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Pathology > Exam III: Inflammation Part III > Flashcards

Exam III: Inflammation Part III Flashcards

1
Q

Acute Phase Response

A

Associated with cytokine-induced systemic reactions
Example: severe bout of a viral illness (influenza)
Cytokines (stimulated by bacterial products such as LPS)
TNF, IL-1, and IL-6 are important mediators of the acute-phase reaction
Type I interferons (also contribute)

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2
Q

Acute Phase Response: Clinical and Pathology Changes

A
  1. Fever from pyrogens
  2. Prostaglandins that increase in body temperature
    Produced in the vascular and perivascular cells of the hypothalamus
    Exogenous pyrogens stimulate leukocytes to release cytokines (endogenous pyrogens)
    Increase the enzymes (cyclooxy­genases) that convert AA into prostaglandins
    In hypothalamus….PGE2 stimulates the production of neurotransmitters that reset temp set point higher
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3
Q

Acute Phase Proteins

A 
Plasma proteins (liver)
Plasma concentrations may increase several hundred-fold

Types of proteins: C-reactive protein (CRP), Fibrinogen, and Serum amyloid A (SAA) protein

Many acute-phase proteins (CRP and SAA)
Bind to microbial cell walls—may act as opsonins and fix complement
Bind chromatin—possibly aiding in clearing necrotic cell nuclei

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4
Q

Fibrinogen

A

Fibrinogen
Binds to red cells
Forms stacks (rouleaux)
Sediment more rapidly at unit gravity than do individual red cells
Increased erythrocyte sedimentation rate

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5
Q

Hepcidin

A

Production is increased
Iron-regulating peptide
Chronically elevated plasma concentrations reduce availability of iron
Responsible for theanemia associated with chronic inflammation

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6
Q

Acute Phase Response: Repair

A

Injury to cells—series of damaging events—initiation of healing process
Regeneration: complete restitution of lost or damaged tissue
Repair: may restore some original structures, but can cause structural derangements
Healthy tissues

Healing (regeneration/repair): occurs after any insult that causes tissue destruction and essential for the survival of the organism

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7
Q

Repair of Superficial and Severe Injury

A

Normal epidermis- see a couple lymphocytes and macrophages just waiting
Superficial injury: just a small layer of tissue is damaged
Severe Injury: epidermis and dermis damaged (deeper) injury that causes bleeding = scar tissue

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8
Q

Regeneration: General Information

A

Proliferation of cells and tissues to replace lost structures
Growth of an amputated limb in amphibians
Mammalian whole organs and complex tissues rarely regenerate after injury
Applied to liver growth after partial resection or necrosis
Compensatory growth rather than true regeneration

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9
Q

Regeneration: Hematopoietic System, Skin, and GI Tract

A

Hematopoietic system, skin, GI tract
High proliferative capacity
Renew themselves continuously
Regenerate after injury

Regeneration in the liver, somewhat in the kidney, and in the skin
Hemeopoietic system: regenerates from bone marrow
GI tract: when you eat, as the food goes down it takes cells with it and those cells are replaced

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10
Q

Repair

A

Combination of regeneration and scar formation
Deposition of collagen

Contribution of regeneration and scarring:
Ability of the tissue to regenerate
Extent of the injury
Example: superficial skin wound heals through the regeneration of the surface epithelium

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11
Q

Regeneration vs. Repair

A

Regeneration = fixes with the same cell type

Repair: fixes with a different type of cell like collagen

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12
Q

Injury to ECM and Cells

A

Injury to hepatocytes = regeneration of the liver = functional tissue
If the cells and ECM are injured, there is no structure whatsoever so the cells will not regenerate properly in a nice pattern like before because no scaffolding for cells = non-functional tissue

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13
Q

Repair of Chronic Inflammation

A

Accompanies persistent injury
Stimulates scar formation
Local production of growth factors and cytokines
Promote fibroblast proliferation and collagen synthesis

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14
Q

Fibrosis

A

Extensive deposition of collagen: starts as loose deposit, then over time becomes hardened

Extracellular matrix (ECM): components are essential for wound healing because it provides the framework for cell migration
Maintain the correct cell polarity for the re-assembly of multilayer structures
Participate in angiogenesis (formation of new blood vessels)
ECM: fibroblasts, macrophages, and others produce growth factors, cytokines, and chemokines critical for regeneration and repair

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15
Q

Normal Cell Proliferation

A

Adult tissues
Size of cell populations determined by rate of cell proliferation, differentiation, and death
Increased cell numbers may result in increased proliferation and decreased cell death

Apoptosis: physiologic process required for tissue homeostasis induced by a variety of pathologic stimuli

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16
Q

Terminally Differentiated Cells

A

Differentiated cells incapable of replication
Impact of differentiation
Depends on the tissue under which it occurs
Differentiated cells are not replaced
Differentiated cells die but are continuously replaced by new cells generated from stem cells

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17
Q

Physiologic Proliferation

A

Proliferation of endometrial cells under estrogen stimulation during the menstrual cycle
Thyroid-stimulating hormone-mediated replication of cells of the thyroid that enlarges the gland
Stimuli may become excessive, creating pathologic conditions

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18
Q

Pathologic Proliferation

A

Nodular prostatic hyperplasia
Dihydrotestosterone stimulation= BPH
Nodular goiters in the thyroid
Increased serum levels of thyroid-stimulating hormone

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19
Q

3 Types of Tissues Within the Body

A

Basis of the proliferative activity of their cells

  1. Labile tissues (Continuously dividing)
  2. Stable tissues (Quiescent)
  3. Permanent tissues (Nondividing)
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20
Q

Labile Tissues

A

Cells proliferate throughout life aka continuous
Replaces destroyed cells

Surface epithelia: stratified squamous epithelia of the skin, oral cavity, vagina, and cervix, lining mucosa of all the excretory ducts of the glands of the body
Salivary glands, pancreas, biliary tract
Columnar epithelium of the GI tract and uterus
Transitional epithelium of the urinary tract
Cells of the bone marrow and hematopoietic tissues

Mature cells are derived from adult stem cells, which have a tremendous capacity to proliferate

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21
Q

Quiescent Tissues

A

Low level of replication
Cells from these tissues undergo rapid division in response to stimuli
Capable of reconstituting the tissue of origin
Parenchymal cells of liver, kidneys, and pancreas
Mesenchymal cells: fibroblasts and smooth muscle
Vascular endothelial cells
Lymphocytes and other leukocytes
Example: ability of liver to regenerate, partial hepatectomy or acute chemical injury

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22
Q

Quiescent Tissue Cell Types

A

Fibroblasts, endothelial cells, smooth muscle cells, chondrocytes, and osteocytes
Quiescent in adult mammals
Proliferate in response to injury
Fibroblasts proliferate extensively

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23
Q

Non-Dividing Tissues

A

Contain cells that have left the cell cycle
Cannot undergo mitotic division in postnatal life
Neurons
Skeletal muscle cells
Cardiac muscle cells
Neurons in the central nervous system (CNS): destruction of cells are replaced by the proliferation of the CNS-supportive elements like glial cells

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24
Q

Mature Skeletal Muscle and Cardiac Muscle: Repair

A

Nondividing tissues
Mature skeletal muscle: cells do not divide
Regenerative capacity through the differentiation of the satellite cells attached to the endomysial sheaths

Cardiac muscle: very limited regenerative capacity
Large injury to the heart muscle like myocardial infarction followed by scar formation

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25
Q

Stem Cells

A

Characterized by: self-renewal properties and capacity to generate differentiated cell lineages

Need to be maintained during the life of the organism
Achieved by two mechanisms:
1. Obligatory asymmetric replication: with each stem cell division, one of the daughter cells retains its self-renewing capacity while the other enters a differentiation pathway
2. Stochastic differentiation: stem cell population maintained by the balance between stem cell divisions that generate either two self-renewing stem cells or two cells that will differentiate

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26
Q

Locations of Stem Cells

A 
Bone marrow
Skin
Gut
Liver
Brain
Muscle
Cornea
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27
Q

Bone Marrow

A

Contains hematopoietic stem cells (HSCs)
Contains stromal cells aka multipotent stromal cells, mesenchymal stem cells or MSCs

Hematopoietic Stem Cells: generate all of the blood cell lineages, reconstitute the bone marrow after depletion caused by disease or irradiation

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28
Q

Hematopoietic Stem Cells

A

Widely used for the treatment of hematologic diseases
Collected directly from:
Bone marrow
Umbilical cord blood
Peripheral blood of individuals receiving cytokines: granulocyte-macrophage colony-stimulating factor, which mobilize HSCs; make the person have a fever and sick because the body is trying to produce all the cells to donate to someone else

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29
Q

Marrow Stromal Cells (MSCs)

A

Multipotent
Potentially important therapeutic applications: generate chondrocytes, osteoblasts, adipocytes, myoblasts, and endothelial cell precursors
Depends on the tissue to which they migrate
Migrate to injured tissues
Generate stromal cells or other cell lineages
Do not participate in normal tissue homeostasis

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30
Q

Liver Regeneration

A

Contains stem cells/progenitor cells in the canals of Hering: junction between the biliary ductular system and parenchymal hepatocytes

Give rise to a population of precursor cells: oval cells, which are bipotential progenitors capable of differentiating into hepatocytes and biliary cells

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31
Q

Oval Cells

A

Cells of the liver
Function as a secondary or reserve compartment, which are activated only when hepatocyte proliferation is blocked
Proliferation and differentiation during fulminant (sudden onset) hepatic failure, liver tumorigenesis, and chronic hepatitis and advanced liver cirrhosis

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32
Q

Brain Regeneration

A

Neurogenesis from neural stem cells (NSCs)
Occurs in the brain of adult rodents and humans
AKA neural precursor cells
Capable of generating neurons, astrocytes, and oligodendrocytes

Identified in two areas of adult brains:
Subventricular zone (SVZ)
Dentate gyrus of the hippocampus

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33
Q

Compensatory Growth

A

Even this process is not one of true regeneration
Resection of tissue does not cause new growth of liver
Triggers a process of compensatory hyperplasia in the remaining parts of the organ

Other organs capable of compensatory growth
Kidney, pancreas, adrenal glands, thyroid, and the lungs of very young animals
Display it in less dramatic form than the liver

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34
Q

Kidney Regeneration

A

New nephrons cannot be generated in the adult kidney
Growth of the contralateral kidney after unilateral nephrectomy
Involves nephron hypertrophy
Replication of proximal tubule cells

In kidney, you take out one kidney, and the other side you will get nephron hypertrophy to increase function and handle the body enough
Process like there were two but in one tissue

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35
Q

Pancreas Regeneration

A

Limited capacity to regenerate exocrine components and islets

Regeneration of pancreatic beta cells
Beta-cell replication
Transdifferentiation of ductal cells
Differentiation of putative stem cells

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36
Q

Human Liver

A

Remarkable capacity to regenerate demonstrated by its growth after partial hepatectomy
Tumor resection or for living-donor hepatic transplantation

Resection of approximately 60% of the liver in living donors
Doubling of the liver remnant in about one month
Portions of the liver that remain after partial hepatectomy constitute an intact “mini-liver” rapidly expands and reaches the mass of the original liver
Restoration of liver mass achieved without regrowth of resected lobes

Growth occurs by enlargement of the lobes that remain after the operation= compensatory growth or compensatory hyperplasia
End point of liver regeneration after partial hepatectomy
Restitution of functional mass rather than the reconstitution of the original

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37
Q

Hepatocytes in the Cell Cycle

A

Hepatocytes are quiescent cells G0 phase, but several hours to enter the cell cycle after a partial hepatectomy
Progress through G1 and reach the S phase of DNA replication

Wave of hepatocyte replication is synchronized followed by synchronous replication of nonparenchymal cells
Kupffer cells, endothelial cells, and stellate cells
Replication of non-paraenchymal cells to make ECM

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38
Q

Restriction Points for Hepatocyte Replication

A

Two major restriction points for hepatocyte replication:

  1. G0/G1 transition that bring quiescent hepatocytes into the cell cycle
  2. G1/S transition needed for passage through the late G1 restriction point

Gene expression in the regenerating liver proceeds in phases
Starts with the immediate early gene response
Transient response that corresponds to the G0/G1 transition

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39
Q

Quiescent Hepatocytes

A

Become competent to enter the cell cycle through a priming phase mediated by the cytokines TNF and IL-6, and components of the complement system

Priming signals activate several signal transduction pathways as a necessary prelude to cell proliferation

Under the stimulation of HGF, TGFα, and HB-EGF, primed hepatocytes enter the cell cycle and undergo DNA replication
Norepinephrine, serotonin, insulin, thyroid and growth hormone: act as adjuvants for liver regeneration and facilitates the entry of hepatocytes into the cell cycle

40
Q

Hepatocytes vs. Stem Cell in Compensatory Growth

A

Individual hepatocytes: replicate once or twice during regeneration and then return to quiescence in a strictly regulated sequence of events

Intrahepatic stem or progenitor cells do not play a role in the compensatory growth that occurs after partial hepatectomy
No evidence for hepatocyte generation from bone marrow-derived cells during this process

41
Q

ECM and Repair

A

Tissue Repair and Regeneration depends on:
1 Activity of soluble factors
2. Interactions between cells and the components of the extracellular matrix
Regulates the growth, proliferation, movement, and differentiation of the cells

42
Q

Functions of ECM: Mechanical, Growth, Maintenance, and Scaffolding

A
  1. Mechanical support- cell anchorage and migration, scaffolding, and maintenance of cell polarity (all lined up in a certain way)
  2. Control of cell growth: ECM components can regulate cell proliferation by signaling through cellular receptors of the integrin family
  3. Maintenance of cell differentiation: type of ECM proteins affect the degree of differentiation of the cells in the tissue
  4. Scaffolding for tissue renewal: maintenance of normal tissue structure
    Requires a basement membrane or stromal scaffold
    Integrity of the basement membrane or the stroma of the parenchymal cells
    Critical for the organized regeneration of tissues
43
Q

Functions of ECM: Microenvironments and Regulatory Molecules

A
  1. Establishment of tissue microenvironments: basement membrane boundary between epithelium and underlying connective tissue that forms part of the filtration apparatus in the kidney
  2. Storage and presentation of regulatory molecules
    Growth factors FGF and HGF are secreted and stored in the ECM in some tissues
    Allows rapid deployment of growth factors after local injury or during regeneration
44
Q

Composition of the ECM

A

Composed of three groups of macromolecules
1. Fibrous structural proteins: collagens and elastins that provide tensile strength and recoil

  1. Adhesive glycoproteins: connect the matrix elements to one another and to cells
  2. Proteoglycans and hyaluronan: provide resilience and lubrication (especially to joints)
45
Q

2 Forms of ECM

A
  1. Interstitial matrix: found in spaces between epithelial, endothelial, and smooth muscle cells, as well as in connective tissue
    Consists mostly of fibrillar and nonfibrillar collagen, elastin, fibronectin, proteoglycans, and hyaluronan
  2. Basement membranes: closely associated with cell surfaces
    Consist of nonfibrillar collagen (mostly type IV), laminin, heparin sulfate, and proteoglycans
46
Q

Skin

A

Human epidermis has a high turnover rate: about 4 weeks
Stem cells are located in three different areas of the epidermis
1. Hair follicle bulge: constitutes a niche for stem cells that produce all of the cell lineages of the hair follicle

  1. Interfollicular areas of the surface epidermis: stem cells are scattered individually in the epidermis and are not contained in niches
    Divide infrequently, generate transit amplifying cells, and denerate the differentiated epidermis
  2. Sebaceous glands
47
Q

Small Intestine Epithelium

A

Small intestine
1. Crypts: monoclonal structures derived from single stem cells
Stem cells regenerate the crypt in 3 to 5 days

  1. Villus: differentiated compartment that contains cells from multiple crypts
48
Q

Skeletal Muscle

A

Skeletal muscle myocytes do not divide, even after injury
Growth and regeneration of injured skeletal muscle
Occur by replication of satellite cells
Located beneath the myocyte basal lamina
Constitute a reserve pool of stem cells
Generate differentiated myocytes after injury

49
Q

Cornea

A

Transparency of the cornea: integrity of the outermost corneal epithelium maintained by limbal stem cells (LSCs)
Located at the junction between the epithelium of the cornea and the conjunctiva

50
Q

Repair by Connective Tissue

A

Severe or persistent tissue injury: damage to parenchymal and stromal cells
Leads to a situation in which repair cannot be accomplished by parenchymal regeneration alone

Repair: occurs by replacement of nonregenerated parenchymal cells with connective tissue

51
Q

4 Steps of Repair by CT

A

Four components of repair process

  1. Angiogenesis
  2. Migration and proliferation of fibroblasts
  3. Deposition of ECM
  4. Remodeling (maturation and reorganization of the fibrous tissue)
52
Q

Tissue Repair

A

Tissue repair begins within 24 hours of injury
Stimulate the emigration of fibroblasts
Induction of fibroblasts and endothelial

By 3-5 days of tissue repair a specialized type of tissue appears
Characteristic of healing “granulation tissue”
Name from pink soft appearance of tissue seen beneath scab
Characterized by fibroblast proliferation and new, thin walled delicate capillaries
Outcome is formation of dense fibrosis (scarring)

53
Q

Angiogenesis vs. Vasculogenesis

A

Blood vessels are assembled by two processes:
Vasculogenesis: assembly of primitive vascular network - from angioblast; in fetus only
Angiogenesis or neovascularization: pre-existing blood vessels send out capillary sprouts

54
Q

Angiogenesis

A

Critical process in the healing at sites of injury
Development of collateral circulations at sites of ischemia is stimulated following MI or atherosclerosis
Allows tumors to grow: inhibit blood flow to “starve” tumor growth

55
Q

Steps of Angiogenesis

A
  1. Vasodilation: response to nitric oxide
    VEGF-induced increased permeability of the preexisting vessel
  2. Proteolytic degradation of the basement membrane of the parent vessel; use matrix metalloproteinases (MMPs)
    Disruption of cell-to-cell contact between endothelial cells by plasminogen activator
  3. Migration of endothelial cells toward the angiogenic stimulus
  4. Proliferation of endothelial cells just behind the leading front of migrating cells
  5. Maturation of endothelial cells: includes inhibition of growth and remodeling into capillary tubes
  6. Recruitment: periendothelial cells, pericytes and vascular smooth muscle cells to form the mature vessel
56
Q

Angiogenesis: FGF

A

FGF (fibroblast growth factor)
Mainly FGF-2
Stimulates proliferation of endothelial cells
Promotes migration of macrophages and fibroblasts to the damaged area
Stimulates epithelial cell migration to cover epidermal wounds

57
Q

Angiogenesis: VEGF

A

VEGF (vascular endothelial growth factor)
Mainly VEGF-A
Stimulates both migration and proliferation of endothelial cells
Initiating the process of capillary sprouting in angiogenesis
Promotes vasodilation by stimulating the production of NO
Contributes to the formation of the vascular lumen
*helps with sprouting of new vessels

58
Q

Cutaneous Wound Healing: Steps

A

Divided into three phases
1. Inflammation: initial injury causes platelet adhesion and aggregation and formation of a clot in the surface of the wound

  1. Proliferation: formation of granulation tissue, proliferation and migration of connective tissue cells, and re-epithelialization of the wound surface; 3-5 days
  2. Maturation: involves ECM deposition, tissue remodeling, and wound contraction
    * Phases overlap; separation is somewhat arbitrary
59
Q

Primary Union/First Intention

A

Simplest type of cutaneous wound repair: healing of a clean, uninfected surgical incision
Approximated by surgical sutures
Referred to as healing by primary union or by first intention

60
Q

Wound Healing: Incision

A

Death of a limited number of epithelial and connective tissue cells
Disruption of epithelial basement membrane continuity
Re-epithelialization to close the wound
Occurs with formation of a relatively thin scar

61
Q

Excisional Wounds

A

Excisional wounds
Repair process is more complicated
Create large defects on the skin surface
Extensive loss of cells and tissue

62
Q

Wound Healing with Secondary Union

A

More intense inflammatory reaction
Formation of abundant granulation tissue
Extensive collagen deposition
Leading to the formation of a substantial scar that generally contracts
Healing by secondary union or by second intention

Pull a wound together, but have granulation tissue deposition and collagen deposition
If you don’t have a suture close the wound: a lot of granulation tissue and collagen = secondary union by second intention
Secondary: big scab, wound contraction and end up with puckering of the skin

63
Q

Clot Formation: General Information

A

Wounding causes the rapid activation of coagulation pathways
Formation of a blood clot on the wound surface
Entrapped red cells, fibrin, fibronectin, and complement components
Clot serves to stop bleeding and as a scaffold for migrating cells
Attracted by growth factors, cytokines and chemokines released into the area
Release of VEGF: increased vessel permeability and edema

64
Q

Clot Formation: Scabs

A

Dehydration occurs at the external surface of the clot
Forms a scab that covers the wound
Within 24 hours, neutrophils appear at the margins of the incision
Use the scaffold provided by the fibrin clot to infiltrate in
Release proteolytic enzymes that clean out debris and invading bacteria
In a cutaneous lesion, neutrophils appear within 24 hours… 6-24 hours for acute inflammation

65
Q

Formation of Granulation Tissue

A

Fibroblasts and vascular endothelial cells
Proliferate in the first 24 to 72 hours of the repair process
Form a specialized type of tissue
Granulation tissue: HALLMARK OF TISSUE REPAIR

66
Q

Appearance of Granulation Tissue

A

Granulation tissue: pink, soft, granular appearance on the surface of wounds
Histologic feature: presence of new small blood vessels (angiogenesis) and proliferation of fibroblasts
*Usually see edema because new vessels will be leaky

67
Q

Granulation Tissue & Edema

A

New vessels are leaky, which allow the passage of plasma proteins and fluid into the extravascular space
New granulation tissue is often edematous
Progressively invades the incision space

68
Q

Amount of Granulation Tissue Formed

A

Amount of granulation tissue that is formed depends on:
Size of the tissue deficit created by the wound
Intensity of inflammation
Much more prominent in healing by secondary union
By 5 to 7 days, granulation tissue fills the wound area and neovascularization is maximal

69
Q

Neutrophils & Repair

A

Neutrophils are largely replaced by macrophages by 48 to 96 hours
Macrophages are key cellular constituents of tissue repair
Clearing extracellular debris, fibrin, and other foreign material at the site of repair
Promoting angiogenesis and ECM deposition

70
Q

Functions of Macrophages

A
  1. Debridement/Removal of injured tissue and debris via phagocytosis, collagenase, and elastase
  2. Antimicrobial activity using nitric acid and ROS
  3. Chemotaxis and proliferation of fibroblasts and keratinocytes via PDGF, TGF beta, TNF, IL-1, and KGF-7
  4. Angiogenesis via VEGF, FGF-2, and PDGF
  5. Deposition and remodeling of ECM: TGF beta, PDGF, TNF, OPN, IL-2, collagenase, and MMPs
71
Q

Fibroblast Migration

A

Migration of fibroblasts to the site of injury driven by chemokines TNF, PDGF, TGF-β, and FGF
Proliferation is triggered by multiple growth factors
PDGF, EGF, TGF-β, FGF, and the cytokines IL-1 and TNF
Macrophages are the main source for these factors
Need fibroblasts and go to site of injury via chemokines that attract them

72
Q

Collagen Fibers and Collagen Deposition

A

Collagen fibers are present at the margins of the incision, which are vertically oriented and do not bridge the incision
24 to 48 hours, spurs of epithelial cells move from the wound edge along the cut margins of the dermis, depositing basement membrane components as they move.
Fuse in the midline beneath the surface scab producing a thin, continuous epithelial layer that closes the wound (re-epithelializing)

73
Q

Primary vs. Secondary Intention Re-Epithelialization

A

Full epithelialization of the wound surface
Much slower in healing by secondary union because the gap to be bridged is much greater
Subsequent epithelial cell proliferation thickens the epidermal layer

In primary intention: quick fix
Secondary intention: takes a lot longer to re-epithelialize

74
Q

Macrophages & Skin Re-Epithelialization

A

Macrophages stimulate fibroblasts to produce FGF-7 (keratinocyte growth factor) and IL-6, which enhance keratinocyte migration and proliferation
Signaling through the chemokine receptor CXCR 3 also promotes skin re-epithelialization

Helps to proliferate the surface of the skin and get rid of scab: IL-6 and FGF-7
Start to see underneath dermis that the collagen fibers become more dense

75
Q

Collagen Replacement of Matrix

A

Concurrently with epithelialization collagen fibrils become more abundant and begin to bridge the incision
Provisional matrix containing fibrin, plasma fibronectin, and type III collagen is formed
Replaced by a matrix composed primarily of type I collagen
Type III collagen replaced by type I because it is much stronger

76
Q

TGF-β

A

TGF-β is the most important fibrogenic agent
Produced by most of the cells in granulation tissue
Causes fibroblast migration and proliferation, increased synthesis of collagen and fibronectin, and decreased degradation of ECM by metalloproteinases
Need more fibroblasts, fibronectin and collagen production to produce the scar

77
Q

Blanching

A

Leukocytic infiltrate, edema, and increased vascularity disappears during the second week and blanching begins
Blanching: increased accumulation of collagen within the wound area and regression of vascular channels
Encouraging scar to form and not allowing anything else to break down
During the 2nd week, the swelling, redness, etc is gone without an infection present and the scar is present after the scab falls off

78
Q

Scar at First Month

A

Original granulation tissue scaffolding is converted into a pale, avascular scar

By the end of the first month
Scar is made up of acellular connective tissue devoid of inflammatory infiltrate, covered by intact epidermis

79
Q

Wound Contraction

A

Generally occurs in large surface wounds
Contraction helps to close the wound by decreasing the gap between its dermal edges and by reducing the wound surface area
Important feature in healing by secondary union
Replacement of granulation tissue with a scar
Involves changes in the composition of the ECM

80
Q

Recovery of Tensile Strength

A

Fibrillar collagens (mostly type I collagen)
Form a major portion of the connective tissue in repair sites
Essential for the development of strength in healing wounds

Net collagen accumulation depends not only on increased collagen synthesis but also on decreased degradation

81
Q

Timeline for Wound to Achieve Maximal Strength

A

Length of time for a skin wound to achieve its maximal strength
Sutures are removed from an incisional surgical wound
End of the first week, wound strength is approximately 10% that of unwounded skin
Wound strength increases rapidly over the next 4 weeks
Slows down at approximately the third month after the original incision
Reaches a plateau at about 70% to 80% of the tensile strength of unwounded skin

82
Q

Process of Recovery of Tensile Strength

A

Lower tensile strength: healed wound area may persist for life

Recovery of tensile strength
Results from the excess of collagen synthesis over collagen degradation during the first 2 months of healing
Structural modifications of collagen fibers (cross-linking, increased fiber size) after collagen synthesis ceases

83
Q

Wound Repair Impairment

A

Adequacy of wound repair may be impaired by systemic and local host factors

Systemic factors include:

  1. Nutrition: protein deficiency: Esp vitamin C deficiency, inhibit collagen synthesis and retard healing
  2. Metabolic status: diabetes mellitus is associated with delayed healing, a consequence of the microangiopathy
84
Q

Circulatory Status and Hormones in Wound Healing

A

Circulatory status:
Modulate wound healing
Inadequate blood supply, usually caused by arteriosclerosis or venous abnormalities (e.g., varicose veins) that retard venous drainage, also impairs healing

Hormones:
Glucocorticoids: well-documented anti-inflammatory effects and influence various components of inflammation
Agents also inhibit collagen synthesis

85
Q

Factors that Delay Wound Healing

A

Infection: sesults in persistent tissue injury and inflammation

Mechanical factors:
Early motion of wounds, can delay healing
Compressing blood vessels and separating the edges of the wound

86
Q

Foreign Bodies and Wound Factors in Healing

A

Foreign bodies: unnecessary sutures or fragments of steel, glass, or even bone, constitute impediments to healing

Size, location, and type of wound:
Richly vascularized areas, such as the face, heal faster than those in poorly vascularized ones, such as the foot
Small incisional injuries heal faster and with less scar formation than large excisional wounds or wounds caused by blunt trauma

87
Q

Factors That Retard Wound Healing

A

Local Factors: blood supply, denervation, local infection, foreign body, hematoma, mechanical stress, necrotic tissue, protection (dressings), surgical techniques, type of tissue
Systemic Factors: age, anemia, drugs, genetic disorders, hormones, diabetes, malignant disease, malnutrition, obesity, systemic infection, temperature, trauma, hypoxia, uremia, vitamin deficiency, trace metal deficiency (zinc and coppe

88
Q

Complications of Wound Healing

A

Arise from abnormalities; three categories

  1. Deficient scar formation
  2. Excessive formation of the repair components/ scar formation
  3. Formation of contractures
89
Q

Deficient Scar Formation

A

Lead to two types of complications
1. Wound dehiscence: rupture of a wound is most common after abdominal surgery due to increased abdominal pressure caused by vomiting, coughing, or ileus

  1. Ulceration: inadequate vascularization during healing
    Areas devoid of sensation
90
Q

Excessive Formation of Scar Tissue

A

Excessive formation of the components of the repair process can give rise to hypertrophic scars and keloids
Accumulation of excessive amounts of collagen may give rise to a raised scar
Hypertrophic scar: develop after thermal or traumatic injury and involves the deep layers of the dermis

Keloid: individual predisposition and more common in African Americans; dense collagen bundles that can arise from a specific dermatome from surgerical incision

91
Q

Exuberant Granulation

A

Deviation in wound healing
Formation of excessive amounts of granulation tissue
Protrudes above the level of the surrounding skin
Blocks re-epithelialization
Must be removed by cautery or surgical excision to permit restoration of the continuity of the epithelium

92
Q

Wound Contraction

A

Important part of the normal healing process
Exaggeration of this process gives rise to contractures and results in deformities of the wound and the surrounding tissues

Contractures are particularly prone to develop on the palms, the soles, and the anterior aspect of the thorax

Contractures are commonly seen after serious burns and can compromise the movement of joints

93
Q

Fibrosis

A

Denote the excessive deposition of collagen and other ECM components in a tissue
Deposition of collagen in chronic diseases

94
Q

End Result of Chronic Inflammation

A

Chronic Inflammation (persistent stimulus) causes:

  1. Activation of macrophages and lymphocytes, which activate growth factors (PDGF, FGF, and TGF beta)
  2. Cytokines (TNF, IL-1, IL-4, and IL-13)
  3. Decreased metalloproteinase activity

GF cause proliferation of fibroblasts, endothelial cells, and specialized fibrogenic cells
Cytokines cause increased collagen synthesis
Decreased metalloproteinase activity causes decreased collagen degradation
*END RESULT = FIBROSIS

95
Q

Injury: Persistent Stimulus vs. Stimulus Removed

A 
Injury and vascular response
Persistent tissue damage= fibrosis caused by chronic inflammatory diseases
Stimulus removed (acute injury): regeneration and repair

Regeneration (restitution of normal structure) if parenchymal cell death with intact tissue framework, superficial wounds, and acute inflammatory process

Repair (scar formation) if parenchymal cell death with damaged tissue framework or deep wounds

Pathology (14 decks)

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