Tissue repair path T2

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Tissue repair powerpoint path test 2

4 stages of Repair with Connective tissue

1. Angiogenesis 2. Migration and proliferation of fibroblasts 3. Deposition of Extra Cellular Matrix (ECM) 4. Remodoling: Maturation and reorganization of fibrous tissue... This are the four steps of???

Healing

(by definition) The laying down of connective or fibrous tissue (scar formation)

Fibrosis

(by definition) Excessive deposition of collagen

Normal Cell Proliferation: 4 stages of cell cycle

Presynthetic growth phase 1 (G1); DNA synthesis phase (S); Premiotic growth phase 2 (G2); Mitotic phase (M)

Correct answer input: "arrest (G1)"

Non dividing cells are in cell cycle _____ (__) or the exit cycle to G0

Labile cells

These cells are continously dividing; Regeneration occurs from a population of stem cells with relatively unlimited capacity for proliferation (Ex's bone marrow cells, epithelial cells); What kind of cells are these?

Stable cells

Quisnent cells (G0 phase);Normal state but are capable of undergoing rapid division in response to injury;
Constitute the parenchyma of most solid glandular tissue
(i.e. Liver, Kidney and pancreas) EX's include:Fibroblast and smooth muscle connective tissue cells

Permanent Cells

Terminally differentiated and non-proliferative in postnatal life
Ex's heart muscle, neurons these DO NOT DIVIDE!!!

Bone Marrow stem cells

Wide differentiation capabilities (fat, bone, muscle, epithelium)

"Regenative Medicine"

Focus is to regenerate or repopulate damaged organs with embryonic stem cells or adult stem cells. (kind of a theraputic cloning, take persons cells and re cloning it)

Polypeptide growth factors

This is a group of soluble mediators, which increases cell size, division and survival
These soluble mediators are also pleotrophic (not isolated to just one path)

Soluble Mediators

Cell growth and differentiation are dependent on extracellular signals derived from _________ and ECM matrix

Growth Factors

Induce cell proliferation , can also effect pathway from normal to abnormal as seen in cancer...
There's about a 1000-1500 types of these...

3 types of signalling mechanisms

These mechanisms allow communication between cells, 3 types
Autocrine: occurs directly within cells
Paracrine: occurs from one cell to a neighboring cell
Endocrine: occurs from one cell to another cell at a much further distance...

Mitogen activated protein (MAP) kinase cascade

intracellular "activator" for many Growth Factors including: Epidermal, vascular, fibroblast, hepatocyte GF's
What's the name of this cascade?

G coupled protein receptors

7 transmembrane _________________
cAMP and IP3 pathways are induced > Ca++ release from ER
Over 1000 different types of receptors
Epinephrine, vasopressin, serotonin, histamine, glucagon, chemokines.

Polypeptide Growth factors: Summary

(THESE) bind to and activate their receptors, many of which possess intrinsic kinase activity
Subsequently, they phosphorylate a number of substrates involved in signal transduction and the generation of second messengers
This is the summary for what???

Cell matrix overview

Constantly remodeling macromolecular complex
Provides turgor to soft tissue and rigidity to bone
Supplies a substratum for cell adhesion and regulates the growth, movement, and differentiation of cells

Interstitial matrix: location and generation

Spaces between the cells of connective tissue, and between epithelium and supportive vascular and smooth muscle structures
Synthesized by fibroblasts (create a gell like substance)

Interstitial matrix: constituents

Fibrillar collagens
Proteoglycan
Glycoprotein
These are the 3 constituents of what matrix

Basement Membrane

Sits beneath epithelium
Synthesized by overlying epithelium and underlying mesenchymal cells (fibroblasts)
Forms a plate-like mesh

Basement Membrane constituents

Amorphous nonfibrillar type IV collagen
Adhesive glycoproteins
These are the constituents of what membrane?

Roles of the Extra Cellular Matrix

Mechanical support for cell anchorage, migration
Control of cell growth
Maintenance of cell differentiation
Scaffolding for tissue renewal
Establishment of tissue microenvironment
Storage and presentation of regulatory molecules
What ??? fullfills these rules listed above???

Components of ECM

Fibrous structural proteins; Elastin; Collagen; Water-hydrated cells; Adhesive glycoproteins; Proteoglycans; Hyaluronin;... These are the components of what matrix???

Components of ECM: Fibrous structural proteins: basic fxn

these give tensile strength to skin, and are components of the ECM

Components of ECM: Water-hydrated cells & their Fxn

allows us to resist permeation (ie synovial joint), and are components of ECM

Components of ECM: Adhesive glycoproteins

Actually connect the cells to each other via integrins;Fibronectin and Laminin may be examples...
this is 1 of the many components of ECM

Components of ECM: Collagen

(This is a type of) Fibrous structural proteins conferring tensile strength, cross links to provide strength, VITAMIN C is needed for this to OCCUR, children with def. vit C are going to have poor wound healing; Which component of the ECM is being described??

Components of ECM: Elastin

Ability of structures to recoil and return to baseline structure
Composed of _______ protein and surrounded by mesh-like network of fibrillin glycoprotein; Which component of the ECM gives structure ability to recoil? (insert answer in blank)

Components of ECM: Proteoglycans

Offer resilience and lubrication (cartilage in joints)
Serve as a reservoirs of growth factors secreted in the ECM
Which component of the ECM is being described here?

Components of ECM: Hyaluronin

Offer resilience and lubrication
Bind volumes of water into a viscous, gelatin-like matrix
Which component of the ECM is being described here?

Repair by connective tissues: First 24 hours

Repair by ______ ______ (2 words) begins within 24 hours
Emigration of fibroblasts and induction of fibroblast and endothelial cell proliferation?
**Fill in the blank***

Repair by connective tissue: 3-5 days granulomation formation

Repair by connective tissues; within _____---_____days
Pink, soft, granular (like the scar under a scab) develops &
Proliferation of fibroblasts, angiogenesis, and loose ECM
**Fill in the Blank***

Vasculogenesis: the assembly of a primitive vascular network by angioblasts (endothelial cell precursors); This is the first process of angiogenesis, which happens to be the first step of "repair by connective tissue deposition"

What occurs in Vasculogenesis, what cells are involved, and what's this a process of???

(1) Neovascularization (a.k.a. angiogenesis, NOTE (2) Angiogenesis is a 2 step process; Neovascularization is the second process)

This sub-process of __________is critical process in healing at sites of injury, in the development of collateral circulations at sites of ischemia, and in allowing tumors to increase in size beyond the constraints of their original blood supply.
(1) What is the (sub) process that's being described???
(2) Fill in the blank

2 steps of scar formation (FIBROSIS)

Emigration and proliferation of fibroblasts into the site of injury
Deposition of ECM by fibroblasts

Why Repair Fails

Infection is the number one cause prolonging inflammatory response, and why this process can fail... Other problems include:
Nutrition: vit C deficiency (usually in children)

Glucocorticoids: Prolonged steroid use, limits inflamatory response.

Mechanical Variants (ex. Dehissence)
Poor perfusion (lack of bloodflow), Foreign Bodies (prolong inflam. Response)
WHAT ARE THESE ALL CONTRIBUTORS TO???

Healing via 1st intension

Epithelial regeneration > fibrosis
Small scar formed, minimal contraction
1st 24 hours lots of neutrophils
By 72 hours lots of macrophages
By day 5 (PEAK) new vessels epidiermic returns to baseline thickness
During week 2 accumaltion of collagen and fibroblasts
By end of month by end of month not a lot of inflammation

Healing via 2nd intension

I.e. large wounds, abscess, ulcer
More intense inflammatory response
Large volume of necrotic debris, exudate, fibrin
Abundant granulation tissue
Needed to fill a larger gap
Myofibroblasts cause wound contraction
Large skin defect may reduce 5-10% in 6 weeks
Accumulation of ECM  large scar

Why repair fails

Aberration in cell growth and ECM production
Excess collagen > keloid formation
Heritable, more common in blacks
Excessive granulation
Protrudes above skin and retards re-epithelialization
A.k.a. exuberant granulation "proud flesh"
Requires cautery to restore epithelialization
THESE ARE ALL EXPLANATIONS FOR WHAT????

Macrophages

These cells Initiate a host of mediators that induce fibroblast proliferation and ECM production, in the process of fibrosis

Granulomatous scaffolding: (1) Scar

Granulomatous scaffolding is found in granulomatous tissue; ___________composed of largely inactive, spindle-shaped fibroblasts, dense collagen, fragments of elastic tissue, and other ECM components
*Fill in the Blank*

Maturation of a scar

Vascular regression occurs and the granulated tissue turns into a pale, largely avascular scar; Which process of fibrosis is this reffering too?

Cutaneous wound healing

Inflammation
Formation of granulation tissue
ECM deposition and remodeling
What are these the three phases of???

Vasculogenesis and Angiogenesis

There are two processes of Angiogenesis, the second process is Angiogenesis, but this cannot occur until the first process takes place which is called____________?

(1) Angiogenesis: the formation of new blood vessels; (2) Migration and proliferation of Fibroblasts; (3) Scar formation: Deposition of ECM; (4) Remodeling: Maturation and reorganization of the fibrous tissue.

Repair by connective tissue deposition consists of four sequential processes; List the four processes in order...

Neovascularization (a.k.a. angiogenesis)

After a primative vascular network is assembled from angioblasts; _____________ occurs, the sprouting of capillaries off of the primative vascular network ( or preexisting vessels) to produce new vessels.
*Fill in the Blank*

Basic fibroblast growth factor (bFGF) and Vascular endthelial growth factor (VEGF)

Angiogenesis is induced by what two growth factors???

Scar Formation

Emigration and proliferation of fibroblasts into the site of injury
Deposition of ECM by these cells.
This is the process of what?

Fibroblasts

Platelet derived growth factor (PDGF): helps stimulate (1) _________(what type of cells).
bFGF
TGF- (TGF-B [TGF-"Beta"])
All of these Growth Factors play a role in the Stimulation and / or recruitment of (1)_____________?

Repair by connective tissue: Remodeling process

(Scar)_________________ is the last step in "Repair by connective tissue" when Maturation and reorganization of the fibrous tissue occurs.

Repair by connective tissue: Remodling process

Transition from granulation tissue to scar
Outcome at each stage is a balance between ECM synthesis and degradation
Degradation accomplished by Metalloproteinases

Metalloproteinases

Group of enzymes dependent on zinc; some of the enzymes in this group are: Interstitial collagenases, gelantinases, and stromelysins; Multiple cells produce this enzyme (s)
Regulated by growth factors, cytokines, phagocytosis and is
Essential in the debridement of injured sites.
What is the group of enzymes described???

Metalloproteinases

The degradation of callagens and other ECM components is accomplished by a family of matrix ______________

"contract"

In cutaneous wound healing, larger wounds ___________
(Fill in the blank)

(1)Neutrophils (2)Macrophages (3) day 5 (4) collagen; (5) fibroblasts

FIRST INTENSION HEALING: FILL IN THE BLANKS
(1)1st 24hrs ______________;
(2)By 72 hrs ______________
(3)by day ______(PEAK) new vessels epidiermic returns to baseline thickness
During week 2 accumalation of(4) _______(ECM component) & (5)_______(cells)
By the end of the month not alot of inflammation

(1)Inflammation (2) necrotic debris, exudate, fibrin (3) Granulation (4) Myofibroblasts (5) 5-10% (in) 6 wks

SECOND INTENSION HEALING: FILL IN THE BLANKS
(1) More intense ________ response
(2) Large volume of _______, _______ & ________
(3)Abundant ________ tissue need to fill larger gap
(4)___________(cells) cause wound contraction
(5)Large skin defect may reduce in _-_% in _____weeks

Presynthetic growth phase 1 (G1); DNA synthesis phase (S); Premiotic growth phase 2 (G2); Mitotic phase (M)

Name the 4 phases of cell cycle: Normal Cell Proliferation

Keloid formation

an over excessive amount of collagen that is layed down, inheritable trait that is more commone in blacks; This is refering to the formation of what?

excessive granulomatous formation.

What is Proud Flesh?

(input) cyclin

Process of cell proliferation is directed by a family of proteins called__________(1) that ultimately control the phosphorylation of proteins involved in cell cycle progression.
**FIll in the Blank**

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