Chapter 3 Tissue Repair Flashcards
Results in the complete restitution of the lost damage or tissue.
Regeneration
The process by which there is extensive deposition of collagen.
Fibrosis
The following are examples of labile tissues EXCEPT:A. Skin epitheliaB. Oral cavityC. Parenchymal cells of the liverD. Lining mucosa of all the excretory ducts
C. Parenchymal cells of the liver
Mechanism of stem cells in which with each stem cell division, one of the daughter cells retains its self-renewing capacity while the other enters differentiation.
Obligatory asymmetric replication
Stem cell mechanism in which there is a balance between self-renewing and differentiated cells.
Stochastic differentiation
A change in differentiation of a cell from one type to another is known as ________________.
Transdifferentiation
The capacity of a cell to transdifferentiate into diverse lineages is referred to as ___________.
Developmental plasticity
Somatic stem cells generate rapidly dividing cells called __________.
Transit amplifying cells
The liver contains stem cells/progenitor cells in the _____________.
Canals of Hering
Neural precursor cells are found in which two areas of the adult brain.
Subventricular zone and dentate gyrus of the hippocampus
This is the rate limiting step for replication in the cell cycle.
Restriction point between G1 and S.
This step in cell cycle monitors the integrity of DNA BEFORE replication.
G1/S checkpoint
Aids in cell scattering and proliferation.
HGF/Scatter factor
Most potent growth factor for vasculogenesis and angiogenesis.
VEGF
Growth factor responsible for migration and proliferation of fibroblasts, smooth muscles
PDGF
Growth factor that acts as a growth inhibitor and a potent fibrinogenic agent.
TGF-B
The following are biochemical pathways that utilize intrinsic tyrosine kinase activity EXCEPT:A. PI3 Kinase PathwayB. MAP-kinase PathwayC. IP3 PathwayD. cAMP Pathway
D. cAMP Pathway
Mobilization of endothelial stem cells and has a role in inflammation.A. VEFGR-1B. VEFGR-2C. VEFGR-3D. None of the above
A. VEFGR-1
Acts on lymphatic endothelial cells to induce lymphangiogenesis.A. VEFGR-1B. VEFGR-2C. VEFGR-3D. None of the above
C. VEFGR-3
Located in endothelial cells and many other cells types and considered to be the main receptors for vasculogenic and angiogenic effect on VEGF.A. VEFGR-1B. VEFGR-2C. VEFGR-3D. None of the above
B. VEFGR-2
Also known as the wear and tear pigment.
Lipofuschin
Provide resilience and lubrication to many types of CT (cartilage in joints).
Hyaluronan
This is the most abundant glycoprotein in BM.
Laminin
Mobilization of endothelial stem cells and has a role in inflammation.A. VEFGR-1B. VEFGR-2C. VEFGR-3D. None of the above
A. VEFGR-1
Acts on lymphatic endothelial cells to induce lymphangiogenesis.A. VEFGR-1B. VEFGR-2C. VEFGR-3D. None of the above
C. VEFGR-3
Located in endothelial cells and many other cells types and considered to be the main receptors for vasculogenic and angiogenic effect on VEGF.A. VEFGR-1B. VEFGR-2C. VEFGR-3D. None of the above
B. VEFGR-2
Also known as the wear and tear pigment.
Lipofuschin
Provide resilience and lubrication to many types of CT (cartilage in joints).
Hyaluronan
This is the most abundant glycoprotein in BM.
Laminin
What is REPAIR?
Repair, sometimes called healing, refers to the restorationof tissue architecture and function after an injury.(By convention, the term repair is often used for parenchymaland connective tissues and healing for surface epithelia,but these distinctions are not based on biology and weuse the terms interchangeably.)Critical to the survival ofan organism is the ability to repair the damage caused bytoxic insults and inflammation. Hence, the inflammatoryresponse to microbes and injured tissues not only serves toeliminate these dangers but also sets into motion theprocess of repair.
Repair of damaged tissues occurs by two types of reactions:
- regeneration by proliferation of residual (uninjured)cells and maturation of tissue stem cells, 2. and thedeposition of connective tissue to form a scar
What is Regeneration?
Some tissues are able to replace thedamaged components and essentially return to a normalstate; this process is called regeneration. Regenerationoccurs by proliferation of cells that survive the injuryand retain the capacity to proliferate, for example, in therapidly dividing epithelia of the skin and intestines, andin some parenchymal organs, notably the liver. In othercases, tissue stem cells may contribute to the restorationof damaged tissues. However, mammals have a limitedcapacity to regenerate damaged tissues and organs, andonly some components of most tissues are able to fullyrestore themselves
What happens in Connective tissue deposition (scar formation)?
If theinjured tissues are incapable of complete restitution, orif the supporting structures of the tissue are severelydamaged, repair occurs by the laying down of connective(fibrous) tissue, a process that may result in scarformation. Although the fibrous scar is not normal, itprovides enough structural stability that the injuredtissue is usually able to function.
The term fibrosis ismost often used to describe the:
extensive depositionof collagen that occurs in the lungs, liver, kidney, andother organs as a consequence of chronic inflammation,or in the myocardium after extensive ischemicnecrosis (infarction).
If fibrosis develops in a tissuespace occupied by an inflammatory exudate, it iscalled ________
organization (as in organizing pneumonia affectingthe lung
The regeneration of injured cells and tissues involves___________, which is driven by growth factors and iscritically dependent on the integrity of the extracellularmatrix, and by the _____________.Before describing examples of repair by regeneration,the general principles of cell proliferation arediscussed.
cellproliferation
development of mature cells fromstem cells
Several cell types proliferate during tissue repair.Theseinclude the:
remnants of the injured tissue (which attemptto restore normal structure), vascular endothelial cells (tocreate new vessels that provide the nutrients needed forthe repair process), and fibroblasts (the source of the fibroustissue that forms the scar to fill defects that cannot be correctedby regeneration).
The ability of tissues to repair themselves is determined,in part, by their intrinsic proliferative capacity.Based on this criterion, the tissues of the body are dividedinto three groups.
- Labile (continuously dividing) tissues
- Stable tissues
- Permanent tissues.
What are Labile tissues?
Labile (continuously dividing) tissues.Cells of thesetissues are continuously being lost and replaced bymaturation from tissue stem cells and by proliferationof mature cells.Labile cells include:
* hematopoietic cellsin the bone marrow and the majority of surface epithelia,
* such as the stratified squamous epithelia of the skin,
* oral cavity, vagina, and cervix;
* the cuboidal epithelia ofthe ducts draining exocrine organs (e.g., salivary glands,pancreas, biliary tract); the columnar epithelium of thegastrointestinal tract, uterus, and fallopian tubes; andthe transitional epithelium of the urinary tract.
Thesetissues can readily regenerate after injury as long as thepool of stem cells is preserved.
What are Stable tissues?
Cells of these tissues are quiescent (in theG0 stage of the cell cycle) and have only minimal proliferativeactivity in their normal state.However, thesecells are capable of dividing in response to injury or lossof tissue mass. Stable cells constitute the parenchyma ofmost solid tissues, such as liver, kidney, and pancreas.They also include endothelial cells, fibroblasts, andsmooth muscle cells; the proliferation of these cells isparticularly important in wound healing. With theexception of liver, stable tissues have a limited capacityto regenerate after injury.
What are Permanent tissues?
The cells of these tissues are consideredto be terminally differentiated and nonproliferativein postnatal life.The majority of neurons and cardiacmuscle cells belong to this category.Thus, injury to thebrain or heart is irreversible and results in a scar, becauseneurons and cardiac myocytes cannot regenerate.Limited stem cell replication and differentiation occurin some areas of the adult brain, and there is some evidencethat heart muscle cells may proliferate after myocardialnecrosis. Nevertheless, whatever proliferativecapacity may exist in these tissues, it is insufficient toproduce tissue regeneration after injury. Skeletal muscleis usually classified as a permanent tissue, but satellitecells attached to the endomysial sheath provide someregenerative capacity for muscle. In permanent tissues,repair is typically dominated by scar formation.
Cell proliferation is driven by signals provided by_____________
growth factors and from the extracellular matrix
Manydifferent growth factors have been described; some act onmultiple cell types and others are cell-selective (Chapter 1,Table 1-1). Growth factors are typically produced by cellsnear the site of damage. The most important sources ofthese growth factors are________ that are activated bythe tissue injury, but epithelial and stromal cells alsoproduce some of these factors. Several growth factors bindto ECM proteins and are displayed at high concentrations.
macrophages
All growth factors activate signaling pathways that ultimatelyinduce the production of proteins that are involvedin driving cells through the cell cycle and other proteinsthat release blocks on the cell cycle (checkpoints) (Chapter1). In addition to responding to growth factors, cells useintegrins to bind to ECM proteins, and signals from theintegrins can also stimulate cell proliferation.
Also, we now realize that cellproliferation is only one pathway of regeneration and thatstem cells contribute to this process in important ways.In the process of regeneration, proliferation of residualcells is supplemented by development of mature cellsfrom stem cells.In Chapter 1 we introduced the majortypes of stem cells. In adults, the most important stem cellsfor regeneration after injury are___________
tissue stem cells.Thesestem cells live in specialized niches, and it is believedthat injury triggers signals in these niches that activatequiescent stem cells to proliferate and differentiate intomature cells that repopulate the injured tissue.
Mechanisms of Tissue RegenerationThe importance of regeneration in the replacement ofinjured tissues varies in different types of tissues and withthe severity of injury.
• In labile tissues, such as the epithelia of the intestinaltract and skin, injured cells are rapidly replaced by proliferationof residual cells and differentiation of tissuestem cells provided the underlying basement membraneis intact.The growth factors involved in theseprocesses are not defined.Loss of blood cells is correctedby proliferation of hematopoietic stem cells in thebone marrow and other tissues, driven by growthfactors called colony-stimulating factors (CSFs), whichare produced in response to the reduced numbers ofblood cells.
Tissue regeneration can occur in parenchymal organswith stable cell populations, but with the exception ofthe_______ this is usually a limited process. Pancreas,adrenal, thyroid, and lung have some regenerativecapacity.The surgical removal of a kidney elicits inthe remaining kidney a compensatory response thatconsists of both hypertrophy and hyperplasia of proximalduct cells. The mechanisms underlying this responseare not understood, but likely involve local productionof growth factors and interactions of cells with the ECM.The extraordinary capacity of the liver to regenerate hasmade it a valuable model for studying this process, asdescribed below.
liver,
Restoration of normal tissue structure can occur only ifthe residual tissue is structurally___________ as after partialsurgical resection.
intact,
By contrast, if the entire tissue isdamaged by infection or inflammation, regeneration is__________.For example,extensive destruction of the liver with collapse of the reticulinframework, as occurs in a liver abscess, leads to scarformation even though the remaining liver cells have thecapacity to regenerate.
incomplete and is accompanied by scarring
The human liver has a remarkable capacity to regenerate,as demonstrated by its growth after partial hepatectomy,which may be performed for tumor resection or for livingdonorhepatic transplantation. The mythologic image ofliver regeneration is the regrowth of the liver of Prometheus,which was eaten every day by an eagle sent by Zeus aspunishment for stealing the secret of fire, and grew backovernight. The reality, although less dramatic, is still quiteimpressive.
Regeneration of the liver occurs by two major mechanisms:__________. Which mechanism plays thedominant role depends on the nature of the injury.
proliferation of remaining hepatocytes
and repopulationfrom progenitor cells
In humans, resection of up to 90% of the liver canbe corrected by __________This classic model of tissue regeneration has been usedexperimentally to study the initiation and control of theprocess.
proliferation of the residual hepatocytes.
Hepatocyte proliferation in the regenerating liver istriggered by the combined actions of_____________
cytokines andpolypeptide growth factors.
Hepatocyte proliferation in the regenerating liver istriggered by the combined actions of cytokines andpolypeptide growth factors.The process occurs in distinctstages
- first, or priming
- second, or growth factor, phase,
- final,termination, phase,
What happens in the first step of heptocyte proliferation?
In the first, or priming, phase,cytokines such as IL-6 are produced mainly by Kupffercells and act on hepatocytes to make the parenchymalcells competent to receive and respond to growth factorsignals.
What happens in the second step of hepatocyte proliferation?
In the second, or growth factor, phase, growthfactors such as HGF and TGF-α, produced by manycell types, act on primed hepatocytes to stimulate cellmetabolism and entry of the cells into the cell cycle.Because hepatocytes are quiescent cells, it takes themseveral hours to enter the cell cycle, progress from G0 toG1, and reach the S phase of DNA replication.Almostall hepatocytes replicate during liver regenerationafter partial hepatectomy.The wave of hepatocyte replicationis followed by replication of nonparenchymalcells (Kupffer cells, endothelial cells, and stellate cells).During the phase of hepatocyte replication, more than70 genes are activated; these include genes encodingtranscription factors, cell cycle regulators, regulatorsof energy metabolism, and many others.
What happens in the final step of hepatocyte proliferationtermination, phase?
hepatocytes return to quiescence.The nature of the stop signals is poorly understood;antiproliferativecytokines of the TGF-β family are likelyinvolved.