cellular injury ( part 1) l General pathology revision for dental students

cellular injury ( part 1) 
CELL RESPONSE TO INJURY l General pathology revision for dental students

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CELL RESPONSE TO INJURY

• Homeostasis: steady state in which normal cell is in balance between physiological demands and function

• cellular response to injury : adaptation , cellular injury , depostion intra & extra cellulary

Causes of Cell Injury:

• Hypoxia: Is a main cause in cell injury. Decrease oxygen supply is caused by

1. Ischemia e.g. arterial occlusion and atherosclerosis.
2. Inadequate oxygenation e.g. cardiac and pulmonary diseases.
3. Decreased oxygen carrying capacity of the red blood corpuscles e.g. anemia and carbon monoxide poisoning.

• Infectious agents: Bacteria, viruses, rickettsia, fungi and parasites.
• Physical agents: Trauma, heat ,cold, radiation and electric shock.
• Chemical agents: Acids, alkalies, animal and plant poisons and some therapeutic drugs.
• Immunologic reactions.
• Nutritional deficiencies.
• Genetic and enzymatic derangements.

Mechanisms of Cell Injury:

1. ATP depletion mainly caused by hypoxia.
2. Defects in membrane permeability.
3. Formation of toxic oxygen-derived radicals as superoxide , hydrogen peroxide and hydroxyl radicals caused by chemicals and radiation.
4. Increase intracellular calcium .The source of Ca is influx from the plasma or release from mitochondria and endoplasmic reticulum. Calcium activates the following cellular enzymes:
5. Phospholipases which degrade membrane phospholipids.
6. Proteases which break down cellular proteins.
7. ATPases which deplete ATP.
8. Endonucleases which fragment chromatin.

Effects of Cell Injury:

• The effects of cell injury depend upon the type of injured cell and nature and severity of injurious agents:

Reversible cell injury(degeneration):

• Caused by mild injury or injury of short duration . Active parenchymatous cells with higher rate of metabolism suffer more than supporting stroma cells. Reversible cell injuries include:

1. Acute cellular swelling(cloudy swelling and hydropic swelling).
2. Fatty change.

Irreversible cell injury:

• Caused by severe injury or injury of long duration . Damage to the nucleus and cell death occur . There are two morphologic patterns of cell death:

1. Necrosis.
2. Apoptosis.

CLOUDY SWELLING

• Reversible cell injury characterized morphologically by swelling of the cells and granularity of the cytoplasm . Cellular swelling is due to water accumulation.

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 enter the cell and potassium diffuse out of the cell . Accumulation of 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.

Pathological Features:

• Organs affected: Highly specialized parenchymatous cells e.g. liver cells, renal convoluted tubules and heart muscles.

Gross picture:

• The affected organ appears swollen , soft , bloodless and pale due to compression of the capillaries by the swollen cells . 

• The borders are rounded. The cut surface appears cloudy(less glistening) , opaque and bulges outwards.

Microscopic picture:

• The cells are swollen due to entry of water . The cytoplasm shows innumerable fine red granules. The nucleus is normal. The capillaries between the cells are compressed.

Clinically:

1. Kidney affection causes proteinuria due to incomplete reabsorption of the filtered proteins by the affected renal tubules.
2. Liver affection causes no significant functional changes.
3. Heart affection results in its dilatation and decreased efficiency.

Fate:

• Cloudy swelling is reversible , if the injury stops the cell returns to normal , but if the injury continues cloudy swelling proceeds to hydropic swelling , or complete necrosis.

HYDROPIC SWELLING

• Hydropic swelling (hydropic degeneration)is a reversible cell injury characterized by excess water accumulation inside the cells forming vacuoles in the cytoplasm .
• The lesion is more advanced than cloudy swelling.

Causes and Pathogenesis:

• Similar to cloudy swelling.

Microscopic Picture:

• The cells are swollen due to excess water accumulation. The cytoplasm is pale and shows multiple vacuoles. The nucleus is normal . Examples of hydropic degeneration are:

1. Epidermal cells in burns, urticaria and viral infections as small pox.
2. Ballooning degeneration of liver cells in viral hepatitis and alcohol poisoning.
3. Beta cells of islets of Langerhans early in diabetes mellitus.
4. Renal tubules in potassium deficiency caused by severe diarrhea.

FATTY CHANGE

• Pathological accumulation of excess neutral fat in parenchymatous cells.

Etiology :

• Pathogenesis: Fat produced at or carried to injured cells cannot be metabolized due to diminished enzyme activity, so it accumulates in the cytoplasm.

Causes:

• Hypoxia.
• Bacterial toxins of acute and chronic infections.
• Chemical agents as alcohol,phosphorous and carbon tetrachloride.
• Because of the importance of the liver in fat metabolism,fatty changes in the liver cells are also caused by:

1. Excess fat brought to the liver cells as in:
2.  Excess intake of fats and carbohydrates.
3. Starvation with excess mobilization of fat from fat stores.

• Diseases of the liver cells as in viral hepatitis.The diseased cells cannot metabolize the normal amount of fat reaching it.
• Deficiency of lipotropic factors as choline and methionine. Lipotropic factors are necessary for transformation of neutral fat to choline containing phospholipids e.g. lecithin in the liver . This is the form of fat which most of the body cells can utilize. So absence of lipotropic factors leads to accumulation of neutral fat inside the liver cells.

Gross Picture:

• The affected organ is enlarged and soft in consistency . The capsule is tense.
• The colour is pale yellow . The borders are rounded.The cut surface bulges and is greasy to touch.

Microscopic Picture:

• The cells appear swollen and show multiple tiny fat globules in the cytoplasm around the nucleus. The fat appears as vacuoles in paraffin sections(fat dissolves in xylol).
• The fat globules fuse together forming a big globule that pushes and flattens the nucleus against the cell membrane giving the cell a signet ring appearance.
• The swollen cells compress the intercellular capillaries . In frozen sections fat can be stained by fat stains, it stains orange with sudan III and black with osmic acid.

Organs Affected:

Liver: Fatty change in the liver is either:

• Diffuse: As in severe toxemia, severe anemia and chemical poisons.
• Patchy: As in chronic venous congestion.

Heart: 

• The heart appears soft, friable, flabby with dilated chambers and atrio-ventricular rings. Microscopically tiny fat globules( vacuoles in paraffin sections)are arranged in longitudinal rows in the muscle fibers.

Fatty changes in the heart are either:

• Diffuse: Occurs in acute infections with marked toxemia as in diphtheria(toxic myocarditis).The myocardium shows a diffuse pale yellow color. The condition may terminate in acute heart failure.
• Patchy: Occurs in severe and chronic anemia . The myocardium shows yellow streaks alternating with brown streaks best seen on the endocardial surface, the appearance is called tabby cat or thrush breast striation.

Kidney : 

• Fat globules are deposited in the cells of the convoluted tubules and ascending loop of Henle's . The cortex becomes swollen and pale yellow.