This document discusses intracellular accumulations, which are manifestations of metabolic derangements that can be transient or permanent. It describes four main types of intracellular accumulations: lipids, proteins, glycogen, and pigments. For lipids, it discusses fatty change (steatosis) in the liver from conditions like alcohol abuse, diabetes, and obesity. It also discusses cholesterol accumulation in atherosclerosis and hereditary hyperlipidemia. For proteins, it describes defective transport leading to protein accumulation. For pigments, it differentiates endogenous pigments like melanin and hemosiderin from exogenous pigments introduced from outside sources.

1. PRESENTATIONON:
Intracellular Accumulation
Presented by: Mohammad Muztaba
Asst. Professor(Jr.)
Department of Pharmacology Bhavdiya institute sibar sohawal
Ayodhya

2. Intracellular accumulations
• Manifestation of metabolic derangement
• Accumulation may be transient & reversible or
permanent. Effects: range from harmless to toxic
• Three categories

3. Accumulations
of Constituents
of Normal
Cell metabolism
Accumulations of
Abnormal
substances of
abnormal
Cell metabolism
Accumulations of
pigments
Fats
Proteins
Carbohydrates
Storage diseases
Inborn errors of
metabolism
Endogenous
pigments
Exogenous
pigments
ACCUMULATIONS

4. Intracellular accumulations
4 different intracellular accumulations
Lipids
Steatosis
Cholesterol and CholesterolEsters
Proteins
Glycogen
Pigments

6. FATTY CHANGE (Steatosis)
• Fatty metamorphosis
• Intracellular accumulation of neutral
fat(triglycerides) within the parenchymal
cells.
• Common in liver
• Can occur in heart, skeletal muscle and
kidneys.

7. • Causes of fatty liver
• - ALCHOL ABUSE (alcohol dependence)
• - DIABETES MELLITUS
• OBESITY (Obesity is a condition in which a person has excess
body fat)
• - PROTIEN MALNUTRION (starvation suffering or death caused
by lack of food.)
• -DRUGS/TOXINS
• -ANOXIA
• -PREGNANCY

8. Excessive entry of
lipids into the liver
Enhanced fatty acid
synthesis by hepatocytes
Decreased
oxidation of fatty
acids by
mitochondria
Increased
esterification
of fatty acids
to
triglycerides
Decreased
apoprotein
synthesis
Impaired lipoprotein
excretion

9. an example of fatty liver
-smooth surface: important distinction
from other liver diseases where livers
develop irregular surfaces
- cut surface is shiny: greasy and yellow

10. Other Lipid Accumulations
• Cholesterol and cholesterol esters
– In atherosclerosis, cholesterol accumulates in
smooth muscle cells and macrophages in the
intima of arteries
– In hereditary hyperlipemia, cholesterol
accumulates in macrophages, usually under
the skin, forming tumor-like structures known
as xanthomas

11. Intracellular Lipid Accumulation
Cholesterol and cholesterol esters
Atherosclerosis
Xanthomas
Cholesterolosis
common causes
of many diseases
less common
lipid storage
disease
1. Xanthomas: Cluster of foam cells in subepithelial connective tissues of skin &
in tendons producing tumorous masses.
2. Atherosclerosis: Smooth muscles cells & macrophages filled with
cholesterol & cholesterol ester forming foam cells within intimae layer of
Accumulations of foam cells
Like cholesterol

13. Xanthoma
lipid ccumulation
in the dermis
knobby
appearance-->
clue that the
patient may
have defect in
lipid metabolism

14. Cholesterolosisciliated epithelium
accumulation of
lipid in gall bladder
submucosa
--may be an
indicator of other
underlying diseases

15. Intracellular Protein Accumulations
Defective intracellular transport and secretion
Excessive amounts of normal proteins
(Multiple myeloma -Russell Bodies)
accumulation
of mucin
(Cystic fibrosis)
proliferation of
plasma cells,
causing
accumulation of
immunoglobin
Defect in proteinfolding;
- defect in intracellular transport & secretion
- ER stress induced by unfolded & missfolded protein
accumulation in ER
- aggregation of abnormal or missfolded proteins in tissues

16. Morphology:Round eosinophilic droplets, vacuoles or aggregates in cytoplasm.
May be amorphous or crystaline.
• Example : amyloidosis

17. Excessive normal proteins (Russell bodies)
PathGuy
normal plasma
cell
Russell body

18. Defective intracellular transport
and secretion (Cystic fibrosis)
trachea
thick
tenacious
mucus in
airway

19. Intra cellular accumulations
GLYCOGEN
Abnormal metabolism of glucose or glycogen result in
excessive intracellular accumulation of glycogen
Example… uncontrolled diabetes mellitus (main example
of abnormal glucose metabolism

20. Intra cellular accumulations
Pigments

21. DEFINITION
• Pigments are coloured substances, some of
which are normal constituents of cells (e.g.,
melanin), whereas others are abnormal and
accumulate in cells only under special
circumstances
• Pigments can be exogenous, coming from
outside the body,
• or endogenous, synthesized within the
body itself.

22. A. ENDOGENOUS PIGMENTS B. EXOGENOUS PIGMENTS
1.Inhaled pigments
3.Injected pigments
1. Melanin
2. Melanin-like pigment
a. Alkaptonuria
b. Dubin-Johnson syndrome
3. Haemoprotein-derived pigments
a. Haemosiderin
b. Acid haematin (Haemozoin)
c. Bilirubin
d. Porphyrins
4. Lipofuscin (Wear and tear pigment)

23. Exogenous pigments
Exogenous pigments are the pigments
introduced into the body from outside such as
by inhalation, ingestion or inoculation.

24. • Exogenous pigments
Carbon (anthracosis accumulation of carbon in the lungs )
Coal dust (pneumoconiosis)
Lung: pick up by alveolar macrophages
regional lymph nods
blackening the tissues of the lungs
(anthracosis)

25. Here is anthracotic pigment
in macrophages in a hilar
lymph node
The black streaks seen
between lobules of lung
beneath the pleural
surface are due to
accumulation of
anthracotic pigment.

26. Injected Pigments (Tattooing)
Pigments like India ink, cinnabar and carbon are introduced into
the dermis in the process of tattooing where the pigment is taken
up by macrophages and lies permanently in the connective tissue.
The examples of injected pigments are
Prolonged use of ointments containing mercury, and tattooing by
pricking the skin with dyes.

27. Lipofuschin
• fine yellow-brown pigment granules
composed of lipid-containing residues
of liposomal digestion.
• found in the liver, kidney, heart muscle,
retina, adrenals, nerve cells, and
ganglion cells

30. Melanin
The pigment that gives human skin, hair, and eyes their
color.
Melanin is produced by cells called melanocytes.
Melanin is group of natural pigments found in most
organisms.
Melanin is produced through a multistage chemical
process known as melanogenesis,
where the oxidation of the amino acid tyrosine, is
followed by polymerization

31. DISORDERS OF
MELANIN
PIGMENTATION
HYPER
PIGMENTATION
HYPO
PIGMENTATION

32. HYPER
PIGMENTATION
GENERALISED
1.
1. Addisons disease 2.
2. Chloasma
LOCALISED
Peutz jeghers
Syndrome
Melanosis coli

33. HYPO
PIGMENTATION
GENERALISED
Albinism
LOCALISED
Vitiligo

34. Hemosiderin
• Hemoglobin-derived, golden yellow-to-
brown, granular or crystalline pigment
• Major storage forms of iron
• Hemosiderin or haemosiderin is an iron-
storage complex. It is only found within cells
(as opposed to circulating in blood) and
appears to be a complex of ferritin,(Ferritin is a
universal intracellular protein that stores iron ) denatured
ferritin and other material. The iron within
deposits of hemosiderin is very poorly
available to supply iron when needed.
Excess of iron

35. Iron pigment appears as a coarse, golden, granular pigment lying
within the cell's cytoplasm