L14- Tissue Repair and Pathologic Calcification

Question 1

define labile tissues, name some examples

Answer 1

• cells are continuously being lost and replaced by tissue stem cells
• possibly controlled by GFs (ex. CSF)
• Ex: intestinal epithelium (crypt cells), epidermis, hemopoietic cells

Question 2

define stabile tissues, name some examples

Answer 2

• cells are in Go phase
• no stem cells
• if injured, cells have ability to replicate (Go –> G1)
• Ex: liver, kidney, pancreas, endothelial cells, fibroblasts, SM cells

Question 3

define permanent tissues, name some examples

Answer 3

• cells are terminally differentiated, no ability to divide
• healing in organs => scar formation
• Ex: cardiac myocytes, brain (glial cell proliferation, no scar)

Question 4

list the conditions where a tissue would heal with scar formation

Answer 4

• extensive injury (any tissue)
• injury to permanent tissue
• undrained pus (ex. abscess)
• foreign body
• some infectious agents

Question 5

list the 4 steps of scar formation

Answer 5

1) maintenance of hemostasis- stops bleeding
2) inflammation- clears invaders
3) cellular proliferation- epithelial cells, endothelial cells, fibroblasts
4) tissue remodeling

Question 6

The 3rd step of scar formation involves the proliferation of the following cells… (include function)

Answer 6

1) epithelial cells- to cover wound area
2) endothelial cells- angiogenesis (new BVs– supplies nutrients for new cell formation)
3) fibroblasts- ECM formation (collagen III –> I)
- all contribute to granulation tissue

Question 7

Gross appearance of granulation tissue: (1)

Microscopic appearance: (2)

Answer 7

1- pink, soft, granular appearance
2- fibroblasts, many thin-walled (new) and delicate capillaries, loose ECM (type III collagen) —– mixed with inflammatory cells (macrophages mainly)

Question 8

Angiogenesis occurs in response to (1), (2), (3); In (3), (4) is produced to enhance angiogenesis.

Answer 8

(NOTE- in adults)
1- tissue repair (following injury)
2- tumors
3- ischemia
4- VEGF (vascular endothelial growth factor)

Question 9

list the 7 steps of angiogenesis

Answer 9

1) vasodilation (+ inc vascular permeability, NO mediated)
2) EPC recruitment to injury site (endothelial precursor cell)
3) capillary sprout formation (VEGF)
4) endothelial cell proliferation behind sprout
5) canalization => lumina formation
6) periendothelial cell recruitment
7) endothelial cell proliferation inhibition

Question 10

Deposition of CT is also called (1). It starts with the (2) of fibroblasts at site of injury and then (3). Some fibroblasts will (4) in order to (5). (1) is followed by (6) and (7).

Answer 10

1- fibroplasia
2- migration and proliferation
3- deposition of ECM
4- differentiate into Myofibroblasts
5- close the wound
6- BV regression
7- scar contraction

Question 11

(1) is the most important CK involved in fibroplasia as it is involved in the synthesis and deposition of (2); it is generated by (3) cells. (4) and (5) are CKs that are also involved in fibroplasia.

Answer 11

1- TGF-β (transforming GF)
2- CT tissue proteins
3- cells of granulation tissue (fibroblasts, endothelial and epithelial precursors) + M2 macrophages
4- PDGF (platelet derived GF)
5- FGF-2 (fibroblast GF)

Question 12

how is tissue remodeling controlled

Answer 12

-Collagen + other ECM components are in a continuous state of synthesis and degradation (MMP enzyme)
-must be controlled to withstand mechanical stresses
(Type III collagen –> Type I collagen –> collagen cross-linking [simultaneous with collagen formation and degradation])

Question 13

cutaneous wound healing can occur either through (1) or (2). (2) has the following steps: (3)

Answer 13

1- regeneration (1st intention)
2- scar formation (2nd intention)
3- hemostasis –> inflammatory phase –> proliferative phase –> remodeling phase

Question 14

list the steps of the proliferative phase of scar formation in cutaneous wound healing

Answer 14

(3rd step of scar formation- the 2nd intention of skin healing)

• keratinocyte migration
• keratinocyte proliferation
• keratinocyte differentiation –> into stratified squamous epithelium
• reconstitution of basement membrane

Question 15

In the remodeling phase of scar formation in cutaneous wound healing, the scar becomes stronger because of (1) and (2) after synthesis of (3) discontinues. The tensile strength of scar reaches up to (4)% of it original strength.

Answer 15

1- excessive collagen synthesis
2- structural modifications of collagen fibers (cross-linking, inc fiber size)
3- collagen
4- 80%

Question 16

healing by first intention (of cutaneous wound) occurs with injury that only involves…

Answer 16

epithelial layer- main repair mechanism is epithelial regeneration

ex- clean surgical incisions, edges have been approximated by sutures (minimizes area of granulation and therefore area of scar formation)

Question 17

healing by first or second intention is also called….

Answer 17

healing by primary or secondary union

Question 18

healing by second intention (of cutaneous wound) differs from first intention healing by the following characteristics…

Answer 18

• larger clot –> more granulation tissue
• wider wound gap (healing involves contraction to approximate the edges)
• more inflammation b/c more necrotic tissue and possible bacterial contamination

Question 19

list the local factors that can slow wound healing

Answer 19

• infection (=> persistent inflammation)
• poor blood supply
• excessive movement
• presence of foreign material
• radiation

Question 20

list the systemic factors that can slow wound healing

Answer 20

• nutritional status
• drugs (i.e. steroids inhibit fibrous tissue formation)
• co-morbidities (i.e. DM, cancer)

Question 21

extensive scar formation (wound healing) results in…

Answer 21

• fibrosis
• keloid formation**
• hypertrophic scar**
• adhesions
• contractures

Question 22

deficient wound healing results in…..

Answer 22

1- chronic ulcer: healing locked in inflammatory phase

2- weak wound, therefore edges separate (called scar dehiscence)

Question 23

list the phases of bone fracture healing

Answer 23

• hematoma formation (+ granulation tissue)
• immobilization by callus formation (cartilage –> bony)
• repair of the fracture gap
• remodeling

Question 24

list some complications that can arise in bone fracture healing

Answer 24

• infection
• delayed union (delayed ossification after fibrous union)
• non-union
• mal-union (healing with angulation)

Question 25

fracture sites are usually (1), so infections only occurs is (2) or (3) happens

Answer 25

1- sterile
2- communication with skin (open fracture)
3- insertion of device for fixation

Question 26

list the local factors that influence bone fracture healing

Answer 26

• excessive mobility
• infection
• interposition of muscles

Question 27

list the systemic factors that influence bone fracture healing

Answer 27

nutrition of specific substances: i.e. VitC deficiency (necessary for collagen formation)

Question 28

Pathologic calcification is when Ca salts deposit in tissues that aren’t (1) or (2). Ca2+ can accumulates in the (3) of dying cells. Ca salts appear as (4) in H&E stains.

Answer 28

1- bones
2- teeth
3- mitochondria (membrane damage)
4- deeply basophilic (purple), irregular, granular

Question 29

list the two types of pathologic calcification

Answer 29

• dystrophic

- metastatic

Question 30

Dystrophic calcification is characterized by Ca-salt deposition in (1) and with (elevated/normal/low) serum Ca. This occurs because the accumulation of (3) in (1) tissue binds with (4), which reacts with Ca ions to create (5). Examples include the following: (6).

Answer 30

1- necrotic or degenerated tissue (expected whenever cell injury/death occurs)
2- normal serum Ca (elevated in metastatic)
3- denatured proteins
4- phosphate ions
5- Ca-PO4 precipitate
6- deformed valves, atherosclerotic coronary arteries, breast tissue after trauma, healing granulomas, necrotic cancer cells

Question 31

Metastatic calcification is characterized by Ca-salt deposition in (1) and with (elevated/normal/low) serum Ca. (2) can occur due to (3) or (4). Common areas of deposition include: (5).

Answer 31

1- apparent normal tissue
2- elevated (hypercalcemia- normal in dystrophic)
3- excess bone metabolism => inc Ca
4- excess Ca absorption in the gut
5- gastric mucosa, skin, kidneys, + everywhere

Question 32

list some causes of metastatic calcification

Answer 32

(Note- same as the causes of hypercalcemia)

• hyperparathyroidism
• renal failure
• vitD intoxication
• tumors: via PTH secretion OR metastasis to bone
• milk alkali syndrome
• prolonged immobilization

Question 33

in scar formation, type (1) collagen is converted to type (2) collagen which will then undergo extensive (3)

Answer 33

1- type III (scaffolding), granulation tissue
2- type I, scar formation
3- cross-linking
Note- new BVs undergo regression

Question 34

compare keloid with hypertrophic scar

Answer 34

• Both are excessive collagen deposition –> raised scar
• Keloid: beyond wound margins –> malignant potential
• Hypertrophic Scar: within wound margin –> no malignant potential