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89 Cards in this Set

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Regeneration, or compensatory growth, is a term that can be applied to what two organs?
Liver- partial hepatectomy
Kidney - unilateral nephrectomy
_______ involves highly proliferating tissues that are constantly renewing marrow, skin, gut, etc.... IF - ____ ____ are not destroyed
Regeneration
Stem Cells
______, or tissue restoration, consists of scar tissue and an element of regeneration (in organs, only if _____ intact)
Healing
scaffold
Healing may restore original structures but involves _______ deposition and ____ formation.
collagen
scar
In parenchymal organs, the replacement of inflammatory infiltrates by granulation tissue and ultimately fibrosis is called _________.
organization
_________ 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.
Regeneration
healing
Acute hepatic injury by a high dose of CCl4 would result in what type of response?
How about multiple small doses?
Complete regeneartion because the scaffold of reticular fibers still intact
ECM components disrupted so repair is by fibrosis
In adult tissues, the size of cell populations is determined by the rates of cell ________, differentiation, and death by ________
proliferation
apoptosis
The cell cycle consists of G1 (presynthetic), S (DNA ______), G2 (premitotic), and M (_____) phases. Quiescent cells are in a physiologic state called __.
sythesis
mitotic
G0
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
labile
Epithelial cells, hematopoeitic cells, mucous membrane cells, columnar of GI, etc...
stem cells
______ 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?
Quiescent
Parenchymal cells of the liver, pancreas, kidney, mesodermal cells, mesenchymal cells, such as fibroblasts and smooth muscle
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.
terminally differentiated
neurons
However, neurons can multiply in the olfactory bulb and the dentate gyrus (hipp.)
Benign cell proliferation can happen physiologically: ______ cycle, thyroid and _____ in pregnancy. Also can happen pathologicallay in the _____ and goitre
menstrual
breasts
prostate (BPH)
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
asymmetric
differentiation
The __________ of embryonic stem cells may be related to the expression of unique transcription factors, such as homeobox protein called
pluripotency
Nanog
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
restricted
bone marrow
Whenever there is a disease in the liver that blocks the normal replication of _______, the stem cells come into action (chronic hepatitis, cirrhosis).
hepatocytes
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 ____
niches
Herring
In liver fibrosis, ______ cell releases cytokines that promote proliferation (PDGF and ___), Contraction (ET-1), Fibrogenesis (____), and Chemotaxis (MCP-1, PDGF) of Stellate cells
Kupffer
TNF
TGF-Beta
Bone marrow ______ cells, depending on the tissue environment, can generate chondrocytes, osteoblasts, adipocytes, myoblasts, and endothelial cell precursors
stromal
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 ________
fibrosis
lungs
fibroblast
fibronectin (in blod, fluid, in tissues, part of mesenchyme)
___-_ inhibits degradation of ECM by metalloproteases
TGF-B
inhibits collagen degradation which would normally allow cells (PMNs, cancer cells) to migrate
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 __________
wounds
fibroblasts
epithelium
ANGIOGENESIS
_____ is important in angiogenesis and vasculogenesis (bv formation in early development). Cancer with the highest overexpression of this chemical?
VEGF (vascular endothelial growth factor)
Renal cell carcinoma
Two drugs used for chemo, Avastin and IFN, both work against what growth factor?
VEGF
Avastin is a monoclonal antibody to VEGF to slow tumor growth
____ is the growth factor most important in chemotaxis and proliferation of stellate cells. This is in the pathogenesis of what major disorder?
PDGF (platelet derived growth factor)
Cirrhosis
What GF do in wounds:
TGF-b: ______ migration, prolif., synthesis, __ influx
PDGF: _______ synthesis (liver), collagenase secretion*
FGF: everything EXCEPT _______ synthesis
VEGF: _______ ONLY
fibroblast
macrophage
collagen (collagenase slows down enzymes that mold collagen)
collagen
angiogenesis
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
T-cells
tumor
T-cells
mesenchymal
Describe the signal transduction pathways:
Tyrosine kinase system
cAMP
JAK / STAT
Steroid (transmembrane)
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
Unlike compensatory growth (liver/kidney), regeneration of pancreatic beta cells involves ____ ____ differentiation or the transdifferentiation of pancreatic ductal cells.
stem cell
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
compensatory
Compensatory growth results in restitution of functional mass by a synchronous wave of ______ replication followed by a synchronous wave of _____, stellate cell replication
hepatocyte
Kupffer
NO stem cells (oval cells)
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
IL-6
autocrine - TGF-alpha
paracrine - TGF-beta
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)
hydroxylation
lysine
triple
Procollagen outside the cell first has a ______ of propeptides. Next there is ____-_____ done by lysyl hydroxylysyl oxidation to become collagen
cleavage
cross-linking -> leads to tensile strength
____-____ syndrome results from a defect in collagen structure that may inhibit proteases... lysyl hydroxylase deficiency
Ehlers-Danlos
Vitamin C deficiency results in:
Failure to activate proline and lysine _______
Unhydroxylated procollagen peptides. Resulting helix is unstable - mostly affects bvs (bleeding - scurvy)
hydroxylation
____ ____ are needed in the ECM to provide recoil to skin, bvs, uterus, lungs
Elastic fibers
Elastin is a core protein rich in ____ and alanine. Cross-linking is done by lysyl _____. Damaged by aging and ____
proline
oxidase
sun
Fibrillin 1 is a gene with over 500 mutations (ex: _____ syndrome), which normally provides scaffolding for assembly of _____ during embryogenesis
Marfan
elastin
Octopia lentus is a condition of ______ syndrome. Lens is atopic and slips upwards and _____. They also typically have invagination of the _____
Marfan
laterally
sternum
Fibronectin is part of the ECM. It is a dual chain _______ associated with the _________ membranes of cells
glycoprotein
basement
Fibronectin helps in cell-matrix adhesion and cell migration via RGD. What is that?
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
________ 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.
Fibronectin
disulfide
_____ 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.
Laminin
endothelial
What type of collagen is in the basement membrane
Type IV collagen (non-fibrillar)
Extracellular matrix glycosaminoglycans (GAGs) include _______ and _______ acid
Proteoglycans
Hyaluronic
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
polysaccharides
permeability
FGF - fibroblast growth factor
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
water
WBC
T-cells
ECM highlights:
_______: RGD
Laminin: aligns sprouting _______ cells
_______: involved in wbc adhesion,signalling
Proteoglycans:promotes ________ of ECM
________ ___: lubricates cartilage in joints
fibronectin
endothelial
integrins
permeability
Hyaluronic acid
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 ________
glycoproteins
fibronectin (RGD)
laminin (cell-binding domain)
cytoskeletal
kinases
Repair by connective tissue is precipitated by damage to two tissue components: parenchyma (hepatocytes, renal tubular cells) and ______.
The endpoint is ______/scarring
scaffold
fibrosis
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
24
fibroblasts
macrophages
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)
sprouting
Hemangioblasts
endothelial
What are EPC and what do they do?
Endothelial progenitor cells - leave the bone marrow and go to sites for angiogenesis
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
basement membrane
endothelial
growth
smooth muscle cells
During angiogenesis from pre-existing vessel, recruit periendothelial cells
-pericytes for _______ (angiopoietin)
- smooth muscle cells for _____
capillaries
arterioles, larger vessels (PDGF for this)
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
migration
integrins
destabilizes
Angiogenesis is regulated by growth factors:
____ increased by TGF-alpha and beta, PDGF
angiopoietin helps recruit _____
PDGF recruits _____ _____ cells and synthesis of elastin for _____
VEGF
pericytes
smooth muscle
arterioles
Granulation tissue has what two components?
bvs and fibroblasts
Angiogenesis has leaky bvs which release _____ and fibronectin.
This forms a provisional _____ which allows fibroblasts and _______ cells to grow in
fibrinogen (turns to fibrin outside bvs)
fibronectin
endothelial
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)
VEGF
IL-1
TGF-Beta
______ promotes migration/proliferation of fibroblasts, synthesis of collagen and fibronectin by fibroblasts, decreased degradation of ECM by _________
TGF-beta
metalloproteinases
Granulation tissue serves as a substrate for ____ tissue formation: dense ______, shards of ______ tissue, plump fibroblasts becoming thin _______
scar
collagen
elastic
fibrocytes
At the end of ECM deposition of scar tissue formation, _______ recedes leaving a pale, _______ scar
angiogenesis
avascular
Organization is bad on ____ surfaces because they tend to stick together. Organization results in ______ formation
serous
collagen
Ex: organizing pneumonia
Net collagen accumulation, however, depends not only on increased collagen synthesis but also on decreased ________
degradation
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
metalloproteinases
zinc
tissue inhibitors of metalloproteinases
Some metalloproteinases:
Interstitial collagenases - cleave ____ ______ unequally
Gelatinases act on type __ collagen and fibronectin
Stromelysins act on most ____ components
triple helices
type IV
matrix
PDGF, EGF, IL-1/TNF all ______ collagenases
TGF-beta and steroids all ________ collagenases
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)
Surgical wounds, paper cuts, superficial stab wounds all heal with ____ intention. Blood clots in space, dehydration of surface forms scab
first
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 _____
neutrophils
mitotic
fusion
In first intention healing, after 48-72 hrs _______ are present, granulation tissue invades, then _____ forms with ____ orientation. Epidermis thickens.
macrophages
collagen
vertical
5 days after first intention wound healing begins, there is much _______ tissue. Maximal vascularization. ______ bridges the incision, epidermis full and mature
Granulation
Collagen
7-14 days after first intention wound healing begins there is much ______ and fibroblasts. Vascularization. What cell type? Edema gone
collagen
leukocytes
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
appendages
tensile
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 __________
fibrin
inflammatory
myofibroblasts
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 __-__%
10%
3 months
70-80%
Factors that slow wound healing: infection, early _____, foreign bodies remaining in wond, location (____ injuries slowly heal, _____ injuries heal quickly due to vascular supply)
motion
foot
face
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
anorexia
atherosclerosis
collagen
Deficient scar results from inadequate ______ tissue formation. Dehiscence after _____ surgery. Athersclerotic/neuropathic ulceration of feet (what condition?)
granulation
abdominal
diabetics don't feel noxious stimuli due to neuropathy, healing slowed from athersclerosis
Contractures are poorly healed wounds. Happens most often in palms, soles, and ______ ____.
Anterior chest
ESPECIALL burns
_____ is excessive wound repair. Common in African Americans. Very dense h______ collagen
Keloid
hyalinized
____ ____ is a condition when even normally sutured wounds have the granulation tissue go wild. Grows into a nubbin that needs to be cut off.
Proud Flesh
Fibromatoses result from incisional scars or trauma and are typically called "______". Tumor most commonly seen in abdomen of ______ women. Massive proliferation of HUGE fibroblasts.
desmoids
pregnant
Joint destruction in Rheumatoid Arthritis due to _______ going crazy and destroying things
collagenases
Actibation of ______ cells in the liver can cause fibrosis and collagen deposition in what conditions involving the liver?
stellate
Alcoholism, Hepatitis B and C
When macrophages eat silica it results in ______ in lung which releases cytokines. You get chronic interstitial ______ (ex: pneumoconiosis)
asbestos
fibrosis
Things that cause fibrosis:
Ionizing radiation: lungs, GIT, kidney
Chronic pancreatitis:
replacement of _____ by fibrosis
Adhesive pericarditis
Organizing _________
______ obstruction due to fibrous bands
acini
pneumonias
bowel