The document discusses cellular injury, death, and adaptation, focusing on intracellular accumulations, including lipids, proteins, glycogen, and pigments, and their implications in various diseases. It highlights the mechanisms of accumulation such as inadequate removal, defective transport, and failure to degrade substances, as well as the concepts of dystrophic and metastatic calcification. Additional topics cover cellular aging, DNA damage, and the role of exogenous and endogenous factors in affecting cell integrity.

1. Dr. Vibhuti Kumar
MD(Path)Mumbai
Assistant Prof. SNHIM
Col. Dr Lal Path,Purnea
Hol. Triveni Diagnostic
CELL
INJURY,DEATH&ADAPTATION
3

2. INTRACELLULAR ACCUMULATIONS
• Inadequate removal
• defects in its folding, packaging, transport, or
secretion
• Failure to degrade
• Deposition and accumulation of an abnormal
exogenous substance

3. LIPID
• Steatosis
The terms steatosis and
fatty change describe
abnormal accumulations
of triglycerides within
parenchymal cells.
(Fatty Change)

4. Cholesterol and Cholesterol Esters
• Atherosclerosis- within the intimal layer
• Xanthomas- within macrophages is also
characteristic of acquired and hereditary
hyperlipidemic states
• Cholesterolosis- lamina propria of the
gallbladder
• Niemann-Pick disease, type C

6. Protein
• Intracellular
accumulations of
proteins usually appear
as rounded, eosinophilic
droplets, vacuoles, or
aggregates in the
cytoplasm.

7. defects in its folding, packaging, transport, or
secretion
• Reabsorption droplets in proximal renal tubules are
seen in renal diseases associated with protein loss in
the urine (proteinuria)
• ER becomes hugely distended, producing large,
homogeneous eosinophilic inclusions called Russell
bodies.
• Defective intracellular transport and secretion of
critical proteins. In α1-antitrypsin deficiency
• Accumulation of cytoskeletal proteins
• Aggregation of abnormal proteins

9. Failure to degrade

10. Deposition and accumulation of an
abnormal exogenous substance

11. Hyaline Change
• The term hyaline usually refers to an alteration
within cells or in the extracellular space that
gives a homogeneous, glassy, pink appearance in
routine histologic sections stained with H&E
• Intracellular hyaline accumulations of protein
include reabsorption droplets, Russell bodies,
and Mallory alcoholic hyaline
• Extracellular hyaline- Collagenous fibers in old
scars may appear hyalinized

12. Glycogen
• Excessive intracellular deposits of glycogen
are seen in patients with an abnormality in
either glucose or glycogen metabolism
Diabetes mellitus
glycogen storage diseases or glycogenoses

13. Pigments
• Endogenous Pigments Lipofuscin is an
insoluble pigment.
• Exogenous Pigments The most common
exogenous pigment is carbon (coal dust), a
ubiquitous air pollutant in urban areas.

14. Lipofuscin (yellow-brown)
• derived through lipid
peroxidation of
polyunsaturated lipids
of intracellular
membranes
• not injurious
• as lipochrome or wear-
and-tear pigment

15. Melanin (brown-black)
• only endogenous brown-black pigment
• formed when the enzyme tyrosinase catalyzes
the oxidation of tyrosine to
dihydroxyphenylalanine in melanocytes.

16. Hemosiderin
• Hemosiderin, a hemoglobin-derived, golden
yellow to-brown, granular, or crystalline
pigment is one of the major storage forms of
iron.
• healing bruise, which typically changes from
red-blue to green-blue to golden-yellow before
it is resolved

17. PATHOLOGIC CALCIFICATION
• Pathologic calcification is the abnormal tissue
deposition of calcium salts, together with
smaller amounts of iron, magnesium, and
other mineral salts
• Begins in mitochondria except kidney
(basement membrane)
• Dystrophic Calcification
• Metastatic Calcification

18. Calcification
Dystrophic
• Seen in dead tissue
• Serum calcium is normal
• Seen at sites of necrosis
• Often causes organ
dysfunction
Metastatic
• Seen in living tissue
• Serum ca is elevated
• Doesn’t cause clinical
dysfunction
• Found in organs which loose
acid & have alkaline
environment inside them.
• Lung m/c
• Kidney,stomach systemic
artery,pulmonary vein.

19. EXAMPLES
Dystrophic
• R – Rheumatic heart D
• A – Atheromatous plaque
• T- Tubercular LN
TUMORS (MOST for PG)
M- meningioma,mesothelioma
O- papillary ca of Ovary
S- papillary ca of Salivary gland
T- papillary ca of thyroid
P- Prolactinoma
G- Glucagnoma
Metastatic
• Hyperparathyroidism
• Renal failure
• Vit-D intoxication
• Sarcoidosis
• Milk-alkali syndrome
• Multiple Myeloma
• Metastatic tumor of bone

20. CELLULAR AGING
• DNA Damage. A variety of exogenous (physical,
chemical, and biologic) agents and endogenous
factors such as ROS threaten the integrity of
nuclear and mitochondrial DNA.
• Cellular Senescence- fixed number of divisions
cells become arrested in a terminally nondividing
state, known as replicative senescence
Telomere attrition
Activation of tumor suppressor genes.

21. • Defective Protein Homeostasis.
- Dysregulated Nutrient Sensing
- Insulin and insulin-like growth factor 1
(IGF-1) signaling pathway.
- Sirtuins

29. THANKS