Cell Injury, Repair, and Wound Healing Flashcards
List the phases of cutaneous wound healing.
- Injury
- coagulation
- early inflammation
- late inflammation
- proliferation
- remodeling
If you undergo an injury, what must be done initially so that proper healing can occur? What cells are responsible for this?
debridement (cleaning up the wound); macrophages
What are some roles of macrophages in wound healing?
debridement (removal of injured tissue and debris)
antimicrobial activity
chemotaxis and proliferation of fibroblasts and keratinocytes
angiogenesis
deposition and remodeling of ECM
What are two ways in which tissues can repair themselves? What’s the most common way?
regeneration
scar formation** most common
After a corneal abrasion, via which mechanism is the eye repaired?
regeneration through corneal stem cells of the limbus area that migrate out and heal the area
What cells of the intestine are responsible for regeneration?
crypt cells
4 places that have regenerative “adult” stem cells
- skin
- intestine
- liver
- cornea
These cells are pluripotent and arise from blastocyst. Can be cultured to produce hepatocytes, neurons, cardiomyocytes, pancreatic islet cells, etc
embryonic stem cells
What is this: resolution of normal structure. Give an example.
regeneration; liver regeneration after partial hepatectomy, healing of lungs after pneumonia.
What is this: scar formation, organization of exudate. Give an example.
healing; myocardial infarction, deep excisional wounds
What is synonymous with scarring and occurs in chronic inflammatory diseases?
fibrosis
Can cardiac myocytes regenerate? So how must they heal? What is layed down during the healing? Can this contract?
no; they heal by scarring; lay down collagen; cannot contract —> can lead to heart failure
Tissues with permanent cells (myocytes or neurons) can replace dead cells with (blank) only
scar tissue
List three types of cells
- continuously cycling (ex: epidermis)
- quiescent or stable cells (ex: hepatocytes)
- nondividing permanent cells (ex: cardiac myocyte or neuron)
Sources: activated macrophages, salivary glands, keratinocytes, and many other cells
Functions: mitogenic for keratinocytes and fibroblasts, stimulates keratinocyte migration, stimulates formation of GRANULATION TISSUE
EGF –> epidermal growth factor
Sources: mesenchymal cells
Functions: chemotactic for neutrophils, macrophages, fibroblasts, and smooth muscle cells; activates and stimulates proliferation of fibroblasts, endothelial, and other cells, stimulates ECM protein synthesis
vascular endothelial growth factor
Function: chemotactic and mitogenic for fibroblasts; stimulates angiogenesis and ECM protein synthesis
fibroblast growth factor or transforming growth factor
This growth factor works at the level of the blood vessels. This growth factor works at the level of the ECM.
VEGF; TGF
One of the main fibrogenic factors as you can see here. Macrophages, platelets and epidermal squamous cells all can produce it. It stimulates fibroblasts to produce collagen which is type III at first and then this type is gradually replaced by type I.
TGF beta
Signals from the growth factors are coordinated with the signals from the ECM via (blank). What is this interaction between signals referred to as?
integrins; cross-talk
What is needed to heal a surgical wound?
angiogenesis!!
It is important for wounds to undergo (blank) to form granulation tissue. What growth factor plays an important role in this?
angiogenesis; VEGF
Angiogenesis mainly occurs via growth factor driven outgrowth of residual endothelium, sprouting of new (blank), and recruitment of (blank) to form new vessels.
vessels; pericytes
Why do you debride a wound?
To get blood vessels to granulate in
Two ways in which blood vessels arise
- angiogenesis from pre-existing vessels
2. angiogenesis by mobilization of EPCs from the bone marrow
These cells can mobilize from the bone marrow to initiate angiogenesis
endothelial precursor cells
4 steps in healing of bone fracture
- hematoma formation
- fibrocartilage (soft) callus formation
- bony callus formation
- bone remodeling
A component of the ECM derived from fibroblasts
collagen
How do you transform immature fibroblasts to mature fibroblasts?
Need fibroblastic growth factor
Skin ulcers occur commonly in diabetic patients. What should you do first? What two things does this allow for?
debride the wound; this allows granulation tissue to form in the dermis and reepithelialization in the epidermis
What is re-epithelialization? Where does it mostly come from?
re-growth of the epidermis following injury; new tissue comes from the periphery (can also come from basilar epidermis where there are skin “stem” cells
What does healing by “first intention” mean? How does this differ from second intention?
First intention = approximate the skin edges around a wound together.
Second intention = Open up wound and let it drain, leave wound open for healing so it can granulate in
Factors that affect wound healing?
medications degree of immobilization foreign material blood supply infection nutrition diabetes size/shape of wound
What do you need to know about steroids, like prednisone, in regards to wound healing?
they are anti-wound healing!! if your patients are on them, no good.
What’s a keloid?
a hypertrophic scar - dermis thickens due to the presence of collagen bundles
How do myocardial infarctions heal?
by scarring
What happens in days 1-3 following a heart attack?
neutrophils are trafficked to the infarcted area
What cells are predominant during days 3-7 follows an MI?
macrophages - they come in and soften the area
By what day of an MI does early formation of granulation tissue occur? By what day is it well developed?
days 7-10; days 10-14
When is scarring complete following an MI?
> 2 months
7-10 days after an MI, are myocytes present yet? What is the only cell present?
NO!; macrophages
Left ventricular rupture can follow an MI and lead to (blank)
cardiac tamponade
List some approaches to cardiac generation
cardiomyocyte replication cardiac stem cells bone-barrow derived cardiac stem cells epicardially derived cardiomyocytes embryonic stem cells induced pluripotent stem cells mesenchymal progenitor cells
