Degenerations

Presented
By

Ahmed El-Rashedy
Professor & Previous Head
of Pathology Department
Al-Azhar University

Prof. Dr. Ahmed Elrashedy

Degeneration
Def.: An abnormal disturbance of metabolism associated
with reversible morphological changes on exposure of a
living tissue or cells to non-lethal irritants.
Types of irritants:
1. Hypoxia.
2. Chemical agents:
Air pollutants & hydrocarbons.
Hypertonic solutions.
Poisons: Cyanide, Mercury, Arsenic.
Insecticides.
Fungicides.
Industrial vapors or fibers (Asbestos, silica).
Drugs: Narcotics.

Prof. Dr. Ahmed Elrashedy

Types of irritants:
3. Physical agents:
Mechanical trauma or crush injury.
Extremes of temperature (excess heat or severe coldness).
Irradiation whether ionizing (cobalt, gamma) or nonionizing (X-, ultraviolet) rays.
Electric shock.
4. Micro-organisms(viable agents):
Bacteria.
Viruses.
Fungi.
Parasites.
Rickettsia.

Prof. Dr. Ahmed Elrashedy

Types of irritants:
5. Immunologic disorders:
Hypersensitivity to a foreign protein (injectable,
ingestible, inhaler).
Hypersensitivity to a self- antigen as extrusion of
eye lens protein or sperm head protein in obstructed
epididymis.
6. Genetic diseases:
Sickle cell anemia: production of Hb-S instead of
Hb-A.
Downs syndrome (Mongolism): aberration in
chromosome no; 21.

Prof. Dr. Ahmed Elrashedy

Types of irritants:
7. Nutritional disorders:
Hyper- or Hypo- vitaminosis A & D.
Protein-Calorie deficiency: Marasmic baby
(Kwashiorkor's disease).
Fat-rich diet intake: Obesity & atherosclerosis.
Sites of degeneration:
Parenchymatous organs because they contain highly
active & energy producing cells. These organs are:
1. Liver (Hepatocytes).
2. Kidney (Renal tubular cells).
3. Heart ( Cardiac muscle cells).

Prof. Dr. Ahmed Elrashedy

Cloudy Swelling
(Hydropic Degeneration=Ballooning
Degeneration=Vacuolar Degeneration)
Def.: An abnormal accumulation of water inside the living cell.
Pathogenesis: Hypoxia (or ischemia)
Early mitochondrial
condensation
Mitochondrial swelling lack in energy supply
causing failure of sodium /potassium pump
Retention of
sodium inside the cell Increase of intracellular osmotic pressure
with
imbibation of water from extracellular compartment
producing droplets of water within the cytoplasm (fine granules
representing swollen mitochondria = Cloudy swelling). Then, large
vacuoles (representing distended endoplasmic reticulum)
accumulate within the cell
Clear cytoplasm (Hydropic
degeneration).

Prof. Dr. Ahmed Elrashedy

Pathology:
A) Gross: The affected organ becomes:
1. Color: Pale.
2. Size: Enlarged (Swollen).
3. Weight: Increased (Heavy).
4. Cut surface: Bulges over the capsule.
B) L/M (in kidney):
1. Renal tubules:
Size: Swollen &enlarged.
Lining cells:
Shape: Pyramidal (normally cubical).
Cytoplasm: Pale, granular or clear.
Lumen of tubules:
Star-shaped or obliterated (normally patent, oval
& regular).
2. Capillaries in-between the swollen tubules:
Compressed.

Prof. Dr. Ahmed Elrashedy

B)
1.

2.

E/M (in kidney):

Changes in cell membrane:
Cellular swelling.
Loosening of intercellular attachments
(Desmosomes).
Formation of myelin fingers.
Blunting & distortion of microvilli.
Changes in cytoplasmic organelles:
Mitochondrial swelling with indistinct
cristae, double short basal infolding
membrane with bizarre mitochondria,
rupture & calcification.
Deformed Golgi zone.
Lysosomal swelling.
Dilated rough endoplasmic reticulum.
Detached free ribosomes & protein
synthesis.
Cytoplasmic droplets & clear vacuoles
of water.

Prof. Dr. Ahmed Elrashedy

Electron micrograph showing:

(a) Proximal convoluted tubule cell
with focal loss Brush Border (BB),
numerous apical vesicles (V),
numerous lysosome (L) deformed
Golgi zone (G), nucleus (N) with
marginal heterochromatin in dense
cytoplasm.
(b) Swollen round mitochondria (M)
with indistinct cristae, vesicles (V)
and secondary lysosome (L).
(c) Apoptotic cell with nucleus have
invaginated nuclear envelope and
heterochromatin condensation.
(d) Double short basal infolding
membrane (arrows) with bizarre
mitochondria (M)

Prof. Dr. Ahmed Elrashedy

Electron micrograph showing:

(a) Part of tubule cell reveals normal
Brush Border (BB), small lysosome
(L), nucleus (N) and large elongated
mitochondria
(M)
in-between
extended basal infolding (arrows).
(b) Details intact Brush Border (BB)
and well developed vesicles (V).
(c) Details part of nucleus (N) with
peripheral
heterochromatin,
lysosome
(L),
homogenous
mitochondria (M) with normal
cristae, double membrane basal
infolding (arrow) & free ribosome
(R).

Prof. Dr. Ahmed Elrashedy

Fatty changes (Fatty Degeneration)

Def.: An abnormal accumulation of fat within the parenchymatous cells.
Sites:
1. Liver.
2. Heart & muscles.
3. Kidney.
Pathogenesis:
Excess accumulation of triglycerides within the liver due to one of the
followings:
1. Excess free fatty acid entry into the liver.
2. Excess FFA synthesis from acetate.
3. Increased FFA esterification into triglycerides (through
glycerophosphate).
4. Decreased FFA oxidation.
5. Decreased apoprotein synthesis (Apoprotein normally conjugates
with triglycerides to form lipoprotein).
6. Impaired lipoprotein secretion from the liver.

Prof. Dr. Ahmed Elrashedy

Causes of Fatty liver:

1. Chronic alcoholism (Hepatotoxic
methyl alcohol drinking).
2. Protein malnutrition (starvation).
3. Diabetes mellitus.
4. Obesity.
5. Hepatotoxic chemicals: as carbon
tetrachloride& phosphorus.

Prof. Dr. Ahmed Elrashedy

Pathology:
I) Liver:
Gross:
1. Mild: No abnormality.
2. Severe Fatty liver:
Size: Enlarged.
Color: Yellowish.
Consistency: Soft& greasy.
Outer Surface: Smooth.
Border: Round.
Differential Diagnosis:
Amyloid liver:
Size: Enlarged.
Color: whitish.
Consistency: Firm & waxy.
Outer Surface: Smooth.
Border: Sharp.

Prof. Dr. Ahmed Elrashedy

L/M:
1. Early:
Small fat vacuoles in the cytoplasm near
the nucleus.
2. Later :
Union of these vacuoles to give clear
spaces displacing the nucleus into the
periphery against the cell membrane
(Signet ring appearance).
3. Late:
Rupture of the fat-filled hepatocytes with
union of the fat globules together giving
fatty cysts.

Prof. Dr. Ahmed Elrashedy

II) Heart: (Tabby Cat Striations) or (Thrush

Breast):
Occurs in case of chronic or severe anemia
(due to a prolonged moderate ischemia).

Gross:
Size: Enlarged.
Color & Pattern: Alternating layers of

yellowish fatty myocardial fibers & dark redbrown congested uninvolved fibers.
Consistency: Soft.
Outer Surface: Smooth.

L/M:
Similar to those detected in the liver.

Prof. Dr. Ahmed Elrashedy

Identification of fatty globules:

1. Hematoxylin & Eosin stain: Clear vacuoles
(dissolution of fat by xylene used in preparing
the slide).
2. Sudan IV & Red oil stains: Bright-red globules.
3. Osmic acid & Sudan black : Black fatty
vacuoles.
N.B.:
Fatty
ingrowth
or
stromal
fatty
infiltration: An abnormal accumulation
of fat within the stromal C.T. cells.
It occurs in obesity.
Sites:
1. Pancreas: Fat in the C.T. septa of the
pancreatic lobules.
2. Heart: Fat in the C.T. in-between the
muscle bundles.

Prof. Dr. Ahmed Elrashedy

Hyaline Change (Hyaline Degeneration)

Def.: Abnormal accumulation of Proteinaceous
homogenous structureless translucent material
inside the living cell.
Cause: Disturbance in the protein metabolism
inside the cell.
Chemical Nature:
Protein-Phospholipid Complex.
Examples:
1. Kidney: Hyaline droplets within the proximal
renal convoluted tubular cells.
2. Liver: Hyaline droplets within the
hepatocytes in alcoholic cirrhosis (Mallory
bodies).
3. Brain: Cytoplasmic round, oval or bullet
shaped inclusion viral particles called Negri
bodies in the neurons.
4. Plasma cells: Hyaline spherical droplets
within the plasma cells called Russell bodies.

Prof. Dr. Ahmed Elrashedy

5. Diaphragm & Rectus abdominis muscle:

(Zenkers Degeneration)
Cause:
A complication of typhoid fever.
Pathology:
A) Gross: The involved muscle is:
1. Friable.
2. Pale.
3. May rupture giving minute hemorrhages.
B) L/M:
I) Early:
1. Swollen homogenous pink muscle fibers.
2. Loss of striations.
II) Late:
Necrosis with loss of the cellular details
with fragmentation or lysis of their nucleus.

Zenkers
Degeneration

Prof. Dr. Ahmed Elrashedy

Extracellular Degenerations
(Intercellular Damage)
I) Damage of the fibers:
1. Fibrosis.
2. Elastosis.
3. Extracellular hyalinosis:
C.T. Hyalinosis.
Vascular Hyalinosis.
4. Fibrinoid Necrosis.
II) Damage of the matrix:
1. Myxomatous Degeneration.
2. Amyloid Degeneration (Amyloidosis).

Prof. Dr. Ahmed Elrashedy

Damage of Fibers

1. Fibrosis
Def.: Excess formation of mature collagen fibers.
Examples:
1. Nodal fibrosis: in L.N. draining an area of
chronic infection.
2. Bilharzial liver fibrosis.
3. Liver cirrhosis.
4. Pulmonary fibrosis.

2. Elastosis
Def.: Formation of elastic fibers.
Examples:
1. Normal Skin following a prolonged exposure
to ultraviolet light.
2. Skin cancer following a prolonged sunlight
exposure.

Bilharzial liver fibrosis

Pulmonary fibrosis
( Masson trichrome)

Elastosis

Prof. Dr. Ahmed Elrashedy

3. Hyalinosis (Extracellular Hyaline Change)

Def.: Abnormal extracellular accumulation of hyaline
material.
Pathogenesis:
A. C.T. Hyalinosis: Fusion of the collagen fibers.
B. Vascular Hyalinosis: Leakage of plasma proteins
through the damaged endothelium into the interior of
arterial wall.
Examples:
I) C.T. hyalinosis:
1) Hyalinosis of collagen fibers in old scar.
2) Hyalinosis of splenic capsule & trabeculae in congestive
splenomegaly.
3) Neoplastic Hyalinosis: e.g. as secondary change in
fibromyoma (leiomyoma).
II) Vascular hyalinosis:
1. Arteriolar wall hyalinosis: in renal benign HPT & in
diabetes.
2. Glomerular hyalinosis: in chronic glomerulonephritis.

Prof. Dr. Ahmed Elrashedy

4. Fibrinoid Necrosis
Def.: It is a descriptive process including:
1) Swelling of the collagen fibers.
2) Fragmentation of these fibers.
3) Degeneration of the collagen fibers (increased
eosinophilia).
Examples:
Ashoff Nodules
1. Collagen Diseases: as
Systemic Lupus (SLE).
Systemic sclerosis.
Rheumatoid arthritis.
Polyarteritis nodosa (PN).
2. Malignant Hypertension.
3. Rheumatic endocarditis (Ashoff Nodules).

Prof. Dr. Ahmed Elrashedy

Damage of Matrix
Myxomatous Degeneration
Def.: Pathological condition characterized by increase in
the ground substance + degeneration of the stromal
fibers.
Pathology:
Gross:
Soft, jelly-like tissue resembling
Wharton jelly of the umbilical cord.
L/M:
Star or stellate-shaped branching
cells interlacing with each other found in a faint blue
mucopolysaccharide matrix.
Example:
Myxomatous degeneration occurring as a 2ry change in
fibromyoma.
D.D.: Myxedema:
Only an increase in the ground substance appearing as
homogenous blue material.



Prof. Dr. Ahmed Elrashedy