This document discusses intracellular accumulations, which occur due to metabolic derangements within cells. It defines intracellular accumulations and categorizes them as normal cellular constituents or abnormal endogenous or exogenous substances. Accumulations can occur in the cytoplasm or nucleus. The document then discusses the processes and sites of accumulations, including accumulation of lipids (resulting in steatosis), cholesterol, proteins, glycogen, and pigments. Specific diseases associated with accumulations of these substances are provided as examples.

1. INTRACELLULAR
ACCUMULATIONS
DR. USMAN NASIR

2. DEFINITION:
Accumulation of abnormal amounts of various
substances due to manifestations of metabolic
derangements in the cell.

3. CATEGORIES:
1. Normal cellular constituents
e.g., water, lipids, CHO
2. Abnormal substances
a) Exogenous
e.g., mineral or products of infectious agents
b) Endogenous
e.g., products of abnormal synthesis or metabolism

4. SITES:
a) Cytoplasm (phagolysosomes)
b) Nucleus
SOURCE:
. Produced by the affected cell
. Produced elsewhere in the body, but stored in the
cell

5. PROCESSES OF
ACCUMULATIONS
FOUR PROCESSES
1. Production of a normal endogenous substance at
normal or increased rate, but the rate of metabolism is
inadequate to remove it.
e.g., fatty liver, reabsorption protein droplets in tubules
of kidney

6. 2. Accumulation of an abnormal endogenous substance
(product of mutated gene) due to defects in protein
folding, transport & inability to degrade abnormal proteins
efficiently.
e.g., accumulation of mutated proteins in liver cells

7. 3. Accumulation of normal endogenous substance due
to inherited defect in enzymes required for metabolism
of the substance.
e.g., Lipid & Glycogen storage diseases

8. 4. Accumulation of abnormal exogenous substance due
to unavailability of enzymatic & transport mechanisms
to degrade & transport it to other sites.
e.g., Silicosis & Anthracosis

9. ACCUMULATION OF LIPIDS
triglycerides, cholesterol/cholesterol esters,
phospholipids
STEATOSIS ( FATTY CHANGE)
Abnormal accumulations of TGs within parenchymal
cells.
SITES:
.Liver (most common site)
. may also occur in heart, skeletal muscle, kidney,
and other organs

10. CAUSES:
.Toxins (most importantly: Alcohol abuse)
.diabetes mellitus
.Protein malnutrition (starvation)
.Obesity
.Anoxia

11. MECHANISMS OF FATTY CHANGE

12. MORPHOLOGY OF FATTY CHANGE
MOST COMMON SITE:
• liver
•heart.
• with increasing accumulation, the organ enlarges and
becomes progressively yellow, soft & greasy.

14. LIGHT MICROSCOPY OF FATTY
CHANGE
Early:
small fat vacuoles in the cytoplasm around the nucleus.
Later stages:
the vacuoles coalesce to create cleared spaces that displace
the nucleus to the cell periphery
Occasionally contiguous cells rupture (fatty cysts)

16. ACCUMULATION OF CHOLESTEROL
AND CHOLESTEROL ESTERS
CONDITIONS:
1. ATHEROSCLEROSIS:
. In atherosclerotic plaques, SMCs and macrophages
within intimal layer of aorta & large arteries are filled
with lipid vacuoles, most of which are made up of
cholesterol & cholesterol esters.
. Have foamy appearance (foamy cells)
. produce yellow cholesterol-laden atheromas

17. 2. XANTHOMAS:
formed by clusters of foamy cells found in the
subepithelial connective tissue of the skin and in
tendons
3.CHOLESTEROLOSIS:
focal accumulations of cholesterol-laden
macrophages in the lamina propria of gallbladder
4. NIEMANN-PICK DISEASE, TYPE C:
Lysosomal storage disease caused by mutations
affecting an enzyme involved in cholesterol trafficking,
resulting in cholesterol accumulation in multiple organs

18. Foam cells

19. ACCUMULATION OF PROTEINS
Appear as rounded, eosinophilic droplets, vacuoles or
aggregates in cytoplasm.
On Electron Microscopy they can be amorphous,
fibrillar, or crystalline in appearance.

20. Protein reabsorption droplets in renal
tubular epithelium

21. MODES OF PROTEIN
ACCUMULATION
1. Reabsorption droplets in proximal renal tubules are
seen in renal diseases associated with protein loss in
urine (proteinuria).in disorders with heavy protein
leakage across the gromerular filter there is increased
reabsorption of protein into vesicles and the protein
appears as pink hyaline droplets within the cytoplasm
of the tubular cell

22. 2. Proteins accumulated may be normal secreted
proteins that are produced in excessive amounts as
occurs in certain plasma cells engaged in active
synthesis of immunoglobulins.ER becomes hugely
distended producing large, homogenous eosinophilic
inclusions called Russell Bodies.
3. Defective intracellular transport and secretion of
critical proteins
e.g., α1- antitrypsin deficiency

23. 4. Accumulation of cytoskeleton proteins
e.g.,
.Microtubules
.Actin filaments
.Myosin filaments
.Intermediate filaments-----keratin filaments,
neurofilaments, desmin filaments, vimentin filaments &
glial filaments
5. Aggregation of abnormal proteins
e.g., Amyloidosis (proteinopathies or protein –
aggregation diseases)

24. HYALINE CHANGE
Refers to alteration within cells or in the extracellular
space that gives a homogeneous, glassy, pink
appearance in routine histologic sections stained with
H&E.
EXAMPLES:
. Reabsorption droplets
. Russell bodies
. Alcoholic hyaline
. Hyalinization of walls of renal arterioles in long
standing HTN & DM

25. ACCUMULATION OF GLYCOGEN
Excessive intracellular deposits of glycogen are seen
in patients with an abnormality in either glucose or
glycogen metabolism.
EXAMPLES OF DISORDERS OF GLYCOGEN
METABOLISM:
. Diabetes Mellitus
. Glycogen storage diseases

26. PIGMENTS
Colored substances, some of which are normal
constituents of cells (e.g., melanin), whereas others are
abnormal and accumulate in cells only under special
circumstances.
EXOGENOUS PIGMENTS:
.Carbon (coal dust) most common
Examples:
. Anthracosis
. Pneumoconiosis
. Tattooing
. Silicosis

27. ENDOGENOUS PIGMENTS:
Examples:
. Lipofuscin
. Melanin
. Hemosiderin----Hemosiderosis