Cell Injury Flashcards
When does cell injury occur
Once the adaptive capacity of the cell is surpassed is it is no longer able to respond to functional demands
Broad definition of cell injury
Any change in a cell which, if not reversed, could lead to the death of that cell. In other words, a loss of ability to respond to functional demands
Causes of cell injury
- Hypoxia
- Physical agents
- Genetic factors
- Inflammation
- Immunological responses
What are the two most important requirements for the maintenance of homeostasis and normal cell function?
- Intact membranes
2. Energy supply
Outline the importance of intact cell membranes to maintaining homeostasis
Selective barrier which maintains correct internal osmolarity
What is the result of damaged cell membrane?
- -> influx of NA, Ca2+, H2O
- -> Swelling
- -> Altered spatial arrangement
- -> Substrates diffuse around cell
What is the most common cause of a damaged membrane
Free radicals = highly reactive small molecules with unpaired electrons, often O2 mols
“Leak” out of many normal biochemical reactions - usually mopped up by cell’s own antioxidants, but when they are released faster than the cell can mop up –> cell injury
Enzyme induction
Cell injury resulting from excess free radicals
How do free radicals cause damage to membranes?
Perioxidation of membrane lipids = free radicals react with membrane lipids –> membrane damage –> inc permeability
Examples of agents that cause direct damage to cell membranes
Irradiation, toxins, complement, deficiency of Vitamin E or selenium
Protection against oxidative injury
Superoxide dismutases - catalyse conversion of superoxide anion to hydrogen perioxide
Antioxidants - remove free radicals by becoming oxidised themselves
Are free radicals always harmful?
No!
They are actually utilised by the phagocytic leukocytes as mechanisms for the killing of micro-organisms
What do cells need energy for?
- Driving ion pumps to maintain osmotic gradients
- Synthesis of structural molecules and enzymes
- Heat production
- Carrying out specialised functions (e.g. contraction)
What is the earliest and most significant manifestation of energy depletion?
Swelling of the cell and its organelles due to failure of the energy dependent Na-K-ATPase ion pump
Mitochondria are most affected by the swelling –> energy shortage is accentuated and protein synthesis is disrupted
Anaerobic glycolysis
Stimulated following mitochondrial damage as a result of swelling
Less efficient, causes build up of lactic acid –> further inhibits the respiratory and other enzymes
What is the most common cause of energy (ATP) depletion?
Hypoxia (oxygen shortage) –> failure of aerobic respiration
No O2 –> electron transport cannot occur
–> ATP production via oxidative phosphorylation inhibited
Potential causes of hypoxia
- Oxygen not reaching the blood
- Oxygenated blood not reaching the tissues
- “Respiratory poisons” - O2 available but cannot be utilised
Which cells are most susceptible to hypoxia?
Cells with high metabolic rates
e.g. brain, heart, kidney
What is the most common manifestation of cell injury?
Cellular swelling, sometimes referred to as oncosis
- Cell becomes enlarged
- Staining characteristics alter
- Formation of intracellular vacuoles
Vacuolar degeneration/hydropic degeneration
Cellular swelling and the formation of intracellular vacuoles
Why do intracellular vacuoles from?
- Failure of membrane function and resulting influx of water
- Loss of cytoplasmic organelles in particular areas
- Accumulation of small lipid droplets in cytoplasm
What does reversible cell injury usually involve?
Cloudy swelling, hydropic change or fatty degeneration or fatty change
- Cells often able to maintain homeostasis and stay alive but unable to carry out normal functions
What is an example of reversible cell injury?
Outline the mechanisms involved, and the gross and histological pathology
Hepatic Lipidosis
Mechanisms of lipidosis
- Excess delivery of free fatty acids to liver when body fat is rapidly metabolised
- Reduced capacity to syntesis apolipoprotein
(both impact ability to export triglycerides)
