Block V, Week IV
Terms
undefined, object
copy deck
- In regards to cellular proliferation, cells in the body can be classified into three categories. What are they?
-
1. labile
2. stable
3. permanent - What are the four major phases of the cell cycle?
-
1. M phase
2. G1 phase
3. S phase
4. G2 phase - What is one additional phase of the cell cycle and when is this seen?
- G0 - cells remain quiescent after M phase and do not divide unless stimulated.
- G1, S and G2 phases are collectively known as ?
- interphase
- A non-dividing hepatocyte working in the liver would be in which phase of the cell cycle?
- Go
- In which cell phase are there duplicate copies of DNA?
-
DNA synthesized in S phase
G2 is where duplicated DNA is found - A tissue that is constantly in the state of renewal would have which type of cell population?
- labile
- In which body tissues would labile cells be most commonly found? (8)
-
1. Surface epithelia (skin)
2. oral cavity
3. vagina
4. cervix
5. lining mucosa of excretory ducts of glands in the body
6. GI tract
7. uterus
8. cells of the bone marrow and hematopoietic tissues - how is the stem cell population maintained?
- for each division: one daughter cell becomes a stem cell, the other undergoes terminal differentiation.
- What are the different phases of the cell cycle for a labile cell?
-
M
G1
S
G2
(NO G0) - do labile cells need stimulation to replicate?
- No, they do not enter into the G0 phase of the cell cycle
- Which cell type is normally found in the G0 stage of the cell cycle?
- Quiescent cells - they renew very slowly but are capable of rapid renewal when stimulated.
- give some examples of quiescent cells
-
1. parenchymal cells of liver, kidney, pancreas
2. mesenchymal cells such as fibroblasts and smooth muscle cells
3. vascular endothelial cells - what factor determines whether or not regeneration will be organized or haphazard?
-
basement membrane intact - organized regeneration
Basement membrene destroyed -haphazard regeneration - Which stage of the cell cycle are permanent cells found in?
- Permanent cells are totally out of the cell cycle. They have lost all capacity for cell regeneration.
- give three examples of permanent cells
-
1. nerve cells
2. cardiac muscle cells
3. skeletal muscle cells - Although permanent cells do not divide, what do they do as maintenance?
- permanent cells renew their organelles
- What is the main theme surrounding molecular signals that mediate proliferation and differentiation?
- phosphorylation
- what is an autocrine growth promoting signal?
- a growth factor secreted by a cell to stimulate its own growth
- differentiate between paracrine and endocrine growth promoting signals.
-
paracrine - growth factor secreted into the immediate environment to stimulate local cell growth.
endocrine - growth signal secreted into the bloodstream to effect distant cell types - what are the three receptor systems that mediate proliferation, migration and altered gene expression in the healing process?
-
1. Tyrosine kinase
2. G protien coupled receptors
3. Integrin receptors - what is special about the structure of the G protien?
- one G protien has 7 trans membrane spanning receptors. Each receptor can bind a chemokine.
- where is the integrin receptor found and what does it bind to?
- integrin receptor is bound to molecules in the ECM - it creates attachment sites for the actin cytoskeleton
- which two pathways can integrin receptors activate?
-
1. MAP kinase (via a phosphorylation cascade)
2. PIP3K pathway - Which pathway is also known as the "growth factor" receptor pathway?
- The Tyrosine kinase receptor is also known as the growth factor receptor because it binds to growth factor.
- What happens in the tyrosine kinase pathway when growth factor binds to the receptor?
-
growth factor binds,
receptors dimerize and autophosphorylate,
a protein phosphorylation cascade is activated, which results in stimulation of the quiescent cell to undergo replication. - growth factor binds to its receptors: where are these receptors found (on cell membrane or inside cell)
- the receptors can be located located on the plasma membrane or inside the cell.
- what are two examples of growth factor receptors found inside the cell?
-
steroid receptors
retinoic acid receptors - what are the 3 protien families that transduce signals to the nucleus?
-
1. GTPases
2. PI3K (phosphoinositol-3 Kinase)
3. Phospholipase C - what are two powerful subfamilies/protiens of GTPases that, when used to initiate the MAP kinase cascade, cause massive signals to divide?
-
1. Ras-
2. Rho- - Why is Ras so important in the cellular division process?
- when the Ras gene is mutated cancer is often a result. 33% of human cancers have a mutated Ras gene.
- which type of receptors indirectly activate GTPases? (2)
-
tyrosine kinase receptors
integrin receptors - PI-3K has pathways dependant and independent of the MAPK pathway. Which receptor pathways does PI-3K use when undergoing the MAPK pathway? (2)
- integrin or tyrosine kinase receptor pathways are used by PI-3K when it is undergoing the MAPK pathway.
- What is the phospholipase C pathway activated by?
- chemokine receptors (found on endothelial, epithelial, mast cells and leukocytes) activate the phospholipase C pathway.
- phospholipase C hydrolizes __1__ into __2___ and __3___.
-
1. PIP2 (phosphoinositide bisphosphate)
2. IP3 (inositol trisphoshate)
3. DAG (diacyl glycerol) - what is the function of IP3?
- IP3 stimulates Ca++ release and together with DAG activates PKC. PKC then activates MAPK.
- the three major structural components of the ECM are:
-
1. collagens
2. glycoprotiens
3. proteoglycans - what role does the ECM play in cell proliferation of organs?
- The ECM controls cell proliferation and stops proliferation when an organ is complete.
- Discuss collagens in relation to degradation
- collagens have a very long 1/2 life, they are very resistant to degradation.
- The Adhesive proteins (2) function to link the ECM components to one another and to cells. What are these protiens?
-
1. Fibronectin
2. Laminin -
Fibronectin associates with the cell surface via _____1___ receptors, whereas laminin associates with the cell surface via ____2_____ receptors.
3. what are the implications of this? -
1. integrin receptors (major player)
2. laminin receptors
3. laminin does not have as much functional capacity as fibronectin. - which cell types produce fibronectins? (3)
-
1. fibroblasts
2. monocytes
3. endothelial cells - what is the role of proteoglycans in wound healing?
- proteoglycans tend to be the early organizers in wound healing.
- once the MAPK finally transmits the signal for growth to the nucleus, early growth-regulated genes are produced. name 4 of these early growth regulated genes.
-
1. c-fos
2. c-jun
3. c-myc
4. egr-1 - what is significant about early growth regulated genes?
- many are transcription factors and are involved in the regulation of cell synthesis, and most of them are oncogenes
- what is a late growth-related gene?
- a gene whose mRNA starts to increase in mid G1 or at the G1-S boundary
- what is a major difference between early and late growth related genes?
-
the early genes are induced in the absence of protien synthesis,
the late genes need new protien synthesis for induction. (These protiens are products of early growth regulated genes) - in general, what are cyclins?
- cyclins are major positive regulators of the cell division cycle.
- what is the result when cyclins form a complex with Cdk (cyclin dependant kinases)?
- the cyclin-cdk complexes are master regulators of the major cell cycle transitions.
- what is the restriction point and where in the cell cycle is it found?
- the restriction point is the point-of-no-return for the cell: bypassing it means committing yourself to complete the division cycle. It is found at the G1/S phase border
- what are the two major mechanisms by which the cdks can be regulated?
-
1. phosphorylation (must be phosphorylated to be active)
2. regulation by specific inhibitors (cdkI) -
1. at what phase of the cell cycle do cdkIs influence?
2. significance? -
1. cdkIs arrest the cell in G1
2. arresting the cell gives the cell time to undergo processes such as terminal differentiation, cellular senescence or damaged DNA repair. - what is the connection between cdkIs and p53?
- p53 regulates several cdkIs. Normally p53 will increase cdkIs - this gives the cell a chance to repair damaged DNA. When p53 is mutated the cdkIs aren't activated and therefore don't arrest the cell in G1
- Rb (retinoblastoma gene) is regulated by?
- cyclin-kinase complexes.
- What kind of a gene is Rb?
- Rb is a tumor suppressor gene (a negative regulator that acts in the G1 phase)
- what is the result of the pRb being unphosphorylated?
- an unphosphorylated pRb stops cell proliferation by binding to and inactivating transcription factors.
- what is the result of the pRb being phosphorylated?
- a phosphorylated pRb frees up transcription factors to function in cell division.
- which type of damage results in a fibrous scar?
- destruction of the basement membrane results in a scar
- when is primary healing of the skin observed?
- when a surgeon closely approximates the edges of the wound. this minimizes myofibroblast action and allows regeneration of the epidermis
- when is secondary healing of the skin observed?
- secondary healing occurs when a large area of hemorrhage and necrosis cannot be completely corrected.
- why is the scarring so bad in secondary healing?
- the myofibroblasts contract the wound and scarring repairs the defect.
- what happens when a liver injury occurs and the stroma is still intact?
- the liver parenchymal cells regenerate and function is restored.
- what happens when a liver injury occurs and the stroma is damaged?
-
broad collagenous scars develop (cirrhosis).
Cirrhosis obstructs blood and bile flow, resulting in portal hypertension and jaundice.
Hepatocytes do regenerate, but they are disconnected and therefore functionless. - give an example of liver injury that leaves the stroma intact.
- fulminant viral hepatitis, acute chemical injury (drug toxicity)
- give an example of liver injury that damages the stroma.
- alcoholism, chronic hepatitis
- in the kidney which area has the most regenerative capacity?
- the cortical (proximal) renal tubules
- how does regeneration of the proximal tubule occur?
- existing cortical tubular cells undergo regeneration. (no reserve cells)
- what is tubulorrhesis?
-
rupture of the tubular basement membrane.
varied results (some tubules regenerate, some undergo fibrosis). Have a focal loss of nephrons. - what parts of the kidneys do not regenerate? how does an injury to this area heal then?
-
glomeruli.
heal via scarring - describe the regeneration capacity of medullary tubules. Significance?
-
little regeneration capacity.
necrotic tubules fall into urine; fibrotic healing results in urinary obstruction. - what dictates the regeneration capacity of the lung's epithelial lining?
- the underlying ECM framework cannot be destroyed.
- what is the result of lung alveolar injury which includes the basement membrane?
-
incapacitating fibrosis.
alveoli not injured to this extent have increased regeneration potential. - how does myocardial necrosis heal?
- heals by formation of granulation tissue and eventual scarring
- what is the functional significance of scarring in parenchymal organs?
- scarring NEVER improves function - results in a modified organ organ structure
- what is rigor mortis and how is it used in forensic pathology?
-
chemical change in muscle
used in time estimation and to reveal post-mortem movement of the body - what is livor mortis and how is it used in forensic pathology?
-
gravitational settling of blood
Used in:
time estimation
post mortem movement
note: blood doesn't pool in areas where there is pressure - what is stippling indicative of?
- a close range shot (pattern left on skin in a 4-6 inch pattern)
-
where are contusions:
1. more common
2. more extensive -
1. soft tissue with high vascularity (ie. eyelids)
2. fatty tissue -
what is the general time frame of contusion appearance?
1. few minutes
2. few hours
3. few days
4. week or more
5. fading (1-2 months) -
1. slight swelling
2. light blue-red
3. dark purple
4. yellow green
5. light brown -
in relation to contusions:
1. how long does hemosiderin stay in the macrophages?
2. for about a week you can see this compound if you use Prussian blue and Gmelin blue? -
1. ~24 hrs
2. hematoidin (yellow intracellular granules) - a brush burn is what kind of burn and where is it most commonly seen?
- second degree burn - seen commonly in MVA victims
- in which injury would you see tissue bridges?
- lacerations (caused by a blunt object, not a clean cut)
- in a MVA where are the two most common places the aorta will rupture?
-
1. ligamentum
2. diaphragm - what is the difference between an incised wound and a stab wound?
-
incised - longer than it is deep
stab - deeper than it is long - where would most defensive wounds be found?
- upper extremity (use arms to protect face)
- what would a lower limb injury indicate?
- sexual assault (indicates victim was on the floor)