WOUND HEALING Flashcards
What are the 3 types of tissues based on REGENERATIVE CAPACITY?
- LABILE
- STABLE
- PERMANENT
Describe the regeneration process of LABILE tissues.
Labile tissues contain STEM CELLS that continuously cycle to regenerate new tissue
Name some labile tissues.
GI - Small bowel and large bowel
Skin
Lung
Bone marrow
Where are the stems cells of the SMALL/LARGE BOWEL located in?
BASE of intestinal crypts
Where are the stem cells of the skin located in?
STRATUM BASALIS of dermis
What are the stem cells of the bone marrow? What is the marker of these cells?
HSC - Marker = CD34+***
Describe the regeneration process of STABLE tissue.
Stable tissue cells are quiescent (Go) BUT can exit and re-enter cell cycle to regenerate when necessary -> Re-enter quiescence
What is the difference between GRANULOMA and GRANULATION TISSUE?
Granuloma = subtype of chronic inflammation (=Epithelioid histiocytes* + multinucleated giant cells/lymphocytic rim)
Granulation tissue = initial phase of REPAIR in wound healing (=Fibroblasts secreting Type III*collagen + Capillaries providing nutrients + Myofibroblasts contracting wound)
What are the stem cells of the lung?
TYPE II PNEUMOCYTE
Name two STABLE tissues.
- LIVER: Partial resection -> Hepatocytes exit quiescence -> Each hepatocyte produces additional cells -> Re-enter quiescence = COMPENSATORY HYPERPLASIA
- RENAL PCT: Takes some time for regeneration of this stable tissue. After ATN -> Pt requires dialysis for support until renal PCT fully regenerates
Name 3 permanent tissues. Do permanent tissues undergo REGENERATION or REPAIR?
Permanent tissues undergo REPAIR (=fibrosis + scar) since they lack stem cells
- Myocardial muscle - POST-MI: White fibrotic scarring
- Skeletal muscle
- Neurons
When are two circumstances that FIBROTIC SCAR REPAIR occur?
- When stem cells of LABILE or STABLE tissue are lost - e.g. deep skin cut (steak knife) to a point that stratum basalis is lost
- Healing of a PERMANENT TISSUE (e.g. myocardial muscle)
What distinguishes GRANULATION TISSUE from SCAR formation?
Granulation tissue = initial phase of repair (Type III collagen)
Scar formation = eventually replaces granulation tissue (Type I collagen) by COLLAGENASE
What is the co-factor required for COLLAGENASE to replace Type III Collagen with Type I collagen in the final phase of scar formation in REPAIR?
ZINC
Where is TYPE ONE I Collagen found in? What is its function?
BONES, SKIN, TENDONS, Most organs
Provide HIGH TENSILE STRENGTH (support and stability)
Where is Type TWO II Collagen found in?
CARTILAGE
Cart-TWO-lage
Where is Type III collagen found in? What is its function?
BV + Granulation tissue + Embryonic Tissue + Uterus + Keloids
Provides pliability and flexibility
Where is Type IV collagen found in?
Basement membrane
Mechanism of tissue regen/repair: What is TGF-alpha?
FIBROBLAST and EPITHELIAL growth factor
Mechanism of tissue regen/repair: What is TGF-beta?
Fibroblast Growth factor + Anti-inflammatory
Mechanism of tissue regen/repair: What is PDGF?
Platelet-derived growth factor = Growth factor for ENDOTHELIUM + SMOOTH MUSCLE (BV) + FIBROBLASTS
Mechanism of tissue regen/repair: What is FGF?
Important for ANGIOGENESIS + Skeletal muscle dvlm/endochondral bone formation
Mechanism of tissue regen/repair: What is VEGF?
Vascular endothelial growth factor - Important for Angiogenesis
What type of CUTANEOUS HEALING is the suturing of a surgical incision in the ER?
PRIMARY INTENTION: Edges ARE approximated to fill the defect and have the skin heal on its own
Pt has a large wound healed by SECONDARY intention. 6wks later, you notice that the wound has significantly reduced in size. What is the mechanism of this size reduction?
MYOFIBROBLASTS of the granulation tissue
Secondary intention- Edges are NOT approximated and defect is filled with granulation tissue (= BV + fibroblasts + myofibroblasts that contract the wound)
How does VitC Deficiency result in delayed, aberrant healing?
VitC = important co-factor of HYDROXYLASE that hydroxylates Pro/Lys residues necessary for cross-linking the collagen
What are 3 possible pathologies that result in DELAYED ABERRANT wound healing?
Deficiencies of Zn, VitC, and Cu
How does Zn Deficiency result in delayed, aberrant healing?
Zn = important co-factor of COLLAGENASE that replaces Type III collagen (secreted by myofibroblasts of granulation tissue) with Type I collagen (scar formation)
How does Cu Deficiency result in delayed, aberrant healing?
Cu = important co-factor of LYSYL oxidase that cross-links the hydroxylated Lys residue of collagen molecules to form STABLE TYPE I COLLAGEN
What is the most common cause of delayed, aberrant wound healing?
INFECTION - most commonly by S.aureus
Continued inflammation resulting in impaired wound healing
Pt is an African American** who recently got her ear pierced. She noticed a large tumor-like mass growing out of her earlobes. What does she have?
KELOID = Excessive granulation tissue formaiton during tissue repair (THICK PINK COLLAGEN BUNDLES on histology)
Genetic predisposition to African Americans, Type III collagen
Classically affects earlobes, face, UE
What are other causes of DELAYED aberrant wound healing?
- Foreign body - Induces chronic inflammation and is a cuase of non-caseating granuloma formation
- Ischemia - Lack of blood supply
- Diabetes
- Malnutrition - Lack of building blocks for wound healing
COMPLICATION 1 OF WOUND HEALING: What is it called when a wound ruptures? When does this most commonly occur?
DEHISCENCE
Most commonly after abdominal surgery
COMPLICATION 2 OF WOUND HEALING: What is it called when there is excess scar tissue localized to the wound? What collagen is it made of?
HYPERTROPHIC SCAR made of TYPE I COLLAGEN
COMPLICATION 3 OF WOUND HEALING: What is it called when there is excess production of scar tissue OUT OF PROPORTION to the wound? What collagen is it made of? Where is it most commonly found?
KELOID made of TYPE III COLLAGEN
Most commonly found in the EARLOBES
Which pathology is associated with type I collagen failure?
OSTEOGENESIS IMPERFECTA
Which pathology is associated with type III collagen failure?
EHLERS-DANLOS SYNDROME Type 3 and 4 - Failure of granulation tissue, skin
Which pathology is associated with type IV collagen failure?
ALPORT SYNDROME (Failure of basement membrane)
