3 - Healing and Repair Flashcards
What type of collagen is most abundant in bone, ligaments, tendon, dermis etc.?
“Type I. [There are > 20 forms of collagen (type I, type II …). Most tissues have a predominance of one collagen type.]”
In which of the four phases of wound healing is granulation tissue production an important feature?
The third phase: proliferation. [The four phases are: 1. Hemostasis; 2. Acute inflammation; 3. Proliferation; 4. Maturation and contraction (remodeling)]
Aside from wound features that predispose to second intention healing (gaping wounds, infection, foreign bodies etc.) name four other factors or conditions that can delay wound healing.
“The four Ds”: 1. Disease (e.g., specific collagen disorders, certain endocrine diseases); 2. Drugs (certain anti-cancer drugs); 3. Deficiencies (vitamin C deficiency in primates & guinea pigs); 4. Diet (starvation, malnutrition & cancer cachexia)
What provides the tensile strength of collagen?
(a) Conversion from its liquid to solid form over time;
(b) Cross-linking of collagen fibrils;
(c) Matrix metalloproteinases;
(d) Transforming growth factor beta;
(e) Vitamin C
(b) Cross-linking of collagen fibrils
What is the term for a mixture of proliferating fibroblasts and endothelial cells with minimal or no collagen deposition that quickly fills in tissue defects?
Granulation tissue
What are three features of a wound that will go on to heal by secondary intention?
- Wound edges are NOT apposed (due to extensive tissue loss, failure to suture gaping wounds or wound instability and repeat trauma)
- Infection is present
- Foreign bodies are present (exogenous, such as sticks or surgical sponges; endogenous, such as neoplasms and sequestra)
The presence of a bony sequestrum in a wound may impede healing. What is a bony sequestrum?
A bony sequestrum is a piece of devitalized (i.e., dead, having lost its blood supply) bone that the animal now recognizes as a foreign body
What are three features of a wound that will go on to heal by primary (first) intention?
- Wound edges are apposed
- There is no infection
- There are no foreign bodies present
How does the use of certain chemotherapeutic drugs, used to treat neoplasia, impair wound healing?
Certain chemotherapeutic drugs -> reduced cellular proliferation -> reduced fibroplasia -> impaired healing
Name 3 cell types that can produce matrix metalloproteinases (MMPs).
MMPs are produced by pretty much every cell type you can think of (fibroblasts, macrophages, neutrophils, endothelial cells, cancer cells …)
The extracellular matrix is composed of proteins, such as collagen, and a hydrated gel made of _______. [Fill in the blank]
Proteoglycans
You vaccinate a cat against rabies and several months later notice a large, fleshy subcutaneous mass at the injection site in the dorsal skin. What should you consider as the most likely diagnosis?
Post-vaccine fibrosarcoma. Fibroblasts are especially responsive to injury in cats and sometimes cross the line from hyperplasia into neoplasia. This is seen relatively commonly following subcutaneous rabies vaccination.
Place the following four steps of wound healing into correct sequence, from earliest to latest: (a) Acute inflammation; (b) Hemostasis; (c) Maturation and contraction; (d) Proliferation
- Hemostasis
- Acute inflammation
- Proliferation
- Maturation and contraction (remodeling)
Name two relatively common endocrine diseases that result in poor wound healing.
- Diabetes mellitus
- Hyperadrenocorticism / Hypercortisolism (Cushing’s disease)
What is the term for a mixture of proliferating fibroblasts and endothelial cells with minimal or no collagen deposition that quickly fills in tissue defects?
Granulation tissue
How does vitamin C deficiency in primates and guinea pigs impair wound healing?
Vitamin C is an essential co-factor in production of collagen alpha chains in ribosomes. Vitamin C deficiency -> reduced collagen synthesis -> poor wound healing (“scurvy”)
What are the most important inflammatory cells in the first 24-96 hours after a wound occurs?
Neutrophils and macrophages
In which animal types does vitamin C deficiency impair wound healing?
Primates and guinea pigs
How long does the proliferative phase of wound healing last, in general?
3-4 weeks depending on the size of the wound
What is the meaning of the term angiogenesis?
The formation of (1) new blood vessels from (2) preexisting vessels. [You need both parts to be fully correct. The formation of vessels de novo in, for example a developing fetus in NOT angiogenesis; it’s called vasculogenesis]
What happens to granulation tissue during the remodeling phase of wound healing?
It is converted into (replaced by) “immature connective tissue”, then “mature connective tissue.” Essentially, collagen content increases and the number of fibroblasts decreases. This can result in return to near normal tensile strength.
Fibroblasts tend to align themselves parallel to lines of tension stress? True or false?
True
What are proteoglycans in the extracellular matrix and what is their function?
Proteoglycans are protein and carbohydrate networks that retain water, allowing tissues to be pliable and elastic
What type of collagen is most abundant in basement membranes?
Type IV. [There are > 20 forms of collagen (type I, type II …). Most tissues have a predominance of one collagen type.]
What is the lay-term for excessive granulation tissue at sites of injury in horses?
“Proud flesh”
What is the meaning of the term scirrhous?
A contracted wound, scar or neoplasm with abundant (excessive) collagen is termed scirrhous.
Granulation tissue is fragile, easily damaged and bleeds a lot when traumatized. True or false?
True
What are myofibroblasts?
Myofibroblasts are specialized fibroblasts with contractile ability
What is the most important factor determining the speed and success of re-epithelialization after a wound?
The presence or absence of an intact basement membrane. Without a basement membrane, proliferating epithelial cells lack a clear path of migration
What is granulation tissue and what is its function?
Granulation tissue is a mixture of proliferating fibroblasts and endothelial cells with minimal or no collagen deposition that quickly fills in tissue defects.
What is the name of the special set of enzymes responsible for breaking down extracellular matrix proteins?
Matrix metalloproteinases (MMPs)
Granulation tissue has near normal tensile strength, relative to unwounded tissues. True or false?
False; granulation tissue is fragile, weak, easily damaged and bleeds a lot when traumatized
What are the 5 cardinal signs of acute inflammation (in Latin)?
Tumor, rubor, calor, dolor, functio laesa. [Functio laesa is a term used in medicine to refer to a loss of function or a disturbance of function. It was identified as the fifth sign of acute inflammation by Galen, who added it to the four signs identified by Celsus]
In which domestic animals are fibroblasts especially responsive to injury, sometimes crossing the line from hyperplasia into neoplasia?
Cats (seen in: 1. Post-vaccine fibrosarcomas; 2. Post-traumatic lens rupture sarcomas)
In the proliferative phase of wound healing, what cellular elements are actually proliferating?
- Epithelium (epithelialization)
- Fibroblasts (fibroplasia)
- Endothelium (angiogenesis)
How long is the acute inflammatory phase of wound healing in an uncomplicated wound?
24-96 hours
How long after an uncomplicated wound does the remodeling phase begin?
Starts at 3-4 weeks post injury, but only if the acute inflammation and proliferation stages are complete
What are the functions of neutrophils and macrophages in the first 24-96 hours following an uncomplicated wound?
- Phagocytosis of the cellular debris caused by the injury
- To secrete (macrophages only) chemotactic and growth factors to prepare for the proliferative phase.
What is the term for the formation of new blood vessels from preexisting vessels?
Angiogenesis
What are the four phases of wound healing, in sequence, from the moment of injury to complete resolution of the injury?
- Hemostasis; 2. Acute inflammation; 3. Proliferation; 4. Remodeling (maturation and contraction)
A contracted wound, scar or neoplasm with abundant (excessive) collagen is termed _______. [Fill in the blank]
Scirrhous
What role do myofibroblasts play in wound healing?
They cause wound contraction during the remodeling phase. In a healing wound this is usually beneficial. If excessive, however, it can cause tension on surrounding structures leading to immobility, pain and deformation. Excessive wound contraction can happen in large wounds (e.g., severe burns, extensive abrasions).
Which domestic animals are prone to development of excessive granulation tissue at sites of injury, and what is this excess tissue called?
Horses; proud flesh
What is granulation tissue and what is its function?
Granulation tissue is a mixture of proliferating fibroblasts and endothelial cells with minimal or no collagen deposition that quickly fills in tissue defects.
Describe the effects of transforming growth factor-beta (TGF-β) on fibroblasts.
Transforming growth factor-beta (TGF-β) has a central role in increasing fibroblast (a) proliferation, (b) migration and (c) collagen deposition
Transforming growth factor-beta (TGF-β) is produced by which cell type(s)? (a) Fibroblasts; (b) Macrophages; (c) Platelets
(b) Macrophages; (c) Platelets
How long after an uncomplicated wound does the remodeling phase last?
Up to 2 years, depending on size!
Describe the histologic appearance of granulation tissue
Granulation tissue has a “lattice-work” appearance, with capillaries oriented perpendicular to the wound surface and fibroblasts oriented parallel to the wound surface. [Histologically, the capillaries go “up” and the fibroblasts go “across.”]
Name the cell types that produce each of the following extracellular matrix (ECM) components: (a) ECM collagen; (2) ECM elastin; (3) ECM proteoglycans.
(a) Fibroblasts; (b) Fibroblasts; (c) Fibroblasts
Name two (rare genetic) diseases that result in defective collagen synthesis.
- Osteogenesis imperfecta 2. Ehlers-Danlos syndrome (cutaneous asthenia; collagen dysplasia, dermatosparaxis)
