Cellular swelling, glycogen

overload, protein and cholesterol

accumulation in cell

Dr Menaka Sethi
Assistant professor
Department of pathology
Glycogen overload

• Variable amount of glycogens are normally stored in hepatocytes and myocytes

• Hepatocytes of starved animals are usually devoid of glycogen
• Excessive amount of glycogen are present in animals in which glucose or glycogen metabolism is
abnormal, such as diabetes mellitus or the animals that have received excess amount of
corticosteroids
• Large amount of glycogen can be found in the livers of young growing animals and in animals that
are well nourished and on diet of commercially produced feeds
• In diabetes glycogen is found not only in hepatocytes but also in the epithelial cells renal proximal
tubules and in B cells of the Islets of Langerhans
• Hepatocytes are highly permeable to glucose and hyperglycemia leads to increased glycogen
concentration in these cells
• Also in diabetes, large amount of glucose are passed out in the glomerular filtrate and exceed the
resorptive capacity of the renal tubule epithelial cells
• These cells, when overloaded with glucose, convert it into glycogen which accumulates
intracellularly
• It is important in humans
• In animals, glycogen infiltration has been observed in some rapidly growing tumors, in cells in
areas of inflammation and around areas of dead tissues
• In suppurative inflammation, the neutrophils in the general circulation and in pus contain many
tiny droplets of glycogen
• Grossly, physiologically deposits of glycogen cannot be detected, but in steroid-
induced hepatopathy, where massive amounts of glycogen are stored, the liver
may be enlarged and pale
• Microscopically the amount of glycogen demonstrated in hepatocytes is chiefly a
function of the original concentration in the cell, the delay between death and
fixation during which time the glycogen is metabolized, and the type of fixation
• Glycogen is best preserved by fixing tissue in an alcoholic fixatives(e.g. absolute
alcohol or 10% buffered neutral formalin solution at 4 C in a refrigerator during
the period of fixation
• This procedure retains most of the glycogen but avoids the excessive shrinkage
and distortion of tissues attributed to fixation in alcoholic fixatives and also avoids
‘’polarization, ’’ the phenomenon whereby the glycogen is displaced to the side of
the cell away from the surface
• Polarization is seen in fixation at room temperature but is worst with alcoholic fixatives
• Histologically, glycogen is demonstrated specifically by the PAS reaction using two serial tissue
sections mounted on glass slides

• Microscopically, glycogen appears as clear vacuoles in the cytoplasm of the cell

• In contrast to intracellular fat whose vacuoles are rounded and sharply delineated, glycogen forms
irregular clear spaces with indistinct outlines
• Usually, the nucleus remains centrally located in the hepatocytes
• However, if very large amounts of glycogen are stored in hepatocytes, as in steroid induced
hepatopathy, hepatocyte nuclei may be displaced peripherally
• In glycogen storage disease (glycogenosis), glycogen accumulates, sometimes in massive amounts
in cells as a result of a defective enzyme and glycogen cannot be metabolized, and massive
accumulation within cells causes secondary injury and cell death
• Exactly which cells store glycogen depends on the defective enzyme, but skeletal muscle is
frequently involved
 • Macroscopically, it is difficult to recognize glycogen infiltration
• Glycogen is the only carbohydrate that can be seen under the microscope
• The glycogen is made visible by special stains
• Iodine stains it reddish brown, and Best’s carmine and periodic acid-Schiff
(PAS), bright red

A PAS stain demonstrates the abundant glycogen that is

present within the cytoplasm of the hepatocytes
Cellular swelling

• Cellular swelling (also known as cloudy swelling, parenchymatous or albuminous

degeneration) is a disturbance of cell metabolism in which cells swell and
cytoplasm of the cell becomes more granular than normal
• Cellular swelling is the most common disturbance of cell metabolism and is the
first reaction of a cell to injury caused by the mildest irritants
• Aetiology
1) Bacterial toxins (the most common cause)
2) Fever
3) Metabolic diseases (diabetes and acetonemia)
4) Organic and inorganic poisons(lead, arsenic, chloroform and alcohol)
5) Circulatory disturbances (anemia, infarction, passive hyperemia and
hemorrhage) when insufficient oxygen brought to the cell
Macroscopic lesion

• Affected organ (liver, kidney) is slightly enlarged, edges are slightly rounded and
there is an increase in weight due to increased amount of fluid in the affected cells
• Organ becomes pale or anaemic, because the swollen cells compress the
capillaries reducing the amount of blood in the organ
• When incised, the cut surface bulges and capsule draws back slightly
• Cut surfaces is cloudy, slightly opaque and appears as if it had been slightly
cooked
Acute cell swelling, liver, mouse : Hepatic swelling in a mouse exposed to chloroform for 24 hours.
The lobular pattern and slightly pallor in the liver on the right are the result of acute cell swelling
(hydropic degeneration) and necrosis of centrilobular hepatocytes. The liver on the left is normal
Microscopic lesion
• Cellular swelling is best observed in the liver, the convoluted tubules of the kidney
or in skeletal and cardiac muscle
• Due to accumulation of fluid within the cells, the cells become swollen, and their
edges become rounded
• The cytoplasm stains slightly more intense with eosin
• The internal structures of the cell are slightly hazy
• Cytoplasm is more granular than normal
• Granules are soluble in acetic acid but not in lipid solvents such as chloroform
Mechanism of cellular swelling
Significance

• Cellular swelling is a reversible injury

• It indicates the cell has been exposed to a mild irritant or that hypoxia
has been present
• As soon as the cause is removed, the granules disappear, the fluid
leaves the cell and the cell returns to normal

If cause is removed
 Proteins
• Accumulation of protein within cells, seen as droplets
• Occurs in the renal epithelial cells of the proximal convoluted tubules and in plasma cells in kidney disease
associated with protein loss in the urine (proteinuria)
• When protein leaks across the glomerular filter, it is reabsorbed by the epithelial cells of the proximal tubule
through pinocytosis
• Protein droplets appears as pink hyaline droplets within the cytoplasm of the tubular cells
• The protein aggregations do not impair cellular function
• If the cause of proteinuria is controlled, the protein is metabolized and the droplets disappear
• Plasma cells engaged in active synthesis of immunoglobulins when overloaded with immunoglobulins to
produce large, homogeneous, eosinophilic inclusions called Russell bodies and seen in case of plasma cell
neoplasm
• With electron microscope, they are found in the cisternae of the endoplasmic reticulum, where protein
synthesis occurs

Plasma cell with an arrow marking Russell bodies. Russell bodies

are cytoplasmic inclusions filled with immunoglobulins.
Cholesterol and cholesterol esters
• Cholesterol and cholesteryl esters accumulate within the cells in a variety of diseases
• Macrophages contains the lipid debris of necrotic cells or abnormal forms of plasma lipids because
of their phagocytic activities
• The macrophages packed with minute vacuoles of lipids that often impart a foaminess to their
cytoplasm, known as foam cells
• Thus foamy macrophages occur in foci of cell injury and inflammation
• In atherosclerosis, macrophages and also smooth muscle cells within the intimal layer of the aorta,
are filled with lipid vacuoles composed of cholesterol and cholesteryl esters and known as
atheroma
• Localized accumulation of cholesterol in the skin produces tumor masses known as xanthomas
• In certain acquired or hereditary conditions associated with elevation of plasma cholesterol,
macrophages are laden with cholesterol and cholesteryl esters
 Lipid droplets in cytoplasm of macrophage

Foam cell (macrophage containing lipid droplets in

its cytoplasm)
Arrow marked showing foam cells (macrophages
containing lipid droplets)
Atheroma (Accumulation of cholesterol in blood
vessels)
 Obesity

• Excessive accumulation of fat in the body is known as obesity or less commonly

as adiposity or lipomatosis
• Associated with excessive intake of fat and carbohydrate
• Calories consumed in excess of the body’s requirements are stored mainly as fat
• Decreased rate of metabolism associated with endocrine disorders of thyroid,
pituitary, testes and ovary also cause obesity
• Obesity increases the risk for a number of conditions, such as diabetes,
hypertension, atherosclerosis, cholelithiasis and several others