Response to Injury
| 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.
| Cellular adaptation|
A. H. H. M. D. I. P
| - Atrophy|
- 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.
| - Disuse|
- 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.
| Metaplasia |
| - 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.
| Intracellular Accumulations|
| - 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)
|Pathogenic Calcification|| - Involves abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium and other minerals|
- Dystrophic Calcification
- Metastatic Calcification
| Dystrophic Calcification|
| - Occurs in Injured cells as a reaction to tissue damage|
- Seen in lesions of advanced atherosclerosis.
| Metastatic Calcification|
| - 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.
| Mechanical Forces|
| - 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|
| Electrical injuries|
| - 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|
| - Ionizing|
| Ionizing Radiation|
| - 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.
| Ultraviolet radiation|
| - Causes sunburn and increases the risk of skin cancer|
- Damages DNA resulting in the formation of pyrimidine dimers
| Nonionizing radiation|
| - Injuries are dermal and subcutaneous|
- Found in Microwaves, radio waves, ultraviolet, radar, cell phones, infrared, and ultrasound
| Chemical Injury|
| - Block enzyme pathways and injure metabolism|
- Heavy metals
- Carbon Monoxide
| Injury from biological agents|
| - Viruses|
|Genetic derangement|| - Produce effects indirectly throuh metabolic disturbances.|
- Also through altered immune responses.
| Nutritional imbalances|
| - Under-nutrition|
- 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.
|Ischemia||- 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
| Cellular swelling|
| - 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|
| - Liquefaction|
| Liquefaction 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
| Coagulation necrosis|
| - Most common type of necrosis|
- Occurs primarily in the kidneys, heart, and adrenal glands
- Characteristic of hypoxia injury
- Clumping together. Caused by protein denaturation
| Caseous Necrosis|
| - Dead cells persist indefinitely as soft, cheeselike debris|
- Thought to result from immune mechanisms
- tissues resemble clumped cheese, soft and granular.
|Gangrene|| - Cellular death invovling a large mass of tissue|
- Moist or Wet
| Dry Gangrene|
| - 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
| Gas gangrene|
|- 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|
| - Stochastic|
| - Aging is a result of lifelong genetic damage.|
- accumulation of lifelong random injuries and events
|Nonstochastic||- Results of genetically controlled developmental program or built-in self destructive processes.|
|Physiological changes of aging|| - Atrophy|
- Decrease in organ funtions
- No replacement of permanent cells
- Decrease adaption to stress