Welcome to sheet 5 pathology! the last lecture of cell injury by Dr.Manar^-^
Intracellular accumulations :accumulations of certain materials in cells.
▪ Four mechanisms for deposition of materials inside cells (four types of
materials):
Inadequate removal (accumulation) of a normal substance (fatty change
in the liver)
Fats/Triglycerides are known to be endogenous products that are normally
present in many cell types,so when there is inadequate removal of these
substances,they accumulate.
Regarding triglycerides,they are normally transported outside of the cell by
binding to proteins (the structure produced may be named lipoprotein ,or
apolipoproteins).So,if any defect happens to this transport,like for example
having lack of proteins transporting lipids - and we did mention this when
explaining cell injury mechanisms,one of them being decreased protein
synthesis - ,lipids will accumulate (figure 1👇)
Accumulation of an abnormal endogenous protein due to folding defect
(a1-antitrypsin deficiency, accumulation of misfolded proteins in
endoplasmic reticulum.)
A1-antitrypsin gene ,which encodes a1-antitrypsin enzyme,can be affected
by a mutation that leads to production of abnormally folded a1-antitrypsin
proteins,meaning that these proteins become non-functional,unable to be
secreted outside the cell,then they accumulate in cells.In peripheral blood
or tissue, a notable deficiency of this protein will be seen,because of its
abnormal shape that can’t be secreted outside the cell so depositing inside
them. (Figure2 👇)
Failure to degrade a metabolite due to inherited enzyme deficiencies
(lysosomal storage diseases, glycogen storage diseases)
What happens here is that we are having deficiency of lysosomal enzymes
or glycogen-metabolizing enzymes due to a genetic mutation, leading to
,accumulation of for example glycogen or other lysosomal metabolic
products that normally get degraded inside the cell. (Figure3👇)
Deposition and accumulation of an abnormal exogenous
substances(Carbon in lungs and Silica).
Carbon is an exogenous substance in nature(not a natural mineral that is
produced in our bodies),so it gets deposited by taking it from outside,there
are many ways such as smoking,it causes carbon deposition in lungs,also
living in settings with polluted air may lead to carbon deposition in
lungs.(figure4 👇)
CLINICAL GLIMPSE:when asking for a lung biopsy then noticing heavy
carbon deposition in lungs,the history of the patient will definitely include a
strong cause,such as smoking ^-^
Also Silica is an another example of accumulating exogenous materials.
This diagram above summarized all aforementioned mechanisms.
, AND NOW,LET’S TALK ABOUT THE SUBSTANCES ABOVE IN MORE DETAIL!!
❖ FATTY CHANGE-STEATOSIS
- The most common affected tissue is LIVER since it is the most organ
involved in fat metabolism ,but also can be seen in
HEART,KIDNEY,MUSCLES).
-It is due to the deposition of Triglycerides in the cells, as you see here the
fatty position is manifested by white fatty droplets inside the cells which
vary in their sizes (some of them are macro and others are micro ).
-Alcohol abuse and DM +obesity are the
most common causes of fatty liver disease in industrialized
countries[RECORDED LEC]
- Causes of fatty liver depend on geographic locations,for example in
Western countries alcohol abuse is the most common cause,whereas in our
part of the world DM+obesity is the most common cause.[LIVE LEC]
- Histologically,fatty cells in a liver section appear as empty white vacuoles
inside the cell,replacing the nucleus to the cell periphery.
- Degree of steatosis may vary between mild steatosis and severe
steatosis,depending on the severity of for example alcohol
consumption,how obese the patient is,duration of diabetes,…
A histological section of the liver
illustrating the presence of fat.
( triglycerides)accumulated in cells
Intracellular accumulations :accumulations of certain materials in cells.
▪ Four mechanisms for deposition of materials inside cells (four types of
materials):
Inadequate removal (accumulation) of a normal substance (fatty change
in the liver)
Fats/Triglycerides are known to be endogenous products that are normally
present in many cell types,so when there is inadequate removal of these
substances,they accumulate.
Regarding triglycerides,they are normally transported outside of the cell by
binding to proteins (the structure produced may be named lipoprotein ,or
apolipoproteins).So,if any defect happens to this transport,like for example
having lack of proteins transporting lipids - and we did mention this when
explaining cell injury mechanisms,one of them being decreased protein
synthesis - ,lipids will accumulate (figure 1👇)
Accumulation of an abnormal endogenous protein due to folding defect
(a1-antitrypsin deficiency, accumulation of misfolded proteins in
endoplasmic reticulum.)
A1-antitrypsin gene ,which encodes a1-antitrypsin enzyme,can be affected
by a mutation that leads to production of abnormally folded a1-antitrypsin
proteins,meaning that these proteins become non-functional,unable to be
secreted outside the cell,then they accumulate in cells.In peripheral blood
or tissue, a notable deficiency of this protein will be seen,because of its
abnormal shape that can’t be secreted outside the cell so depositing inside
them. (Figure2 👇)
Failure to degrade a metabolite due to inherited enzyme deficiencies
(lysosomal storage diseases, glycogen storage diseases)
What happens here is that we are having deficiency of lysosomal enzymes
or glycogen-metabolizing enzymes due to a genetic mutation, leading to
,accumulation of for example glycogen or other lysosomal metabolic
products that normally get degraded inside the cell. (Figure3👇)
Deposition and accumulation of an abnormal exogenous
substances(Carbon in lungs and Silica).
Carbon is an exogenous substance in nature(not a natural mineral that is
produced in our bodies),so it gets deposited by taking it from outside,there
are many ways such as smoking,it causes carbon deposition in lungs,also
living in settings with polluted air may lead to carbon deposition in
lungs.(figure4 👇)
CLINICAL GLIMPSE:when asking for a lung biopsy then noticing heavy
carbon deposition in lungs,the history of the patient will definitely include a
strong cause,such as smoking ^-^
Also Silica is an another example of accumulating exogenous materials.
This diagram above summarized all aforementioned mechanisms.
, AND NOW,LET’S TALK ABOUT THE SUBSTANCES ABOVE IN MORE DETAIL!!
❖ FATTY CHANGE-STEATOSIS
- The most common affected tissue is LIVER since it is the most organ
involved in fat metabolism ,but also can be seen in
HEART,KIDNEY,MUSCLES).
-It is due to the deposition of Triglycerides in the cells, as you see here the
fatty position is manifested by white fatty droplets inside the cells which
vary in their sizes (some of them are macro and others are micro ).
-Alcohol abuse and DM +obesity are the
most common causes of fatty liver disease in industrialized
countries[RECORDED LEC]
- Causes of fatty liver depend on geographic locations,for example in
Western countries alcohol abuse is the most common cause,whereas in our
part of the world DM+obesity is the most common cause.[LIVE LEC]
- Histologically,fatty cells in a liver section appear as empty white vacuoles
inside the cell,replacing the nucleus to the cell periphery.
- Degree of steatosis may vary between mild steatosis and severe
steatosis,depending on the severity of for example alcohol
consumption,how obese the patient is,duration of diabetes,…
A histological section of the liver
illustrating the presence of fat.
( triglycerides)accumulated in cells
