Professional Documents
Culture Documents
Atrophy :
E.g. a broken arm will be fixed for 2-3 months , and the muscles of that arm will
undergo atrophy , due to decrease in the size of the cells due to decrease of
the organelles , with minimal if any apoptosis .
But after physiotherapy , it will be back to its normal form in no time.
E.g. a paralyzed arm , for about 2-3 years , the cells are not going to be used for a
long time , atrophy might be associated with more and more apoptosis for
these cells .
Hypertrophy :
- we use it to note the enlargement of the size of the organ , but later on we
discovered that some organs are going to increase in size not due to the
increase of the size of the cells , but due to the number of the cells
( hyperplasia not hypertrophy ) , but unfortunately we still use it as in the past :\
- So , if we take the heart for example , our heart fibers are going to contain
actine as well as the myosin light chains , and these can be from different types
depending on the genes are transcribed ,
so in the fetal life , we are going to have different myosin and actually actine
filaments than we have in our adult life , because the environment of the fetal
heart is different from that of the adult heart .
The fetal heart there is no high loud because there is no physical effort
floating in a weightless condition
so the effort of the heart is minimal
But there is a problem in the fetus , because we are going to get enough
oxygenation of the heart , because the blood is not going to be oxygenated in
the lungs as adults ( The blood saturation of oxygen is about 99% in the adults ),
But the fetus is going to have the oxygen from the maternal arteries , not from
the lungs themselves , so the heart will be affected will less oxygen ( just like it
is hypoxic )
So those fibers are going to be adapted more to that decreased concentration
of oxygen and actually they can coop with that .
When the heart is hypertrophic , these cells have to have more work load yet
they might also be affected by the hypoxia as we mentioned before ,
They need more oxygen , they have less oxygen themselves and they might be
more vulnerable to hypoxia as compared to the normal non hypertrophic
myocytes .
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- because the hypertrophic cell are thick , so they need more oxygen , and the
chance to suffer from hypoxia is more as well ,
So in order to have fibers that can tolerate with hypoxia , the hypertrophy will be
associated with switching on certain genes for the fetal type proteins , This will
make the heart adapt with the hypoxia in better way but it will be more vulnerable
to injury than the normal muscle fibers .
- Hypertrophy in the heart , the ventricle will be thick , and you can guess that the
remarkable thickening of the myometrium of the heart , make in tough to get
enough oxygen, so infraction is more likely to happen .
- And the hypertrophic muscles will have enlarged nuclei , what we referred to as
box car nuclei , because of their enlarged appearance due to protein transcription
and synthesis in the nuclei of the muscle fibers of the heart .
- for cells that can divide , it is better for them to go for adaptation by increase
the number of cells in that condition , and this is what we referred to as
hyperplasia .
Hyperplasia :
Proliferation of the
cells
Differentiation , shedding
apoptosis
Constant
cell pool
- so in order to have the normal anatomy and normal histology and normal
functionality , we have to have constant number of cells in our tissue\ organ ,
and that is going to be controlled by also genes .
- so we have genes that are responsible for the proliferation , and genes that are
responsible for differentiation and genes that are responsible for apoptosis as
we mentioned .
- so in order to increase the sizes of tissues per tissue volume , we have also to
manipulate the genetic control over that population .
- so again that is not just a reflex enlargement or a reflex increase in the number
of cells , its also include certain genetic re-arrangement that will maintain more
cells in that tissue .
- the increase of the number of cells can be either physiologic or it can be
compensatory or it can be pathologic :
1. Physiologic :
E.g. Breast feeding , in pregnancy , the endometrium after each cycle
this is hormonally dependent , the estrogens affecting certain genes that
will lead to increase proliferation of these cells as to have more cells to
perform more function
2. Compensatory :
E.g. liver transplantation , we go to partial hepatic removal , and the
remaining liver is going to undergo hyperplasia which is adaptational
compensatory hyperplasia , its not pathological .
3. Pathologic :
if the cells are not there to perform a specific function , this will be
pathologic hyperplasia , especially when its not controlled by genes .
- So in order to increase the number of cells , we have to activate \ switch on
certain genes responsible for proliferation or inactivate genes responsible for
apoptosis , and this again should change the control of genes that are
responsible for cell cycle .
Signaling activation of certain genes that are going to increase the cellular
proliferation increase the number of cells in that tissue
Pathological hyperplasia :
E.g. prostate hyperplasia :
- the function of the prostate is to contribute with the seminal fluid and in
the sexual activity to prevent retrograde ejaculation (the semen go to
the urinary bladder not the ejaculatory duct ) .
so the function of the prostate is going to be maintained by the
physiological demands and the hormonal stimulation because its not
functioning all day long ( unlike the heart , so the heart doesnt need
tropic hormone as the prostate does ) .
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so the corpus lutium will undergo involution ( vanish ) , so the level of the
hormone decreases , and the endometrium wont have any hormonal
support , so that endometrium will undergo shedding , apoptosis and
necrosis !
the surface epithelial cells will undergo apoptosis .
the spiral arteries will be coiled , and that might be associated with ischemic
change of the Stroma itself , so what happened is that is physiological
necrosis !
its not legal to call it that way :P
but this is what it is ,
its not apoptosis , because we have death of scattered cells \ groups of cells,
we have an inflammatory reaction, but this is physiological not pathological !
and there is no term to call that condition with , its not necrosis as its not
pathological . and it exceeds what apoptosis is all about ,
this all will lead to menstruation , and the cycle will be repeated again.
Q] is that cancerous ?
NO , not yet cancerous .
but having endometrial hyperplasia for a long time , this will create a
suitable circumstances for a mutation to emerge in those rapidly
proliferative cells leading to carcinoma .
The more cells we have , the more the chances for a mutations leading to
cancer , especially if these cells are proliferative cells .
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Q] what are the mechanisms involved in the regulation of the normal cell
population in the thyroid gland ?
TSH , is going to activate the functional activity of the cells leading to
increase their secretion of T3\T4 on one hand , and on the other hand ,
increase the proliferation of the epithelial cells of the thyroid .
T3\T4 are going to have negative feedback on the pituitary gland
if we have low levels of T3\T4 , the TSH will continue to be produced
So this process is auto regulated .
the TSH will be inhibited from the normal cells but the tumor is going
to continue the secretion of TSH.
this will lead to elevation of the level of T3\T4 and also to hyperplasia.
2. TSH-like substance affecting the receptors n the thyroid cells , for
example : antibodies .
so the antibodies will continuously stimulate the cells of the thyroid
leading to increase T3\T4 secretion that will lead to thyrotoxicosis ,and
also increase in the cellular rate of proliferation leading to diffuse
hyperplasia
that is called clinically Graves disease
3. Iodine deficiency , so T3\T4 will start to decrease , but this is a slow
process , so as soon as the level of T3\T4 are going to decrease , TSH
will increase leading to increase the proliferation of the thyroid gland ,
so increase the cells of the gland .
they will pick the iodine more efficiently and the level of T3\T4 might
get back to normal .
this will be associated with new thyroid state .
so more iodine deficiency , more proliferation of the glad ( become
larger ! )
eventually , these cells are not going to respond to TSH in the same
way , so in certain areas , there will be more proliferation than the
other areas , forming nodular goiter .
the gland will increase in size as long as there is iodine deficiency with
that patient .
the gland might be as big as it become retro-sternal !
nowadays , we dont see this anymore .
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Metaplasia :
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- Particles carried by air we breathe will stuck to mucin on cilia and cilia will
get that mucus escalated and delivered to nasopharynx where its going to
be swallowed.
- By reaching alveolus , air will be clean and no particles will be find even
though bacteria , and that cell lining will allow the diffusion of gas .
so morphology has to keep up with function and environment .
- although all of these cells have same genes , different genes will be
expressed in order to have different morphology and functionality in keeping
with environment .
- if a person started to smoke and this will be associated with deep delivery
of those chemicals of those gases to respiratory tract not only nasophaynx,
he is going to inhale smoke and that is going chemically and mechanically
irritate respiratory epithelium .
Q] So is metaplasia adaptational ?
Yes
Q] Reversible?
on the level of tissue yes , reserved cells when they differentiate in the
suitable environment and with the disappearance of noxious stimuli , will
have cilia
Q] Precancerous?
No, because they are mature cells which replaced another type of mature
cells .
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Q] is metaplasia precancerous ?
NO.
however , lets suppose a patient is smoking for years , he is going to have a
well developed squamous metaplasia of his respiratory tract .
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- this actually happens all the time but fortunately these cells that are going
to have abnormal genes either that genetic abnormality is so profound to
lead to severe metabolic abnormality leading to cell death APOPTOSIS or
viability of these cells is maintained with abnormal genes which can be
detectable and eliminated by p53 leading to APOPTOSIS .
but eventually after so many tries for many years , one of these cells is going
to have the right mutation allowing it to escape apoptosis and immune
system and its going to proliferate with irregular maturation , NO
MATURATION , DYPLASIA .
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- Dysplasia can be :
1. mild , we didnt have maturation at early stage and we treated it
2. Moderate , abnormal maturation extends to middle third of lining
epithelium
3. Severe , involving the whole lining from deep to surface
Q] Is dysplasia adaptational ?
no . Its a problem , it doesnt serve any physiological benefit . Its a reflect to
a problem in genes .
Q] Premalignant ?
yes.
Q] Reversible ?
at the level of tissue yes it is at early stages of mild dysplasia , at the level of
cell no its not .
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Cellular aging :
Theological approach
biological approach
Q] can we be immortal ?
theoretically yes as long as we have DNA templates and resources we can
regenerate everything from scratch but we dont
Q] in another way , why do we live ?
to pass our genetic material to next generation !
- we live long enough theoretically and practically to have the ability to pass
our genes to the next generation and when we are supposed to have done
that genes are not going to sustain and repair organism anymore , theyll let
us die </3
this doesnt apply individually , its applied on race level . i.e. if someone
didnt had children that doesnt mean that hes going to live until he does .
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- genes are not going to repair our damaged cells and DNA as long as we
have fulfilled our purpose
- at the age of 20 we are supposed to have passed our genes and then the
effect of aging will appear
- But later on , other genes on our system will deliberately choose not to
repair .
- As our cells are going to divide telomere will become shorter and shorter
and after the vanish of telomere if the cell decided to divide it will die , so
why telomere becomes shorter ?
because gene responsible for telomerase will become gradually inactivated ,
and thats the normal state !
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- If the gene had mutation telomere will not get shorter and cells will
become immortalized .
- So our genes will decide not to repair DNA and not to reproduce telomere
and this will be associated with a gradual but deliberated decrease of the
abilities of our cells to repair themselves and decrease in the ability to divide
until theyll eventually age and organism will die .
2.
3.
4.
- aging process and rate will differ from one person to another
SLIDE 113 :
Telomerase activity will decrease in somatic cell , as long as they live and
divide and reach 50 times if division telomerase will vanish and any try to
division will fail and cell will die .
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- When they cloned sheep dolly it aged and died before the supposed time ,
because they used somatic cells in cloning which already had decreased
activity of telomerase
Q] What if someone had a baby at the age of 60 ?is that going to affect its
baby telomerase activity ?
No its not , because germ cells have constant activity of telomerase activity.
- Theyll continue to proliferate because they have long life span but on the
level of individual cell of course its going to die
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