CELL INJURY

• ETIOLOGY OF CELL INJURY

• The causes of cell injury, reversible or irreversible, may be broadly classified into two large groups:
• A. Genetic causes
• B. Acquired causes
• Based on underlying agent, the acquired causes of cell injury can be further categorised as under:
• 1. HYPOXIA AND ISCHAEMIA. Hypoxia is the most common cause of cell injury.
• The most common mechanism of hypoxic cell injury is by reduced supply of blood to cells i.e. ischaemia.
• However, oxygen deprivation of tissues may result from other causes as well e.g. in anaemia, carbon
monoxide poisoning, cardiorespiratory insufficiency, and increased demand of tissues.
• 2. PHYSICAL AGENTS. Physical agents in causation of disease are: mechanical trauma (e.g. road
accidents); thermal trauma (e.g. by heat and cold); electricity; radiation (e.g. ultraviolet and ionising); and
rapid changes in atmospheric pressure.
• 3. CHEMICALS AND DRUGS. An ever increasing list of chemical agents and drugs may cause cell injury.
Important examples include: chemical poisons such as cyanide, arsenic, mercury; strong acids and alkalis;
environmental pollutants; insecticides and pesticides; oxygen at high concentrations; hypertonic glucose and
salt; social agents such as alcohol and narcotic drugs; and therapeutic administration of drugs.
• 4. MICROBIAL AGENTS. Injuries by microbes include infections caused by bacteria, rickettsiae, viruses,
fungi, protozoa, metazoa, and other parasites.
• 5. IMMUNOLOGIC AGENTS. Immunity is a 'double-edged sword'- protects the host against various injurious
agents but it may also turn lethal and cause cell injury e.g. hypersensitivity reactions; anaphylactic reactions;
and autoimmune diseases.
• 6. NUTRITIONAL DERANGEMENTS. A deficiency or an excess of nutrients may result in nutritional
imbalances.
• 7. PSYCHOLOGIC FACTORS. There are no specific biochemical or morphologic changes in common
acquired mental diseases due to mental stress, strain, anxiety, overwork and frustration e.g. depression,
schizophrenia. However, problems of drug addiction, alcoholism, and smoking result in various organic
diseases such as liver damage, chronic bronchitis, lung cancer, peptic ulcer, hypertension, ischaemic heart
disease etc.
MORPHOLOGY OF CELL INJURY

• Depending upon the severity of cell injury,

degree of damage and residual effects on
cells and tissue are variable. According to
premises, the cell injury includes following
pathological processes:
• i) dystrophies
• ii) necrosis
• iii) cellular adaptation.
• Dystrophy - a complex pathological
process based on abnormality at pathway
of a histic (cellular) metabolism and
described by quantitative and qualitative
disturubances of cell or tissue structure,
that leads to structural changes and loss
of their functions.
 Morphogenetic mechanisms
• 1. Infiltration- it is penetration of substances into cells or
tissues from the outside where there are lot of them,
most frequently form in the epithelium of renal tubule
when protein, glucose and so on are exude with urine.
(diabetes mellitus, glomerulonephritis)
• 2. Transformation it is transition of one substance into
others, for example in the superfluous use of
carbohydrates and proteins they turn into fats and
adiposity appears. (fat dystrophy of the liver, obesity)
• 3. Decomposition is a disintegration of complex
substances, for example lipoprotein mem­branes in a
cell, in which arise fatty and proteinous dystrophies. (fat
dystrophy of the heart due to destructions of
mitochondrial membrane in myocardial ischemia)
• 4. Perverted (unnatural) synthesis is formation of
substances which in norm are not being found (for
exam­ple an amyloid, Melory bodies in alcoholic
hepatitis, multiple [plasma cell] myeloma).
Classification of dystrophies:
• A. According to primary localization of changes:
1. Parenchymatous (endocellular), 2. Stomal-
vascular (mesenchymal, extracellular), 3. Mixed.
• B. According to mainly broken metabolism: 1.
Proteinous (dysproteinoses), 2. Fatty (lipidoses),
3. Carbohydrate, 4. Mineral
• C. According to development: 1. Acquired, 2.
Congenital
• D. According to prevalence: 1. Local,
• 2. Systemic.
• Parenchymatous dystrophies are
dystrophies in which pathological changes
are localized inside the cells of organs
parenchyma in high- specialized cells,
such as myocardiocytes, hepatocyte,
epithelium of renal tubule .
• Proteinous parenchymatous dystrophies
include:
• 1. hyaline-droplet,
• 2. hydropic,
• 3. keratinization dystrophy and
• 4. congenital form of proteinous
parenchymatous dystrophies.
 Hyaline-droplet dystrophy.
• Hyaline is a descriptive histologic term for
glassy, homogeneous, eosinophilic
appearance of material in haematoxylin
and eosin-stained sections and does not
refer to any specific substance. Hyaline
change is associated with heterogeneous
pathologic conditions and may be
intracellular or extracellular.
 INTRACELLULAR HYALINE.
• 1. Hyaline droplets in the proximal tubular epithelial cells
in cases of excessive reabsorption of plasma proteins
(glomerulonephritis, nephrotic syndrome).
• 2. Hyaline degeneration of voluntary muscle, also called
Zenker's degeneration, occurs in rectus abdominalis
muscle in typhoid fever. The muscle loses its fibrillar
staining and becomes glassy and hyaline.
• 3. Mallory's hyaline represents aggregates of
intermediate filaments in the hepatocytes in alcoholic
liver cell injury.
• 4. Nuclear or cytoplasmic hyaline inclusions seen in
some viral infections.
• 5. Russell's bodies representing excessive
immunoglobulins in the rough endoplasmic reticulum of
the plasma cells (myelomatosis (plasmocytoma, Kahler's
disease)).
• The hyaline-dropical dystrophy is a
severe irreversible kind of dystrophy, it
always ends by coagulation necrosis of
cells and decrease or the loss of the organ
function.
• In the kidney it manifests it self as
proteinuria , cylinderuria, in the blood
arises hypoproteinemia.
 Hydropic [vacuolar] dystrophy.

• This is the commonest and earliest form of

cell injury from almost all causes.
• The common causes of cellular swelling
include: bacterial toxins, chemicals,
poisons, burns, high fever, intravenous
administration of hypertonic glucose or
saline etc.
 Pathogenesis
• Abnormalities of protein-hydro electrolytic
balance, especially for sodium.
• Membranes damage and activation of
lysosomal hydrolyses
• Macroscopically view of organs and
tissue variates little. The affected organ
such as kidney, liver or heart muscle is
enlarged due to swelling. The cut surface
bulges outwards and is slightly opaque.
 Microscopically
• 1. The cells are swollen and the microvasculature
compressed.
• 2. Small clear vacuoles are seen in the cells and
hence the term vacuolar degeneration. These
vacuoles represent distended cisternae of the
endoplasmic reticulum. If there is a lot of liquid and it
fills in the whole cell superseding a nucleus into
periphery, such kind of hydropic [vacuolar] dystrophy
is called ballooning degeneration - especially it is
characteristic of hepatocytes in a viral hepatites.
• Hydropic [vacuolar] dystrophy is severe irreversible
kind of a dystrophy and it always ends in coagulation
necrosis of cells. Except for the liver it happens more
often in a ganglionic cells, adre­nal glands,
myocardium .
 Keratinization dystrophy
• It is accumulation of keratin substance where in norm it
is not present, or excessive accumulation of keratin
substance where it’s can be in norm (skin). The causes
are: i) avitaminosises, ii) developmental anomalies of a
skin, iii) viral infection, iv) chronic inflammation. The
types of a keratinization dystrophy are:
• 1. hyperkeratosis- it superfluous keratinization on a skin,
sometimes it is present as a “skin horn”
• 2. Ichthyosis- is a congenital hyperkeratosis of skin (the
child born with a thick skin similar to the fish scales,
usually he dies at once)
• 3. Leukoplakia is keratinization of mucous membranes
covered with squamous cell non-keratinizing epithelium .
More often it can be in cervix of the uterus, there can
also be in the oesophagus , oral cavity, etc. Leukoplakia
is dangerous as it lead to squamous cell carcinoma .
Severe plantar hyperkeratosis
 Congenital form of proteinous
parenchymatous dystrophies.
• Inheritable parenchymatous proteinous
dystrophias are caused by abnormality of
amino acid metabolism, for example:
• cystianosis,
• tyrosinosis,
• phenyl-pyruvic oligophrenia
(phenylketonuria)
 Parenchymatous fatty
dystrophies.
• Causes of parenchymatous fatty
dystrophies are:
• 1. The hypoxia is the common cause,
especially in such diseases as а) anemias,
b) diseases of the heart, c) lung diseases
• 2. Infections and intoxications, especially
alcohol intoxication
• 3. Ireegular diet and avitaminoses.
 Mechanism
• Destruction of endoceilular organels
membranes by increased transport of
triglycerides or fatty acids to affected cells,
decreased mobilization of fat, decreased
use of fat, overproduction of fat in cells
occurs in chronic hypoxic states.
• This mechanism was named
decomposition (phanerosis).
 Fatty dystrophia of the liver
• ETIOLOGY. The common causes of fatty liver
include the following: i) Excess alcohol
consumption (most common); ii) starvation; iii)
malnutrition; iv) obesity; v) diabetes mellitus; vi)
chronic illnesses (e.g. tuberculosis); vii) late
pregnancy; viii) hypoxia (e.g. anaemia, cardiac
failure); ix) hepatotoxins (e.g. carbon
tetrachloride, chloroform, ether, aflatoxins and
other poisons); x) certain drugs (e.g.
administration of oestrogen, steroids,
tetracycline etc);
 Macroscopically
• The fatty liver is enlarged with a tense,
glistening capsule and rounded margins.
The cut surface bulges slightly and is pale-
yellow to yellow and is greasy to touch, so-
called "goose" liver.
 Microscopically
• There are numerous lipid vacuoles in the cytoplasm of
hepatocytes.
• i) The vacuoles are initially small and are present around
the nucleus (microvesicular).
• ii) But with progression of the process, the vacuoles
become larger pushing the nucleus to the periphery of
the cells (macrovesicular).
• iii) At times, the hepatocytes laden with large lipid
vacuoles may rupture and lipid vacuoles coalesce to
form fatty cysts.
• iv) Infrequently, lipogranulomas may appear consisting
of collections of lymphocytes, macrophages, and some
multinucleated giant cells.
• v) Fat in the tissue can be demonstrated by frozen
section followed by fat stains such as Sudan dyes
(Sudan III, IV, Sudan black), oil red and osmic acid.
Fatty dystrophies of the heart.
• Most common cause is chronic hypoxia
(ischemic heart diseases, lung diseases,
anemias). Morphogenic mechanisms are
decompo­sition and infiltration.
• Macroscopically:The size of heart enlarged, its
cavity dilated, myocardium is flabby, yellow
col­oured. Ochroleucous striation is visible under
the endocardium of ventricles, especial in range
of trabeculas and papillary muscles. It may be
compared with tiger skin (tiger heart). This
striation based on local fatty change of
cardiomyocytes.
 Microscopically
• Small fatty drops, stained by a liposoluble
- Sudan-III, in yellow-orange colour is
observed in cytoplasm of cardiomyocytes,
localized around venuls and veins. Others,
neighbour cardiomyocytes, don't contain
fatty incorporations. Transversal striation
in cytoplasm of cardiomyo­cytes is absent,
nucleus are corrugated, intensively
painted by hematoxylin, or are turgent and
weakly painted (karyolyzis).
 Congenital (systemic) lipidoses
• lipidoses arise owing to inheritable
deficiency of enzymes metabolizing some
kinds of lipids. In dependence on a kind of
lipoids collecting in cells distinguish:
• cerebrosides (Gaucher's disease),
• sphingomyelinoses (Niemann-Pick
disease),
• gangliosides (Tay-Sachs disease or an
amaurotic idiocy)
 Parenchymatous carbohydrate
dystrophies.
• The inheritable carbohydrate dystrophy «glycogenoses»
is caused by absence or failure of the enzyme,
participating in scission of a deposited glycogen. These
are so-called inheritable enzymepaties or storage
diseases. 6 types of glycogenoses are well known:
• Gierke's disease,
• Pompe's disease,
• Mc. Ardle's disease,
• Hers' disease,
• Cori’s disease and
• Andersen disease.
• Morphological diagnostics of a glycogenosis is possi­ble
by biopsy with the help of histocnzymochcmichal
methods
Cytoplasmic organelle damage leads to a variety of injury patterns, most of
which are best seen by electron microscopy. Acute injuries tend to damage an
entire cell, so specific organelle damage is beside the point. However, in some
cases the damage can be cumulative over many years. Here are Mallory bodies
(the red globular material) composed of cytoskeletal filaments in liver cells
chronically damaged from alcoholism. These are a type of "intermediate"
filament between the size of actin (thin) and myosin (thick).
№ 19 HYDROPIC DYSTROPHY OF HEPATOCYTES

Staining: hematoxylin- eosin

Designations:
1- Hydropic (vacuolar) dystrophia of hepatocytes