Cell Injury

What is cell injury caused by?

Cell injury is caused by any factor that disrupts the structure of the cell or deprives it of oxygen and nutrients

What are the major causes of cell injury?

1. Physical (paper cut)

2. Chemical (alcohol)

3. Biological (viruses)

4. Nutritional (excess fats)

What are the three mechanisms of cell injury?

1. Hypoxia

2. Impaired calcium homeostasis

3. Free radicals

What is hypoxia?

Hypoxia is defined as lack of sufficient oxygen for cells, and is the most common cause of cell injury

What causes hypoxia?

• Ischemia: reduced blood supply to blood cells in an area

  • Gradual narrowing of arteries (arteriosclerosis)

  • Sudden acute anoxia (thrombi, embolisms)

• Hypoxemia: low level of oxygen in the blood

  • Low oxygen in air

What are four pathophysiological effects does decreased ATP production from Hypoxia lead into?

1. Increased anaerobic respiration, leading to lactic acid buildup, leading to decreased pH

2. Reduced activity of ATP-dependent enzymes, leading to damaged membranes, leading to necrosis

3. Reduced activity of ATP-dependent sodium-potassium pump, leading to cellular edema (swelling)

4. Reduced activity of ATP-dependent calcium pumps, leading to increased intracellular levels of calcium

How can these pathophysiological effects be measured?

These pathophysiological effects can be measured through leaked cell enzymes

What does impaired calcium homeostasis result in?

1. Activation of inappropriate enzymes which cause cell damage

   1. Membrane damage (phospholipase, protease)

   2. Nuclear damage (endonuclease)

   3. Decreased ATP (ATPase)

2. Increased mitochondrial permeability, which causes decrease in ATP production

What are free radicals and an example of this?

Free radicals are unstable molecules containing unpaired outer electrons

• Example: reactive oxygen species - superoxide anion

Are free radicals highly reactive?

Yes, free radicals are highly reactive, attacking atoms in proteins, fats and carbohydrates

• This can cause cancer, heart disease, and neurodegeneration

What are the two types of free radicals?

Free radicals can either be exogenous or endogenous

• Exogenous: generated from absorption of radiation from X-rays or UV light

• Endogenous: naturally generated during metabolism or drug breakdown

  • Example: Reactive oxygen species

How does the body protect itself from Endogenous Reactive Oxygen Species?

The body protects itself from ROS through ROS scavengers

• Enzymes: superoxide dismutase (SOD)

• Antioxidants: vitamins E and C

What is apoptosis? Examples of this?

Apoptosis is programmed cell death, where it shrinks

Examples:

• Intestinal epithelia turnover

• Endometrial cell breakdown in the menstrual cycle

• Cell death induced by cytotoxic t cells lymphocytes

Describe the steps of Apoptosis

A: cell structures shrink

B and C: nucleus is destroyed by enzymes and arranged into DNA fragments

D: Membrane protrudes (blebs)

E: Fragments pinch off as apoptotic bodies

F: Apoptotic bodies are engulfed by phagocytes

What is Necrosis?

Necrosis is unprogrammed cell death, where it swells and bursts

What causes Coagulative necrosis? Where does this occur?

• Coagulative necrosis is caused by hypoxia and has infarcts (areas of ischemic necrosis)

• Protein denaturation occurs, causing the tissue to become firm and opaque

• Can occur in kidneys and liver

What is Liquefactive necrosis? Where does this occur?

• Liquefactive necrosis occurs in focal bacterial or fungal infections

• Tissues soften and liquefy, forming an abscess

• Can occur in the brain due to ischemia

What is Caseous necrosis? Where can this occur?

• Caseous (cheese-like), with granulomas

• A combination of coagulative and liquefactive necrosis

• Occurs in the lungs due to tuberculosis infections

What is Fat necrosis? How does it occur? Where does it occur?

• Fat necrosis results from leakage of pancreatic lipases

• Fatty acids combine with ions such as calcium, making soap (saponification)

• Occurs in the pancreas (acute pancreatitis)

What is Gangrene (grangrenous necrosis)

Gangrene refers to large areas of tissue that have undergone necrosis

3 Types:

• Dry gangrene: due to coagulative necrosis, skin becomes dry and dark

• Wet gangrene: due to liquefactive necrosis, skin becomes swollen and black

• Gas gangrene: bacteria produces enzymes that destroy tissue, causing gas production

What are the two theories of aging?

1. Programmed (molecular) theories: suggests that aging is programmed genetically

   1. Example: fruit flies with the INDY gene has double the lifespan

2. Damage (senescence) theories: suggests that aging occurs due to the accumulation of DNA damage

   1. Example: effects of free radical damage