MOUNT ST.

MARYS COLLEGE DEPARTMENT OF NURSING NURSING 54/44A INTRODUCTION TO PATHOPHYSIOLOGY Study Guide for CELLULAR RESPONSE TO INJURY I. Concept of Cellular injury: A. Significance of discussing cellular injury *GOAL: -Permit survival -Maintain cell function B. Outcome of cell injury see Figure 5-8 in Porth 1. Reversible cellular injury- cell recovery & return to normal function. 2 results are: - cellular swelling (due to impairment of Na+/k+ pump, there is an increase of Na+ in the cell which causes swelling & leads to hypoxic cell injury) - fatty change (due to an increased fat load or the inability of a damaged cell to metabolize Fat) 2. Programmed cell death (a.k.a.- APOPTOSIS). Programmed to remove injured and worn out cells; Controls tissue regeneration. 3. Cell death and necrosis Occurs in irreversible damaged cells; Refers to cell death in an organ or tissue that is still part of a living organism. (Example: GANGRENE); Necrosis often interferes with cell replacement and tissue regeneration *Necrosis undergoes 3 pathways: -Liquefaction (solid tissue fluid or semi fluid state) -Coagulation (clumping together due to protein denaturation. HEAT plays an important role) -Caseous (dead cells that become cheese-like debris) II. Cellular adaptation: A. Atrophy- a DECREASE in cell size due to a decrease in work demand; as cells become smaller reduce their O2 consumption which can lead to hypoxia; when a sufficient amount of cells are involved, the entire muscle or tissue atrophies. *5 Causes of ATROPHY are: - Disuse (when there is a reduction in skeletal muscle use; Example: when muscle of an extremity is in a cast, it becomes smaller because it is not being

used; but muscle size can be restored when cast is removed and muscle use is resumed) - Denervation (loss of nerves = loss of electrical impulses; occurs in muscles of paralyzed limbs - Loss of Endocrine stimulation (a type of disuse atrophy; in women loss of estrogen stimulation during menopause casue atrophic changes in reproductive system) - Inadequate nutrition (cells not getting enough energy) - Ischemia/ blood flow (leads to decreased O2 of the cells which can lead to necrosis/cell death.) B. Hypertrophy- an INCREASE in cell size due to an increased workload or increased stimulation of growth hormone Commonly seen in Cardiac & Skeletal cells Exercise is an example of Physiologic Hypertrophy Pathologic Hypertrophy occurs as a result of disease ATP Depletion initializes Hypertrophic process!! (cells are not getting enough nutrients for energy so muscle begins to HYPERTROPHY)

C. Hyperplasia- is an increase in the number of cells in an organ or tissue - It occurs with cells that are capable of mitotic division such as: Epidermis, Intestinal epithelium. Glandular tissue It is a controlled process that occurs in response to a stimulus and ceases after the stimulus has been removed. Although HYPERTROPHY and HYPERPLASIA are two distinct processes, they may occur together and are often triggered by the same mechanism.

D. Metaplasia- Reversible Change- in which one adult cell type is replaced by another adult cell type. usually occurs as a result of chronic inflammation and irritation and allows for a better substitution of cells that are better able to survive Example would be: substitution of Stratified squamous epithelium for Ciliated columnar epithelium in the trachea and large airways of a habitual SMOKER.

E. Dysplasia- deranged cell growth; results in abnormal changes in size, shape, structure; can be found in epithelium of respiratory tract or cervix. Although it is abnormal, it is adaptive in that it is potentially Reversible after the irritating cause has been removed. Dysplasia is strongly implicated as precursor of Cancer, however it does not necessarily lead to cancer. F. Intracellular accumulations- represent a build up of substances that the body cannot immediate use or eliminate. These substances may accumulate in the cytoplasm or nucleus. These substances can be classified into 3 groups: - normal substances: carbs, proteins, lipids abnormal endogenous sunstances: those resulting from inbron errors of metabolism (LIVER will become Endogenous and Fatty if it does not metabolize/break down substances working so hard that it becomes fatty and leads to CIRRHOSIS) exogenous substances: environmental agents and pigments that cannot be broken down by the cell; may be harmless or in some cases toxic. Example: CARBON (can blacken the lung and cause lung disease)

G. Pathologic calcifications abnormal deposition of calcium salts with smaller amounts of Magnesium, Iron and other Minerals -Dystrophic calcification: occurs in injured or dying/dead tissue; commonly seen in Atherosclerosis aorta, blood vessels and damaged heart valves. **Leads to Organ Dysfunction** **Example: Calcification of aortic valve leads to aortic stenosis in elderly** -Metastatic calcification: in the media of the arteries; occurs in normal tissues as a result of increased Calcium levels (HYPERCALCEMIA) III. Cellular injury A. Major causes of cellular injury 1. Injury from physical agentsmechanical forces- body impact with another object (tear tissue, obstruct blood vessels, impair blood flow, fracture bones) extreme temperatures- cause damage to cells & their organelles (burns, severe heat stroke, frostbite, hyperthermia)- exposure to cold can cause Vasoconstriction and decrease blood flow and lead to Hypoxic tissue injury; with more intense HEAT, coagulation occurs.

electrical injury- cause severe tissue injury and disrupts cardiac (heart) & neural (brain) impulses- electrical energy turns to heat which is why tissue damage by electrical injuries is caused by heat production in the tissues. 2. Radiation injuryIonizing radiation- radiation energy above the UV range (X-rays, electromagnetic)- can damage DNA and CYTOPLASM and lead to organ dysfunction Ultraviolet radiation- (UV rays, Sun)- UV rays also damage DNA; Can cause sunburn and increases the risk of skin cancer; We need sunlight to metabolize Vitamin D, but too much can lead to abnormalities (such as skin cancer); degree of risk depends on the type of UV rays and the intensity of the exposure Non-Ionizing radiation- (Infrared light, Ultrasound, Microwaves, Laser energy)- All this energy is converted to thermal energy. Injury from these sources tend to involve DERMAL and SUBCUTANEOUS tissue injury. 3. Chemical injury- chemical agents can injure the cell membrane and other structures, block enzymatic pathways, coagulate proteins - Air & water pollution - Tobacco smoke - Processed & Preserved foods - Drugs & Alcohol (can directly or indirectly damage tissues) Acetaminophen: a common over the counter drug that is detoxified by the liver; when large amounts are ingested, it becomes toxic, causing liver necrosis. Alcohol: large and persistent amount can cause Cirrhosis of the liver - Heavy metals (Lead & Mercury) - Carbon Monoxide (this is not good because cell wont bing to oxygen anymore which leads to ischemia and eventually necrosis) 4. Injury from biologic agents- able to replicate & produce injurious effect (Viruses) - Viruses - Bacteria - Rickettsiae - Mycoplasms - Fungi - Protozoa 5. Genetic derangements can cause metabolic disturbances & an altered immune response 6. Injury from nutritional imbalances- Undernutrition &

Overnutrition Undernutrition: unable to meet the metabolic needs of the cell **Dietary deficiency can occur in the form of starvation, in which there is a deficiency of all nutrients & vitamins. Starvation can cause widespread tissue damage** Overnutrition: more than the body needs or requires; excess makes the cells work harder

**OBESITY & diets hugh in saturated fats can predispose a person to atherosclerosis** B. Mechanisms of cell injury 1. Free radical injury- when a molecule has an unpaired electron that causes it to be unstable & highly reactive. When cells are susceptible, Free Radicals can take over. The actions of Free Radicals may damage cells and tissues 2. Hypoxic cell injury- Hypoxia deprives the cell of oxygen (Hypoxia O2 deficiency leads to ischemia then Necrosis/Cell death) we see this with MI (heart attack); It can also result from inadequate oxygen in the air (Ex: @ High Altitudes) Some cells, such as those of the BRAIN, HEART & KIDNEY, require large amounts of Oygen. Brain cells begin to undergo permanent damage after 4-6 minutes of No Oxygen *Causes of Hypoxia: - DECREASED blood supply to the area - DECREASED oxygen carrying capacity of blood - Ventilation Perfusion (mismatch; unable to transfer O2 & CO) - DECREASED O2 in the air 3. Impaired calcium homeostasis- normally, Intracellular Ca+ levels are kept lower compared with Extracellular levels; The Increased Ca+ level may inappropriately activate a number of enzymes with potentially damaging effects. (**In our notes, ATP depletion is also mentioned**) C. Responses/ results of reversible cell injury 1. Cellular swelling- caused by impairment of Na+/K+ membrane pump; This causes increased K+ levels and Increased Na+ into the cell (with water following) and results in hypoxic cell injury

2. Fatty cellular changes Fat is dispersed in cytoplasm; usually an indication of severe injury; may occur from an increased Fat load or the inability of injured cells to metabolize fat properly. D. Cell death and necrosis 1. Apoptosis- Programmed Cell Death- (Normal cell deletion & Renewal) programmed to remove injured or worn out cells; controlled tissue regeneration 2. Necrosis- refers to cell death in an organ or tissue that is still part of a living organism (ex: GANGRENE); necrosis interferes with cell replacement & tissue regeneration 3. Types of necrosis a. Liquefaction- conversion of solid tissues to fluid or semi-fluid state. Some cells die, but enzymes are not destroyed. b. Coagulation Most common type!- characteristic of hypoxic injury; Clumping together due to protein denaturation; HEAT plays an important role (it Denatures) c. Caseous- dead cells that become soft- cheese like debris (Soft & Granular) d. Gangrene- when a considerable amount of tissue undergoes necrosis. Can be classified as: - Dry Gangrene: the part becomes dry and shrinks, the skin wrinkles and its color changes to dark brown or black. The spread of dry gangrene is slow; ususally results from interference with Arterial Blood Supply. Wet/Moist Gangrene: the area is cold, swollen and pulseless; the skin is moist and black; the spread of tissue damage is rapid; it results from interference with Venous Return; it is Smelly and has a foul odor; Moist Gangrene may affect internal organs or the extremities unlike Dry Gangrene that is confined exclusively to the extremity. Bacterial invasion plays a HUGE role Gas Gangrene: a serious and potentially fatal disease (gas forming microorganism); caused by Clostridium Bacteria; amputation may be required to prevent spread Diabetic Gangrene: result of neuropathy nerve-endings; Feet is an important teaching with diabetes (diabetic neuropathy cant feel cuts or other things on feet)

IV. Cellular, tissue, and systemic aging A. Cellular basis of aging - normal physiologic process - not considered a disease

gradual result of wear-and-tear

B. Theories of Aging 1. Stochastic: aging as a result of lifelong genetic damage; Accumulations of lifelong random injuries and events 2. Nonstochastic: aging results from genetically controlled developmental program, or built in self-destructive processes C. Physiologic Changes of Aging 1. Atrophy- cells/tissue decrease in size 2. Sclerosis- thickening or hardening of organ or tissues 3. Decrease in organ functions- Lungs (lung capacity diminishes w/ age) - GI - GU (problems with incontinence) 4. No replacement of permanent cells 5. Decrease adaptation to stress- the older you get, the less adaptation to stress you get