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168 Cards in this Set

  • Front
  • Back

Parenchyma

made of functional cells (cells that actually do the organ's work)

Stroma

supporting structures (mostly connective tissue)

Regeneration

process of restoring full function to damaged tissue

In order to regenerate, tissues require the presence of ___________ and an intact ____________

stem cells; ECM

What is the ECM use for?

- cell migration


- maintain cell polarity


- contains essential cells and chemicals for repair

Why must regeneration be tightly controlled?

uncontrolled cell division leads to cancer

Repair

proliferative response that "patches" rather than restores a tissue

Repair is a tissue response to what?

- wound


- inflammatory processes in internal organs


- cell necrosis in tissues incapable of regeneration

Repair involves what?

tissue regeneration and formation of fibrous tissue (scar formation)

Static

populations of cells in any given tissue tend to be relatively stable, showing little or no change

Cells remain relatively stable due to a balance of:

- proliferation


- differentiation


- cell death

What are the 4 phases of the cell cycle?

G1, S, G2, M

Non-dividing cells stay in which phase of the cell cycle?

5th phase, G0

Labile

continuously dividing throughout life


ex: GI epithelium

Stable

quiescent low levels of replication usually in response to stimuli


ex: liver cells

Permanent

non-dividing, have left the cell cycle


- neurons

Regeneration requires __________

stem cells

Stem cells

undifferentiatied biological cells that can differentiate into specialized cells and can divide to produce more stem cells

What happens when a stem cell divides?

One daughter cell remains a stem cell while the other differentiates

Pluripotent cells

can give rise to all tissues of the body


e.g. embryonic stem cells

Multipotent cells

more restricted but still have capacity to make multiple differentiated cell types


e.g. hematopoetic cells

adult stem cells are very restricted and are usually: what type?

multipotent or unipotent

What tissues have adult stem cells been identified in?

skin


lining of the gut


cornea


hematopeoietic tissue


CNS

Adult stem cells can give rise to which kind of cells?

progenitor cells

Chronic inflammation often leads to __________

fibrosis

Which type of tissue would you expect to find stem cells?

Labile

Would you expect to find stem cells in skin? Bone marrow? Adipose? GI tract?

Yes, you would find stem cells in all of those tissues

What triggers cell division?

growth factors

growth factors

chemicals that control many cellular function including:


- proliferation


- survival


- locomotion


- contractility


- differentiation


- angiogenesis

What kinds of cells secrete growth factors?

- macrophages


- fibroblasts


- endothelial cells


- platelets

Growth factors act as what?

ligands

What do ligands do?

float in environment and Bind to receptors on the membrane of target cells

some receptors need to __________ after binding to their respective ligand

dimerize/trimerize

Briefly explain the process of growth factors and cell signaling

- GF binds to receptor


- triggers dimerize/trimerize (changes shape)


- activation follows


- cascade of events occurs


- triggers transcription and translation


- certain genes are turned on

Activation of cell division is often through ?

phosphorylation

G protein

7 pass membrane receptor, causes phosphorylation

When are G proteins activated?

by binding of a growth factor to its receptor

What does not occur when a growth factor binds to its receptor?

transcription of genes involved in triggering apoptosis

Functions of the ECM

- provides support for anchorage and migration of cells


- defines cell polarity


- contributes to proliferation and differentiation


- scaffolding for renewal of tissues


- storage of regulatory molecules

What are the 3 types of ECM?

- basement membrane

- interstitial matrix


- granulation tissue



What 3 molecules make up the ECM?

- fibrous molecules


- adhesive molecules


- proteoglycans and hyaluronic acid

Fibrous molecules serve what purpose for the ECM?

provide structure

Adhesive molecules serve what purpose for the ECM?

establish cell to ECM and cell to cell interactions

What purpose to proteoglycans and hyaluronic acid serve to the ECM?

bind water


create turgor/firmness in tissues


produce gel, soft tissue

collagen accounts for how much of body weight?

20-30%

What is the basic structure of collagen?

3 polypeptides twisted around each other in a triple helix

Which type of collagen are the most common in the body?

I, III, and V

Collagens I, III, and V are known as what?

fibrillar collagens

Fibrillar collagens are ideal for what?

structures that provide support like bone and tendon


- very stable and very high tensile strength

Which vitamin is required as a cofactor in the production of collagen?

Vitamin C

Elastin

fibrous protein


allows tissues to be stretched or otherwise deformed, and still return to their original shape

What are the adhesive proteins

sticky proteins


- Laminin and fibronectin


both are glycoproteins that bind to integrins on cells and promote cell to ECM interactions

Where are laminins abundant?

in the basement membrane

Fibronectin

V-shaped molecules


important in forming new epithelial coverings for wound healing (guide cell migratioN)

What do cellular adhesion molecules do

mediate cellular interactions

What are the 4 molecules that are part of the cellular adhesion molecules

1) immunoglobulin family


2) cadherins


3) integrins


4) selectins

Immunoglobulin family

mediate binding between similar cells or different cells

Cadherins

join cells of similar type

Desmosomes

strong cell junctions

Integrins

bind to collagen, laminins, fibronectins, fibrinogen


link cell-to-cell or cell-to-ECM


mediate inside-out or outside-in signaling


stopping of WBC

selectins

play a role in maringation and rolling of leukocytes

The bristles of proteoglycans are made up of what?

disaccharides called glycosaminoglycans (GAGs)

Basic structure of proteoglycans

central core protein + extensive sugars

Proteoglycans are excessively negatively charged, meaning what?

Good ability to attract water

Most GAGS create hydrated gels that can what?

resist compression

Proteoglycans and hyaluronic acid help to do what?

help tissues resist compression

Stages of tissue healing

- inflammation


- proliferation and migration of new cells


- angiogenesis and formation of granulation tissue


- creation of new ECM


- wound contraction


- tissue remodelling; strengthening of new tissue

What are the 3 phases of cutaneous wound healing?

- inflammation


- proliferation


- maturation

What does healing begin with?

thrombosis

How is a scab formed?

Clot structured by fibrin


forms mesh that traps RBC, debris


held together by fibronectin



Fibroblasts do what?

lay down collagen

pericytes

contractile cells

What shows up at the site of injury to start rebuilding?

fibroblasts, pericytes, and smooth muscle cells

Angiogenesis results in the creation of?

granulation tissue

What are the 2 methods to get new blood vessels?

1) Mobilzation of endothelial precursor cells from bone marrow


2) Mobilization of pre-existing endothelial cells

What occurs during the mobilization of pre-existing endothelial cells?

New blood vessels branch off pre-existing vessels


- make new BV from existing


- endothelial cells divide repeatedly, extending outward from existing BVs

What is granulation tissue characterized by?

formation of numerous small blood vessels and the proliferation of fibroblasts

New vessels are leaky, causing __________

edema

Leaky vessels leads to what?

exudation and deposition of plasma proteins

deposited proteins provide what - for fibroblasts and endothelial cells?

provisional stroma


- supply scaffolding for cells to move

Migration of fibroblasts to the site of injury is triggered by what?

multiple growth factors


e.g. TGF (transforming growth factor)

TGF is produced by:

all cells at the injury site

Functions of TGF

- fibroblast migration and proliferation


- increased synthesis of collagen and fibronectin


-decreased degradation of ECM


- chemotaxis


- angiogenesis

When does the repair phase begin?

when macrophages arrive

Collagen synthesis begins within how many days after injury?

3-5 days

vascular regression

transformation of the richly vascularized granulation tissue into a pale, avascaular scar

fibroblasts differentiate into what?

myogibroblasts

what do myofibroblasts do?

contract, making the wound tissue tighter

matrix metalloproteases

enzymes responsible for ECM degradation

MMPs are produced by what cells?

fibroblasts, macrophages, neutrophils, synovial cells, epithelial cells

What do MMPs do?

allow cells to move through the ECM


digest clotting factors, various adhesion molecules, ECM proteins

Basal cells are attached by what?

cadherins

True/False: Fibrosis is associated with granulation tissue

False: fibrosis has nothing to do with granulation, occurs during later events

What is the correct oder of steps in wound healing?

- Macrophage recruitment, angiogenesis, collagen deposition, ECM remodelling

What are the 2 forms of healing of wounds?

- primary intention


- secondary intention

Healing by primary intention refers to wounds with what?

very minimal tissue loss


- e.g. surgically-created wounds

Healing by secondary intention occurs when?

When there is tissue damage, usually resulting from accidents


- bigger wounds, ragged edges, no sutures

What pulls the edges of a wound together?

myofibroblasts

What are some factors that may affect healing?

- nutritional status


- circulatory status


- hormones


- infection


- pre-existing conditions (DM)


- location/size of wound


- contaminants in wound

How can hormones affect healing?

anti-inflammatory hormones such as glucocorticoids can inhibit collagen synthesis and act as anti-inflammatory agents

True/False: Collagen fibers eventually replace granulation tissue in primary intention

True

True/False: Healing by primary intention does not involve granulation tissue

False

True/False: In Healing by primary intention, granulation tissue forms after collagen fibers are deposited

False: Granulation tissue begins forming within 24 hours of injury

What are some complications in cutaneous wound healing?

- deficient scar formation


- excessive formation of repair components


- contractures


- wound dehiscence


- keloid scars


- adhesions

Contracture occurs:

when an excess of wound contraction leads to physical deformity

What is contractures characterized by?

skin constriction and functional limitations

What are contractures due to?

"over-enthusiastic" myo-fibroblasts

If a contracture occurs in the digestive tract, what can result?

Can lead to a stricture that will block passage of GI contents

What is a wound dehiscence?

when the wound ruptures along the surgical suture

What could cause a wound dehiscence?

If ECM synthesis is impaired, scar tissue may be weak and may fail

When does a wound dehiscence most often occur?

in abdominal surgery

Wound dehiscence occurring from an abdominal surgery can lead to an incisional _________

hernia

What is an incisional hernia

part of internal organ pushes through opened wound


blood supply may be cut off, leading to ischemia and necrosis

Keloid scars are due to what?

deposition of excess collagen

When do adhesions occur?

Can result when scar tissue begins replacing damaged tissue in wounds involving serous membranes

Where are adhesions especially common?

in thoracic and abdominal surgeries

parenchymal scarring is called:

cirrhosis

Kidney damage is ________

permanent

If damage is confined to the tubules in the cortex, is it able to be repaired?

Yes, repair can occur as long as basement membrane is intact

Tubulorrhexis

scarring of the tubules of the kidney due to damaged basement membrane

Damage to the medulla results in:

scarring, creates blockages to urine flow

Can lung tissue regenerate?

Yes, if basement membrane undamaged

What happens if inflammatory mediators can't clean up debris in alveoli?

Intraalveolar fibrosis can result

When the basement membrane in the lungs is damaged, what results?

fibrosis

What happens when the basement membrane in the lungs is damaged?

fibroblasts and myofibroblasts secrete ECM into alveoli

Are neurons capable of regeneration?

No

What must neurons do to re-establish function?

Surviving neurons have to take over job of dead ones

The scar tissue that replaces dead neurons is made up of what?

astroycytes and microglia

In which nervous system can neurons regenerate axons?

Peripheral nervous system

If severed ends of nerves get out of line, or too much inflammation or scar tissue intervenes, it can develop a ______________

traumatic neuroma

What is a traumatic neuroma

Mess of Schwann cells, axons, fibroblasts

True/False: Hyperactive fibroblasts could cause wound dehiscence

True: Hyperactive myofibroblasts cause wound dehiscence

What does innate immunity involve?

- mechanical defenses


- chemical defenses


- inflammation


- commensal bacteria (normal flora)


- cells

Mechanical defenses of innate immunity include:

- skin


- mucuous membranes

epidermis

thin outer layer of epithelial tissue

What does the epidermis contain?

Langerhans cells, dead cells, and keratin

dermis

thick inner layer of connective tissue

Sebum

oily substance produced by sebaceous glands that forms a protective layer over skin

What does sebum contain?

unsaturated fatty acids which inhibit growth of certain pathogenic bacteria and fungi

Chemical defenses of the innate immune system include:

- sebum


- pH


- perspiration


- lysozyme

granulocytes

cytoplasmic granules

Where are neutrophils formed?

from stem cells in bone marrow

what are the 3 ways neutrophils directly attack microorganisms?

- phagocytosis of microbes


- release of anti-microbial granules (degranulation)


- form neutrophil extracellular traps

what are NETs composed of?

composed of granule proteins and DNA

Where are monocytes/macrophages derived from?

the myeloid cell line

Macrophages

large, long-lived phagocytes that reside in tissues

Macrophages are a major player in ______________

inflammatory response

Along with dendritic cells, macrophages are major _________________

antigen-presenting cells

Antigen presenting cells (APC)

initiate immune responses by displaying antigens from pathogens to lymphocytes

What do macrophages get activated by?

cellular mediators released by damaged cells or by cells of the immune system


molecules located on or released from the microorganism itself

Once activated, what do macrophages upregulate?

major histocompatibility complex II (MHC-II)

What are the different cytokines that activated macrophages release?

tumor necrosis factor and interleukin-1

What do TNF and interleukin-1 stimulate?

expression of adhesion molecules on endothelial cells to promote leukocyte margination, rolling, and extravasation

TNF stimulates

dendritic cells and causes them to migrate to the nearest lymph nodes

Chemokines stimulate ___________ and ___________ of leukocytes into the infected tissue

motility and migration

MHC-II is responsible for ?

antigen presenting

What happens if a macrophage cannot digest what it engulfs?

may form a granuloma


may become an epithelioid cell or may fuse with other macrophages to form a multinucleated giant cell



What happens when a macrophage becomes an epithelioid or giant cell?

macrophages stop phagocytosing and simply become storage cell

Dendritic cells are

phagocytic APCs

where do dendritic cells reside?

in epithelial tissues and migrate to lymphoid tissues when they are exposed to an antigen

What do dendritic cells express?

MHC-II molecules


- cell adhesion molecules


- receptors for chemotaxis

Where do natural killer cells descend from?

lymphoid lineage

Natural killer cells are the first line of defence against ___________ and some __________

viral infections; tumour cells

Natural killer cells are full of what?

granules containing perforin and granzymes


- also have receptors for antibodies

perform and granzymes trigger what?

apoptosis in target cells

Where is MHC-I found?

found on all nucleated cells (identifies self)

How do NK cells know what cells to kill?

NK cells express inhibitory receptors that prevent them from killing all cells that express MHC-I


- cells that don't have MHC-I, NK cell will kill it

When does the activation of T cells by macrophages occur?

After phagocytosis