CELL INJURY

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CELL INJURY
Normal cell acts in a steady state to handle its
physiologic demands. When there is stress , the
cell responds by Normal cell (hemeostasis) adapta
tion
Cell injury
inability to adapt
-Exceeded limits of adaptive ability
-No adaptive response

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Adaptation -The cell achieves a new steady
state with preserved viability and function. -
Hyperplasia, hypertrophy, atrophy metaplasia.
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• Types (forms) of Cell InjuryAccording to the
  duration and
• severity of the injurious agent.
• Reversible
  Irreversible
• Milder form More severe form
• Biochemical Morphological
  Death of cells
• changes changes
• DEGENERATION
  NECROSIS

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• Causes of cell injury
• Acquired
  Genetic
• -Hypoxia
  chromosomal
• -Biological
  abnormalities
• -Physical
• -Chemical
• -Immunological
• -Nutritional

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Pathogenesis of cell injury

• The cell
• Na pump
• K
  
• 
  Na
• 
  
• 
  water
• 
  

Ka
Ka
K
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-Failure of sodium pump by
-Affect mitochondria.decrease ATP
-Damage of Na pumps-Damage of cell membrane

The cell is swollen

• Na

K
Water
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Morphological changes of reversible cell injury
-Cloudy swelling
-Hydropic change

• Cloudy swelling
• -Swelling of cells
• -Cytoplasm pale, vacuolated , clear
  or granular
• -EM.Mitochondrial swelling Dilated
  endoplasmic
• reticulum
• -Occur in highly specialized
  parenchymatous organs
• as liver cells renal
  tubules.

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• Hydropic change
• -There is excessive accumulation of
  intracellular water.
• -Marked swelling of the cells
• -e.x. Skin in Chicken small pox
• Liver cells in viral hepatitis
• Islets of langerhans in early
  diabetes mellitus

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IRREVERSIBLE CELL INJURYNECROSIS

• Death of group of contiguous cells within a
  living tissue or organ.
• Autolysis is dissolution of dead cells by its own
  digestive enzymes
• Another form of cell death is
• Apoptosis Single cell death during
  life

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• NECROSIS
• Morphological changes
• Nuclear
  Cytoplasmic
• -Pyknosis
  -Homogeneous or granular
• ( Shrunked dense)
• -Karyorrhexis
  -Eosinophilic
• (Fragmentation into small particles)
• -Karyolysis
• (Disppearance)

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• EM changes of necrosis
• -Clumping disappearance of chromatin.
• -Fragmentation disappearance of organelles.
• Pathological lesions associating necrosis
• -Acute inflammation
• -Liquefaction
• -Absorption of liquefied
  necrotic tissue (b.v lymphatics).
• -Healing by organization or
  regeneration.
• -Encapsulation by fibrous
  tissue (incomplete fibrosis)
• -Pathological calcification.
• -Gangrene

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TYPES OF NECROSIS

• 1-COAGULATIVE NECROSIS
• 2-LIQUEFACTIVE NECROSIS
• 3-CASEOUS NECROSIS
• 4-FAT NECROSIS

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• COAGULATIVE NECROSIS
• e.gInfarction heart, spleen kidney
• Grossly Area of necrosis is pale yellow,
• 
  swollen (raised on the surface)
• 
  firm
• 
  opaque
• Microscopic picture
• -Architectural necrosis with preserved
  architecture
• -Acute inflammation at the surrounding tissue

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• LIQUEFATIVE NECROSIS
• e.g. An abscess
• Amoebic abscess
• Infarction of the brain
• Grossly -necrotic tissue consists of a turbid
  fluid
• -Leaves a cavity after absorption

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• CASEOUS NECROSIS
• e.g. Tuberculosis
• Grossly -Partially liquefied necrotic tissue
• -grayish yellow
• -creamy like cream cheese or
  casein of milk
• Microscopic picture necrotic tissue is
• -Structureless
• -homogeneous or
  granular
• -eosinophilic

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• FAT NECROSIS
• Traumatic
  Enzymatic
• e.g.breast trauma
  e.g acute hemorrhagic
• 
  pancreatitis
• Grossly Necrotic area is
• -opaque white
• -calcification
• Microscopic picture
• -Cloudy fat cells
• -Chronic inflammatory
  cells FB giant cells

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APOPTOSIS

• Death of single cells during life (Programmed
  obsolescence)
• An active process (needs energy)
• Not associated by inflammatory reaction
• Physiological or Pathological
• -To maintain a steady state number
  e.g
• of cells in tissues
  Tumors
• e.g. endometrial shedding
  atrophy
• 
  irradiation
• 
  liver cells in viral
  hepatitis

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Stages of apoptosis
Apoptotic bodies
Plebs
Cell
engulfed
-Condensed fragmented Chromatin -Fragmented
organelles

• Shed from surface

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• INTRACELLULAR ACCUMULATIONS
• Increases amount of abnormally present
  pigment
• Normally present substance
• Substance
• e.g.lipids,
• Carbohydrates
• proteins
• Accumulated substance may be
• Harmless
  harmful toxic

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Intracellular accumulation by lipidsFatty change

• Abnormal accumulation of triglycerides (neutral
  fat) within parenchymatous cells.

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Fatty change is not due to unmasking of the
normally present fat but due to the presence of
excessive amounts of triglycerides

• Pathogenesis

Blood
Glycerol
Apoprotein
Fatty acids From blood
Triglycerides
Lipoprotein
insoluble
soluble
emulsification
Liver cell
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• Causes of FATTY CHANGE
• Hypoxia Toxins Alcohol Diabetes
  Malnutrition
• 
  mellitus
• -Anaemia -Bacterial
• -Hear failure -chemical
• -Ischemia

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• Grossly The organ is enlarged soft
• Liver
• -size enlarged
• -consistency soft
• -edge rounded
• -cutsurface bulging, yellow
  greasy.
• Heart -
• -size
  enlarged
• -consistency flappy
• -Endocardial surface yellow and
  brown streaks
• 
  (tigroid appearance)

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Microscopic picture HE Clear vacuoles Special
stains Frozen sections Sudan III Oil red
stain--------orange color of fat

• Liver

Fat vacuole
Signet ring appearance
Fat vacuoles
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• Heart

Multiple small vacuoles
On either side of the nucleus
Cardiac muscle fiber
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• Other LIPID accumulations
• Cholesterol Stromal fatty
  Abnormal lipids
• 
  Infiltration
• e.g . e.g.
  e.g.
• -Old hemorrhage -obesity
  -lipid storage disease -Gall bladder
• (cholesterolosis)
• -Atherosclerosis
• (arterial intema)

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• GLYCOGEN
• Abnormal glucose
  Abnormal glycogen
• metabolism
  metabolism
• e.g. Diabetes mellitus e.g.
  Glycogen storage disease

Tissue is preserved in alcohol and stained by PAS
stain for glycogen
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• PROTEINS
• e.g.
• -Plasma cells Russel bodies
  due to increased intracellular immunoglobulins
  (eosinophilic bodies).
• -Lining epithelium of renal tubules in heavy
  proteinuria (eosinophilic droplets) .
• MUCOPOLYSACCHARIDES
• Rare hereditary diseases

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• Disturbance of
• MUCIN SECRETION
• Epithelial mucin
  Connective tissue mucin
• e.g.
  E.g.
• -Catarrhal rhinitis -
  Marfan syndrome
• (Inflammation)
  (medionecrosis of aorta)
• -Tumors adenocarcinoma -Tumors myxoma
• mucoid change
  myxoid change
• -Abnormal mucin
  -Myxoedema mucoviscidosis
  Dermis in hypothyroidism

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• FIBRINOID CHANGE
• -Other terms Fibrinoid necrosis fibrinoid
  degeneration
• -Its nature is unknown but it shows the same
  staining reaction of fibrin
• -Microscopically a granular eosinophilic
  material
• -e.g. - Wall of arteries in malignant
  hypertension
• - Collagen diseases Rheumatoid
  arthritis
• 
  Rheumatic fever
• -Type III hypersensitivity
  reaction

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• HYALINE CHANGE
• -Other terms
• Hyaline degeneration, hyalinosis
  hyalinization.
• -A descriptive term to
• homogenous refractile eosinophilic material.
• e.g.
• Connective tissue
  Epithelial
• -Wall of blood vessels (old age)
  -lumen of prostatic acini
• -Collagen as in scars keloid
  (corpora amylacea)
• -Tumors as leiomyoma
  -hepatocytes in viral hepatitis
• -Kidney glomeruli as end stage
  -Kidney cytoplasm and lumen
• arteries in benign hypertension
  of tubules in heavy proteinuria
• 
  

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AMYLOIDOSIS

• -An extracellular deposition of amyloid material
  in connective tissue and walls of blood vessels.
• -Amyloid consists of protein with
  mucopolysaccharide
• -It causes cell injury as the extracellular
  deposition of amyloid causes pressure atrophy of
  the cells
• -It does not induces inflammatory reaction

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• CLASSIFICATION OF AMYLOIDOSIS
• Chemical
  clinical
• -AA (amyloid associated) protein -Secondary
• Not an immunoglobulin
  amyloidosis
• 
  
• -AL (amyloid light chain) protein -Primary
• An immunoglobulin produced by
  amyloidosis
• plasma cells.

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• 1ry amyloidosis 2ry
  amyloidosis
• -Heart, tongue, GIT, -liver,
  spleen, kidney
• nerves skin
  lymph nodes
• -Unknown cause -In
  chronic diseases as
• -common with multiple suppurative
  diseases, TB,
• myeloma
  leprosy malaria
• 
  -Rheumatoid arthritis.

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• Grossly
• The affected organ is enlarged
• -Consistency firm elastic
• -Cut surface flat, translucent and waxy
• light brown in color
• -Edge sharp
• Microscopically
• HE refractile eosinophilic substance
• Congo red stain Apple green birefringence under
• polarized light
• Thioflavin-T Yellow fluorescence

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HE
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Congo red with polarized light
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Thioflavin -T
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Effect of amyloidosis on organs

• _Kidney Nephrotic syndrome
• - Adrenal gland Addisons disease
• -Small intestine Malabsorption syndrome
• -Liver Fatty change
• Portal hypertension
• Pressure atrophy
• -Spleen Sago spleen (localized form)
• Marked splenomegaly(diffus
  e form)