Useful for MBBS students

1. Dr Neha Mahajan
MD Pathology

2.  Autolysis
 Necrosis
 Gangrene
 Apoptosis

3.  It is disintegration of the cell by its own hydrolytic
enzymes liberated from lysosomes.
 Can occur in living body or postmortem.
 Morphologically, autolysis is identified by
homogenous & eosinophilic cytoplasm with loss
of cellular details & remains of cell as debris.

4.  Def: It is defined as focal death along with degradation
of tissue by hydrolytic enzymes liberated by cells and is
accompanied by inflammation.
 Causative agents:
Hypoxia
Chemical and physical agents
Microbial agents
Immunological injury

5. MORPHOLOGY
Cytoplasm
Increased eosinophilia due to loss of RNA
Glassy homogenous appearance due to loss of glycogen
particles
Vacuolated or moth eaten appearance
Myelin figures
Electron microscopy- discontinuities in plasma & organelle
membranes, marked dilation of mitochondria,
amorphous densities

6. Nucleus
Pyknosis
Nuclear shrinkage due to condensation of nuclear
chromatin
Karyolysis
Chromatin fades- loss of DNA due to enzymatic
degradation by endonucleases
Karyorrhexis
Pyknotic nucleus undergo fragmentation

7.  Coagulative
 Liquefactive
 Caseous
 Fatty
 Fibrinoid
 Gangrenous

8.  Most common type due to ischaemia
 Organs- heart, kidney, spleen
 Grossly- foci of necrosis
Early pale, firm & slightly swollen and shrunken
Later yellowish softer & shrunken
 Microscopy-
Conversion of normal cells into their tombstones i.e cell
outline preserved but nuclear details lost
Cells swollen, more eosinophilic with nuclear changes

9. Wedge shaped kidney infarct

10. Microscopy of edge of infarct showing normal kidney and
necrotic cells in infarct

11.  It is characterised by digestion of the dead cells,
resulting in transformation of the tissues into liquid
viscous mass
 Seen in focal bacterial and fungal infections
 Examples- infarct brain, abscess cavity
 Grossly- affected area is soft with liquefied centre
containing necrotic debris, cyst wall
 Microscopically- cystic space shows necrotic cell debris
and macrophages

12. Liquefactive necrosis.
Infarct brain showing dissolution of tissue

13. Liquefactive necrosis in the brain

14. Combines featues of coagulative and liquefactive necrosis
Example:
◦ tuberculosis lesions
◦ fungal infections
 Coccidioidomycosis
 Blastomycosis
 Histoplasmosis
Gross- Dry cheese, soft, granular and yellowish
Microscopy- necrosed foci are structureless eosinophilic with
granular debris surrounded inflammatory cells (granulomas)

15. Caseous necrosis:
confluent cheesy tan granulomas in the lung in a patient
with tuberculosis

16. Pulmonary tuberculosis:tubercle contains amorphous finely
granular, caseous ('cheesy') material typical of caseous necrosis.

17.  Focal area of fat destruction, resulting from release of
pancreatic lipases
 Traumatic fat necrosis
 Gross- fat necrosis seen as yellowish white and firm
deposits, chalky white appearance.
 Microscopy-
Necrosed fat cells have cloudy appearance & are
surrounded by inflammatory reaction.

18. Fat necrosis secondary to acute pancreatitis

19.  It is characterised by depostion of fibrin like material
which has staining properties of fibrin
 Seen in immunological tissue injury( immune complex
vasculitis,autoimmune diseases,arthus reaction)
Arterioles in hypertension and peptic ulcer

20. Fibrinoid necrosis: afferent arteriole and part of the glomerulus
are infiltrated with fibrin, (bright red amorphous material)

21. Fibrinoid necrosis- wall of artery shows circumferential
bright pink area of necrosis

22.  Gangrene is a form of necrosis of tissue with
superadded putrefaction
 Usually coagulative type due to ischaemia
 Example- gangrene of bowel
gangrene of limb
 Gangrenous or necrotising inflammation- gangrene
lung, gangrenous appendicitis
 Types- Dry gangrene
Wet gamgrene
Gas gangrene

23.  It begins in the distal part of a limb due to ischaemia.
 Examples- dry gangrene in toes & feet of an old person
due to arteriosclerosis
Thromboangitis obliterans( Buerger`s disease)
Raynaud`s disease
Trauma
Ergot poisoning
Line of separation is formed between gangrenous and
viable part.

24. Gross- Affected part is dry, shrunken and dark black (foot
of mummy)
black due to liberation of Hb from haemolysed RBC`s
which is acted upon by H2S produced by bacteria
resulting in formation of black iron sulphide.
Line of separation- separation with falling off the
gangrenous tissue
Microscopy-
Necrosis with smudging off tissue. Line of separation
consists of inflammatory granulation tissue.

25. Dry gangrene

26.  It occurs in moist tissues and organs such as mouth,
bowel, lung, cervix, vulva,etc
 Examples:
Diabetic foot
Bed sores
 Wet gangrene develops due to blockage of venous and
less commonly arterial.
 Affected part is stuffed with blood- growth of putrefactive
bacteria
 No clear cut line of demarcation, may spread to
peritoneal cavity causing peritonitis.

27. Gross-
Affected part is soft, swollen, putrid, rotten and dark.
Microscopy-
Coagulative necrosis with stuffing of affected part with
blood.
No clear cut line of demarcation.

29. Feature DRY GANGRENE WET GANGRENE
SITE Commonly limbs More common in bowel
MECHANISM Arterial occlusion More commonly
venous obstruction
MACROSCOPY Organ dry, shrunken
and black
Part moist,
soft,swollen,rotten and
dark
PUTRFACTION Limited due to very
little blood supply
Marked due to stuffing
of organ with blood
LINE OF DEMARCATION Present at the junction
between healthy and
gangrenous part
No clear cut line of
demarcation
BACTERIA Bacteria fail to survive Numerous present
PROGNOSIS Generally better due to
little septicemia
Generally poor due to
profound toxemia

30.  It is form of wet gangrene caused by gas forming
clostridia.( gram positive anaerobic bacteria)
 Gross-
Affected tissue swollen, oedematous, painful and
crepitant due to accumulation of gas bubbles within the
tissues.
Later tissue becomes dark black and foul smelling.
 Microscopy-
Muscle fibres show coagulative necrosis with liquefaction,
oedema and leucocytic infiltrate

31. Def: Apoptosis is a pathway of cell death that is
induced by a tightly regulated suicide program in
which cells destined to die activate enzymes that
degrade the cells' own nuclear DNA and nuclear
and cytoplasmic proteins.

33. CAUSES OF APOPTOSIS
 Physiological
 Pathological

34. Apoptosis in Physiologic Situations
 The programmed destruction of cells during
embryogenesis, including implantation, organogenesis,
developmental involution, and metamorphosis.
 Involution of hormone-dependent tissues upon hormone
withdrawal.
 Cell loss in proliferating cell populations, such as
immature lymphocytes in the bone marrow and thymus
that fail to express useful antigen receptors, B
lymphocytes in germinal centers, and epithelial cells in
intestinal crypts, so as to maintain a constant number
(homeostasis).
 Elimination of potentially harmful self-reactive
lymphocytes.
 Death of host cells that have served their useful
purpose.

35. Apoptosis in Pathologic Conditions
 DNA damage. Radiation, cytotoxic anticancer
drugs, and hypoxia can damage DNA, either
directly or via production of free radicals. If
repair mechanisms cannot cope with the injury,
the cell triggers intrinsic mechanisms that
induce apoptosis.
 Accumulation of misfolded proteins.
 Cell death in certain viral infections.
 Pathologic atrophy in parenchymal organs
after duct obstruction, such as occurs in the
pancreas, parotid gland, and kidney.

36. MORPHOLOGIC AND BIOCHEMICAL CHANGES IN
APOPTOSIS
Morphology
 Cell shrinkage. Cell smaller, cytoplasm dense and the
organelles, though relatively normal, are more tightly
packed.
 Chromatin condensation. This is the most characteristic
feature of apoptosis. The chromatin aggregates
peripherally, under the nuclear membrane, into dense
masses.
 Formation of cytoplasmic blebs and apoptotic bodies.
Extensive surface blebbing, then undergoes fragmentation
into membrane-bound apoptotic bodies composed of
cytoplasm and tightly packed organelles, with or without
nuclear fragments.
 Phagocytosis of apoptotic cells or cell bodies, usually
by macrophages. Apoptotic bodies are rapidly ingested by
phagocytes and degraded by the phagocyte's lysosomal
enzymes.

37. On histologic examination, in tissues stained with
hematoxylin and eosin, the apoptotic cell appears as
a round or oval mass of intensely eosinophilic
cytoplasm with fragments of dense nuclear
chromatin.

38. FEATURE APOPTOSIS NECROSIS
Definition Programmed &
coordinated cell death
Cell death along with degradation
of tissue by hydrolytic enzymes
Causative
agents
Physiological &
Pathological processes
Hypoxia,toxins
Morphology •No inflammatory reaction
•Death of single cells
•Cell shrinkage
•Cytoplasmic blebs on
membrane
•Apoptotic bodies
•Chromatin condensation
•Phagocytosis of
apoptotic bodies by
macrophages
•Inflammatory reaction present
•Death of many adjacent cells
•Cell swelling initially
•Membrane disruption
•Damaged organelles
•Nuclear disruption
•Phagocytosis of cell debris by
macrophages
Molecular
changes
•Lysosomes & other
organelles intact.
•Genetic activation by proto
oncogenes & oncosupressor
genes & cytotoxic T cell
mediated target cell killing.
•Lysosome breakdown with liberation
of hydrolytic enzymes.
•Cell death by ATP depletion,
membrane damage, free radical
injury.

39. Activation of Caspases.
Initiator caspases- caspase-8 and caspase-9.
Executioners caspase-3 and caspase-6
DNA and Protein Breakdown.
“Typical DNA” ladders-apoptotic cells.
“Smeared” pattern of DNA fragmentation necrosis.
Membrane Alterations and Recognition by
Phagocytes.
Movement of some phospholipids (notably
phosphatidylserine) from the inner leaflet to the outer
leaflet of the membrane- recognised by phagocytes
Annexin V

40.  Initiation phase
1.Intrinsic pathway
2.Extrinsic pathway
 Execution phase
Activation of caspases

41. Initiators:
Absence of stimuli required for normal cell survival
(absence of certain hormones, growth factors, cytokines)
Regulators of Apoptosis:
Pro apoptotic genes: Bax, Bak,Bid,Bim
Anti apoptotic genes: Bcl-2,Bcl-X
Activation of Caspases:
Caspase 9

43.  FAS receptor activation
 Activation of caspases
Caspase 8, 10

45. Two initiating pathways converge to a cascade of
caspase activation, which mediate final phase of
apoptosis
Mitochondrial(Intrinsic)- caspase 9
Extrinsic- caspase 8 & 10
Executioner caspases- caspase 3 & 6

47. Apoptosis summary

48.  Growth factor deprivation.
 DNA damage.
 Protein misfolding.
 Apoptosis induced by TNF receptor family.
 Cytotoxic T lymphocyte mediated apoptosis.
 Disorders associated with dysregulated apoptosis.

49. Necrosis
Coagulative
Liquefactive
Caseous
Fatty
Fibrinoid
Gangrenous
Gangrene
Dry
Wet
Gas
Apoptosis
SUMMARY

50. Questions

51. THANK YOU