Ward - Healing And Wound Repair

Front 1

Regeneration, or compensatory growth, is a term that can be applied to what two organs?

Back 1

Liver- partial hepatectomy
Kidney - unilateral nephrectomy

Front 2

_______ involves highly proliferating tissues that are constantly renewing marrow, skin, gut, etc.... IF - ____ ____ are not destroyed

Back 2

Regeneration
Stem Cells

Front 3

______, or tissue restoration, consists of scar tissue and an element of regeneration (in organs, only if _____ intact)

Back 3

Healing
scaffold

Front 4

Healing may restore original structures but involves _______ deposition and ____ formation.

Back 4

collagen
scar

Front 5

In parenchymal organs, the replacement of inflammatory infiltrates by granulation tissue and ultimately fibrosis is called _________.

Back 5

organization

Front 6

_________ requires an intact connective tissue scaffold. By contrast, _______ with scar formation occurs if the extracellular matrix framework is damaged, causing alterations of the tissue architecture.

Back 6

Regeneration
healing

Front 7

Acute hepatic injury by a high dose of CCl4 would result in what type of response?
How about multiple small doses?

Back 7

Complete regeneartion because the scaffold of reticular fibers still intact
ECM components disrupted so repair is by fibrosis

Front 8

In adult tissues, the size of cell populations is determined by the rates of cell ________, differentiation, and death by ________

Back 8

proliferation
apoptosis

Front 9

The cell cycle consists of G1 (presynthetic), S (DNA ______), G2 (premitotic), and M (_____) phases. Quiescent cells are in a physiologic state called __.

Back 9

sythesis
mitotic
G0

Front 10

In continuously dividing tissues (also called _____ tissues) cells proliferate throughout life, replacing those that are destroyed. Name some examples.
In these tissue mature cells derived from ____ _____ which have unlimited capacity to proliferate

Back 10

labile
Epithelial cells, hematopoeitic cells, mucous membrane cells, columnar of GI, etc...
stem cells

Front 11

______ tissues normally have a low level of replication; however, cells from these tissues can enter G1 and are thus capable of reconstituting the tissue of origin (good for injury). What type of cells does this include?

Back 11

Quiescent
Parenchymal cells of the liver, pancreas, kidney, mesodermal cells, mesenchymal cells, such as fibroblasts and smooth muscle

Front 12

Nondividing (permanent) tissues contain _______ _______ cells that have left the cell cycle and cannot undergo mitotic division in postnatal life. To this group belong _______ and skeletal and cardiac muscle cells.

Back 12

terminally differentiated
neurons
However, neurons can multiply in the olfactory bulb and the dentate gyrus (hipp.)

Front 13

Benign cell proliferation can happen physiologically: ______ cycle, thyroid and _____ in pregnancy. Also can happen pathologicallay in the _____ and goitre

Back 13

menstrual
breasts
prostate (BPH)

Front 14

Stem cells are characterized by their prolonged self-renewal capacity and by their ______ replication. This means in every cell division, one of the cells retains its self-renewing capacity while the other enters a _______ pathway and is converted to a mature, nondividing population

Back 14

asymmetric
differentiation

Front 15

The __________ of embryonic stem cells may be related to the expression of unique transcription factors, such as homeobox protein called

Back 15

pluripotency
Nanog

Front 16

Adult stem cells have _______ differentiation capacity and are usually lineage-specific; however, stem cells with broad differentiation potential exist in adult ____ _______ and from cord blood

Back 16

restricted
bone marrow

Front 17

Whenever there is a disease in the liver that blocks the normal replication of _______, the stem cells come into action (chronic hepatitis, cirrhosis).

Back 17

hepatocytes

Front 18

Stem cells are located in sites called ______, which differ among various tissues. Ex: gastrointestinal tract, they are located at the isthmus of stomach glands and at the base of the crypts of the colon, liver stem cells (oval cells) in canal of ____

Back 18

niches
Herring

Front 19

In liver fibrosis, ______ cell releases cytokines that promote proliferation (PDGF and ___), Contraction (ET-1), Fibrogenesis (____), and Chemotaxis (MCP-1, PDGF) of Stellate cells

Back 19

Kupffer
TNF
TGF-Beta

Front 20

Bone marrow ______ cells, depending on the tissue environment, can generate chondrocytes, osteoblasts, adipocytes, myoblasts, and endothelial cell precursors

Back 20

stromal

Front 21

Transforming Growth Factor-beta (TGF-B) presides over healing in the form of ______ in the kidney, liver, and ____. Stimulates _______ proliferation and migration and induces them to make collagen and ________

Back 21

fibrosis
lungs
fibroblast
fibronectin (in blod, fluid, in tissues, part of mesenchyme)

Front 22

___-_ inhibits degradation of ECM by metalloproteases

Back 22

TGF-B
inhibits collagen degradation which would normally allow cells (PMNs, cancer cells) to migrate

Front 23

Fibroblast Growth Factor (FGF) helps in repair of ______. Causes migration of macros, _______, and endothelial cells in damaged tissue.
Causes _______ migration inwards from margins
MOST important in __________

Back 23

wounds
fibroblasts
epithelium
ANGIOGENESIS

Front 24

_____ is important in angiogenesis and vasculogenesis (bv formation in early development). Cancer with the highest overexpression of this chemical?

Back 24

VEGF (vascular endothelial growth factor)
Renal cell carcinoma

Front 25

Two drugs used for chemo, Avastin and IFN, both work against what growth factor?

Back 25

VEGF
Avastin is a monoclonal antibody to VEGF to slow tumor growth

Front 26

____ is the growth factor most important in chemotaxis and proliferation of stellate cells. This is in the pathogenesis of what major disorder?

Back 26

PDGF (platelet derived growth factor)
Cirrhosis

Front 27

What GF do in wounds:
TGF-b: ______ migration, prolif., synthesis, __ influx
PDGF: _______ synthesis (liver), collagenase secretion*
FGF: everything EXCEPT _______ synthesis
VEGF: _______ ONLY

Back 27

fibroblast
macrophage
collagen (collagenase slows down enzymes that mold collagen)
collagen
angiogenesis

Front 28

Where do GF come from?
TGF-b: everything in clean gran. tissue & _-cells
PDGF: everything in clean gran. tissue & ____ cells
FGF: everything in clean gran. tissue & _-cells
VEGF: _________ cells ONLY

Back 28

T-cells
tumor
T-cells
mesenchymal

Front 29

Describe the signal transduction pathways:
Tyrosine kinase system
cAMP
JAK / STAT
Steroid (transmembrane)

Back 29

Binding of the ligand induces dimerization of the receptor, tyrosine phosphorylation, and activation of the receptor tyrosine kinase
Seven transmembrane G-protein-coupled receptors (GPCRs).
The JAKs link the receptors with and activate cytoplasmic transcription factors called STATs (signal transducers and activation of transcription), which directly shuttle into the nucleus and activate gene transcriptionThe ligands for these receptors diffuse through the cell membrane and bind to receptors located in the nucleus

Front 30

Unlike compensatory growth (liver/kidney), regeneration of pancreatic beta cells involves ____ ____ differentiation or the transdifferentiation of pancreatic ductal cells.

Back 30

stem cell

Front 31

Restoration of liver mass is achieved without the regrowth of the lobes that were resected. Instead, growth occurs by enlargement of the lobes that remain after the operation, a process known as ______ growth

Back 31

compensatory

Front 32

Compensatory growth results in restitution of functional mass by a synchronous wave of ______ replication followed by a synchronous wave of _____, stellate cell replication

Back 32

hepatocyte
Kupffer
NO stem cells (oval cells)

Front 33

Liver Regeneration:
1) TNF/IL-_ for priming ( gets GO to G1)
2) _______ activity of TGF-a, HGF after G1
3) _______ activity of TGF-β (inhibition)
- deriving from non-parenchymal cells

Back 33

IL-6
autocrine - TGF-alpha
paracrine - TGF-beta

Front 34

Collagen is a very important part of ECM. It is made from the _______ of proline and lysine, then glycosylation of _____. The 3 alpha procollagen chains align and form a _____ helix (still procollagen, leaves cell in this form)

Back 34

hydroxylation
lysine
triple

Front 35

Procollagen outside the cell first has a ______ of propeptides. Next there is ____-_____ done by lysyl hydroxylysyl oxidation to become collagen

Back 35

cleavage
cross-linking -> leads to tensile strength

Front 36

____-____ syndrome results from a defect in collagen structure that may inhibit proteases... lysyl hydroxylase deficiency

Back 36

Ehlers-Danlos

Front 37

Vitamin C deficiency results in:
Failure to activate proline and lysine _______
Unhydroxylated procollagen peptides. Resulting helix is unstable - mostly affects bvs (bleeding - scurvy)

Back 37

hydroxylation

Front 38

____ ____ are needed in the ECM to provide recoil to skin, bvs, uterus, lungs

Back 38

Elastic fibers

Front 39

Elastin is a core protein rich in ____ and alanine. Cross-linking is done by lysyl _____. Damaged by aging and ____

Back 39

proline
oxidase
sun

Front 40

Fibrillin 1 is a gene with over 500 mutations (ex: _____ syndrome), which normally provides scaffolding for assembly of _____ during embryogenesis

Back 40

Marfan
elastin

Front 41

Octopia lentus is a condition of ______ syndrome. Lens is atopic and slips upwards and _____. They also typically have invagination of the _____

Back 41

Marfan
laterally
sternum

Front 42

Fibronectin is part of the ECM. It is a dual chain _______ associated with the _________ membranes of cells

Back 42

glycoprotein
basement

Front 43

Fibronectin helps in cell-matrix adhesion and cell migration via RGD. What is that?

Back 43

arginine, glycine, aspartic acid - part of fibronectin that gives a tow hold to cells passing through it, otherwise they would be sliding all over the place.
RGD is a LIGAND for the INTEGRIN RECEPTORS on neutrophils, lympocytes, tumor cells ,etc

Front 44

________ is a larger protein that binds to many molecules, such as collagen, fibrin, proteoglycans, and cell-surface receptors. It consists of two glycoprotein chains, held together by _____ bonds.

Back 44

Fibronectin
disulfide

Front 45

_____ is the most abundant glycoprotein in basement membranes. Its function is to align sprouting _______ cells to form tubes. It also binds integrins on traveling neutrophils. Cell binding domain in the middle of the cross.

Back 45

Laminin
endothelial

Front 46

What type of collagen is in the basement membrane

Back 46

Type IV collagen (non-fibrillar)

Front 47

Extracellular matrix glycosaminoglycans (GAGs) include _______ and _______ acid

Back 47

Proteoglycans
Hyaluronic

Front 48

Proteoglycans are core proteins linked to one or more ________. They regulate the _______ of ECM. They also bind ___ and other proteins thereby modulating cell growth/differentiation

Back 48

polysaccharides
permeability
FGF - fibroblast growth factor

Front 49

Hyaluronic acid is repeats of simple disaccharide which results in a viscous hydrated gel. Resists compression forces by expulsion of _____. Binds CD44 on ___, especially _-cells, and keeps in them in the arena

Back 49

water
WBC
T-cells

Front 50

ECM highlights:
_______: RGD
Laminin: aligns sprouting _______ cells
_______: involved in wbc adhesion,signalling
Proteoglycans:promotes ________ of ECM
________ ___: lubricates cartilage in joints

Back 50

fibronectin
endothelial
integrins
permeability
Hyaluronic acid

Front 51

Integrins are transmembrane _________ on cells. Extracellular domains bind to _________ and _______ of the ECM. Intracellular domains link with _________ complexes
Engagement of intengrin with ECM causes cell growth and differentation via ________

Back 51

glycoproteins
fibronectin (RGD)
laminin (cell-binding domain)
cytoskeletal
kinases

Front 52

Repair by connective tissue is precipitated by damage to two tissue components: parenchyma (hepatocytes, renal tubular cells) and ______.
The endpoint is ______/scarring

Back 52

scaffold
fibrosis

Front 53

Repair by connective tissue begins as early as __ hrs. Granulation tissue forms by 3-5 days and includes angiogenesis and proliferation of ______. Sprinkling of _____ for clean up

Back 53

24
fibroblasts
macrophages

Front 54

Angiogenesis can occur from _______ from pre-existing vessels or from precursor cells such as _____________ in the bone marrow which result in hematopoietic cells and angioblasts (which diferentiate into ________ cells)

Back 54

sprouting
Hemangioblasts
endothelial

Front 55

What are EPC and what do they do?

Back 55

Endothelial progenitor cells - leave the bone marrow and go to sites for angiogenesis

Front 56

Angiogenesis from pre-existing vessels requires degradation of the ______ ____ of parent vessel via proteolysis.
Migration of _______ cells towards stimulus
Maturation of those cells -> inhibition of ______, remodeling into tubes
Recruitment of surrounding cells including pericytes and _______ _____ cells

Back 56

basement membrane
endothelial
growth
smooth muscle cells

Front 57

During angiogenesis from pre-existing vessel, recruit periendothelial cells
-pericytes for _______ (angiopoietin)
- smooth muscle cells for _____

Back 57

capillaries
arterioles, larger vessels (PDGF for this)

Front 58

Regulation of angiogensis by ECM proteins is important in motility and directed ______ of endothelial cells.
_____ on endothelial cells help in formation/maint. of bvs
Thrombospondin 1 ________ cell-matrix interactions to help stimulate angiogenesis
Proteinases - active in remodeling

Back 58

migration
integrins
destabilizes

Front 59

Angiogenesis is regulated by growth factors:
____ increased by TGF-alpha and beta, PDGF
angiopoietin helps recruit _____
PDGF recruits _____ _____ cells and synthesis of elastin for _____

Back 59

VEGF
pericytes
smooth muscle
arterioles

Front 60

Granulation tissue has what two components?

Back 60

bvs and fibroblasts

Front 61

Angiogenesis has leaky bvs which release _____ and fibronectin.
This forms a provisional _____ which allows fibroblasts and _______ cells to grow in

Back 61

fibrinogen (turns to fibrin outside bvs)
fibronectin
endothelial

Front 62

Migration of fibroblasts is triggered by: All GF's (except ____), IL-_, TNF.
Main GF is: _____ which is widely produced in granulation tissue. Also fibrinogenic cytokines (FGFs, IL-1, TNF-a)

Back 62

VEGF
IL-1
TGF-Beta

Front 63

______ promotes migration/proliferation of fibroblasts, synthesis of collagen and fibronectin by fibroblasts, decreased degradation of ECM by _________

Back 63

TGF-beta
metalloproteinases

Front 64

Granulation tissue serves as a substrate for ____ tissue formation: dense ______, shards of ______ tissue, plump fibroblasts becoming thin _______

Back 64

scar
collagen
elastic
fibrocytes

Front 65

At the end of ECM deposition of scar tissue formation, _______ recedes leaving a pale, _______ scar

Back 65

angiogenesis
avascular

Front 66

Organization is bad on ____ surfaces because they tend to stick together. Organization results in ______ formation

Back 66

serous
collagen
Ex: organizing pneumonia

Front 67

Net collagen accumulation, however, depends not only on increased collagen synthesis but also on decreased ________

Back 67

degradation

Front 68

Degradation of collagen and other ECM proteins is achieved by a family of matrix ___________ (MMPs), which are dependent on ___ ions for their activity. TIMPs (what does that stand for?) eventually control metalloproteinases

Back 68

metalloproteinases
zinc
tissue inhibitors of metalloproteinases

Front 69

Some metalloproteinases:
Interstitial collagenases - cleave ____ ______ unequally
Gelatinases act on type __ collagen and fibronectin
Stromelysins act on most ____ components

Back 69

triple helices
type IV
matrix

Front 70

PDGF, EGF, IL-1/TNF all ______ collagenases
TGF-beta and steroids all ________ collagenases

Back 70

stimulate
inhibit (If someone is on glucocorticoids for autoimmune, but gets a wound they have counteracting systems so they won’t heal unless you take them off steroids)

Front 71

Surgical wounds, paper cuts, superficial stab wounds all heal with ____ intention. Blood clots in space, dehydration of surface forms scab

Back 71

first

Front 72

In first intention healing, after 24 hrs _____ are present, there is _____ activity in basal cells, spurs that come out of basal cells. All present to help _____

Back 72

neutrophils
mitotic
fusion

Front 73

In first intention healing, after 48-72 hrs _______ are present, granulation tissue invades, then _____ forms with ____ orientation. Epidermis thickens.

Back 73

macrophages
collagen
vertical

Front 74

5 days after first intention wound healing begins, there is much _______ tissue. Maximal vascularization. ______ bridges the incision, epidermis full and mature

Back 74

Granulation
Collagen

Front 75

7-14 days after first intention wound healing begins there is much ______ and fibroblasts. Vascularization. What cell type? Edema gone

Back 75

collagen
leukocytes

Front 76

30 days after the onset of first intention wound healing it is entirely collagen with loss of _______ (sweat and sebaceous glands). _____ strength continues to increase for months

Back 76

appendages
tensile

Front 77

Second intention healing has a larger defect. It's different from first intention because it has more ____, necrotic debris, exudate to be removed so ________ reaction is more intense, more granulation tissue, wound contraction due to __________

Back 77

fibrin
inflammatory
myofibroblasts

Front 78

At suture removal, the wound is at __% of original tensile strength. Rapid increase over next 4 weeks, slows at month _ to reach a plateau of __-__%

Back 78

10%
3 months
70-80%

Front 79

Factors that slow wound healing: infection, early _____, foreign bodies remaining in wond, location (____ injuries slowly heal, _____ injuries heal quickly due to vascular supply)

Back 79

motion
foot
face

Front 80

Systemic factors slowing wound healing:
Nutrtional: protein and Vit C deficiences (what condition?), diabetes, inadequate blood supply arterial (condition?) or delayed venous drainage (varicose veins, thrombi), glucocoritcoids interfere with inflammatory response, _____ synthesis, and remodeling

Back 80

anorexia
atherosclerosis
collagen

Front 81

Deficient scar results from inadequate ______ tissue formation. Dehiscence after _____ surgery. Athersclerotic/neuropathic ulceration of feet (what condition?)

Back 81

granulation
abdominal
diabetics don't feel noxious stimuli due to neuropathy, healing slowed from athersclerosis

Front 82

Contractures are poorly healed wounds. Happens most often in palms, soles, and ______ ____.

Back 82

Anterior chest
ESPECIALL burns

Front 83

_____ is excessive wound repair. Common in African Americans. Very dense h______ collagen

Back 83

Keloid
hyalinized

Front 84

____ ____ is a condition when even normally sutured wounds have the granulation tissue go wild. Grows into a nubbin that needs to be cut off.

Back 84

Proud Flesh

Front 85

Fibromatoses result from incisional scars or trauma and are typically called "______". Tumor most commonly seen in abdomen of ______ women. Massive proliferation of HUGE fibroblasts.

Back 85

desmoids
pregnant

Front 86

Joint destruction in Rheumatoid Arthritis due to _______ going crazy and destroying things

Back 86

collagenases

Front 87

Actibation of ______ cells in the liver can cause fibrosis and collagen deposition in what conditions involving the liver?

Back 87

stellate
Alcoholism, Hepatitis B and C

Front 88

When macrophages eat silica it results in ______ in lung which releases cytokines. You get chronic interstitial ______ (ex: pneumoconiosis)

Back 88

asbestos
fibrosis

Front 89

Things that cause fibrosis:
Ionizing radiation: lungs, GIT, kidney
Chronic pancreatitis:
replacement of _____ by fibrosis
Adhesive pericarditis
Organizing _________
______ obstruction due to fibrous bands

Back 89

acini
pneumonias
bowel