Section 2
Tissue and Cellular
Damage
1. Degenerations
Definition: When cellular injury is sublethal
and sustained, cells and tissues tend to
accumulate substances in abnormal quantities.
These materials may be endogenous or
exogenous.
Location: Intracellular and/or Extracellular
Nature: Normal substances: increase
Exogenous materials: appearance
(1) Intracellular edema (cloudy swelling)
Definition: Accumulation of watery fluid in cells.
Morphologic change:

Gross features: cloudy swelling

Light microscopic features( LM): Parenchymal
cells swollen.

Early stages: granularity degeneration—
—a fine granularity like ground-glass in
the cytoplasm.

Later stages: hydropic degeneration—
—clear vacuoles in the cytoplasm
Progressive dilatation of the swollen cell

E.M. features: watery fluid in the dilated
mitochondria and endoplasmic
reticulum.
Normal cell
Granularity change
Hydropic change
Left Granularity change in kidney
Right Hydropic change
Mechanism:



Lack of oxygen
Toxic
Osmotic effect
Damage to mitochondria or its
enzymatic pathways. The diminished
formation of ATP affects all the energy
requiring reaction in the cell but in
particular leads to failure of the sodium
pump. Sodium ions enter the cell in
exchange for potassium and as the
former have a larger hydration shell,
there is a net influx of water.
(2) Fatty change:
Definition: There is the accumulation
of fat in non-fatty cells. Morphologic
change:
 Gross features: The organ enlarges and
becomes yellow, soft, and greasy.

LM: An Fatty change appears as clear
vacuoles within parenchymal cells.

Liver: Since this organ plays a central
role in fat metabolism, the accumulation
of fat in toxic conditions can be very
considerable, fatty distribution varies
with the cause, e. g. :
Poison, Toxins: alcohol, infections,
organic solvents etc. fat is found
nearest the afferent blood supply
(portal venue and hepatic arteriole).
Fatty change of liver
Left: Gross photograph .Center: HE Stain. Right: Oil Red-O Stain .
（offered by Prof.Orr）
（From ROBBINS BASIC PATHOLOGY，2003）
Confirmation
Fresh frozen section
 Special stain

Sudan Ⅲ : orange red
Osmic acid: black
 Heart:
It occurs in two patterns, in one, prolonged
moderate hypoxia, such as that produced by
profound anemia, causes intracellular
deposits of fat, which create grossly apparent
bands of yellowed myocardium alterations
with bands of darker, red-brown, uninvolved
myocardium (tigered effect). In the other
pattern of fatty change produced by more
profound hypoxia or diphtheritic myocarditis,
the myocardial cells are uniformly affected.
tigered effect
Prof. （From CIBA PHARMACEUTICAL PRODUCTS, INC. 1948） Orr

Kidney:
In most cases fatty change is confined
to the epithelium of the convoluted
tubules, but in severe poisoning it may
affect all structures including the
glomerule.
Causes:








Poisons.
e.
g.
carbon
tetrachloride,
phosphorus (liver)
Chronic alcoholism (liver)
Infections
Congestive cardiac failure
Severe anaemia
Ischaemia
Diabetes mellitus
Malnutrition and wasting disease.
Mechanism:


Impaired metabolism of fat
Excessive triglyceride into the
cell.
（From ROBBINS BASIC PATHOLOGY，2003）
Slide 2.9
(3) Hyaline change:
Definition: Not a distinct chemical entity.
Various histological or cytological
alterations
characterized
by
homogeneous, glasslike appearance in
hematoxylin and eosin-stained sections.
Types:
① arterioles hyalin

In long-standing hypertension and
diabetes mellitus, the walls of arterioles,
especially in the kidney, become
hyalinized, owing to extravasated plasma
protein and deposition of basement
membrane material.
② Collagenous fibrous tissue hyalin
in old scars may appear hyalinized, but
the
physiochemical
mechanism
underlying this change is not clear.
 With H. E. stains, the protein amyloid
also has a hyaline appearance.
 Intracellular hyaline:
Restorative droplets: Renal tubules with
phagolysosomes filled with plasma
protein during proteinuria.
 Mallory alcoholic bodies: liver
cytoplasmic aggregates of fragmented
fine filaments and tubules, derived from
hepatocyte cytoskeleton.
 Russell bodies

Protein reabsorption
droplets in the renal
tubular epithelium
（From ROBBINS BASIC
PATHOLOGY，2003）
W.B. Saunders Company items
and derived items Copyright (c)
1999 by W.B. Saunders Company
(4) Mucoid degeneration:
Definition:
Change
characterized
by
accumulation of mucin in intracellular or
extracellular loci.
Types: Epithelial: Mucin is composed of
sialomucin plus neutral mucopolysaccharide.
May
accumulate
in
intracellular
or
extracellular (if secreted) locations.
Connective tissue: Mucin is predominantly acid
mucopolysaccharide, sulfated or carboxylated.
Mechanisms of accumulation:


Acute injury: Inflammation (as common
cold ) causes hypersecretion by
epithelium.
Late injury, repair: Overproduction by
fibroblasts as in atherosclerosis, cardiac
“myxoma”.

Neoplasia: lack of access to duct

Endocrine: Thyroid hypofunction
results in intracellular (signet ring) or
extracellular accumulation when cancer
secretes much mucin (colloid carcinoma,
cystadenoma of ovary).
produces increase in
mucopolysaccharide in dermis
(myxedema).
(5) Amyloid degeneration
General features: a ‘waxy substance’
(amyloid substance) composed
essentially of an abnormal protein is
deposited in the extracellular tissue,
particularly around the supporting fibres
of blood vessels and basement
membranes.
Detection:
Post-mortem organs:
Amyloid: deep brown
Lugol’s iodine
Normal tissue: yellow
Biopsy materials:
Amyloid: red and specific apple

LM: Congo red

EM: specific appearance: closely packed
interlacing fibrils 70 to 100 A0 in diameter.
green fluorescence in polarized light.
Normal tissue: pale pink or yellow:
No fluorescence.
Nature of amyloid:
Chemical:

protein: variable. related to acute phase
reactive protein, which appears in the serum
in many inflammatory conditions or derived
from fragments of immunoglobulin molecules
(particularly lambda light chains).

Carbohydrate: a glycosaminoglycan (e. g.
heparin sulphate)——this give the iodine
stain.
Physical: the fibrils are organized uniquely—
—β-pleated.
Pathological effects
AMYLOID DEPOSITION
Pressure on adjacent cells
Atrophy
Blood vessels
Narrowing
Increased permeability
Transudation of protein
out of vessels
Amyloidogenic
proteins
and
polypeptides may also occur in other
circumstances, e. g. in tumors of
endocrine glands producing polypeptide
hormones and in cases of rare familial
amyloidosis.
In old age, minor deposits of amyloid
may occur in the heart and brain; the
amyloidogenic protein in these cases is
related to prealbumin.
Types:

Primary: without know cause

Secondary: i. e. associated with chronic
inflammatory
diseases
such
as
tuberculosis, osteomyelitis, rheumatoid
arthritis.

Systemic:

Localized:
(6) Pathologic calcification
Definition: Abnormal deposits of calcium
salts occur in any tissues except bones
and teeth.
Type:
① Dystrophic calcification:
Local deposits of calcium may occur in:

Necrotic tissue which is not absorbed.

Tissues undergoing slow degeneration.
The mechanism may be as follows:
alteration of enzymes or PH.
View looking down onto the unopened aortic valve in
a heart with calcific aortic stenosis.
（From ROBBINS BASIC PATHOLOGY，2003）
② Metastatic calcification:
This alteration may occur in normal tissues whenever
there is hypercalcemia. The causes of hypercalcemia
include hyper Para thyroidism, vitamin D intoxication,
systemic sarcoidosis, hyperthyroidism Addison’s
disease.
Metastasis calcification may occur widely throughout
the body but principally affects the interstitial tissues
of the blood vessels, kidneys, lungs, and gastric
mucosa
(7) Pigments:
exogenous
Pigments are colored substances
endogenous
① Hemosiderin
Local breakdown of red cells in tissues, e.
g. in internal haemorrhage.
Extravasated red cells
Phagocytosis of red cells
by macrophages
Haemosiderin (yellow)
(Prussian Blue reaction)
Iron free pigments
Left HE Stain
Hemosiderin granules in liver cells
（From ROBBINS BASIC PATHOLOGY，2003）
Right Prussian blue reaction.
② Bilirubin:
When the bilirubin content of the
serum rises above 34μmol/L,
jaundice appears.
③ Lipofuscin
This is a yellowish brown pigment
having high lipid content, often found in
the atrophied cell or old age. It is
particularly common in the heart muscle,
and the term “brown atrophy” is often
applied. It is also found in liver cells,
testes and nerve cells.
Lipofuscin granules
in a cardiac myocyte
（From ROBBINS
BASIC PATHOLOGY，
2003）
W.B. Saunders Company items
and derived items Copyright (c)
1999 by W.B. Saunders Company
④ Melanin
Melanin is a normal pigment found in the
form of fine brown granules in the skin,
choroids of the eye, adrenal medulla.
 Local melanin pigmentation e. g. pigmented
nevus, melanoma.
 Generalized melanin pigmentation e. g.
Addison’s disease.
⑤ Dust