10. Wound Healing II Flashcards

1
Q
Growth Factors/Cytokines
•Survival/Proliferation/Migration/Differentiation 
• Activate cell surface Receptors
• \_\_\_\_
• Gene Expression
– Promote \_\_\_\_ entry
– Relieve \_\_\_\_ on cell cycle Progression 
– Prevent \_\_\_\_
– Growth control genes (\_\_\_\_)

Phosphorylated at tyrosine residues > activate downstream signaling pathways

GPCR > chemoattractants, leukotrienes > increased vascular permeability > resolution of inflammation (during inflammation)
[REWATCH ABOVE]

Cytokines > IL1, IL6, TNF > produced from inflammtory cells > targets: ____ cells; if IL1/IL6 produced from macro’s > activate receptors on surface of endothelial cells to increase expression of ____

Activated GPCR to bring in neutrophils, but for fibroblasts and EC you bring in GF

A
pleiotropic
cell cycle
block
apoptosis
proto-oncogenes
endothelial cells
ICAM-1
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2
Q

AUTOCRINE
____ Proliferation by cytokines
____hyperplasia
(____ Regeneration)

PARACRINE
Recruitment of ____ Cells

ENDOCRINE

GF/cytokines mechanisms
Autocrine > secretes particular protein > receptors on same cell; lymphocyte prolif by cytokines, and compensatory hyperplasia (inc cell growth; chops off part of liver, and replaced by new liver > damaged cell is producing ____, and working back on itself to promote regeneration)

Paracrine > cell secretes, and works on receptor that is present on different cell; recruitment of inflam cells

Endocrine > taken up by blood

Macrophages that produce cytokines, enter BS, activated liver > produces ____ that have effect on systemic inflammation

A

lymphocyte
compensatory
liver

inflammatory

GF

acute phase proteins

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3
Q

Initiation of the Healing response after clot formation:
Platelet-Derived Growth Factor (PDGF)

• Produced by \_\_\_\_, macrophages, endothelial
 cells and keratinocytes 
• \_\_\_\_ for:
– neutrophils, monocytes and fibroblasts
• Proliferation of:
– \_\_\_\_ cells and \_\_\_\_.
• Synthesis/remodeling of \_\_\_\_.

____ is used clinically for the treatment of diabetic ulcers.

____ > first cell to be activated at site of injury > PDGF is a GF produced from platelets, and from macro’s/EC/and keratinocytes

Fact that platelets is first activated at site of injury; important in ____ healing process

Most GF are ____; produced from multiple sources, and has an effect on multiple cell types

A
platelets
chemoattractant
endothelial
macrophages
ECM

recombinant PDGF (regranex)

platelet
initiating
pleiotropic

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4
Q

Re-Epithelialization:
Epidermal Growth Factor (EGF)

  • Produced by ____, Macrophages, Keratinocytes etc…
  • Proliferation and migration of ____
  • Initiates ____
  • Proliferation of ____
  • ____formation

EGF > promotes re-epithelialization; promotes the ____ process (produced from the salivary gland, licking the wound)

A
salivary gland
keratinocytes
re-epithelialization
fibroblast
granulation tissue

healing

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5
Q

Angiogenesis/Granulation tissue

Vascular Endothelial Growth Factor (VEGF)

  • Produced by ____ cells in response to PDGF, TGF-β and ____
  • Promotes migration and proliferation of ____ cells
  • Capillary sprouting in ____
  • Promotes vasodilation and contributes to the formation of ____
  • ____ in ischemic wound (MI).
  • Saliva ; ____ homeostasis
  • Cancer (____ against some cancers)

New BV > granulation tissue formation

PDGF > EC > ____

Hypoxia > ____ > VEGF

Target VEGF via antibody, or antagonists that bind to the VEGF receptor

A
endothelial
hypoxia
endothelial
angiogenesis
vascular lumen
collaterals
oral
antibodies

VEGF
myocardial infarct

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6
Q

Extracellular Matrix (ECM)
• Basement membrane
– ____ required for regeneration

• Interstitial matrix:
\_\_\_\_ to soft tissue 
Minerals; Hardness to bone
Regulates proliferation/differentiation
Reservoir for \_\_\_\_ 
Substrate for cell \_\_\_\_/migration
A

intact ECM (BM)
turgor
growth factors
adhesion

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7
Q

Basement membrane

  • “Chicken wire” mesh beneath epithelial, Endothelial, Smooth muscle structures
  • Type ____ collagen/____/____
  • Synthesized by overlying ____ and underlying ____ cells
  • Scaffolding for tissue renewal (____)
A
IV
laminin
proteoglycan
epithelium
mesenchymal
labile/stable
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8
Q

Interstitial matrix

Reservoir for growth factors

Proliferation/Differentiation
migration

No ____ > lack of ____ strength; upon conversion of Type III to Type I > weakness, pathogenic

ECM protein provide reservoir for ____, contained, and they are not activating random ____

Impt for proliferation/differentiation

A

cross-linking
tensile
GF

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9
Q

ECM Deposition and Scar Formation:
Transforming Growth Factor-β (TGF-β)

Platelets/Mac/Endo/Ker

Chemoattractant for ____

Promotes collagen/ECM synthesis

Inhibits ____

Induces ____

Fibrosis (____) Chronic Inflammation

Anti-inflammatory: Inhibits ____ activity and ____ proliferation

A
macro's/fibroblasts
collagen degradation
TIMPs (tissue inhibitor of metalloproteinases)
kidney/lung/liver
leukocyte
T cell
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10
Q

Transforming Growth Factor-β (TGF-β

TGF-beta: impt in ECM deposition and scar formation

In fetal wounds, it heals without forming a ____ > TGFb is produced in a sufficient to heal the wound, but then it disappears > no scar

____ > excessive production of TGFb > promoting fibroblasts to produce excess amounts of collagen

Produced by most cells

Balance between synthesis and degradation; promoting synthetic and decrease degrad > increase synthesis; TGFb promotes not only synthesis, but also inhibits ____

Do not need ____ cells at this stage of wound healing > wound is focused only on this part of the ____ process

A
scar
liver cirrhosis
degradation
inflammatory
healing
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11
Q

Remodeling of Connective Tissue (MMPs/TIMPs)

  • Matrix Metalloproteinases (MMPs) degrade ECM components (collagen)
  • Produced by ____ cells

• During scarring:
– MMPs ____ (modify) the deposited ECM
– MMP activity shut down by ____ (produced by fibroblasts)
– ECM deposition depends on the ____ between synthesis and degradation:
• ____
• ____
• ____

A
macro's/fibro's/epithelial
remodel
TIMPs
balance
TGF-beta
MMPs
TIMPs
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12
Q

Oral mucosa - regeneration. This is seen in all the ____ deficiencies. Oral mucosa gets damaged and can get ulceration when neutrophil number goes down. Especially in ____. When neutrophil mucosa goes back up, and the oral mucosa goes back to normal. And there’s no scarring here because we don’t damage the ____. And it ____.

fetal wound - regenerates cause ____ responsible for scar formation is only there transiently.

Liver - these contain ____ cells, and livers have regeneration, but if the ____ of the liver is damaged like in ECM, we can get ____ and fibrosis

Lung - same as ____

Kidney - has some capacity of regeneration in cortical ____, but not to same extent as liver. Only for mild injury. So if see disease process here, the injury must be pretty ____. If someone has kidney disease and we stain area with trichome, most of the blue staining would be on ____ and not on tubules (at least in early stages). The tubules may be involved later but for glomeruli, these would form scar tissue/fibrosis mostly.

Heart - would form ____ and fibrosis.

Nervous system - CNS form ____ and when astrocytes proliferate, they get ____, which would be like the scarring we see in other tissues. The peripheral nervous system’s axons and dendrites have capacity to ____. We will talk about that a lil later.

A

LAD/leukocytes
cyclic neutropenia
BM
regenerates

TGFbeta

labile
framework
scar

liver

tubules
severe
glomeruli

scar

scar
gliosis
regenerate

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13
Q

IF HAVE CHRONIC INFLAMMATION OF KIDNEY, IT WOULD FIRST BE ON ____ BECAUSE THIS HAS LEAST ABILITY TO REGENERATE.

A

glomeruli

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14
Q

Day 1: not very uniform, presence of ____
2-3 days: ____ invade to remove dead tissue
7-10 days: ____ invade to remove apoptotic and dead tissue
10-14 days: ____ > new BV formation, and the presence of blue areas
2-6 weeks: formation of a ____

A
inflammation
neutrophils
macrophages
granulation tissue
scar
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15
Q

Traumatic Neuroma
• Not a ____
• Reactive proliferation of ____ tissue after damage
of nerve bundles
• Encounter ____ tissue/cannot reestablish ____
• ____ mass develops at the site of injury.
• Trauma/extraction
• Common sites: ____, tongue, ____ lip.
• Painful
• ____ excision.

A
neoplasm
neuronal
scar
innervation
tumor-like
mental foramen
lower
surgical
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16
Q

Bone Formation/Fracture Repair
• Intramembranous ossification (e.g.skull, maxilla, mandible)
– ____ differentiation of mesenchymal cells into Osteoblasts
– Collagen + organic ECM = (____)
– ____ -Mineralized bone matrix
– Osteoclasts- bone remodeling
– Long bone grows in ____

• Endochondral ossification (long bones)
– Mesenchymal cells into ____
– Replacement of hyaline cartilage template by ____ – Long bone grows in ____

A

direct
osteoid
osteoid + Ca++/phosphates
width

hyaline chondrocyte
bone
length

17
Q

Bone

• 1. Hematoma
– PMN/Macrophage
– \_\_\_\_
– \_\_\_\_ to initiate healing
• 2. Fibrocartilaginous callus
– \_\_\_\_/\_\_\_\_ tissue
– Chondrocytes/Collagen proteoglycans
– \_\_\_\_ callus
• 3. Bony callus
– \_\_\_\_ ossification
– (Hyaline cartilage to bone)
– \_\_\_\_ bone replaces the soft callus
• 4. Remodeling
– \_\_\_\_ bone replaces woven bone
– Heals without \_\_\_\_

Important to maintain blood supply > placement of a cast is important to align the ____

Similar to what happens to regeneration, but the mechanism is via ____

A

debridement
GF

angiogenesis
granulation
fibrocartilage-soft
endochondral
woven
cortical
scar

blood supply
cartilage

18
Q

Cellular Dynamics During Extraction of Socket Healing

Early phase > blood clot/neutrophil (hemostatic/inflamm)

Macro’s > new ____

Fibroblasts > secrete new ____

Osteoblasts/osteocytes > bone formation + ____

A

BV
ECM
remodeling

19
Q

Healing of a socket wound

First pic - we have extracted tooth with blood clot for cessation of hemorrhage. If blood clot doesn’t form, we have complications.

2nd - Blood clot also has ____ tissue formation. Exactly by same mechanism that we talked about.

3rd - Now we have connective tissue and ____ forming. The ____ is beginning to come back

20 - Can see epithelium now, and can see the inner part of bone is becoming to get filled in.

40 - CT, and epithelium is coming back. And beginning to be filled by ____ bone.

Last pic - With time, we have immature bone which will remodel to give us ____ bone.

A

granulation
osteoid
epithelium
immature

mature

20
Q

DRY SOCKET (Alveolar Osteitis)

• 1-3% of extractions
• Infection/Trauma
• Pain/Foul \_\_\_\_
• Dissolution of the blood clot
• Predisposing factors:
– \_\_\_\_
– Site of \_\_\_\_
(mandible)
– Trauma
– \_\_\_\_

Mandibular extraction > 20-30% develop into dry socket

Excessive trauma, and if tooth is infected (mandibular third molar is removed chance of dry socket is greater with infection)

Trauma/infection > inflammation of BM space > plasminogen > ____ > lyses the fibrin clot and formation of kinin > clot is resorbed

Reason it’s called dry: expect to see the formation of a clot > but clot is resorbed and ____

A

smell
oral contraceptives
trauma
smoking

plasmin
necrotized

21
Q
DRY SOCKET (Alveolar Osteitis)
Treatment and prognosis:
• Socket irrigation
• Packed with
\_\_\_\_ dressing
• \_\_\_\_ in socket
• Dressing changed every 24 h then 2/3 days until \_\_\_\_ covers exposed bone.

Prior to treatment of dry socket > ____

No teeth, okay, only facilitating regrowth of granulation tissue

Once gran tissue covers exposed bone, normal wound healing process takes over

A

obtundent/antiseptic
antibiotic
granulation tissue

x-ray

22
Q

Infection/Inflammation

• INFECTION:
– Prolongs \_\_\_\_
Infection/Inflammation
  – Delays \_\_\_\_ regeneration
– Increases \_\_\_\_ tissue
– Increased risk of \_\_\_\_ formation
– Common causes of death in \_\_\_\_ injuries
A
inflammation
epithelial
granulation
scar
burn
23
Q

“Proud Flesh”

____ nodule; ____-surface; may be ____

At high power > see lots of ____ and some macro’s and fibro’s, moreso than you would see in normal tissue (velvety, granular, etc.)

A

erythemetous
smooth
ulcerated
BV

24
Q

Pyogenic Granuloma

____ or ____ mass, usually ____ but some are ____

Surface typically ____ (red/pink), easily ____

____: ~75% of all cases

Pyogenic granuloma on a histological slide would look identical to ____

Sometimes women manifest with ____: pregnancy-tumor, it will regress over time

A

smooth
lobulated
pedunculated
sessile

ulcerated
bleeds

gingiva

“proud flesh”

pregnancy

25
Q

Keloid

This scar does not contract, but ____ instead. After shaving and leaving a scar, it doesn’t contract and close. Grows this monstrosity instead.

1st pic - person got small incision from shaving.
2nd - woman got ear pierces and this happened
3rd pic - just from some guy stepping on a thorn walking barefoot.
4th pic - person gave birth through ____.

SCAR that expands. This is actually ____ than surrounding tissue

A

expands
C-site
darker

26
Q

Keloid Pathogenesis

  • Increased fibroblast proliferation and collagen synthesis
  • Overexpression of ____
  • Type ____ collagen
  • Reduced fibroblast ____?

• Genetics:
– Occurs more frequently ____
– ____ genes may be involved
– Genes not yet ____

A

TGFbeta
III
apoptosis

African/Asian
multiple
identified

27
Q

Hypertrophic Scar

Does not continue to ____ like keloid does; the color is a little ____; not as ____ as keloid

A

expand
redder
dark

28
Q

Hypertrophic Scar

Excessive ____, continue to deposit collagen, and they contract (that’s why they do not ____)

A

myofibroblasts

expand

29
Q

Keloid vs. Hypertrophic Scar

Keloid
Complexion: \_\_\_\_
Growth: \_\_\_\_
Treatment: \_\_\_\_
Common scar: \_\_\_\_
HTS
Complexion: \_\_\_\_
Growth: \_\_\_\_
Treatment: \_\_\_\_
Common scar: \_\_\_\_

Keloid is ____ in color.

Treatment for keloid - can do cosmetic treatment to get rid of keloid, but its NO, because its gonna ____. This is genetic disposition, so it will happen again. Not a common scar (occurs in few individuals of ____ descent). HTS is more common.

A

dark
yes
yes/no
no

light
no
yes
yes

grow back

african/asian

30
Q

Liver Cirrhosis

When we see liver cirrhosis, we also seeing ____.
Myofibroblasts - synthesis of collagen and contractioon. This liver, instead of being smooth surfaced, its ____ and ____ surface.
Normal liver cells, then we have one that is crazy surrounded by ____ (trichome pic)

A

myofibroblasts
nodular
rough
collagen

31
Q
Ehlers-Danlos-Syndrome (EDS)
Abnormal collagen synthesis or structure:
• Deficiency of \_\_\_\_
– Decreased collagen \_\_\_\_
– Skin \_\_\_\_
– \_\_\_\_ hypermobile

• Deficient synthesis of type ____ collagen
– Blood vessel ____ wall
– Predisposed to ____

Mutations in different collagen genes > abnormal collagen synthesis/structure

LH > hydroxylation of ____ residues > important for cross-linking

A

lysyl hyrdroxylase
cross-linking
hyperextendible
joint

III
bowel
rupture

lysine

32
Q

Ehlers-Danlos-Syndrome (EDS)

Wound healing defects:
Minor injuries produce ____ defects
Surgical repair abnormal (____ strength)
____

Ruptureof____ Ruptureof____

A

gaping
tensile
dehisence

colon
arteries

33
Q

Local Factors in Wound Healing

• NECROTIC TISSUE IN WOUND
– Promotes ____ growth
– ____ barrier
– Delays ____

• FOREIGN MATERIAL IN WOUND
– Harbor ____
– Promote ____

A

bacterial
physical
healing

bacteria
inflammation

34
Q
Inadequate Blood Supply
Decubitis Ulcer (Bed sore, Pressure Ulcer)

DECUBITIS ULCER
– ____ induced Ischemia

TREATMENT:
– \_\_\_\_ relief
– \_\_\_\_ and \_\_\_\_debridement
– Clean/Moist
– \_\_\_\_?
A
pressure
pressure
enzymatic
surgical
PDGF
35
Q

LOCAL FACTORS IN WOUND HEALING

• Necrotic Tissue
• Foreign
materials

• INADEQUATE BLOOD SUPPLY:
– Decubitus ulcers
– \_\_\_\_ 
– \_\_\_\_
– \_\_\_\_
• Others: 
– \_\_\_\_
– Direction and location of wound
– Movement of \_\_\_\_
– Drying out
– \_\_\_\_

For enderteritis oblisterans, there is inflammation of ____ and size of ____ is decreased, compromising blood supply.

-if bone that we wanna make sure there’s no ____, want healing area to be ____. And no trauma.

A

endarteritis obliterans
atherosclerosis
smoking

radiation
wound
trauma

BV
lumen
movement
moist

36
Q

MALNUTRITION

• ____:
– Decreased collagen synthesis

• Reduced Carbohydrate & Fat intake:
– ____ is used as an energy source

• ____ Deficiency:
– Abnormal collagen synthesizes

• Vitamin A Deficiency:
– Defective ____

• Vitamin D Deficiency:
– Defective ____

• Zinc Deficiency:
– Decreased cell ____ and ____ tissue formation

A
hypoproteinemia
protein
vitamin C
epithelization
bone healing
proliferation
granulation
37
Q

DIABETES MELLITUS

• \_\_\_\_ depresses leukocyte function
 • Peripheral \_\_\_\_
• Depressed \_\_\_\_ and
\_\_\_\_ Blood Supply
• Ischemia
• Infection
• Decreased \_\_\_\_
 Treatment:
• \_\_\_\_
• HBO (Hyperbaric Oxygen)
• \_\_\_\_
• Antimicrobial
• \_\_\_\_
A
hyperglycemina
neuropathy
arterial
peripheral
GF

PDGF
SDF (stromal cell-derived factor)
amputation