REVERSIBLE CELL INJURY INTRACELLULAR ACCUMULATIONS
(DGENERATION)
It is a morphological change which occurs in the cytoplasm only and not the nucleus. It is a reversible process; the cell can return to the original state when the cause is removed.
1- HYDROPIC SWELLING OR CLOUDY SWELLING
It is a reversible cell injury in which the cell swells and becomes pale due to damaged cell organelles.
By EM, the mitochondria are swollen and there is dilatation of endoplasmic reticulum.
The cause:
1- Bacterial toxins: e.g. in diphtheria, typhoid fever, bacillary dysentery, lobar pneumonia, and scarlet
fever.
2- Hypoxia and ischemia.
3- Endogenous toxic metabolites e.g. aceto acetic acid and ketone bodies in diabetes mellitus.
4- Exogenous poisons: as phosphorus and chloroform.
Pathogenesis: Injurious agents mainly hypoxia inhibit oxidative phosphorylation and ATP formation by the mitochondria. Loss of ATP which is the energy source causes:
1- Failure of the active cell membrane transport (sodium pump). Sodium enters the cell and potassium diffuses out of the cell. Accumulation of the sodium is followed by entry of water.
2- Anaerobic ATP synthesis starts, and catabolites as lactate and inorganic phosphates accumulate and increase the intracellular osmotic load.
Organs affected (sites): It affects the highly specialized or parenchymatous organs mainly cardiac muscle, convoluted tubules of the kidney and hepatocytes.
Appearances:
I. Naked eye appearance (gross picture):
- The affected organ is slightly enlarged (swollen).
- It is opaque and appears cloudy, pale and bloodless due to compression of capillaries by the swollen degenerated cells.
3. The consistency is soft and in the heart it is flabby.
II. Microscopic appearance:
- The cells are swollen.
- The cytoplasm appears granular due to fragmentation of the mitochondria (cloudy).
3. The nucleus is normal.
Effects of cloudy swelling on the body:
- On the heart: rapid and weak pulse.
- On the kidney: albuminurea.
2- INTRACELLULAR ACCUMULATIONS OF LIPIDS (FATTY CHANGE)
Definition:
It is a disturbance in the fat metabolism of cells in which the fat normally brought to them is inadequately utilized, remains free in the cytoplasm and accumulates as large droplets of fat.
Causes:
- Bacterial toxins usually of acute infection.
- Anoxia and ischemia.
- Deficiency of lipotropic factors as choline leads to fatty change of the liver, because these substances are essential for the normal metabolism of fat in the liver.
- Exogenous toxins e.g. phosphorous, chloroform and carbon tetrachloride.
Organs affected: liver, kidney and heart. Appearances:
I- Naked eye:
- The organ affected is enlarged.
- It is yellow in color and soft in consistency and greasy to the touch.
- In cut section the margins are rounded and the surface is bulging. In case of the heart it forms yellow streaks known as “tabby cat heart”.
II- Microscopically:
- In paraffin section: The affected cells appear vacuolated. At first the fat droplets are small, but later they fuse forming larger globules pushing the nucleus to one side giving the signet ring appearance.
- In frozen section: Fat can be stained by fat stains and appears as follows:
■ By Sudan III stain the fat stains orange.
■ By osmic acid stain the fat stains black.
N.B.: Fatty change should not be confused with obesity which is an excessive accumulation of fat in sites where fat is normally stored e.g. subcutaneous tissues and pericardium due to:
- Excess intake of food rich in fats and carbohydrates.
- Some endocrinal diseases.
3- HYALINE CHANGE Feature and types:
It appears structureless, homogenous, and stains bright red with eosin.
Two types of tissues are affected:
A. Connective tissue hyalinosis e.g.
- Keloid.
- Scar.
- Fibrotic glomeruli.
B. Epithelial tissue hyalinosis: The cells are dead.
- Desquamated prostatic epithelial cells (corpora amylacia).
- Beta cells of islets of Langerhan in diabetes mellitus.
4- AMYLOIDOSIS
Definition: It is the extracellular deposition of a protein substance in connective tissue stroma and walls of blood vessels.
Physical nature: Amyloid material is a fibrillary protein. Stains:
- By hematoxylin and eosin stain, it appears as homogenous pale red material.
- By methyl violet stain, it appears rosy pink while other tissues stain blue.
- By iodine solution, the amyloid takes the brown color and other tissues stain yellow.
- By congo red stain, it stains red and gives an apple green color when examined under polarized light and other tissues stain pale yellow.
Classification of Amyloidosis:
Chemical classification: Two classes of amyloid proteins are identified:
1. Amyloid light chain (AL) protein: Made up of immunoglobulin light chains mainly lambda “X” light chain. It is found mainly in primary amyloidosis as in cases of multiple myeloma (malignant tumor of plasma cells) and are secreted by plasma cells & B-lymphocytes.
2. Amyloid associated (AA) protein: Non-immunoglobulin protein and found in secondary amyloidosis.
Clinical classification
- Primary amyloidosis: it is a rare type, which usually affects the heart, gastrointestinal tract, tongue, skin, lymph nodes and skeletal muscle. It usually develops with multiple myeloma. It also develops with B-cell Non Hodgkin’s lymphoma (malignant tumor of B lymphocytes), in this type the amyloid protein is the amyloid light chain type (AL).
- Secondary: develops secondary to some diseases. This is the commonest type and the organs affected are: kidney, liver, spleen and lymph nodes.
Causes of secondary amyloidosis:
- Chronic inflammatory diseases e.g. T.B and Leprosy.
- Chronic suppurative diseases e.g. suppurative osteomyelitis, bronchiectasis, chronic lung abscess and chronic empyema.
- Rheumatoid arthritis and systemic lupus erythematosus.
- Tumors e.g. Hodgkin’s disease and leukemia.
Gross appearance:
The affected organ is enlarged, heavy in weight, firm in consistency, has sharp edges, brown in color, and the cut surface is translucent and waxy.
Microscopically:
The amyloid material is homogenous, refractile and red-stained.
Some important organs affected in amyloidosis:
1- The kidney: both kidneys are the most commonly and important organ affected, whether primary amyloidosis especially with multiple myeloma and with reactive systemic secondary amyloidosis. The amyloid substance, usually of the light chain type (AL), is deposited in the mesangeal matrix, which is replaced by the amyloid substance and in the basement membrane of the convoluted tubules and in the wall of the renal arterioles.
2- The liver: the amyloid material is deposited in the walls of the hepatic arterioles and in the walls of the sinusoids, affecting first the mid-zonal area and then the remaining of the lobules. The liver cells are not primarily affected, but they show pressure atrophy by the amyloid material.
3- The spleen: amyloidosis of the spleen, appears in one of two forms:
A) The localized type or sago spleen: is the most common type, in which the amyloid substance is deposited in the walls of the central arterioles and the lymphoid follicles which become replaced by the amyloid substance i.e. it is localized to the white pulp of the spleen only.
B) The diffuse type: is less common, in which the amyloid substance is deposited in the wall of sinusoids of the red pulp with pressure atrophy of the lymphoid follicles.
4- The gastrointestinal tract:
-The intestine: the amyloid substance is deposited in the interstitial tissue of the intestinal villi, and in the remaining parts of the intestinal walls.
- The tongue: a localized amyloid nodule may develop in the tongue.
The clinico-pathological effects of amyloidosis (complications):
1- Amyloidosis of the kidney: it is the most important and
most common type of the disease. It leads to heavy
albuminurea with hypoproteinemia, hyperlipidemia, and
generalized edema of the nephrotic type i.e. these are the
manifestation of the nephrotic syndrome, progressive renal
failure is rapid and is the usual fatal end result.
2- Amyloidosis of the liver: inspite of the extensive
involvement of the liver, hepatic failure is rare and late, but
obstruction of the portal circulation inside the liver by the
amyloid deposits, may lead to ascites.
3- Amyloidosis of the gastrointestinal tract:
a) Amyloidosis of the intestine: usually leads to malabsorption syndrome (diarrhea and defective absorption of the digested food). Ulceration and intestinal hemorrhage, together with intestinal obstruction due to large amyloid deposit may be also seen.
b) Amyloidosis of the tongue: leads to enlargement of the tongue i.e. macroglossia.
4- Amyloid of both adrenals: leads to Addison’s disease.
5- Amyloidosis of the heart: may be symptoless or may lead to restrictive cardiomyopathy, arrythmias, and congestive heart failure.
6- Amyloidosis of the spleen: leads to enlargement of the spleen (splenomegaly).
7- Amyloidosis of the nervous system: leads to
Alzheimer’s disease
Other important types of amyloidosis:
1- Dialysis associated amyloidosis: the amyloid material is B2M amyloid substance. It develops in patients with chronic hemodialysis and it affects mainly the joints.
2- Heredo familial amyloidosis: which include three subtypes:
a) Familial Mediterranean fever: the amyloid substance is AA amyloid. The kidney and the joints are the most commonly affected. It is due to recurrent inflammation which occurs in these patients.
b) Familial amyloid polyneuropathy: the amyloid substance is Transthyretin and the peripheral nerves are the most commonly affected.
3- Amyloid of aging: which include two types:
a) Senile cardiac amyloidosis: the amyloid substance is Transthyretin. It may be asymptomatic or leads to cardiac dysfunction.
b) Senile cerebral amyloidosis: in Alzheimer’s disease, the amyloid substance is B2 amyloid protein. It is deposited in the wall of cerebral vessels and in amyloid plaques.
4- Endocrine associated amyloidosis: the Procalcitonin is deposited in the stroma of medullary carcinoma. It is also deposited in the islets of Langerhans of pancreas in patients with type II diabetes mellitus.
