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Cellular Adaptation: Pathophysiology The cell is the fundamental unit of disease Wanda Lovitz, MSN, APRN Objectives: Cellular Adaptation Cite the general purpose of changes in cell structure and function that occur as the result of normal adaptive processes. Describe cell changes that occur with atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia, anaplasia, and neoplasia. Cite three sources of intracellular accumulations. Differentiate between the effects of ionizing and non-ionizing radiations. State how biological, physical, and chemical agents injury cells. Describe cell changes that occur with ischemia and hypoxic cell injury. Cite the reasons for the changes that occur with wet, dry, and gas gangrene. Cellular Adaptation Permits survival and maintenance of cell function May alter differentiation of genes enabling a cell to change size or form. Is a normal adaptive response to an appropriate stimulus Abnormal cellular changes may also occur Atrophy (cells shrink) D/t workload or adverse environmental conditions Is adaptive and reversible results in a decrease in cell size Types Unilateral Disuse atrophy (paralysis) Degeneration atrophy (MS) Ischemic atrophy (kidney, heart) Malnutrition atrophy (starvation) Loss of endocrine stimulation (uterine, breast) Bilateral Atrophy Brain atrophy Research has shown we are less likely to loose brain function if we continue to engage all parts of the brain (Brain atrophy with Alzheimer's) - Atrophic cells have lost endoplasmic reticulum, have fewer mitrochrondria, and myofliaments. HYPERTROPHY ( size of cells) D/T workload requirement of an organ part Causes an increase in cell size & cell function *See protein in cellular components with no in cellular fluid Results in an increase in tissue mass Seen in cardiac, skeletal, and muscle tissue These cells are not capable of mitosis (so, no number or hyperplasia) May be a normal physiologic response as seen in an increase in muscle size with exercise HYPERTROPHY May be a pathological response as in myocardial hypertrophy from HTN or valve disease Example: Left ventricular hypertrophy (LVH) – A PATHOLOGICAL HYPERTROPHY resulting in size of heart d/t workload caused by HTN. There is an increase in size but function is compromised However, there is a LIMIT to the amount the tissue can enlarge • Left Ventricular Hypertrophy LVH) – seen with poorly controlled HTN • Myocardial cells enlarge d/t workload of pumping HYPERPLASIA ( # of cells) Occurs d/t to a response from appropriate stimulus and ceases when stimulus is removed An increase in NUMBER of cells Restricted to cells capable of mitosis epidermis, intestinal epithelium, and glandular tissue. Physiological hyperplasia uterus and breast enlarge in pregnancy HYPERPLASIA (cont) May be a PHYSIOLOGICAL response and occur with hypertrophy ( in both cell size & number) Hyperplasia is important in wound healing May also be a non-physiologic hyperplasia Seen in prostatic hypertrophy (BPH), endometrial hyperplasia d/t increased hormone stimulation, or thyroid enlargement Goiter – thyroid hyperplasia Benign Prostatic Hypertrophy/Hyperplasia (BPH) – can cause difficulty with urination Hyperplasia seen in finger warts: epidermal hyperplasia d/t viral stimulation Verrucae vulgaris – common warts Plantar warts in # of epidermal cells ( DNA synthesis and mitotic division) METAPLASIA One cell type is replaced by another May predispose to cancer Involves reprogramming of undifferentiated stem cells Allows to cells to better survive in a hostile environment Is REVERSIBLE Is a response to chronic irritation and inflammation METAPLASIA Cells that are normally columnar or stratified may change to squamous. Examples: With continued smoke exposure, ciliated columnar cells are changed to stratified squamous cells Cervical cells change when exposed to STDs or HPV Think metamorphosis or change from one form to another Continued exposure may predispose to cancerous transformations. Ciliated columnar cells Stratifiied squamous cells DYSPLASIA*(ATYPICAL HYPERPLASIA) Deranged cell growth resulting in cells of varying size, shape, and appearance May be associated with chronic irritation or inflammation May be reversible if offending agent is removed Dysplasia is considered A STRONG PRECURSOR OF CANCER!!! Example: Cervical dysplasia However, dysplasia is an adaptive process – may or may not lead to cancer Decrease risk if irritation is removed or inflammation treated. Anaplasia Cells differentiate to a more IMMATURE or embryonic form. Malignant tumors are characterized by anaplastic cell growth. Ovarian cancer cells dividing Summary: Cellular Changes Then anaplasia/neoplasia CELLULAR ACCUMULATIONS *(cellular infiltrations) Is a buildup of substances the cells are unable to dispose of Is a result of cell injuries Examples Carbon/coal dust Lipids Fluid/edema Cellular Infiltrations carbon, triglycerides Carbon can accumulate via inhaled coal dust. Can cause black lung disease (pneumonconiosis) Organs enlarged, i.e., “MEGALY” Ex. spleenomegaly, hepatomegaly hepatomegaly Diseases d/t cellular accumulations MAY BE REVERSIBLE if d/t a correctable systemic disorder Example: elevated triglyceride levels can result in a “FATTY” liver. This may reverse when triglyceride level is lowered with medication CELLULAR ACCUMULATIONS: lipids and edema If the offending cause is not or cannot be corrected CELL DEATH may occur Example: Abnormal lipids in the brain of child with Tay-Sachs disease (a genetic disorder) ultimately results in cell death, and a shortened life span. cellular swelling – extracellular water shifts into cells Cerebral edema *Causes of cell injury Chemical agents Hypoxia Free radicals Infectious agents (bacteria, viruses, fungi) Physical and mechanical agents Genetic factors Nutritional imbalances **Individuals have different abilities to adapt to these stressors What are Free Radicals? Some free radicals are formed during normal metabolism Free radical – atoms or groups of atoms with an odd (unpaired) number of electrons Free radical theory of aging states that organisms age because cells accumulate free radical damage over time Antioxidants are believed to protect against free radical damage CELLULAR INJURY Cause: Mechanical Forces Cellular injury may be reversible or irreversible determined by: the severity of the insult, blood supply, nutritional status, and regeneration capability Physical Agents – trauma Electrical Temperature extremes Radiation Mechanical Injury: Physical Agents Cause: Physical Agents • Mechanical forces such as physical trauma resulting in lacerations, fractures, burns, injury to blood vessels, and disruption in blood flow. laceration Compound fracture Mechanical force injury: Electrical Can cause extensive tissue injury and disruption of neural and cardiac impulses Vessels degenerate and create thrombi or clots The body acts as a conductor of electrical current. Can see seizures or cardiac arrhythmias Extent of injury determined by the amount of voltage and duration of exposure. Lightning and high voltage wires produce most severe damage. Mechanical force injury: Temperature extremes Heat stroke or partial-thickness burns cause cellular injury With an increase in intensity of heat, blood vessels coagulate and tissue protein loss occurs Fried egg effect Cold exposure increases blood viscosity and induces vasoconstriction which may cause tissue hypoxia Disrupts the cell membrane Mechanical force injury: Ultraviolet Radiation Sunburns increase the risk of skin cancers Damage to melanin-producing processes in skin and damage to DNA occurs Risk of skin cancers with number and severity of sunburns Average 20 years from exposure to development of skin cancer Radiation injury: Ionizing radiation Direct injury causes immediate cell death or deranged replication The endothelial cells in blood vessels are very sensitive Radiation dermatitis stomatitis Radiation Injury Ionizing radiation Chronic effect causes scarring or fibrosis Most radiation injury is d/t localized irradiation used to treat cancer Effects DNA synthesis and interferes with mitosis Bone marrow and intestines are very vulnerable to radiation exposure Mechanical force: Chemical Injury Cells may be damaged by a vast array of chemicals A biochemical interaction between a toxic substance and the cell’s plasma membrane occurs and leads to cell permeability Examples air and water pollution tobacco smoke some processed or preserved foods carbon monoxide insecticides trace metals such as lead, and DRUGS Chemicals in tobacco smoke Tylenol/acetaminophen can cause chemical injury to cells. The cells in which organ are most affected by Tylenol? A. Kidney B. Brain C.Liver D.Heart 0% A. 0% B. 0% C. 0% D. Chemical injury: Drugs May damage cells directly or indirectly Both prescription (RX) and over-the-counter (OTC) medication can cause cell damage. Tylenol can damage liver cells Ibuprofen can injure kidney cells ETOH can harm gastric mucosa (gastritis) and liver cells and harm the developing fetus Fetal Alcohol Syndrome ↔ Chemical injury: Drugs Anti-cancer drugs can directly injure normal cells Some drugs produce metabolic end-products that are toxic to the cells Example: Tylenol, which is detoxified in the liver, can cause massive liver necrosis when taken in large amounts Lead paint tastes good. A. True B. False 0% A. 0% B. Chemical injury: Lead Toxicity Lead is absorbed via the GI Lead is very toxic to the cells Sources include: flaking paint, lead-contaminated dust and soil, leadcontaminated root vegetables, lead water pipes, and newsprint Inhaled or ingested lead accumulates over time tract or via the lungs into the blood Lead is toxic d/t multiple biochemical effects: RBC’s become small and pale (anemia) Since lead is excreted by the kidneys, kidney damage leading to renal failure can occur Lead (cont) Lead causes demyelination of NERVE CELLS in the cerebral and cerebellar matter causing death of neural and cortical cells Lead toxicity can cause a decrease in IQ impaired neurobehavioral development in children In adults see peripheral neuropathy Injury from biological agents: viruses, bacteria, and parasites Biological agents are able to replicate and thus can continue to cause injury to cells Viruses incorporate themselves into the DNA of the cell Bacteria secrete exotoxins or endotoxins that interfere with cellular reproduction of ATP, or release antitoxins that cause injury Parasites can cause direct injury to the cell bacteria virus salmonella Injury from nutritional imbalances Nutritional excesses such as obesity and diets high in fats can predispose to atherosclerosis leading to ischemia The body needs minerals, vitamins, certain fatty acids, and specific amino acids. Nutritional and vitamin deficiencies interfere with cell metabolism and delay wound healing Infected decubitus ulcer Hypoxic/Ischemia Cell Injury *(the most common cell injury) Hypoxic injury Generalized Is an inadequate supply of O2 in BLOOD affecting the entire body. Sx include change in LOC, confusion, combativeness Low pulse oximetry (less than 90%) Localized Causes ischemia of TISSUES If not corrected, can see infarction or death of tissues (heart, renal) Ischemia affects local tissue and is reversible Sx include pain, cyanosis,weak or absent pulses Infarction is tissue death and is not reversible. Hypoxic injury (cont) The cell reverts to anaerobic metabolism causing a fall in PH lactic acid accumulates in the cell lactic acidosis Causes of hypoxia Decrease of oxygen in the air Respiratory disease Ischemia Anemia d/t hemoglobin Edema Cellular Death Apopthosis Is essentially “cell suicide” or programmed cell death Apopthosis is the process that eliminates: Worn out cells (RBCs) Cells which have been produced in excess ex. WBCs with infectious response/hepatocytes with hepatitis) Cells which have developed improperly ex. spontaneous abortion Cells which have genetic damage Ex cancer eschar Necrosis Interferes with cell replacement and tissue regeneration. Necrotic cells or tissue can: Liquefication cells becomes liquefied Ex: abcess, brain tissue May result in wet gangrene INFARCTION cells die and become BLACK AND SHRIVELED A heart attack or myocardial infarction results in irreversible cell damage. A. True B. False 0% A. 0% B. The picture below is an example of: A. Wet gangrene B. Dry gangrene C.Gas gangrene 0% A. 0% B. 0% C. Gangrene Gangrene is necrosis of a mass of tissue Death of many cells! Results from severe hypoxia and subsequent ischemia Often seen with impaired circulation to lower extremities (PVD, Diabetes) Three types of gangrene: 1) 2) 3) Dry gangrene Wet gangrene Gas gangrene Dry Gangrene Part of the tissue becomes dry and shrinks, the skin wrinkles and color changes to brown or black Shriveled/mummified Spread is slow Results from chronic ischemia of tissue Symptoms not as marked as with wet gangrene Dry Gangrene Line of inflammatory reaction occurs between dead tissue and health tissue Usually d/t interference IN ARTERIAL supply to a part without interfering with venous return so no swelling No bacterial infection Mostly confined to extremities Note the clear line of demarcation Moist or wet gangrene Frequently occurs in internal organs (appendix) If on the skin, surrounding area is cold, swollen, and pulseless Skin in moist, black, and under tension Blebs form on the skin, liquefaction occurs, and foul odor develops from bacteria No line of demarcation Spread is rapid Moist or wet gangrene Severe systemic symptoms may develop Changes in VS, LOC, kidney function Death may occur Venous return is impaired so see swelling Bacterial invasion is present May affect extremities or internal organs Dry gangrene may become wet gangrene if a bacterial invasion occurs Gas Gangrene *(destroys connective tissue and cellular membranes) Is a specialized type of wet gangrene Results from infection of devitalized with clostridium bacteria Anaerobic and spore forming, clostridium are often found in the soil Gas gangrene is more prone to occur when there is trauma with a compound fracture Gas gangrene Note characteristic gas bubbles Bacteria produce toxins which dissolve cell membranes causing: death of muscle cells massive spreading edema hemolysis of RBCs renal toxicity Characteristic bubbles of hydrogen (sulfide gas) form in the muscle Can be fatal