells
153
What is a granuloma?
It is a compact, centrally located area of macrophages, epitheliod cells, giant cells surrounded by lymphocytes and loose connective tissue
154
What would you notice that would help you determine if the granuloma was new or old?
Mature granulomas are ensheathed by fibroblasts and collagen
155
What is granulation tissue?
Tissue in healing that consists of loose connective tissue of fibroblasts and angioblasts to make new cells (found under a scab)
156
In granulation tissue, how are fibroblasts and angioblasts oriented?
Fibroblasts are parallel to the surface of the wound and angioblasts are perpendicular
157
What is a granulocyte?
a synonym for neutrophil
158
Describe the classic pathway of macrophage activation.
LPS, IFNgamma from lymphocyes or foreign bodies will activate the macrophages which will kill by secreting ROS and NO from lysosomes
159
Describe the alternative pathway of macrophage activation.
IL4 and IL13 stimulate the macrophage which will help healing by secreting growth factors that encourage fibroblasts and angioblasts
160
What term is used to describe the systemic responses that occur during chronic inflammation?
acute phase response
161
What are acute phase proteins?
| Name 3 + and 3 - acute phase proteins.
They are proteins whose plasma concentrations change during inflammation.
+ serum amyloid A, fibrinogen and c-reactive protein
- albumin, transferrin, insulin growth factor 1
162
What organ plays a large role in the acute phase response?
liver because it synthesizes acute phase proteins in response to TNF, IL1 and IL6
163
What is the function of c-reactive protein?
It is a positive acute phase protein that eliminates infecting organisms
164
What lab test is done to see if the level of fibrinogen has risen?
the sedimentation test- excess fibrinogen binds to erythrocytes and forms rouleaux making then sedimentary faster
165
What are the major pyrogens that change set point to cause fever?
IL1, IL6, TNF, or bacterial LPS
166
What prostaglandin increased the set point of temperature in the hypothalamus?
PGE2
167
In addition to the hypothalamus raising set point, how else does the body achieve a temperature increase?
1. shivering
| 2. vasoconstriction of extremities
168
How does fever aid the healing process?
1. increased leukocyte mobility
2. enhance phagocytosis
3. T-cell proliferation
4. compromise survival temp of pathogens
169
What is leukocytosis?
| What stimulates this?
increased white blood cell count stimulated by TNF and IL1 which releases neutrophils from bone marrow
170
What is it called when neutrophils are released from the bone marrow before they are mature?
Leukocytosis with a left shift
171
What is a leukemoid response?
Extremely elevated WBC count (40,000-100,000 instead of 4000 to 10,000)
172
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
1. neutrophilia
2. lymphocytosis
3. eosinophilia
173
What are the three steps of wound repair?
1. inflammation
2. epithelialization and formation of granulation tissue
3. Tissue remodeling (maturation/scar contraction)
174
What cells are involved in the inflammation portion of wound repair?
Platelet-derived growth factor is released from platelets which recruits macrophages and fibroblasts to the site of injury
175
After neutrophils infiltrate lesions and digest bacteria and necrotic debris, what happens?
TGFb recruits monocytes to infiltrate the wound.
| M2 macrophages use integrin to attach to the ECM to become reparative macrophages
176
What are the three major things expressed by M2 macrophages and what are the roles?
1. Colony-stimulating factor-1 to promote longevity
2. TNFa to augment inflammation
3. PDGF to recruit fibroblasts
177
Describe the process of epithelialization.
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
What cells migrate into a wound when forming granulation tissue?
macrophages, fibroblasts and angioblasts
179
When does granulation tissue reach its peak in an uncomplicated wound repair?
5 days after injury
180
In granulation tissue, fibroblasts form a new matrix of _________ and _______ to support _________ while the angioblast provide _________ and ______.
collagen and elastin to support cell migration while the angioblasts make vessels to provide oxygen and nutrients
181
During tissue remodeling and contraction of scar, fibroblasts change to become what?
myofibroblasts that have characteristics of smooth muscle cells and fibroblasts to contract the wound
182
What happens to the majority of fibroblasts and capillaries that were in granulation tissue when remodeling begins?
They undergo apoptosis and leave an acellular scar
183
What controls collagen degradation during remodeling?
proteolytic enzymes called metalloproteinases
184
What cells secrete metalloproteinases?
macrophages, endothelial cells, keratinocytes, fibroblasts
185
What is healing by first intention?
the resolution and repair of a wound that has apposed edges (sutured or glued) and was uninfected
186
What is healing by second intention?
There is a gaping would like an ulcer or burn and the edges are not closely apposed.
187
What type of cell is CRUCIAL for second intention healing of a wound?
Myofibroblasts because the smooth muscle properties are necessary to contract the scar
188
What are the six common things that can compromise wound healing?
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
Why does sepsis compromise wound healing?
Because inflammation is extended
190
Why does vit C deficiency compromise wound healing?
It impairs collagen synthesis
191
What are the two proposed reasons for poor healing of diabetic ulcers?
1. vascular disease narrows vessels so reduces O2 and nutrients to the granulation bed
2. Ulcers get infected bc neutrophil function is impaired
192
What is exuberant wound healing?
When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across
193
How does the histology of acute inflammation differ from chronic?
Acute- edema, vascular congestion, neutrophils, exudate
| Chronic- fibroblasts, angioblasts, macrophages, lymphocytes
194
What is an example of a chronic infection that occurs on a clinically acute time frame?
Poison ivy or contact dermatitis (they are considered chronic because of the lymphocytes and macrophages)
195
What are the four major causes of chronic inflammation?
1. Infectious agents (mycobacterium, fungal, leprosy, syphilis)
2. Foreign bodies
3. Products of metabolism (urate crystals)
4. Immune reactions
196
What are foreign bodies that are particularly difficult for a macrophage to digest (leading to chronic inflammation)?
hair, talc, sutures, silicone, wood splinters
197
What inflammatory response is seen with hypercholesterolemia?
Cholesterol moves into the tissue and forms a xanthoma on the eyelids, elbows, joints or tendons
198
What is the structure called when macrophages, lymphocytes and fibrosis surround urate crystals in the joints?
tophus which is characteristic of gout
199
What happens in rheumatoid arthritis?
autoantibodies form and cause inflammation which swells synovial joints with macrophages, plasma cells, B and T cells
200
When an infection becomes chronic, what changes are made by the macrophage?
They become activated (epithelioid cells with eosinophilic cytoplasm).
Epitheloid cells fuse to become giant syncitial cells
201
What is a nodular region composed of epitheloid and giant cells called?
Granuloma
202
What is meant by granulomatous?
It is an adjective to describe chronic inflammation with epitheloid macrophages and giant cells
203
What is a granuloma?
It is a compact, centrally located area of macrophages, epitheliod cells, giant cells surrounded by lymphocytes and loose connective tissue
204
What would you notice that would help you determine if the granuloma was new or old?
Mature granulomas are ensheathed by fibroblasts and collagen
205
What is granulation tissue?
Tissue in healing that consists of loose connective tissue of fibroblasts and angioblasts to make new cells (found under a scab)
206
In granulation tissue, how are fibroblasts and angioblasts oriented?
Fibroblasts are parallel to the surface of the wound and angioblasts are perpendicular
207
What is a granulocyte?
a synonym for neutrophil
208
Describe the classic pathway of macrophage activation.
LPS, IFNgamma from lymphocyes or foreign bodies will activate the macrophages which will kill by secreting ROS and NO from lysosomes
209
Describe the alternative pathway of macrophage activation.
IL4 and IL13 stimulate the macrophage which will help healing by secreting growth factors that encourage fibroblasts and angioblasts
210
What term is used to describe the systemic responses that occur during chronic inflammation?
acute phase response
211
What are acute phase proteins?
| Name 3 + and 3 - acute phase proteins.
They are proteins whose plasma concentrations change during inflammation.
+ serum amyloid A, fibrinogen and c-reactive protein
- albumin, transferrin, insulin growth factor 1
212
What organ plays a large role in the acute phase response?
liver because it synthesizes acute phase proteins in response to TNF, IL1 and IL6
213
What is the function of c-reactive protein?
It is a positive acute phase protein that eliminates infecting organisms
214
What lab test is done to see if the level of fibrinogen has risen?
the sedimentation test- excess fibrinogen binds to erythrocytes and forms rouleaux making then sedimentary faster
215
What are the major pyrogens that change set point to cause fever?
IL1, IL6, TNF, or bacterial LPS
216
What prostaglandin increased the set point of temperature in the hypothalamus?
PGE2
217
In addition to the hypothalamus raising set point, how else does the body achieve a temperature increase?
1. shivering
| 2. vasoconstriction of extremities
218
How does fever aid the healing process?
1. increased leukocyte mobility
2. enhance phagocytosis
3. T-cell proliferation
4. compromise survival temp of pathogens
219
What is leukocytosis?
| What stimulates this?
increased white blood cell count stimulated by TNF and IL1 which releases neutrophils from bone marrow
220
What is it called when neutrophils are released from the bone marrow before they are mature?
Leukocytosis with a left shift
221
What is a leukemoid response?
Extremely elevated WBC count (40,000-100,000 instead of 4000 to 10,000)
222
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
1. neutrophilia
2. lymphocytosis
3. eosinophilia
223
What are the three steps of wound repair?
1. inflammation
2. epithelialization and formation of granulation tissue
3. Tissue remodeling (maturation/scar contraction)
224
What cells are involved in the inflammation portion of wound repair?
Platelet-derived growth factor is released from platelets which recruits macrophages and fibroblasts to the site of injury
225
After neutrophils infiltrate lesions and digest bacteria and necrotic debris, what happens?
TGFb recruits monocytes to infiltrate the wound.
| M2 macrophages use integrin to attach to the ECM to become reparative macrophages
226
What are the three major things expressed by M2 macrophages and what are the roles?
1. Colony-stimulating factor-1 to promote longevity
2. TNFa to augment inflammation
3. PDGF to recruit fibroblasts
227
Describe the process of epithelialization.
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
What cells migrate into a wound when forming granulation tissue?
macrophages, fibroblasts and angioblasts
229
When does granulation tissue reach its peak in an uncomplicated wound repair?
5 days after injury
230
In granulation tissue, fibroblasts form a new matrix of _________ and _______ to support _________ while the angioblast provide _________ and ______.
collagen and elastin to support cell migration while the angioblasts make vessels to provide oxygen and nutrients
231
During tissue remodeling and contraction of scar, fibroblasts change to become what?
myofibroblasts that have characteristics of smooth muscle cells and fibroblasts to contract the wound
232
What happens to the majority of fibroblasts and capillaries that were in granulation tissue when remodeling begins?
They undergo apoptosis and leave an acellular scar
233
What controls collagen degradation during remodeling?
proteolytic enzymes called metalloproteinases
234
What cells secrete metalloproteinases?
macrophages, endothelial cells, keratinocytes, fibroblasts
235
What is healing by first intention?
the resolution and repair of a wound that has apposed edges (sutured or glued) and was uninfected
236
What is healing by second intention?
There is a gaping would like an ulcer or burn and the edges are not closely apposed.
237
What type of cell is CRUCIAL for second intention healing of a wound?
Myofibroblasts because the smooth muscle properties are necessary to contract the scar
238
What are the six common things that can compromise wound healing?
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
Why does sepsis compromise wound healing?
Because inflammation is extended
240
Why does vit C deficiency compromise wound healing?
It impairs collagen synthesis
241
What are the two proposed reasons for poor healing of diabetic ulcers?
1. vascular disease narrows vessels so reduces O2 and nutrients to the granulation bed
2. Ulcers get infected bc neutrophil function is impaired
242
What is exuberant wound healing?
When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across
243
How does the histology of acute inflammation differ from chronic?
Acute- edema, vascular congestion, neutrophils, exudate
| Chronic- fibroblasts, angioblasts, macrophages, lymphocytes
244
What is an example of a chronic infection that occurs on a clinically acute time frame?
Poison ivy or contact dermatitis (they are considered chronic because of the lymphocytes and macrophages)
245
What are the four major causes of chronic inflammation?
1. Infectious agents (mycobacterium, fungal, leprosy, syphilis)
2. Foreign bodies
3. Products of metabolism (urate crystals)
4. Immune reactions
246
What are foreign bodies that are particularly difficult for a macrophage to digest (leading to chronic inflammation)?
hair, talc, sutures, silicone, wood splinters
247
What inflammatory response is seen with hypercholesterolemia?
Cholesterol moves into the tissue and forms a xanthoma on the eyelids, elbows, joints or tendons
248
What is the structure called when macrophages, lymphocytes and fibrosis surround urate crystals in the joints?
tophus which is characteristic of gout
249
What happens in rheumatoid arthritis?
autoantibodies form and cause inflammation which swells synovial joints with macrophages, plasma cells, B and T cells
250
When an infection becomes chronic, what changes are made by the macrophage?
They become activated (epithelioid cells with eosinophilic cytoplasm).
Epitheloid cells fuse to become giant syncitial cells
251
What is a nodular region composed of epitheloid and giant cells called?
Granuloma
252
What is meant by granulomatous?
It is an adjective to describe chronic inflammation with epitheloid macrophages and giant cells
253
What is a granuloma?
It is a compact, centrally located area of macrophages, epitheliod cells, giant cells surrounded by lymphocytes and loose connective tissue
254
What would you notice that would help you determine if the granuloma was new or old?
Mature granulomas are ensheathed by fibroblasts and collagen
255
What is granulation tissue?
Tissue in healing that consists of loose connective tissue of fibroblasts and angioblasts to make new cells (found under a scab)
256
In granulation tissue, how are fibroblasts and angioblasts oriented?
Fibroblasts are parallel to the surface of the wound and angioblasts are perpendicular
257
What is a granulocyte?
a synonym for neutrophil
258
Describe the classic pathway of macrophage activation.
LPS, IFNgamma from lymphocyes or foreign bodies will activate the macrophages which will kill by secreting ROS and NO from lysosomes
259
Describe the alternative pathway of macrophage activation.
IL4 and IL13 stimulate the macrophage which will help healing by secreting growth factors that encourage fibroblasts and angioblasts
260
What term is used to describe the systemic responses that occur during chronic inflammation?
acute phase response
261
What are acute phase proteins?
| Name 3 + and 3 - acute phase proteins.
They are proteins whose plasma concentrations change during inflammation.
+ serum amyloid A, fibrinogen and c-reactive protein
- albumin, transferrin, insulin growth factor 1
262
What organ plays a large role in the acute phase response?
liver because it synthesizes acute phase proteins in response to TNF, IL1 and IL6
263
What is the function of c-reactive protein?
It is a positive acute phase protein that eliminates infecting organisms
264
What lab test is done to see if the level of fibrinogen has risen?
the sedimentation test- excess fibrinogen binds to erythrocytes and forms rouleaux making then sedimentary faster
265
What are the major pyrogens that change set point to cause fever?
IL1, IL6, TNF, or bacterial LPS
266
What prostaglandin increased the set point of temperature in the hypothalamus?
PGE2
267
In addition to the hypothalamus raising set point, how else does the body achieve a temperature increase?
1. shivering
| 2. vasoconstriction of extremities
268
How does fever aid the healing process?
1. increased leukocyte mobility
2. enhance phagocytosis
3. T-cell proliferation
4. compromise survival temp of pathogens
269
What is leukocytosis?
| What stimulates this?
increased white blood cell count stimulated by TNF and IL1 which releases neutrophils from bone marrow
270
What is it called when neutrophils are released from the bone marrow before they are mature?
Leukocytosis with a left shift
271
What is a leukemoid response?
Extremely elevated WBC count (40,000-100,000 instead of 4000 to 10,000)
272
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
1. neutrophilia
2. lymphocytosis
3. eosinophilia
273
What are the three steps of wound repair?
1. inflammation
2. epithelialization and formation of granulation tissue
3. Tissue remodeling (maturation/scar contraction)
274
What cells are involved in the inflammation portion of wound repair?
Platelet-derived growth factor is released from platelets which recruits macrophages and fibroblasts to the site of injury
275
After neutrophils infiltrate lesions and digest bacteria and necrotic debris, what happens?
TGFb recruits monocytes to infiltrate the wound.
| M2 macrophages use integrin to attach to the ECM to become reparative macrophages
276
What are the three major things expressed by M2 macrophages and what are the roles?
1. Colony-stimulating factor-1 to promote longevity
2. TNFa to augment inflammation
3. PDGF to recruit fibroblasts
277
Describe the process of epithelialization.
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
What cells migrate into a wound when forming granulation tissue?
macrophages, fibroblasts and angioblasts
279
When does granulation tissue reach its peak in an uncomplicated wound repair?
5 days after injury
280
In granulation tissue, fibroblasts form a new matrix of _________ and _______ to support _________ while the angioblast provide _________ and ______.
collagen and elastin to support cell migration while the angioblasts make vessels to provide oxygen and nutrients
281
During tissue remodeling and contraction of scar, fibroblasts change to become what?
myofibroblasts that have characteristics of smooth muscle cells and fibroblasts to contract the wound
282
What happens to the majority of fibroblasts and capillaries that were in granulation tissue when remodeling begins?
They undergo apoptosis and leave an acellular scar
283
What controls collagen degradation during remodeling?
proteolytic enzymes called metalloproteinases
284
What cells secrete metalloproteinases?
macrophages, endothelial cells, keratinocytes, fibroblasts
285
What is healing by first intention?
the resolution and repair of a wound that has apposed edges (sutured or glued) and was uninfected
286
What is healing by second intention?
There is a gaping would like an ulcer or burn and the edges are not closely apposed.
287
What type of cell is CRUCIAL for second intention healing of a wound?
Myofibroblasts because the smooth muscle properties are necessary to contract the scar
288
What are the six common things that can compromise wound healing?
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
Why does sepsis compromise wound healing?
Because inflammation is extended
290
Why does vit C deficiency compromise wound healing?
It impairs collagen synthesis
291
What are the two proposed reasons for poor healing of diabetic ulcers?
1. vascular disease narrows vessels so reduces O2 and nutrients to the granulation bed
2. Ulcers get infected bc neutrophil function is impaired
292
What is exuberant wound healing?
When the granulation bed proliferates beyond the margins of the wound blocking the migration of epidermal cells across
293
What is a keloid?
Keloid is a raised scar from overproduction of collagen due to atypical fibroblasts that deposit too much collagen, elastin, proteoglycans and fibronectin
294
Whether or not regeneration of tissue occurs depends on what three factors?
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
When scientists analyzed C14 DNA in cardiac myocytes, what were they able to determine?
The turnover rate for cardiac myocytes is 1% annually (so essentially it is permanent tissue)
296
Stem cells are what replace injured cells or replenish labile tissue. What are the three major divisions of stem cells?
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
What are labile cells? Give examples.
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
What are stable cells? Give examples.
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
What are permanent cells? Give examples.
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
What is a keloid?
Keloid is a raised scar from overproduction of collagen due to atypical fibroblasts that deposit too much collagen, elastin, proteoglycans and fibronectin
301
Whether or not regeneration of tissue occurs depends on what three factors?
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
When scientists analyzed C14 DNA in cardiac myocytes, what were they able to determine?
The turnover rate for cardiac myocytes is 1% annually (so essentially it is permanent tissue)
303
Stem cells are what replace injured cells or replenish labile tissue. What are the three major divisions of stem cells?
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
What are labile cells? Give examples.
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
What are stable cells? Give examples.
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
What are permanent cells? Give examples.
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
What are the three growth factors most important for wound repair?
What are the major functions of these growth factors?
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
What is the ECM?
| Where is it located and what does it help regulate?
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
Where do the macromolecules that make up the ECM come from?
| What are the two main macromolecules?
Fibroblasts secrete Glycosaminoglycan (GAG) and fibrous proteins
310
What are GAGs usually covalently bound to? What does this form?
What is the GAG that is an exception?
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
What is the function of proteoglycans and hyluronic acid on the ECM?
They allow diffusion of nutrients and signalling molecules
312
What are the four major fibrous proteins in the ECM?
1. collagen
2. laminin
3. elastin
4. Fibronectin
313
What do the fibrous proteins in the ECM do?
provide strength and elasticity to the newly forming tissue
314
Proteoglycans can affect chemical signaling between cells by binding growth factors etc and depending on context can ______ or _______ their signaling.
enhance or inhibit
315
What are the 5 ways by which proteoglycans can enhance or inhibit signaling from growth factors and inflammatory molecules?
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
When proteoglycans in the ECM bind fibroblast growth factor (FGF), what happens?
It allows oligomerization so that the FGF can cross link and activate cell-surface receptors
317
What is decorin?
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
Disturbances to ECM will release ______ which was bound to proteoglycan in the matrix. This growth factor will then recruit ______, ______, and ______/
FGF2 which will promote fibroblasts, angiogenesis and neutrophil recruitment
319
Patients with Marfan's syndrome have a mutation in _________ which is a glycoprotein associated with ECM that is critical for __________ formation.
Fibrillin-1 which is important for making elastin
320
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?
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
What is typically used to treat Marfan's patients?
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
What pathway makes TGF-B? How does this knowledge allow us to better treat Marfan's?
Ang II- now we can use losartan to reduce TGFB levels to reduce the low grade inflammation associated with weakened aorta (aortic dissection)
323
What is the major function of fibronectin?
It is an ECM glycoprotein that helps cells bind to the matrix via integrins.
It also helps cell migration.
324
Cells that are forced to spread out _______ and ___________ than cells that are not spread out/
PRoliferate faster and survivebetter
325
Where is laminin found?
Basal lamina of the ECM. It it survives the wounding event, they provide a scaffold for cells to regenerate and migrate
