Test 2 - Inflammation/Healing/Repair

Question 1

Define Repair.

What are the different types?

Answer 1

Repair is the process by which lost or necrotic cells are replaced by vital cells.

Types:

• Parenchymal regeneration
• Fibrosis

Question 2

Parenchymal Regeneration

Answer 2

Replacement of damaged tissue with cells of identical type, sometimes leaving no residual trace of the previous injury.

Parenchymal regeneration can only occur if:

• the tissue has the capacity to regenerate
• the connective tissue framework of the tissue is maintained, so that regenerating cells have an architectural framework upon which to build.

Question 3

Repair by Fibrosis

Answer 3

Fibrosis is replacement by fibrous connective tissue or fibroplasia.

• This process results in an increase in collagen within tissues.
• Fibroblasts are active in synthesizing proteoglycans and collagen.

Question 4

Fibrosis results in an increase in _______ within tissues.

Answer 4

Collagen

Question 5

The cells of the body are divided into three groups on the basis of their regenerative capacity and their relationship to the cell cycle. What are these three groups?

Answer 5

1. Labile cells
2. Stable/Quiescent Cells
3. Nondividing or Permanent Cells

Question 6

Labile Cells

Answer 6

• They follow the cell cycle from one mitosis to the next.
• They continue to proliferate throughout life, continuously replacing cells that have been destroyed.
• Tissues composed of labile cells regenerate after injury, provided that enough stem cells remain.

Examples:

• Surface epithelia: stratified squamous surfaces of the skin, oral cavity, vagina and cervix
• Lining mucosa of all the excretory ducts of the glands of the body (e.g., salivary glands, pancreas, biliary tract)

• The columnar epithelium of the gastrointestinal tract, uterus, and fallopian tubes

• The transitional epithelium of the urinary tract
• Cells of the splenic, lymphoid, and hematopoietic tissue.

Question 7

Stable/Quiescent Cells

Answer 7

• These cells usually demonstrate a low normal level of replication. However, stable cells can undergo rapid division in response to a variety of stimuli.
• • Stable cells are capable of reconstituting the tissue of origin.
• Examples of stable cells:
• Epithelial cells of the liver, kidney, lung, pancreas.
• Smooth muscle cells
• Fibroblasts
• Vascular endothelial cells

Question 8

Nondividing / Permanent Cells

Answer 8

These cells have left the cell cycle and cannot undergo mitotic division in postnatal life.

• Examples of permanent cells:

• Neurons
• Cardiac muscle cells

Question 9

Nonregenerated parenchymal cells are replaced by ________. This process is known as ______.

Answer 9

Connective Tissue

Fibrosis

Question 10

What are the four components of fibrosis?

Answer 10

• Migration and proliferation of fibroblasts
• Deposition of extra cellular matrix
• Formation of new blood vessels (angiogenesis)
• maturation and organization of the scar, also known as remodelling.

Question 11

What are the factors favoring fibrosis over regeneration with like tissue?

Answer 11

• Severe and prolonged tissue injury
• Loss of tissue framework (basement membranes)
• Large amounts of exudate
• Lack of renewable cell populations (tissue with permanent cell population)

Question 12

What are the consequences of fibrosis?

Answer 12

• Loss of functional parenchymal tissue
• Alteration of physical properties of tissue:
• Skin with scar is more prone to tearing
• Pulmonary fibrosis • Compliance • vital capacity • work for respiration

Question 13

__________ is the hallmark of healing.

Answer 13

Granulation tissue

Question 14

When does repair begin? Healing?

Answer 14

• The process of repair begins early in inflammation.
• As early as 24 hours after injury, fibroblasts and vascular endothelial cells (angiogenesis) begin to proliferate.
• Granulation tissue, the hallmark of healing, forms by 3 to 5 days.

Question 15

Granulation Tissue

What is the characteristic hallmark feature?

Answer 15

• The term granulation tissue derives from its pink, soft, granular appearance on the surface of wounds.

Proliferation of new small blood vessels and fibroblasts are its characteristic histological features.

Question 16

What is this?

Answer 16

Exuberant granulation tissue (proud flesh), chronic ulcer, skin, distal hindlimb. Note the large proliferating mass of fibrous tissue on the lower portion of the left hind limb. Often lacks superficial epithelium.

Question 17

Granulation Tissue is composed of four recognizable zones. What are they?

Answer 17

1. Zone of necrotic debris and fibrin: superficial area of variable thickness.
2. Zone of macrophages (clean‐up) and in‐growing capillaries (angiogenesis, neovascularization)
3. Zone of proliferating capillaries and fibroblasts: budding young blood vessels grow from the more mature vessels in the deeper zone up into the granulation wound. These vessels grow perpendicular to the surface of the defect
4. Zone of mature fibrous connective tissue: represents the oldest portion of the healing process (a mature collagenous scar tissue has resulted)

Question 18

What is the maturation of granulation tissue?

Answer 18

Maturation is the process by which the amount of collagen deposition is increased. Occurs in the following sequence of events:

1. Bed of granulation tissue matures
2. Deposits of collagen and ground substance (glycosaminoglycan)
3. Granulation bed contracts as it matures
4. Specialization of some fibroblasts into contractile cells

Question 19

Granulomas and granulomatous inflammation correspond to ________ inflammation.

Answer 19

CHRONIC

Question 20

Granulation tissue is part of the _______. Granulation tissue is characterized by _________.

Answer 20

Repair process

Large amount of fibrous connective tissue and neovascularization

Question 21

What is this an example of?

Answer 21

Granulation tissue and chronic inflammation

Question 22

Wound Healing

Answer 22

A process including connective tissue replacement and regeneration by which restoration of tissue continuity is achieved.

Question 23

Healing by First Intention

Answer 23

Possible when there is little exudate and when tissue elements are closely approximated. Example: surgical wound.

• Result: healing with like tissue and little scar formation (fibrosis)

Question 24

Healing by Second Intention

Answer 24

It occurs when the edges of wounds are widely separated.

• Wound may contain a large amount of exudate and necrotic debris
• Granulation tissue will slowly replace the fibrin and necrotic debris (process of organization)
• Fibroplasia and scar formation will fill in defect
• Organization ‐ granulation tissue replaces fibrin and necrotic debris in a wound

Question 25

What are the steps in healing?

Answer 25

1. Initial Gap (wound) with formation of the blood clot. 2. Epithelial continuity is restored, often as quickly as the first 24-48 hours if edge apposition is good. 3. Initially the epithelial cells lose contact with one another and the basement membrane-\> migration of cells (advancing edge) - \> mitoses (in cells behind the leading edge) - \> gradual covering of epidermal defect. 4. An inflammatory reaction develops in the incised dermis with neutrophil infiltration followed by macrophage infiltration. 5. Neovascularization occurs with the ingrowth of new capillary buds to bridge the wound. 6. Fibroblast proliferation occurs to provide a sufficient cellular base for the manufacture and laying down of collagen. 7. Devascularization occurs as a consequence of the gradual accumulation of collagen. 8. Egress of inflammatory cells and fibroblast regression due to absence of a nutrient vasculature. 9. Scar: this acellular and avascular, pale, collagenous tissue is the end product of wound healing.

Question 26

Healing of the Liver

Answer 26

* Healing is achieved by the combination of complete parenchymal regeneration and scar formation. * The outcome of hepatic healing is dependent upon the insult, the location, extent, chronicity. * Example: Massive Hepatic Necrosis: the remaining hepatocytes regenerate and some extracellular matrix framework is destroyed, resulting in formation of irregular hepatocyte nodules (nodular regeneration) separated by fibrous connective tissue (scars). * Liver regeneration with restoration of normal tissue requires an intact extracellular matrix * If the ECM is damaged repair occurs by fibrous connective tissue/ scar formation

Question 27

Healing of the Kidney

Answer 27

* This organ, in general, has limited regenerative capacity: * **maximal** regenerative capacity in renal cortical tubules * **minimal** regenerative capacity in medullary tubules * **no** regenerative capacity in glomeruli * In cases of mild injury with no destruction of the extracellular matrix (tubular basement membrane intact), the result is tubular epithelium regeneration. * Destruction of the extracellular matrix framework with epithelium necrosis results in repair with scar formation with incomplete regeneration

Question 28

Describe Repair of Kidney by regeneration.

Answer 28

* Cortical Tubules without tubulorrhexis (rupture of tubular basement membrane). * The surviving tubular cells in the vicinity of the wound flatten, acquire a squamoid appearance and migrate into the necrotic area along the basement membrane. * Tubular morphology and function are normal by 3‐4 weeks.

Question 29

What is this?

Answer 29

Ruminal ulcer Star‐shaped scar tissue

Question 30

Answer 30

Scarring secondary to traumatic injury

Question 31

What is this? | (Pig)

Answer 31

Mutifocal fibrosis due to parasite migration. Pig liver.

Question 32

What is this?

Answer 32

Unilateral fibrosis secondary to renal transplantation‐ canine.