Cell injury-necrosis.ppt,types of necrosis, morphology

This ppt is regarding cell injury and various types of necrosis. Also in deatil about the morphology of types of necrosis with examples.

1. ADAPTATION, INJURY and DEATH
of CELLS

Subject incharge
Mrs. Anjali M Wankhade
Depatment of Pharmacology

2. Pathology: the Study of Disease
•Etiology or cause: infection, genetic etc. and often
mutifactoral
•Pathogenesis: progression of the disease
•(Molecular and Morphologic Changes)
•Clinical Manifestations: signs and symptoms

3. Cellular Adaptations
•Hypertrophy
•Hyperplasia
•Atrophy
•Metaplasia
•Dysplasia

4. HYPERTROPHY
•Increase in cell size with
subsequent increase in
organ size

5. Causes of Hypertrophy
1.Increased functional
demand
2.Hormonal stimulation

6. Hypertrophy of Uterus During Pregnancy

7. Hypertrophy of Uterus During Pregnancy
No new cells; Cells just bigger

8. •Hypertrophy can be
physiologic or pathologic

9. Cardiac Muscle Hypertrophy and Infarction

10. Results from increased production of cellular proteins

11. HYPERPLASIA
•Increase in the number of cells in an
organ which may then increase
organ size.
•Physiologic or Pathologic

12. PHYSIOLOGIC
HYPERPLASIA
1.Hormonal hyperplasia-
female breast at puberty and
in pregnancy
2.Compensatory hyperplasia-
liver regeneration after
partial resection

13. Female Breast Tissue after
Puberty

14. Lactating breast during pregnancy

15. Causes of Pathologic
Hyperplasia
1.Excess hormone-
endometrial hyperplasia
due to estrogens

16. •Hyperplasia is NOT a neoplastic
process, but it may be fertlie soil for
malignancy
•“Atypical Hyperplasia” in the
endometrium carries an increased risk
for development of endometrial
adenocarcinoma

18. Endometrial Hyperplasia

19. Normal Proliferative Endometrium

20. Endometrial Hyperplasia

21. Benign Prostatic Hypertrophy

22. ATROPHY
•Decrease in the size of a
cell or organ by loss of cell
substance (both size and
number)

23. Physiologic Atrophy
•Normal development
–Notochord
–Thyroglossal duct
•Uterus following childbirth

24. Causes of Pathologic Atrophy
1.Decreased workload
2.Loss of innervation
3.Decreased blood supply
4.Inadequate nutrition
5.Loss of endocrine stimulation
6.Pressure

26. **Central skeletal muscle bundle is atrophic
*
*

27. Atrophic Brain
Normal Brain

28. Atrophy results from both…
•Decreased protein synthesis
•Increased protein degradation

29. Protein degradation is
important in atrophy
A.Lysosomes with hydrolytic
enzymes
B.The ubiquitin-proteasome
pathway

30. HYPOPLASIA
•Incomplete development
of an organ so that it fails
to reach adult size

31. Examples of Hypoplasia
Hypoplastic Left Ventricle
Hypoplastic Kidney

32. METAPLASIA
•A reversible change in
which one ADULT cell type
is replaced by another
ADULT cell type

33. Metaplasia
•Caused by:
–Chronic irritation (cigarette smoke; calculi in ducts)
–Vitamin A deficiency
•Cervix- squamous epithelium of the endocervix replaces
columnar (dysplasia and squamous CA may develop)
•Barrett esophagus- gastric reflux results in columnar
epithelium replacing squamous epithelium in the esophagus
(dysplasia and adenocarcinoma may occur)

34. Squamous cells replace columnar cells

36. Esophagus: glandular epithelium (R) is metaplastic

37. Hyperplasia and Metaplasia are not
premalignant changes, however they are
“fertile fields” for Dysplasia which is a
premalignant change

38. DYSPLASIA
•Atypical proliferative
changes due to chronic
irritation or inflammation;
•Premalignant change

39. Mild dysplasia Moderate
dysplasia
Marked
dysplasia
DYSPLASIA IN THE CERVIX

41. CELL INJURY PRINCIPLES
1.The cellular response to injurious stimuli
depends on the type of injury, its duration
and its severity.
2.The consequences of cell injury depend on
the type, state, and adaptability of the
injured cell
3.Cell injury results from different
biochemical mechanisms acting on several
essential cellular components

42. 1. The cellular response to injurious stimuli depends on the type of
injury, its duration and its severity.

43. Cellular Changes Secondary to
Injury
REVERSIBLE
•Cellular swelling
•Cell membrane blebs
•Detached ribosomes
•Chromatin clumping
IRREVERSIBLE
•Lysosomes rupture
•Dense bodies in
mitochondria
•Cell membrane
rupture
•Karyolysis,
karyorrhexis,
pyknosis

47. Myocardial Infarction Markers
•Cardiac specific enzymes and proteins appear
in serum within 2 hours post infarction
•Morphologic (light microscopic) changes in 4-
12 hours

48. Normal
Myocardium
Coagulation Necrosis
at 24-48 hours post MI

49. A.Normal kidney
B.Reversible changes
C. Dying Cell

50. Normal Kidney Histology

51. Normal Tubules

52. Tubules Accumulate Water (cloudy swelling)

53. 2. The consequences of cell injury depend
on the type, state, and adaptability of the
injured cell

54. Cell Proliferation Varies
•Labile cells – continuously dividing
(epithelium, bone marrow)
•Stable cells – quiescent (in G0 stage;
hepatocytes, smooth muscle,
lymphocytes)
•Permanent cells – nondividing
(neurons, skeletal and cardiac muscle)

56. Susceptibility of Cells to
Ischemic Necrosis
HighHigh Neurons (3-4 min)Neurons (3-4 min)
IntermediatIntermediat
ee
Myocardium, hepatocytes, Myocardium, hepatocytes,
renal epithelium (30 min-2hr)renal epithelium (30 min-2hr)
LowLow Fibroblasts, epidermis, Fibroblasts, epidermis,
skeletal muscle (many hours)skeletal muscle (many hours)

57. 3. Cell injury results from different biochemical mechanisms
acting on several essential cellular components

58. Depletion of ATP
•Na+ pump fails Na+ and water enter and K+
is lost
•Glycolysis depletes glycogen and lowers pH
(loss of enzyme activity)
•Ca++ pump fails- Ca++ into cells (toxic)
•Decreased protein synthesis (ribosomes
detach)
•Unfolded protein response

60. Mitochondrial Damage
•3 major consequences:
–Mitochondrial permeability transition (MPT) pore
opens  loss of mitochondrial membrane
potential  decreased oxidative phosphorylation
w/ decreased ATP
–Production of reactive oxygen species
– Leakage of pro-apoptotic proteins

63. Loss of Ca++ Homeostasis
•Extracellular Ca++ is 15X higher than
cytosolic Ca++
•Loss of ATP increases intracellular Ca++
•Increased Ca++ activates phospholipases,
proteases, endonucleases, and ATPases
•Increased Ca++ also increases
mitochondrial permeability triggering
apoptosis

65. Free Radical Formation
•Single unpaired electron; highly reactive
•Normal metabolism produces superoxide
anion, hydrogen peroxide and hydroxyl
ion; superoxide is produced in neutrophils
•Reactive oxygen species (ROS) are a type
of free radical
•Excess of ROS within cell leads to
oxidative stress

66. Pathologic Effects of ROS
•Lipid peroxidation leading to membrane
damage
•Protein damage
•DNA damage

69. Major Antioxidants
•Antioxidants block the formation of ROS or
inactivate them
•Antioxidant Enzymes: superoxide dismutase,
catalase, glutathione peroxidase
•Vitamins: A, E, ascorbic acid, glutathione

70. Membrane Permeability Defects
•Plasma membrane
•Mitochondrial membrane
•Lysosomal membrane- release of RNases,
DNases and proteases

72. CAUSES OF CELL INJURY
•Oxygen deprivation
•Physical agents
•Chemical agents and drugs
•Infectious agents
•Immunologic reactions
•Genetic derangements
•Nutritional imbalances

73. Hypoxia and Ischemia
•Hypoxia- deficiency of oxygen; causes:
cardiorespiratory failure, anemia, CO
poisoning
•Ischemia- loss of blood supply (oxygen and
nutrients); more rapidly and severely injures
tissues than does hypoxia alone

75. NECROSIS vs APOPTOSIS
•Necrosis- death of GROUPS of cells after injury;
usually with inflammation
•Apoptosis- genetically controlled, ATP and
enzyme-dependent death of individual cells;
usually no inflammation
–More details in part 2

77. NECROSIS
•Morphologic changes in GROUPS of cells that
follow the death of living tissue; cells and
PMNs leak lytic enzymes
•CYTOPLASM: eosinophilia, vacuoles,
calcification, myelin figures
•NUCLEUS: pyknosis, karyorrhexis, karyolysis

78. Patterns of Necrosis
•Coagulative- hypoxic death (except brain)
•Liquefactive- bacterial infections; *also hypoxic
death in brain tissue (infarction)
•Caseous- tuberculosis
•Fat- enzymatic or traumatic damage to fatty
tissue; eg. Pancreatitis (enzymatic)
•Gangrenous- usually involves lower extremities
and often is a type of coagulative necrosis
•Fibrinoid- immune complexes in arteries

80. Coagulative Necrosis in Kidney

81. Brain Abscess with
Liquefactive Necrosis

82. Abscess/Liquefactive Necrosis

83. Caseous Necrosis of
Lung

84. Granulomatous Inflammation with Central Necrosis

85. Fat Necrosis

86. Fat Necrosis (L) and Normal Pancreas (R)

87. Gangrenous Necrosis

88. Fibrinoid Necrosis

89. Acknowledgement

This powerpoint presentation has been adapted
from instructional materials devloped by
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Elsevier.inc