The intracellular accumulation of substances

The intracellular accumulations include the

1. Lipids  they are acted on by the liver so they can accumulate there
they can also accumulate in the circulation in the wall of the blood vessels
and this is atherosclerosis

What causes the liver to have intracellular accumulation?

Lack of the receptors for the lipoproteins that carry the lipids
Etc
Etc

What happens in proteins?

Errors in post-translational modifications in the ER and if this process fails
there would be a long protein without folding due to the lack of the process
of folding to secondary and teriary structure and an examples of that is
Alpha 1 antitrypsin deficiency which is a protease that breaks down the
proteins especially the ones produced by the neutrophils & macrophages.?
The protease are regulated by Alpha 1 antitrypsin and if there is a
deficiency there would be an accumulation of protease and this will cause
the protease to eat the tissue resulting In destruction of the tissue in the
liver which could cause things like liver cirrhosis

This could also happen in lack of enzymes that play part in digestion which
would cause lysosomal storage diseases.. another example is glycogen
storage diseases
 Another scenario would be where the body is incapable of getting rid of the
substances with the help of macrophages that digest them. The
macrophages would be unable to digest in and it would accumulate inside
of it.. an example of that is carbon, the carbon particles would get through
to the alveoli because theyre very small and the alveoli has alveolar
macrophages but it would be able to digest the carbon
Also, Iron, is an indigestible material, excess iron is stored in the body but if
the excess surpasses the limit , Hemocydrin ladding macrophages

Another cause is Streatosis ( which is a fatty liver ), this firstly could be through
alcohol
This is the deposition of the lipids in the liver
Lipogenesis is stimulated and lipolysis is inhibited
It could develop from non-alcoholic diseases like diabetes and obesity where
there is hyperlipidemia
This could also happens through carbon tetrachloride which is a toxic
substance and in patients who are malnourished.. here there is a reduced
synthesis in proteins and among these proteins are apoproteins
Hypoxia is another example because it inhibits fatty acid oxidation when the
lipids are oxidized the body is unable to get rid of them..?
Starvation is also a cause?

The commonest site of finding intracellular atherosclerosis plaque is in the liver

and the blood vessels
Intracellular lipid accumulation can be found in the eye lids and

Indigestible material: pigments

Exogenous pigments – carbon in lung = anthracosis

Endogenous pigements
Billirubin since it is produced by the body itself and if the body to use it or
unable to get rid of it it will accumulate in the body and that’s why you see
bilirubin patients with a deposition of bilirubin in the sclera and the mucous
membarane because of the deposition of the bilirubin

Same happens with melanin where some patients have melanocyte collection
where out of his body contour you find a black area  it can accumulate in the
eye and other points in the body

It could also be due to hemosiderin following bleeding there would be a brown

area where ..? due to partially digested iron which is toxic because it is the
ferric form which is the toxic form
It can destroy the cardiac muscles, the spleen, the pancreas

In the lung slide the blacker parts are due to deposition of carbon because the
patient inhaled carbon and its an example of an exogenous pigment

The brown color are remnants of RBC—partially digested

And this is an example of endogenous pigments

A playing part is the presence, deposition of calcium we can see it as an

intracellular accumulate  which is extracellular
Regulation of calcium maintains the bones homeostasis
But sometimes the calcium may become excess in the circulation and when
that happens it will go to the tissues and normally one of the common tissues
it goes to is the bones but it may also be deposited in a normal tissue and this
is called metastatic calcification
On top of that, calcium has a tendency to accumulate in damaged tissue in
cases of necrosis or atherosclerosis and this is referred to as dystrophic
calcification
However, calcium is normal in dystrophic calcification because it is eager to
deposit but it is high in cases of metastatic calcification because it isn’t eager to
deposit as with the dystrophic
Causes of Metastatic Calcification
 Excess PTH
 Destruction of bone  due to excessive osteoclastic activity
 Vitamin D disorders
 Renal failure

Antiapoptotic factors are PCL2 and PCLX these are stimulated whne we don’t
want apoptosis
But when we do want it we have the BAX&BADS..? which will go to the
mitochondria and a cause a leak of cytochrome which will cause a cascade
The other mechanism is through the direct stimulation through cytocases
which is through cytokines that go and directly stimulate cascade 3,6 and 7…??
Ligand will cause a direct effect to the membrane causing damage causing
calcium release and stimulating of (Casphase???)