Principles of cell injury and cellular adaptation .ppt

Causes and pathogensis of cell injury and cellular adaptation

1. Chapter
Chapter
:1
:1
Principles
Principles


of
of


cell
cell


injury
injury


and
and


adaptation
adaptation
Presented by: Prof.Mirza Anwar Baig
Presented by: Prof.Mirza Anwar Baig
Anjuman-I-Islam's Kalsekar Technical Campus
Anjuman-I-Islam's Kalsekar Technical Campus
School of Pharmacy,New Pavel,Navi
School of Pharmacy,New Pavel,Navi
Mumbai,Maharashtra
Mumbai,Maharashtra
1
1

2. Contents:
•
Causes of cell injury
•
Pathogenesis and morphology of
cell injury.
•
Cellular adaptation
•
Cellular atrophy and hypertrophy.

3. CELL INJURY
•
Cell injury results from a disruption of one
or more of the cellular components that
maintain cell viability.

•

D
efined as variety of stresses a cell encounters
as a result of internal or external environmental
changes.
•
Cell injury is common to all pathologic
processes.
3

4. CELL INJURY
•
Cellular adaptation
•
Reversible or irrversible cell injury
•
Subcellular changes and intracellular accumlation

Injury at one point induces a cascade
of effects.
4

5. Etiology:
•
Hypoxia and Ischamia:
•
Physical agents
•
Chemicals and drugs
•
Microbial agents
•
Immunologic agents
•
Nutritional derangemtns
•
Psychogenic diseases
•
Iatrogenic causes
•
Idiopathic diseases

6. HYPOXIC INJURY
Cerebral infarction
Myocardial infarction
Renal atrophy 6

7. INFECTIOUS DISEASE
Primary HerpesCandidiasis
Tuberculosis Actinomycosis
7

8. PHYSICAL INJURY
Thermal Burn Traumatic ulcer
8

9. CHEMICAL/DRUG INJURY
Asprin Burn
9

10. Pathogenesis of cell injury
•
General principles of pathogenesis
1. Type, duration and severity of injurious agents
2. Type, status and adaptability of target cell
3. Underlying intracellular phenomena
eg. Mitochondrial damage, cell wall damage, free
radicals
4. Morphological consequences
eg. Ultrastrucal changes, swelling
10

11. OUTCOMES OF CELL INJURY
REVERSIBLE
CELL DEATH CELL
ADAPTATIONS
NORMAL CELL
CELL INJURY / CELL STRESS
ACUTE
CHRONIC
11

12. 1.Pathogenesis of ischemic and
hypoxic injury
Reversible cell injury:
1. Decreased generation of cellular ATP
2. Intracellualar lactic acidosis:
Nuclear clumping
3. Damage to plasma membrane pump
-
ATP dependent Na /K pump, Ca pump
4. Reduced protein synthesis-
Dispersed ribosomes
Irreversible cell injury:
1. Mitochondrial damage-
↑
ca influx
2. Activated phospholipase- membrane damage
3. Intracellular proteases- cytoskeleton damage
4. Activated endonucleases- nuclear damage
12

13. 1.1: Ischemia reperfusion injury and free
radical mediated cell injury
3 different consequences:
1. from ischaemia to reversible injury
2. from ischaemia to reperfusion injury
3. from ischaemia to irreversible injury
Mechanism:
1. Calcium overload:
↑
lipid peroxidation of cell
membrane
2. Generation of ROS:
3. Subsequent inflammatory reactions neutrophils
utilize oxygen and gives free radicals
13

14. 2. Pathogenesis of chemical injury:
•
Direct cytotoxic effect
–
Direct cytotoxic effect: Hgcl2 poisoning,
Anticancer agents
Conversion to reactive toxic metabolites
metabolites kills the cells eg, CCl
4
affects liver
Acetaminophen poisoning
3. Pathogenesis of physical injury:
Ionizing radiations.-
cell membrane & DNA
damage
14

15. Cellular adaptation:
Classifcation:
a)
Atrophy and Hypertrophy
(
↑
or
↓
in size
)
b)
Hyperplesia
(
↑
number of cells
)
c)
Metaplasia
(change from one type to another
type)
and dysplasia
(changed phenotypic
differentiation)

16. a. Atrophy
1.
Physiologic atrophy:
Brain,Gonads,
2.
Pathologic atrophy
a)
Starvation atrophy
b)
Ischaemic atrophy eg, atropic kidney
c)
Disuse atrohy eg, atropy of pancreas
d)
Neuropathic atrophy eg. Motor neuron
disease
e)
Endocrine atrophy eg, atropy of thyroid
and adrenal
16

17. ATROPHY & ISCHEMIA
Renal atrophy
17

18. ATROPHY & AGING
Normal Brain Atrophic Brain
18

19. b. Hypertrophy
–
Physiologic hypertrophy eg uterus in
pregnancy
–
Pathologic hypertrophy
•
Hypertrophy of cardiac muscle

•
Hypertrophy of smooth muscle
–
Cardiac achalasia
–
Pyloric stenosis
–
Intestinal strictures
–
Muscular arteries in hypertension
•
Hypertrophy of skeletal muscle
•
Compensatory hypertrophy
eg, nephrectomy of
one side, removal of one adrenal gland
19

20. HYPERTROPHY & INCREASED
FUNCTIONAL DEMAND
A
A
A = Normal heart
B
B
B = Hypertensive heart
C
C
C = Dilated heart
20

21. c. Hyperplasia:
•
Temporary Increase
in the number of the parenchymal cells.
•
Resulting in
enlargement
of organ.
•
Often hypertrophy and hyperplasia occures simultaneously
•
Occures due to increased in mitosis of the resting cells.
•
Neoplasia causes change in the genetic composition of the
cells.
CAUSES:
A. PHYSIOLOGICAL HYPERPLASIA:
I) Hormonal hyperplasia eg:
↑
in size of breast during pregnancy
and lactation. Pregnant uterus
ii) Compensatory hyperplasia: Eg: Regenration of liver cells after
hepatectomy,epidermis after skin abrasion.
B.PATHOLOGIC HYPERPLASIA:
I) Endometrial hyperplasia in excess oestrogen
ii) In wound healing: proliferation of fibroblasts cells
iii) Formation of skin warts: papilloma viral infection

22. d. Metaplasia:
•
It is defined as a reversible change of one type of
epithelial or mesenchymal cells to another type of adult
epithelium or mesenchymal cells.
•
long time metaplasia may result in cancer.
•
Divided in 2 types:
A. EPITHELIAL METAPLASIA:
1. Squamous metaplasia:
Eg: In bronchus of chronic smokers
Utreus of old age
2. Columnar metaplasia:
Eg: Intestinal metaplasia in healed chronic gastric
ulcer.
B. MESENCHYMAL METAPLASIA:
1. Osseous metaplasia: Eg: arterial wall in old age
2. Cartilaginous metaplasia: Eg; healing of fractures

23. e. Dysplasia:
•
Means 'disordered cellular development'.
•
Often accompanied with metaplasia and hyperplasia.
•
Often occurs in epithelial cells.
•
Observed charactertics are
–
Increased number of layers of epithelial cells
–
Increased mitotic activity
–
Disorderly arrangement of cells from basel layer to
surface layer.
–
Cellular and nuclear pleomorphism (variability in the
size, shape and staining of cells and/or their nuclei.)

24. Morphology of Reversible cell injury
1.
Hydropic change-swelling-kidney, liver,pancreas
2.
Hyaline change- glass like
3.
Mucoid change- mucus
4.
Fatty change- fat accumlation eg fatty liver
24

25. Morphology of Irreversible cell
injury
a)
Autolysis or self digestion
b)
Necrosis
c)
Apoptosis
d)
Gangrene
e)
Calcification
25

26. CONCEPTS - CELL DEATH
•

There is no singal biochemical event that
equates with cell death.
•

Necrosis =
“
cell murder
”
•

Apoptosis =
“
programmed cell death or cell suicide
”

26

27. NECROSIS
•
Morphologic types of necrosis
–
Coagulative
–
Liquifactive
–
Caseous
–
Enzymatic (fat)
•
The type of necrosis is dependent upon patterns of
enzymatic degradation of cells and extracellular
matrix, the type of necrotic debris, and by
bacterial products when present.
27

28. Coagulative necrosis:
•
Common type of necrosis
•
caused by irreversible focal injury,ischemia.
•
Foci are pale,firm and slightly swollen.
•
Hall mark is presence of tombstones.
Liquefaction necrosis:
Caused due to ischaemic injury or bacterial
infection.
Eg: infarct brain.
Affected area is soft containing necrotic debris.
Caseous necrosis:
Found in foci of tuberclosis infection.
have the features of coagulative and liquefaction
necrosis.
Appears like dry cheese,soft, granular and yellowish.

29. Fat necrosis:
•
Present at pancrease and breast.
•
Yellowish white firm deposits.
•
Fat cells have cloudy appearance and
surrounded by inflammatory reactions.
•
Calcium soaps are present in the cells.
Fibrinoid necrosis:
•
Deposition of fibrin like material.
•
Present in immunological tissue injuries.
•
Arterioles of hypertension,peptic ulcers.
•
Appears like brightly eosinophillic in vessel
wall.

30. COAGULATIVE NECROSIS
•
Cell outline
•

Pink cytoplasm
•
Anucleated cells
30

31. COAGULATIVE NECROSIS
31

32. CASEOUS NECROSIS
Tuberculosis
32

33. Apoptosis:
In 2 process:
A. Physiological process:
1. During development of embryo
2. Cells of hormone dependent tissues eg: endometrial sheeding,
regression of lactating breast.
3. Involution of thymus gland in early age.
B. Pathological process:
1. Cell death in tumour exposed to chemotherapeutic agents
2. Cell death by cytotoxic T cells in graft rejection.
3. Progressive depletion of CD
4
cells in AIDS.
4. Cell death in viral infection
5. Pathological atropy
6. Cell death after exposure of radiations, hypoxia etc
7. Degenerative diseases of CNS eg: Alzheimers disease etc
8. Heart diseases

34. MORPHOLOGY OF
APOPTOSIS
Progressive cell shrinkage
Chromatin condensation
Plasma membrane blebbing
Apoptotic bodies
Phagocytosis - no inflammation
34

35. MECHANISMS OF APOPTOSIS
35

38. THANK YOU