This document discusses various types of cellular adaptations, injuries, and deaths. It describes adaptations like hypertrophy and hyperplasia that occur in response to stress. It also discusses different types of cell injuries and deaths including necrosis, apoptosis, necroptosis, and pyroptosis. Various intracellular accumulations are also summarized such as lipids, proteins, glycogen, and pigments.

1. Dr. Ajit Kumar Singh
2nd Year PGT
Chittaranjan National Cancer Institute
Kolkata 700160
Adaptations, Cell Injury, Cell Death
Dr Namrata Maity
MD Pathology
Assistant Professor
Department of Laboratory Medicine
Chittaranjan National Cancer Institute
Kolkata 700160

2. Adaptations
When a cell is exposed to stress physiologic (pregnancy,
exercise) or pathologic (hypertension), it undergoes a
reversible functional and structural response during which
new but altered steady states are achieved allowing the cell
to survive and continue to function.

3. Adaptations

4. Hypertrophy
• Hypertrophy refers to an increase in the size of cells,
that results in an increase in the size of the affected
organ.
• The increased size of the cells is due to the synthesis
and assembly of additional intracellular structural
components.
• Eg. Cells that can not multiply
• Muscles in body builders
• Cardiac muscle in hypertension

5. Hyperplasia
• Hyperplasia is defined as an increase in the number of cells in an
organ or tissue in response to a stimulus
• Physiologic
• Female breast during pregnancy (epithelium)
• Liver - In individuals who donate one lobe of the liver for
transplantation, the remaining cells proliferate so that the organ
soon grows back to its original size
• Bone marrow in response to supplements
• Endometrium – after menstruation
• Pathologic
• Endometrium – in response to hormones
• Hyperplasia of prostate
• Epidermal hyperplasia (warts) in response to viral infection

6. Mechanisms
of Hyperplasia
• Hyperplasia is the result of
• growth factor-driven proliferation of
mature cells and
• by increased output of new cells from
tissue stem cells

7. Atrophy
• Atrophy is defined as a reduction in the size of
an organ or tissue due to a decrease in cell size
and number
• Physiologic
• Embryonic structures – notochord,
thyroglossal duct
• Post partum uterus
• Pathologic
• Disuse atrophy
• Denervation atrophy
• Ischemic atrophy
• Loss of nutrition – Marasmus, cachexia
• Loss of endocrine stimulation
• Breast after menopause
• Pressure atrophy
• Tumor compressing normal tissue

8. Mechanisms
Decreased
protein
synthesis
Increased
protein
degradation
Through
proteasomes

9. Metaplasia
• Reversible change in which one
differentiated cell type (epithelial
or mesenchymal) is replaced by
another differentiated cell type.
Barret’s esophagus – squamous to columnar
Respiratory epithelium – columnar to squamous
Mechanism
• Reprogramming of stem cells that
are known to exist in normal
tissues.

10. Injury
(ALTERED HOMEOSTASIS)

11. Most important organelles involved during cell injury
o Plasma membrane
o Mitochondria
o Nucleus
o Endoplasmic reticulum

12. Morphology of cell injury

13. Causes of cell injury
• Hypoxia – lack of blood supply or lack of oxygen
• Physical agents – Heat, Mechanical trauma
• Chemical agents – glucose or salt in high concentrations, PCM ,
poisons
• Microorganisms causing infections
• Autoimmunity
• Genetic derangements – accumulation of damaged DNA can trigger
apoptosis
• Nutritional defects – Anorexia nervosa, Atheroscleosis

14. Mechanisms of cell injury
Source:Robbins Textbook of pathology,
10E

15. TIMELINE
Source:Robbins Textbook of pathology, 10E

16. Irreversible
cell injury
NECROSIS – Irreversible cell death
caused due to denaturation of
proteins and enzymatic digestion of
cell.
APOPTOSIS - Genetically
programmed cell death.

17. Morphology of necrosis
• The morphology of necrosis can be explained in following tissue patterns
• Coagulative necrosis
• Liquefactive necrosis
• Gangrenous necrosis
• Caseous necrosis
• Fat necrosis
• Fibrinoid necrosis

18. Coagulative
necrosis (infarct)
• Coagulative necrosis is a form of
necrosis in which the architecture
of dead tissues is preserved.
• The injury denatures not only
structural proteins but also
enzymes and so blocks the
proteolysis of the dead cells
• Cause is mainly Ischemia caused
by obstruction in a vessel
Source:Robbins Textbook of pathology, 10E

19. Liquefactive necrosis
• Liquefactive necrosis, in contrast to coagulative necrosis, is
characterized by digestion of the dead cells, resulting in
transformation of the tissue into a liquid viscous mass
• The necrotic material is frequently creamy yellow because
of the presence of dead leukocytes and is called pus
• Best example is necrosis in brain
Source: Robbins Textbook of pathology, 10E

20. Gangrenous necrosis
• It is a type of coagulative necrosis with superimposed
bacterial infection.
• Best example is a limb, generally the lower leg, that has lost
its blood supply
Source:Robbins Textbook of pathology, 10E

21. Caseous necrosis
• Caseous necrosis is encountered most often in foci of
tuberculous infection
• The term “caseous” (cheese like) is derived from the friable
white appearance of the area of necrosis
Source: Robbins Textbook of pathology, 10E

22. Fat necrosis
• It refers to focal areas of fat destruction, typically resulting
from release of activated pancreatic lipases into the
substance of the pancreas and the peritoneal cavity.
• This occurs in acute pancreatitis
Source:Robbins Textbook of pathology, 10E

23. Fibrinoid necrosis
• Fibrinoid necrosis is a special form of necrosis usually seen
in immune reactions involving blood vessels.
• This pattern of necrosis typically occurs when complexes of
antigens and antibodies are deposited in the walls of
arteries.
• Deposits of these “immune complexes,” together with
fibrin that has leaked out of vessels, result in a bright pink
and amorphous appearance in H&E stains, called
“fibrinoid” (fibrin-like) by pathologists.
Source:Robbins Textbook of pathology, 10E

24. Source:Robbins Textbook of pathology, 10e

25. Apoptosis
• Apoptosis occurs normally both during
development, throughout adulthood,
and serves to remove unwanted, aged,
or potentially harmful cells.
• Physiologic apoptosis
• Pathologic apoptosis

26. Physiologic
apoptosis
destruction of cells during
embryogenesis
• Such as endometrial cell breakdown
during the menstrual cycle
• Ovarian follicular atresia in
menopause
• The regression of the lactating
breast after weaning
• Prostatic atrophy after castration
Involution of hormone-
dependent tissues upon
hormone withdrawal

27. Pathologic apoptosis
DNA damage - Radiation, cytotoxic anticancer
drugs, and hypoxia can damage DNA
Accumulation of misfolded proteins. Improperly folded
proteins may arise because of mutations. Excessive
accumulation of these proteins in the ER leads to a
condition called ER stress
Cell death in certain infections, particularly viral
infections. An important host response to viruses
consists of cytotoxic T lymphocytes, which induce
apoptosis of infected cells
Pathologic atrophy in parenchymal organs after duct
obstruction, such as occurs in the pancreas, parotid
gland, and kidney

28. Morphology
• Cell shrinkage
• Chromatin condensation
• Formation of cytoplasmic
blebs and apoptotic bodies
• Phagocytosis of apoptotic cells
or cell bodies, usually by
macrophages

29. • Apoptosis occur in 3 phases
1. Initiation
2.Execution
3.Removal of dead cells
• Enzyme involved in apoptosis
• Caspases
• Endonuclease
• Factors involved in apoptosis
• Pro apoptotic factors ( BH1-3 )
• Anti-apoptotic factors ( BH1-4 )
• Regulated initiators of apoptosis (BH3-only proteins )

30. Mechanisms of apoptosis

33. Necroptosis
• It’s a hybrid of necrosis and apoptosis.
• The cell start as apoptosis and ends as necrosis.
• Mechanism- apoptosis .
• Morphological features- necrosis.
• Also known as programmed necrosis.
• It is caspase independent process

34. Pyroptosis
Cell death associated with release of IL-1
Microbial products/toxins enter the infected cell.
Recognized by NOD like receptors
Inflammasome
Activation of casp-1
Activation of IL-1
Cause death of infected cell

35. Intracellular
accumulations
• Metabolic derangements lead to accumulation
of different substances in the cytoplasm or in
organelles or in nucleus

36. Intracellular accumulations
Lipid Proteins
Hyaline
Change
Glycogen Pigments
Exogenous
Endogenous
Calcium
Dystrophic
calcification
Metastatic
calcification

37. Pathways
Source:Robbins Textbook of pathology, 9E

38. Pathologic calcification
• Pathologic calcification is the abnormal tissue deposition of calcium
salts, together with smaller amounts of iron, magnesium, and other
mineral salts
• Types
• Dystrophic
• deposition occurs locally in dying tissues
• it occurs despite normal serum levels of calcium
• In absence of derangements in calcium metabolism
• Metastatic
• deposition of calcium salts in otherwise normal tissues
• results from hypercalcemia
• secondary to some disturbance in calcium metabolism.

39. Hayflick limit: normally cells undergo 60-70 cell
divisions in entire life span.
Telomeres : Telomers are short, repeat sequence of
nucleotides at the end of chromosome.
With each cell division telomere shortens.
Telomere shortening leads to cellular aging.
Telomerase : The level of telomere is maintained by
an enzyme telomerase.
Telomerase inhibits aging(aka immortality gene).
Its activity is high in germ cells , stem cells .
Low in somatic cell
Cellular aging

40. Dystrophic
calcification
• Examples
• in the atheromas of advanced atherosclerosis
• develops in aging or damaged heart valves
• Morphology
• Gross - fine, white granules or clumps, often felt as gritty
deposits
• Microscopy–
• intracellular or extracellular, basophilic, amorphous
granular, sometimes clumped appearance
• The progressive acquisition of outer layers may
create lamellated configurations, called psammoma
bodies – In papillary lesions of thyroid,
meningiomas etc
• In asbestosis of the lung, iron and calcium
deposition creates dumbbell shaped forms
Source:Robbins Textbook of pathology,
10E

41. Metastatic calcification
• Causes
• Increased secretion of parathyroid hormone (PTH) with subsequent bone resorption
• hyperparathyroidism due to parathyroid tumors, and
• ectopic secretion of PTH-related protein by malignant tumors
• Resorption of bone tissue
• primary tumors of bone marrow (e.g., multiple myeloma, leukemia)
• diffuse skeletal metastasis (e.g., breast cancer), accelerated bone turnover (e.g., Paget disease)
• Immobilization
• Vitamin D–related disorders
• vitamin D intoxication,
• sarcoidosis (in which macrophages activate a vitamin D precursor
• idiopathic hypercalcemia of infancy (Williams syndrome) - characterized by abnormal sensitivity to
vitamin D
• Renal failure
• which causes retention of phosphate, leading to secondary hyperparathyroidism.

42. Lipid
• Fatty change
• Atherosclerosis
• Xanthomas
• Cholesterosis
• Neimann Pick disease type C
Source:Robbins Textbook of pathology,
10E

43. Atherosclerosis
• In atherosclerotic plaques,
smooth muscle cells and
macrophages within the
intimal layer of the aorta and
large arteries are filled with
lipid vacuoles, most of which
are made up of cholesterol
and cholesterol esters.
• Such cells have a foamy
appearance (foam cells)
Source:Robbins Textbook of pathology, 9E

44. Xanthomas
• Clusters of foamy cells are found in the
subepithelial connective tissue of the skin and
in tendons
Source:Robbins Textbook of pathology, 9E

45. Cholesterosis
• This refers to the focal accumulations of
cholesterol-laden macrophages in the lamina
propria of the gallbladder
Source: Robbins Textbook of pathology, 9E

46. Neimann pick disease type C
• This lysosomal storage disease is caused by mutations
affecting an enzyme involved in cholesterol trafficking,
resulting in cholesterol accumulation in multiple organs

47. Proteins
• Resorption droplets in proximal
renal tubules in proteinuria
• Russel bodies
• α1 antitrypsin deficiency
• Neurofibrillary tangle found in
Alzheimer’s
Source:Robbins Textbook of pathology, 9E

48. Hyaline Change
• An alteration within cells or in the extracellular space that gives a
homogeneous, glassy, pink appearance in routine histologic
sections stained with hematoxylin and eosin
• This morphologic change is produced by a variety of alterations
and does not represent a specific pattern of accumulation

49. Hyaline Change
• Intracellular Hyaline
• Intracellular accumulations of protein,
described earlier (reabsorption droplets,
Russell bodies, alcoholic hyaline), are
examples of intracellular hyaline deposits.
• Extracellular Hyaline
• Collagenous fibrous tissue in old scars may
appear hyalinized
• In long-standing hypertension and diabetes
mellitus, the walls of arterioles, especially in
the kidney, become hyalinized, resulting
from extravasated plasma protein and
deposition of basement membrane material

50. Glycogen
• Glycogen is a readily available energy source stored in the
cytoplasm of healthy cells.
• Excessive intracellular deposits of glycogen are seen in
patients with an abnormality in either glucose or glycogen
metabolism – Diabetes mellitus/Glycogen storage disorders
Source:Robbins Textbook of pathology,
10E

51. Pigments
• Exogenous
• Carbon
• Lipofuscin
• Melanin
• Hemosiderin
• Melanin
• Homogentisic acid
• Bilirubin and biliverdin

52. Carbon
• The most common exogenous pigment is carbon (coal dust), a
ubiquitous air pollutant in urban areas.
• ANTHRACOSIS
• When inhaled Carbon is picked up by macrophages within the alveoli and is
then transported through lymphatic channels to the regional lymph nodes
• Accumulations of this pigment blacken the tissues of the lungs and the
involved lymph nodes.
• COAL WORKER’S PNEUMOCONIOSIS
• In coal miners the aggregates of carbon dust may induce a fibroblastic
reaction or even emphysema and thus cause a serious lung disease
(Chapter 15).
• TATTOOING
• is a form of localized, exogenous pigmentation of the skin. The pigments
inoculated are phagocytosed by dermal macrophages, in which they reside
for the remainder of the
• The pigments do not usually evoke any Inflammatory response.
Source:Robbins Textbook of pathology,
10E

53. Lipofuscin
• It is seen in cells undergoing slow, regressive
changes and is particularly prominent in the
liver and heart of aging patients
• Tell-tale sign of free radical injury and lipid
peroxidation
• not injurious to the cell or its functions
Source:Robbins Textbook of pathology,
10E

54. Hemosiderin
• Hemosiderin, a hemoglobin-derived, golden yellow
to-brown, granular or crystalline pigment derived
from iron
• Under normal conditions small amounts of
hemosiderin can be seen in the mononuclear
phagocytes of the bone marrow, spleen, and liver,
which are actively engaged in red cell breakdown
• Local excesses of hemosiderin - Common bruise
• Systemic overload of iron - HEMOSIDEROSIS
• Hemochromatosis - increased absorption of
dietary iron due to an inborn error of
metabolism called
• Hemolytic anemias - premature lysis of red
cells leads to release of abnormal quantities of
iron
• Repeated blood transfusions - transfused red
cells constitute an exogenous load of iron
Source:Robbins Textbook of pathology, 9E

55. Melanin
• brown-black, pigment
formed when the enzyme
tyrosinase catalyzes the
oxidation of tyrosine to
dihydroxyphenylalanine in
melanocytes

56. Homogentisic acid
• Black pigment that occurs in patients with
alkaptonuria
• Here the pigment is deposited in the skin,
connective tissue, and cartilage, and the
pigmentation is known as oochronosis
Source:Robbins Textbook of pathology,
10E

57. 4. Protein misfolding and DNA damage
Source:Robbins Textbook of pathology,
10E

58. MORPHOLOGY OF
REVERSIBLE CELL INJURY
• Best examples are cellular swelling and fatty change
• Cellular swelling
• Cellular swelling is the first manifestation of
almost all forms of injury to cells
• Gross - It causes some pallor, increased
turgor, and increase in weight of the organ
• Light microscopy - small clear vacuoles may
be seen within the cytoplasm; these
represent distended and pinched-off
segments of the ER
Source:Robbins Textbook of pathology,
10E

59. 3. Membrane damage
Source:Robbins Textbook of pathology,
10E

60. 2. Influx of calcium
Source:Robbins Textbook of pathology,
10E

61. 1. Mitochondrial damage
Source:Robbins Textbook of pathology,
10E

62. MECHANISMS

63. Metastatic calcification
• Principally affects the interstitial tissues of the gastric mucosa,
kidneys, lungs, systemic arteries, and pulmonary veins
• All of these tissues excrete acid and therefore have an internal
alkaline compartment that predisposes them to metastatic
calcification

64. THANK YOU…