Cell injury - Lecture 4

Cell injury :
If adaptive capability of the cell is exceeded, cell injury occur.

Types of Cell injury:
1- Reversible cell injury: the morphological and structural changes are reversible , if the damaging stimulus is removed.
2- Irreversible cell injury and cell death: state in which the cell can not recover (point of no return), and its of two types ( 1- necrosis , 2- apoptosis).

Causes of cell injury:
1-Hypoxia: deficiency of oxygen, due to (cardio-respiratory failure, anemia, and carbon monoxide poisoning).
2-Ischemia: decrease blood supply to the tissue either due to arterial block or reduced venous drainage.
3-Physical agents: burn, deep cold, mechanical trauma, radiation, electric shock.
4-Chemicals and drugs: poisons like cyanide, insecticides, drugs.
5-Microbiologic Agents: bacteria, parasites, viruses, and fungi
6-Immunologic Reactions: such as anaphylaxis or immune complex damage
7-Genetic defects: Sickle cell anemia causing red blood cell injury.
8-Nutritional imbalances: protein-calorie, vitamin deficiencies, excess lipid intake.
9-Aging: injury occurs via programmed cell death or Lipofuscin pigment excess.

Morphological changes in revertible cell injury:
• Grossly:
The affected organ is pale, increased turgor and increased weight.
• Microscopically:
Ultrastructural morphological changes:
1- Plasma membrane alteration such as blebbing, distortion of micro-villi, and loosening of intracellular attachments.
2- Mitochondrial changes such as swelling and the appearance of phospholipids-rich small amorphous densities.
3- Dilation of endoplasmic reticulum with detachment of ribosomes.
4- Clumping of nuclear chromatin.

Light microscopic morphological changes:
1- Cell swelling, hydropic changes :
small, clear vacuoles seen within the cytoplasm, these represent distended and pinched-off segments of endoplasmic reticulum.
2- Fatty changes"
manifested by the appearance of lipid vacuoles within the cytoplasm.


Morphological changes in Irreversible cell injury Necrosis :
Necrosis refers to a sequence of morphological changes that follow cell death in living tissue (not fixed specimens).
The morphological appearance of necrosis is due to two processes:
1- Enzymatic digestion of the cell.
2- Denaturation of the proteins.
The hydrolytic enzymes may derived either from the dead cells themselves, in which case the digestion is referred as autolysis , or from the lysosomes of invading inflammatory cells termed hetrolysis .
• Cytoplasm changes in necrotic cell:
Dead cell show:
1- Increased eosinophilia (pink staining from eosin dye), this is due to increased binding of eosin to denaturated intracytoplasmic proteins, and in part to loss of the basophilia that is normally imparted by the RNA in the cytoplasm.
2- The necrotic cell have more glassy homogenous appearance than viable cells due to mainly to loss of glycogen particles.
3- When enzyme have degraded the organelles, the cytoplasm becomes vacuolated and appears moth-eaten .
4- The calcification of the dead cell may occur.
• Nuclear changes in necrotic cell:
1- Pyknosis:
It characterized by nuclear shrinkage and increased basophilia of the nucleus, the DNA condenses into a solid shrunken mass.
2- Karyolysis:
DNAse activation lead to non-specific DNA breakdown, and this lead to decrease basophilia of the nucleus.
3- Karyorrhexis:
Fragmentation of the nucleus .