Cell Injury

Dr. Meena Patil

 Cell Injury

 Responses of cell injury to stimulus- Adaptation

 -Reversible cell injury
 - Irreversible cell injury
 -Cell death
 Adaptations- Atrophy
 -Hyperplasia
 -Hypertrophy
 -Metaplasia
 Cell Injury
 Cellular adaptations
 Causes of cell injury-
 Hypoxia & ischaemia
 Physical agents
 Chemical agents & drugs
 Infectious agents
 Immunologic reactions
 Genetic derangements
 Nutritional imbalances
 Mechanisms of cell injury-
 Depletion of ATP
 - Mitochondrial damage
 Influx of intracellular Ca
 -Accumulation of oxygen-derived free radicals
 -Defects in membrane permeability

 Reversible and irreversible injury

 If injured cells recover their normal functions when

the stress is removed, the injury is said to be
reversible .

 If the injury is severe enough, however, a “point of no

return” is reached and the cell suffers irreversible
injury & dies .
 Cell Injury

 Cell Injury – Reversible

– Irreversible
- Intracellular accumulation of substances

 Cell Death – Necrosis

– Apoptosis
 Cell Injury
 Cell Injury- Morphology-Reversible injury

 Types of reversible cell injury or Degeneration-

 1. Cellular swelling/ Cloudy change/ Hydropic

change/ Vaculoar degeneration
 2. Hyaline change
 3. Mucoid change
 4. fatty change
Cell Injury

Necrosis
 Necrosis
 Necrosis- Definition
 - Types
 -Morphological changes
 - Mechanisms of cell injury
 1. Coagulation necrosis
 2. Liquifactive necrosis
 3. Fat necrosis
 4. Caseous necrosis
 5. Fibrinoid necrosis
 Fate of necrosis
Necrosis

Reversible
 Cell injury
Irreversible

“ Point of no return ” ?
 Two Phenomena consistently characterize irreversible
cell injury

1 . Inability to reverse mitochondrial dysfunction

2. Profound disturbances in membrane function

 Necrosis

 Definition-
 Localised area of death of tissue followed by degradation
of tissue by hydrolytic enzymes liberated from dead cells;
it is invariably accompanied by inflammatory cells.

 Cell contents leak out & damage the surrounding living

cells which offer a reaction
Morphologic appearance is the result of-

1. Denaturation of intracellular proteins &

2. Enzymatic digestion of cell

 If enzymes are from the injured cells itself – Autolysis

 Enzymes can be of immigrant leucocytes - Heterolysis

 Morphologic changes take hours to develop

 the earliest evidence of cell death is

….Raised blood levels of cellular enzymes &

proteins e.g. CK – MB, Troponins in MI
 Morphology of dead cells
 Cytoplasm -  Eosinophilia & glassy
homogeneous appearance due to
1. Loss of normal basophilia of RNA
2.  binding of eosin to denatured
cytoplasmic proteins
3. Loss of glycogen

 After enzymatic digestion – Vacuolation


Nuclear changes :

 Pyknosis – Shrinkage , density & basophilia

 Karyolysis – Dissolution – DNA-ase

 Karyorrhexis – fragmentation
CELL DEATH( NECROSIS)
 NECROSIS
Cell swelling
Inflammatory response
Death of many contiguous cells
Plasma membrnne disruption
Nuclear swelling & lysis
Lysosomal breakdown
Cell lysis & disentegration
Phagocytosis by infl ‘ cells
Hypoxia , toxins mainly
Damaged organelles
Cell death by ATP depletion
 Types of Necrosis

 Coagulative – Infarction

 Liquefactive – Brain infarct, abscess

 Caseous – Tuberculosis

 Fat – Acute pancreatitis

 Fibrinoid- Immunologic injury

 Coagulative Necrosis
 Cell’s basic outline is preserved (ghost like or tombstone
app.)

 Homogeneous, glassy eosinophilic appearance due to loss

of cytoplasmic RNA (basophilic) and glycogen (granular)

 Nucleus may show pyknosis, karyolysis or karyorrhexis

 Denaturation of both structural and enzymatic proteins by

injury or the subsequent increasing intracellular acidosis.
 COAGULATIVE NECROSIS

ETIOLOGY -

 Due to sudden stoppage of blood supply to part of

tissue or organ.( Ischemia)

 Less often from bacterial and chemical agents.

Organs commonly affected-

Heart, Kidney, Spleen
 Mechanism

Lack of oxygen in cells (Hypoxia)

Injured capillary allows leakage of plasma, absorption of tissue

fluid by dying cells and release of thromboplastin like substance.

Coagulation of plasma and tissue fluid

Stiffened cells get trapped in coagulum of plasma

Hence coagulative area has firm consistency

 Due to lack of oxygen the LYSOSOMAL ENYZYMES get
denatured and do not produce lysis of cell membrane.
But nuclear changes in form of karyolysis will take place.

 HENCE, THE ARCHITECTURE OF THE CELLS IS WELL

PRESERVED BUT THE NUCLEAR AND CYTOPLASMIC
DETAILS ARE LOST.
COAGULATIVE NECROSIS -MYOCARDIUM
COAGULATIVE NECROSIS -MYOCARDIUM
 Coagulative necrosis- AMI

 Coagulative necrosis of cardiac myocytes with a prominent

leukocytic infiltrate and hemorrhage in the interstitium.
The inflammatory cells are polymorphonuclear leukocytes.
Coagulative necrosis- AMI

 Contraction band
necrosis occurs
when there is no-
flow/reflow.

 Note inflammatory
cells percolating
through the tissue -
these are mostly
polymorphonuclear
leukocytes.
Renal Infarct – Coagulative necrosis
Coagulatine necrosis - Infarct of Kidney
Spleen Infarct - Coagulative necrosis
 Liquefactive Necrosis
 Usually due to enzymatic dissolution of necrotic cells
(usually due to release of proteolytic enzymes from
neutrophils)

 Most often seen in

- Bacterial or fungal infections
- Central nervous system infarction
 Liquefactive necrosis

• Enzymatic digestion
– Autolysis + WBC
• Liquid, viscous mass
• May contain pus
• Bacterial infections
(via inflammation)
• Hypoxic brain injury
• .
 Liquefactive necrosis

Grossly, the cerebral

infarction at the upper
left here demonstrates
liquefactive necrosis.
Eventually, the
removal of the dead
tissue leaves behind a
cavity.
Liquefactive necrosis of
the brain demonstrates
many macrophages at the
right which are cleaning
up the necrotic cellular
debris.
Skin Abscess
Liquefactive necrosis in Liver
 A subtype of coagulation necrosis
 White and cheesy
 Completely obliterated tissue architecture
 Gross: Resembles cheese
 Micro: Amorphous, granular eosinophilc material
surrounded by a rim of inflammatory cells
 No visible cell outlines – tissue architecture is obliterated
 Usually seen in tuberculous infections
 GROSS APPEARANCE

 Dry cheese like appearance

 Soft, granular, yellowish.

 This appearance is partly attributed to histotoxic effects

of lipopolysachharide present in the cell wall of tubercle

bacilli
Caseation necrosis in lung
 Liquefactive necrosis

Microscopically,
caseous necrosis is
characterized by
acellular pink areas of
necrosis, as seen here
at the upper right,
surrounded by a
granulomatous
inflammatory process
Liquefactive necrosis
 Fat Necrosis
 Special form of cell death occurring at 2 anatomically different

locations, having morphologically similar lesion.

 It is occurring at Pancreas & Breast as,

 Acute pancreatic necrosis & traumatic fat necrosis in

breast.
 Pathogenesis of Fat necrosis
Acute Traumatic breast
Pancreatitis Necrosis

Release of pancreatic lipase from injured tissue

Resulting into hydrolysis of neutral fat

Producing glycerol and free fatty acids

Glycerol diffuses into blood and free fatty acid

combines with calcium to form soap—this gives
cloudy appearance to the adipocytes
• Microscopically, fat necrosis
adjacent to pancreas is seen
here. There are some
remaining steatocytes at the
left which are not necrotic.
The necrotic fat cells at the
right have vague cellular
outlines, have lost their
peripheral nuclei, and their
cytoplasm has become a
pink amorphous mass of
necrotic material.
• Microscopically, fat necrosis
adjacent to pancreas is seen
here. There are some
remaining steatocytes at the
left which are not necrotic.
The necrotic fat cells at the
right have vague cellular
outlines, have lost their
peripheral nuclei, and their
cytoplasm has become a
pink amorphous mass of
necrotic material.
 Fibrinoid necrosis
 Fibrinoid necrosis – Mechanism unknown

 Fibrin like appearance of necrotic tissue

 Ex: Hypersensitivity vasculitis

Peptic ulcer
B.V. in malignant HPTN
• Microscopically, fat necrosis
adjacent to pancreas is seen
here. There are some
remaining steatocytes at the
left which are not necrotic.
The necrotic fat cells at the
right have vague cellular
outlines, have lost their
peripheral nuclei, and their
cytoplasm has become a
pink amorphous mass of
necrotic material.
Usually seen in the walls of blood
vessels (e.g., in vasculitides)
Glassy, eosinophilic fibrin-like
material is deposited within the
vascular walls
 Fate of a necrotic focus
 Most necrotic cells & debris disappear due to
fragmentation, enzyme digestion, & phagocytosis

 If this does not occur promptly, dystrophic

calcification

 Repair by fibrosis

 Gangrene
 Summary
 Irreversible injury- Necrosis
 - Apoptosis
 Necrosis- Definition
 - Types
 -Morphological changes
 - Mechanisms of cell injury
 1. Coagulation necrosis
 2. Liquifactive necrosis
 3. Fat necrosis
 4. Caseous necrosis
 5. Fibrinoid necrosis
 Fate of necrosis