2. INTRODUCTION
• Degeneration and infiltration are retrogressive changes
• abnormal structural changes and decreased functions
• nonspecific responses of cells and tissues (variety of
injuries)
• processes may be reversible if the injury is mild. If the
injury is severe and persistent, it may progress to the
point where the involved cell dies. The distinction
between the point where the cells would recover and the
point where the process is irreversible and leads to cell
death is arbitrary.
3. • 1) Degeneration
• - the accumulation of metabolites or other
substances in a cell damaged by
preceding injury;
2) Infiltration
• - the overloading of previously normal
cells by materials which are abnormal in
either type of quantity
4. • dominant expression of injury as:
• 1) Water overload
2) Metabolite overload which involves excessive
accumulation of normal metabolic products,
such as fat, glycogen, or protein (hyaline
or proteinaceous); and
3) Storage loading, which involve overloading by
non-degradable products such as pigments,
minerals, and exogenous substances.
5. WATER OVERLOAD Hydropic degeneration
(Acute cellular swelling, Cloudy Swelling)
• marked mitochondrial damage,
• cessation of ATP production and failure of
sodium pump
• alteration of selective permeability of
cellular membranes leading to influx of
water molecules.
• leading to increased osmotic pressure
within cells
6. • failure of the injured cells to maintain
electrolyte balance through the "Sodium-
Potassium pump"
• energy dependent mechanism
• fall in ATP in injured cells causes the efflux
of Potassium ions
• influx of Sodium ions, the increasing
osmotic pressure in the cytoplasm attracts
water molecules
7. • swelling of the cells occurs
• Grossly
– enlarged pale, and heavy organ
• Microscopically
• affected cells show clear vacuoles in the
cytoplasm with no distinct borders, cytoplasm
is diluted, and dispersed.
• liver, kidneys, and brain
• Acute cell swelling in epithelial surfaces -----
blisters, wheals and flares, including ulcers
9. II. METABOLITE OVERLOAD
1) FAT OVERLOAD: - overload of fat occurs in
parenchymal cells particularly liver cells, and in tubular
epithelial cells of the kidney, and myocardial cells.
Normally, fatty acid is oxidised and combined to proteins
to form lipoproteins that are released into the circulation.
mechanisms result to the accumulation of lipids in cells:
• 1) Abnormally high levels of fat in the diet with a
resultant overload in fat metabolism;
2) Interference in protein production impeding lipoprotein
production;
3) Impairment in the conjugation process,
4) Interference in oxidation of fat, and
5) Interference in the release of lipoprotein from the
cytoplasm of cells
10. • Grossly, (usually the liver) shows uniform
paleness with a greasy cut surface.
• degeneration is common in conditions
where fat is abnormally utilized due to
failure in carbohydrate utilization as a
source of energy (example in diabetes), or
in the absence of carbohydrate as a
source for energy (example in starvation).
11. • a) Fatty change (Fatty degeneration, Fat phanerosis)
- implies the presence multiple small droplets of fat
within the cytoplasm of cells without nuclear
displacement.
• Microscopically, vacuoles with distinct borders appear in
the cytoplasm of affected cells.
• vacuoles make the cytoplasm to appear foamy, and may
coalesce to form large globules.
• b) Fatty infiltration (Steatosis) - characterised by the
presence of a single globule of fat displacing the nuclei
to one side; the fat globule being a "transport fat" derived
from fat depots and carried in the blood stream. This
change is similar to fatty degeneration.
13. 2) PROTEIN OVERLOAD
• a) Hyaline Change (Hyalinisation, Hyaline degeneration) -
"hyaline" describes pink-staining homogenous glassy cytoplasmic
droplets in cells.
• degeneration of cell protein.
• Included also is the accumulation of protein within cells following
abnormal metabolism.
• b) Fibrinoid - a special type of protein accumulation so named due
to its resemblance to coagulated fibrin, and found in degenerating
blood vessel walls and connective tissue.
• includes plasma proteins including fibrin, albumin and globulin
particularly immunoglobulins and complement.
• c) Amyloidosis - a special form of protein accumulation
characterized by the deposition of pertinacious material in basement
membrane.
• Amyloid consists of fibrillar beta-pleated protein molecules similar in
structure to immunoglobulins.
14. • d) Mucopolysaccharidosis (myxoid or
myxomatous degeneration, mucoid
degeneration) - Mucopolysaccharides are
conjugates of protein and carbohydrates
normally found in secretions of epithelial cells.
These substances are also found in the ground
substance of connective tissues and cartilage.
Excessive accumulation of these substances is
currently called mucopolysaccharidosis.
• Mucoid degeneration refers to overproduction of
mucinous secretion by cells.
15. • Myxomatous degeneration is described as
the transformation of tissues into a jelly-
like structure. The latter two terms are no
longer in use.
16. 3) CARBOHYDRATE OVERLOAD
• a) Glycogen degeneration - Glycogen degeneration
involves the presence of abnormally large amount of
glycogen in the cytoplasm of the cells.
• Glycogen is normally present in the cytoplasm of the
cells (particularly in liver cells).
• However, excessive accumulation occurs in some
disease processes characterized by prolonged
hyperglycaemia such as diabetes mellitus.
• microscopic changes are similar to acute cell swelling
where clear vacuoles are present in the cells.
17. III. STORAGE LOADING
• 1) LIPIDOSIS - Lipidosis refers the accumulation of lipid
degradation products in the cytoplasm of cells.
• degradation products are usually stored in lysosome
bound vacuoles.
• These materials are usually products of peroxidation of
fat and may be lipofuscins, ceroid, or cholesterol.
Chronic fatty change may progress to lipidosis, with the
lipid particles accumulating in the cytoplasm of cells
converted into complex, non-degradable products.
• Microscopically, the stored materials are distinct particles
in the cytoplasm of cells, assume a brown colour in
routinely stained sections.
18. • 2) CALCIFICATION - calcification refers to a
pathological deposition of calcium salts in cells and
tissues.
• (a) Dystrophic calcification - when calcium salts are
deposited in degenerate and necrotic cells and tissues.
• (b) Metastatic calcification - because of excess ionised
calcium in the blood. Tissue injury is not required for
calcium to be deposited in tissues.
• excessive mobilisation of calcium from skeleton as in
hypervitaminosis D, and hyperparathyroidism.
• In both processes, the organ or tissues affected have a
gritty texture on cut surface. Microscopically, the
deposited calcium salts are intensely basophilic and
breaks into fragments.
19. • 3) PIGMENTATION - pigments of either exogenous or
endogenous origin may accumulate within cells.
• (a) Exogenous pigmentation - following injection,
inhalation, or absorption from the gut of some colored
foreign materials. Exogenous pigments include the
following groups of materials:
• a.1) Metals - silver, bismuth, gold, lead, and iron.
a.2) Coarse Materials - dust, carbon, silica, and
asbestos.
a.3) Colored substances - carotene, tetracycline.
a.4) Fungi - monilia, aspergilli
20. • (b) Endogenous pigmentation - due to altered
metabolism of breakdown products of hemoglobin,
melanin and fat.
• b.1. hemoglobin derivatives
• (1) Haematins - iron-negative pigments that occur
following the action of acids to hemoglobin (artefacts),
parasites in blood (e.g., malaria), or following trauma to
tissues.
• (2) Haemosiderin - iron-positive pigment chemically
known as ferritin (the storage form of iron), seen in cases
of trauma, excessive haemorrhage or haemolysis.
• These pigments occur abundantly in the cytoplasm of
cells of the reticulo-endothelial system such as in the
spleen, Kupffer cells in the liver, and bone marrow.
• excessive formation because of haemolysis.
• (3) Haematoidin or Bilirubin - following excessive
haemorrhage or haemolysis, and failure of the liver to
conjugate bilirubin into bile, and/or secrete bile.
21. • (4) Porphyrins - Porphyrin pigments may accumulate in
tissues in rare disease conditions (example congenital
porphyria) characterized
• by a defect in hemoglobin formation. Apart from this, it is
a normal component in the formation of hemoglobin.
However, it occurs in some disease conditions following
ingestion of toxic plants (for porphyrin is formed following
breakdown of the chlorophyll in plants).
• This pigment is photo reactive, i.e. it causes activation of
some processes (production of toxic oxygen free
radicals) that cause per oxidation of lipid membranes.
The resultant condition is called photosensitization.
22. • b.2 Melanin pigmentation - granular protein
containing pigment produced by melanocytes.
Increased production occurs in association with
tumours of the melanocytes (melanoma),
excessive irradiation, and effects of sunlight.
• b.3 Lipid derived pigment (Lipofuscins) -
these pigments represent partially degraded
lysosome-bound indigestible residues of
autophagic vacuoles in cells. They are also
known in many names as "Wear and Tear
Pigment, Pigment of Brown Atrophy, Ceroid, or
Lipochrome".