Significance of Discussing Cellular injury
- Must understand physiologic mechanisms as a whole.
- Person has both internal and external environment. Information and matter are exchanged between each.
- Goal is to produce a steady state. Homeostasis.
Outcome of cell injury
- Reversible Injury
- Programmed cell death
- Cell death and necrosis.
A. H. H. M. D. I. P
- Intracellular Accumulations
- Pathologic calcifications
- Shrinkage in size of cell which leads to decrease in organ size.
- Most common in skeletal muscle, heart, secondary sex organs and brain.
Causes of Atrophy
D. D. L. I. I.
- Loss of endocrine signals
- Inadequate nutrition
- Increase in cell size, leading to an increase in organ size.
- Is in response to increased physiological or pathophysiologic demand
- Subsides when increased demand is removed.
- ie: muscles when you work out, uterus and mammary glands during pregnancy
- Increase in number of new cells because of increased rate of cellular division.
- Usually results from increased physiological demands or hormonal stimulation.
- ie: breast changes in puberty, new RBCs in blood loss or response to high altitudes.
- One adult cell type is replaced with another adult cell type.
- Adaptation to persistent injury with the replacement cell type being better able to tolerate injurious stimulation.
- reversible when stimulus removed.
- ie: changes in epithelial cells lining bronchi in response to smoke irritation.
- Deranged cellular growth
- Abnormal changes in size, shape, and organization of mature cells.
- Most likely an adaptive effort gone astray.
- Regarded as a precursor of cancer, it has the potential to transform into cancerous cells.
- buildup of substances cells cannot use or dispose of.
- Normal body substances (ie Lipids, proteins, carbs etc)
- Abnormal endogenous products. (originate from within the body, ie an Inborn error in metabolism, like Tay-sachs disease)
- Exogenous products (ie environmental agents or pigments, carbon in coal dust)
- Involves abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium and other minerals
- Dystrophic Calcification
- Metastatic Calcification
- Occurs in Injured cells as a reaction to tissue damage
- Seen in lesions of advanced atherosclerosis.
- occurs in normal tissues as the result of increased calcium levels
- Caused by hyperparathyroidism, renal failure, cancer, immobilization and vitamin D intoxication.
Major Causes of Cellular injury: Function and types
P. R. C. B. G. N
- Any Stressor that alters homeostasis can lead to cell injury.
- physical agents
- Radiation Injury
- Chemical Injury
- biologic agents
- Genetic derangement
- Nutritional Imbalances
Injury from physical Agents
- Mechanical forces
- Extremes of temperature
- Electrical Injuries.
- Injury or trauma as a result of body impact with another object.
- These types of injuries split and tear tissue, fracture bone, injure blood vessels, and disrupt blood flow.
Extremes of Temperature
- Injuries as a result of either hypo- or Hyperthermia
- Can affect the body through extensive tissue injury and disruption of neural and cardiac impulses.
mainly determined by
- its voltage
- the type of current (ac/dc)
- Its amperage
- the resistance of the intervening tissue
- the pathway of current
- the duration of exposure.
Radiation Injury types
- Affects cells by causing ionization of molecules and atoms in the cell.
- vary with dose, dose rate, and sensitivity of the exposed tissue.
- Cells that divide most frequently are the ones most susceptible.
- Causes sunburn and increases the risk of skin cancer
- Damages DNA resulting in the formation of pyrimidine dimers
- Injuries are dermal and subcutaneous
- Found in Microwaves, radio waves, ultraviolet, radar, cell phones, infrared, and ultrasound
- Block enzyme pathways and injure metabolism
- Heavy metals
- Carbon Monoxide
Injury from biological agents
- Produce effects indirectly throuh metabolic disturbances.
- Also through altered immune responses.
- Inadequate consumption of food or calories
Mechanisms of injury
- Free radical injury
- Hypoxic cell injury
- Impaired calcium homeostasis
Free Radical Injury
- Highly reactive chemical species arising from an atom that has a single unpaired electron in outer orbit.
- cell normally has mechanisms that protect them from injurious effects.
- Mechanisms break down when cell deprived of O2, exposed to certain chemical agents, or other injurious agents
- Vitamin's A, C, E or other antioxidants help against this type injury
Hypoxic cell injury (hypoxia)
- Oxygen deficiency or insufficient levels of oxygen in the blood or tissue.
- Interrupts oxidative metabolisms and generation of ATP.
- Causes power failure in the cell with widespread effects on the cell's structural and functional components.
- Local and temporary deficiency of blood supply due to obstruction of circulation to a part.
Causes of hypoxia
- decreased blood supply to area
- Decreased 02 carrying capacity of blood
- ventilation-perfusion problems
- problem with cell's enzyme system
- decreased O2 in air
Effects of Hypoxia
- Failure of sodium/potassium-ATPase membrane pump.
- K leaves the cell and Na and water enter, causing swelling.
- Cellular changes reversible if O2 restored.
Impaired Calcium Homeostasis
- Messenger for release of many intracellular enzymes
- Intracellular levels much lower than extracellular levels
- Changes calcium/magnesium ATPase exchange system.
- High Ca levels activate number of enzymes with damaging effects.
Responses/results of reversible cell injury
- Cellular swelling
- Fatty cellular changes
- Increased sodium in cell
- Creates osmotic gradient for water entry
Fatty Cellular changes
- small vacuoles of fat disperse in cytoplasm.
- Usually indicates severe injury
- May occur because normal cells have increased fat load or injured cell unable to metabolize fat properly
Cell Death and Necrosis
- Control of cell number regulated by balance of cell proliferation and death.
- Cell death can involve apoptosis or necrosis
- "point of no return" is biochemical puzzle.
- Controlled cell destruction
- Normal cell deletion and renewal
- "cell suicide"
- Cell death resulting in organ or tissue damage that is still part of a living person
- often interferes with cell replacement and tissue regeneration
- Different types occur in different organs or tissues
- Sometimes can indicate mechanisms or cause of cellular injury
Types of Necrosis
- Conversion of solid tissues to fluid or semi-fluid state.
- Some cells die but catalytic enzymes are not destroyed.
- From lecture: Softening in the center or an abscess with a discharge of the contents liquifies and walled off from healthy tissue
- Most common type of necrosis
- Occurs primarily in the kidneys, heart, and adrenal glands
- Characteristic of hypoxia injury
- Clumping together. Caused by protein denaturation
- Dead cells persist indefinitely as soft, cheeselike debris
- Thought to result from immune mechanisms
- tissues resemble clumped cheese, soft and granular.
- Cellular death invovling a large mass of tissue
- Moist or Wet
- Part becomes dry, shrinks, the skin wrinkles, and its color changes to dark brown or black.
- Spread is slow
- Obvious line of demarcation between gangrenous area and healthy tissue.
Moist or Wet Gangrene
- area cold, swollen and pulse-less.
- Skin is moist, black and under tension
- Bleps form on the surface, liquefaction occurs, and a foul odor is caused by bacterial action
- Primarily results from interference with venous return from the part
- Results from infection of devitalized tissues by one of several Clostridium bacteria.
The bacteria produces toxins that
- dissolve cell membranes,
- causing death of muscle cells,
- massive spreading edema,
- hemolysis of red blood cells,
- hemolytic anemia,
- renal failure.
Cellular Basis of aging
- Normal physiological process
- not considered a disease
- Gradual result of wear and tear
theories of aging
- Aging is a result of lifelong genetic damage.
- accumulation of lifelong random injuries and events
- Results of genetically controlled developmental program or built-in self destructive processes.
Physiological changes of aging
- Decrease in organ funtions
- No replacement of permanent cells
- Decrease adaption to stress