1. Apoptosis Necrosis

2. Apoptosis
• Cell death that is induced by a tightly
regulated intracellular program
“Programmed Cell Death”
• Causes of Apoptosis
- Physiologic situations
- Pathologic conditions

3. Morphology of
Apoptosis
Cell shrinkage
Chromosome
condensation
Formation of
cytoplasmic blebs and
apoptotic bodies
Phagocytosis of
apoptotic cells or cell
bodies

4. Apoptosis in Physiologic Situations
• Programmed destruction of cell during embryogenesis
• Hormone-dependent involution
- endometrial cells (menstrual cycle)
• Cell deletion in proliferating cell population
• Death of host cells - neutrophils
• Elimination of self reactive lymphocyte
• Cell death induced by cytotoxic T-cells
- viral infected or tumor cells

5. Apoptosis in Pathologic Conditions
• Cell death produced by injurious stimuli –
radiation, cytotoxic drug
• Cell injury in certain viral diseases – viral
hepatitis
• Pathologic atrophy
• Cell death in tumors

6. Intracellular Accumulations
• Manifestation of “metabolic derangements”
:intracellular accumulation of abnormal amounts
of various substances
Fat
Protein
Glycogen
Pigments

7. Mechanisms of
intracellular accumulations
(1) abnormal metabolism
(2) alterations in protein folding
and transport
(3) deficiency of critical enzymes
(4) inability to degrade
phagocytosed particles

8. Intracellular Accumulations of Lipids
• Accumulation of Lipids
- Triglycerides
- Cholesterol
• Steatosis (fatty change)
: abnormal accumulation of triglycerides within
parenchymal cells
– fatty liver in chronic alcoholism

9. Lipid circulation
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM)
© 2005 Elsevier

10. Fatty liver
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM)
© 2005 Elsevier

11. Intracellular Accumulations of
Lipids
• Cholesterol and Cholesterol Esters
:Atherosclerosis
- accumulation of cholesterol-laden
macrophage (foam cell) and smooth muscle
cells in the intima of aorta and arteries
:Cholesterolosis
- accumulation of foam cells in the lamina
propria of gallbladder

12. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM)
© 2005 Elsevier

13. Intracellular Accumulations of Proteins
• Accumulation of protein droplets in proximal
renal tubule
- renal disease with heavy protein leakage
across the glomerular filter

14. Protein reabsorption droplets in the renal tubular epithelium.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM)
© 2005 Elsevier

15. Intracellular Accumulations of Proteins
• Defects in protein folding
:Defective intracellular transport and
secretion
:ER stress induced by unfolded and misfolded
protein – cell death
:Aggregation of abnormal folded protein -
amyloidosis

16. Intracellular Accumulations of
Glycogen
“Patients with abnormal metabolism of glucose
or glycogen”
• Diabetes mellitus
:disorder of glucose metabolism
- glycogen accumulate in epithelial cells of
renal tubules, liver cells, beta-cells of the
islets of Langerhans and heart muscle cells

17. Intracellular Accumulations of
Glycogen
• Glycogen storage disease (Glycogenosis)
- genetic diseases
- defect of enzymes in the synthesis or
breakdown of glycogen
accumulation cell injury death

18. Accumulation of Pigments
• Exogenous pigments
Carbon ( anthracosis)
Coal dust ( pneumoconiosis)
Lung: pick up by alveolar macrophages
regional lymph nods
blackening the tissues of the lungs
(anthracosis)

19. Accumulation of Pigments
• Endogenous pigment
:Lipofuscin – aging pigment
lipid, phospholipid-protein complex (lipid
peroxidation)
:Melanin – in melanocyte
:Hemosiderin – aggregates of ferritin micelles (iron +
apoferritin = ferritin)

20. Pathologic Calcification
• Abnormal tissue deposition of Calcium Salts
• Two forms
1. Dystrophic calcification
2. Metastatic calcification

21. Pathologic Calcification
 Dystrophic Calcification
- Area of tissue necrosis
- Aging or damage heart valve
- Atherosclerosis
- Single necrotic cell
“psammoma body”

22. Pathologic Calcification
 Metastatic Calcification
- Occur in normal tissue in
“hypercalcemia”
Hypercalcemia
• Hyperparathyroidism
• Destruction of bone tissue
• Renal failure

23. Morphology of Cell Injury and
Necrosis
• Cell Injury – Reversible
– Irreversible
• Cell Death – Necrosis
– Apoptosis

24. Morphology of Cell Injury
Reversible Injury
Cellular swelling
Fatty change
• Plasma membrane alteration
• Mitochondrial Changes
• Dilation of Endoplasmic reticulum
• Nuclear Alteration

26. Morphology of Necrotic Cells
• Increased Eosinophilia
- loss of RNA (basophilia)
- denatured cytoplasmic protein
• Nuclear Changes
- Pyknosis
- Karyorrhexis
- Karyolysis
• Myelin figure
– large, whorled phospholipid mass
(phospholipid precipitate)

27. HISTOLOGIC FEATURES OF
COAGULATIVE NECROSIS
Normal cell Karyorrhexis
Reversible
cell injury
with Irreversible
cytoplasmic & cell injury Karyolysis
organelle with rupture of
swelling, blebb membrane &
ing & organelles, &
ribosome nuclear
detachment pyknosis

29. Morphologic pattern of Necrotic Cell
mass
• Coagulative necrosis
• Liquefactive necrosis
• Caseous necrosis
• Fat necrosis

30. Morphologic pattern of Necrotic Cell mass
• Coagulative Necrosis
:intracellular acidosis
– protein denatured
– proteolysis inhibited

31. Ischemic necrosis of the myocardium
A, Normal myocardium.
B, Myocardium with coagulation necrosis

32. Morphologic pattern of Necrotic Cell mass
• Liquefactive Necrosis
:focal bacterial (or fungal) infections
– accumulation of inflammatory
cells
:hypoxic death of cells within CNS

33. Coagulative and liquefactive necrosis
A, Kidney infarct exhibiting coagulative necrosis
B, A focus of liquefactive necrosis in the kidney

34. Morphologic Pattern of Necrotic Cell Mass
• Caseous necrosis
:gross appearance
:microscopic – granulomatous
inflammation

35. A tuberculous lung with a large area of caseous necrosis

36. Tuberculous granuloma showing an area of central necrosis, epithelioid
cells, multiple Langhans-type giant cells, and lymphocytes.

37. Foci of fat necrosis with saponification in the mesentery

38. Ischemic injury

39. Mechanisms of Cell Injury
Ischemic injury

40. Chemical
injury
Figure: Sequence of
events leading to fatty
change and cell necrosis
in carbon tetrachloride
(CCl4) toxicity. RER,
rough endoplasmic
reticulum; SER,
smoothendoplasmic
reticulum.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:23 PM)
© 2005 Elsevier