Cell Response to Stress, Injury, and Aging PDF

CELL RESPONSE TO STRESS, INJURY, & AGING Inadequate nutrition Cells Respond to their Internal Environment  Restriction of nutrition leads to atrophy to survive with few resources  This...

CELL RESPONSE TO STRESS, INJURY, & AGING Inadequate nutrition Cells Respond to their Internal Environment  Restriction of nutrition leads to atrophy to survive with few resources  This allows the organism to respond to external environment Ischemia  Most cells of the body are efficient (Lazy)  Cells can respond to increased demands (get  Prolonged periods with decreased blood flow force the cells to adapt to fewer nutritional resources larger or increased in number)  May reversibly change in response to adverse Hypertrophy conditions  Cells must adapt – usually by gene expression  An increased in size of an organ or body part - Size associated with increased demand - Number  Common in cardiac & skeletal muscles - Differentiation – changing cell types  Why? Can muscle cells undergo mitotic  If they cannot overcome the stressor, they may not division? survive (apoptosis or necrosis) o Genes are turned on in muscles cells to make new actin & myosin Atrophy as well as increasing the size &/or number of organelles, enzymes,  Cell (& therefore the organ or tissue (becomes more ATP, etc. SMALLLER (commonly because of damage)  Advantages Left Ventricular Hypertrophy - Decrease in oxygen consumption - Fewer & smaller organelles to support  What “increased demand” may cause this? (mitochondria, E.R., etc)  Common result of unmanaged - Fewer proteins are made which also hypertension decreases energy & resource use and demand. Types of Atrophy Disuse Atrophy - common in muscle cells  Example: arm encased in a cast  Patient on a ventilator  Prolonged immobility Types of Hypertrophy Normal Physiologic  Increase in muscle mass associated with exercise or other workload demands  Adaptive - Example thickening of urinary bladder due to outflow obstruction  Compensatory – Example: increase in size of one kidney after the other is removed Denervation Atrophy PLASIA- development or formation  A form of disuse atrophy. If the nerve supplying a  Hyperplasia muscle or organ is damaged, the target lacks - increase in cell number stimulation & feedback & will atrophy  Metaplasia - Can be complete or partial denervation - change from one cell type to another - E.g. patients with spinal cord injury (reversible) Hormonal  Dysplasia - “Deranged: cell growth resulting in cells  hormones may affect tissue & organ size that vary in size, shape, & organization - Examples: Hyperplasia - Breast & sex organ atrophy with prolonged decrease in estrogen (such as associated  Organ may become larger, but due to MORE with menopause CELLS, NOT larger cells - Testosterone abuse may lead to testicular  Almost exclusively found in cells that are capable atrophy of mitotic cell division (make sense) – NOT muscle cells & neurons   Examples Injurious Agents - Regeneration of liver after a partial hepatectomy  Physical: trauma, heat & cold, electricity - Breast enlargement during pregnancy  Radiation: ionizing, ultraviolet - Callouses  Chemical: drugs, lead, mercury - Hormones may affect endometrium  Biological agents: bacteria, viruses, parasites (estrogens) or the prostate gland  Nutritional imbalances: fats, minerals, vitamins, (androgens) amino acids Metaplasia  Reversible change in a cell type (usually epithelial)  Usually a response to chronic irritation & inflammation  Allows a fragile cell to survive adverse reactions Examples of Metaplasia - Cigarette smoking may switch ciliated columnar epithelial tissue to stratified epithelial tissue - GERD (Gastroesophageal Reflux Disease) – acid Injurious Agents - Physical exposure changes squamous to columnar mucosal  Trauma – directly damages cells epithelium  Heat– (43-46 C) changes protein function (they - Barrett’s Esophagus – metaplasia that predisposes work at specific temperatures), causes coagulation to cancer development of blood & proteins, & disrupts membranes *While not cancer, Metaplasia is often associated with a  Cold – Vasoconstricts, may cause hypoxic injury by higher risk of cancer (precancerous)* restricting blood flow, formation of ice crystals, increased blood viscosity & edema from increased Dysplasia capillary permeability, slows down chemical process  “deranged” cell growth – also reversible  Electrical– causes burns due to tissue resistance.  Often associated with chronic irritation or Also interrupts electrical activity such as cardiac inflammation impulses - Human Papilloma Virus (HPV)  Results in various sizes, shapes, and organization Injurious Agents - Radiation  Histological analysis of pap smear can detect dysplastic cells on the cervix indicating an  Electromagnetic radiation increased risk for cancer - Like radio waves that your cellphone uses (but those are low energy) Intracellular Accumulations - At high energies above Ultraviolet, radiation can knock electrons off of molecules,  Build up of substances cells cannot immediately creating ions (ionizing radiation) use or eliminate - Can damage molecules (including DNA) in  Normal body substances in large amounts the cell causing cell damage or even - Examples cancer. Sunburn is radiation injury but - Fats – fatty acids delivered to the liver may melanin attempts to protect the nucleus build up –fatty liver disease - At very high levels, radiation quickly kills - Carbs – glucose can build up on dividing cells which is why it is used to treat membrane proteins & damage small blood cancer. vessels (diabetes mellitus) - Bilirubin – breakdown product of RBS – Injurious Agents - Chemicals causes jaundice  Drugs can cause injury to issues by disrupting cell  Abnormal endogenous products from within the processes in various ways body - Metabolic enzymes may not work properly  Lead & mercury can build up & interfere with leading to a build up protein function, damaging brain & other cell types - Example – if you can’t break down Injurious Agents - Biologicals glycogen, it build up in cells and less glucose is available  Viruses divide in a host cell & utilize its resources.  Exogenous products from outside the body Retrovirues “upload” themselves into a host DNA – - Coal dust (black lung), Lead, etc… causes a range of symptoms - (also pigments including tattoos!)  Bacteria may produce endotoxins or exotoxins which interrupt normal protein & other cell functions.  Bacteria also cause an increase in capillary permeability (inflammatory process Retroviruses Hypoxia effect on Energy production  Aerobic metabolism in the mitochondria stops - less ATP is produced - Na/K ATPase decreases - increased intracellular sodium – cell swells (osmotic activity) with water  Anaerobic metabolism (glycolysis) required – lactic acid is produced - Acid damages cell membranes, DNA & interferes with protein function  Without enough ATP, enzymatic reactions can’t take place and the cell can’t perform properly  The build up of water & lactic acid interferes with normal cell function  All of these problems can lead to cell death fairly quickly depending on the cell’s Cell Injury Mechanisms requirements (4-6 minutes for irreversible  Most cell injury happens due to damage to occur in the brain) 1. Free radical formation Intracellular Intracellular Calcium 2. Hypoxia/ Ischemia 3. Disruption of calcium homeostasis  Cell injury can lead to undesired release of calcium - Ischemia Free Radicals & other Reactive Oxygen Species - Toxins  Using oxygen to make ATP causes some problems - Etc… with chemical reactions – Reactive Oxygen Species  Cells usually maintain low cytosolic calcium  When released, Calcium acts as a “second Free Radicals messenger” - Turns on intracellular enzymes  Chemicals with an unpaired electron in the outer - Causes muscle contractions electron shell - Regulates heart rate  Extremely unstable and reactive - Allows neurons to releases  Can react with normal cell components neurotransmitter  Reactions with normal cell components: - Can damage the cell if not regulated - Lipid oxidation – cell membrane - Damage / modification of proteins Cell Death – sometimes cells die =( - DNA damage – possibly also associated with aging  Apoptosis - programmed cell death or “cell  Ionizing & UV radiation can produce free radicals suicide”  Normally “deactivated” by antioxidants - Good thing is that it doesn’t damage nearby cells Hypoxia - Replaces “worn out” cells to make room for more  Low oxygen causes ATP depletion or “Power - Gets rid of cells that are no longer Failure” necessary (why we don’t have webbed  Many things lead to hypoxia fingers) - Ischemia (decreased blood flow to tissues) - Immune cells trigger apoptosis to kill - Inadequate amounts in the air infected cells (extrinsic) - Respiratory disease - Apoptosis also gets rid of immune cells - Etc… following an infection  Without oxygen, ATP production in the mitochondria - Many uses for normal physiological can’t take place apoptosis  Enzymes that require ATP can’t function properly  Necrotic Cell Death - BAD  Many enzymatic processes are affected, but  Unregulated death caused by injuries to cells  The SODIUM/POTASSIUM pump is a MAJOR  Cells swell and rupture - inflammation ATP USER! (up to 60% of TAP in a cell is used to power the Na/K Atpase) Apoptosis  Prevents injury to surrounding cells  Extrinsic – (death receptor) – signal from outside the cell  Intrinsic pathways – start from within the cell – often through malfunction of mitochondria  Ultimately both intrinsic & extrinsic pathways turn on intracellular enzymes: caspase family of enzymes   Activation of both intrinsic and extrinsic pathways: - C. Caseous (soft, cheesy)  Ultimately leads to: o Dead cells persists - DNA & cellular fragmentation o Distinctive form of coagulation - Digestion of their own cell proteins process - Cell fragments are then digested by o Most commonly associated with immune cells (such as macrophages) tubercular lesions o Thought to result from immune Example pathology in apoptosis mechanisms  Pathology Lung gross Caseous Necrosis in Tuberculosis - BCL-2 is a gene product that blocks the apoptotic pathway – It’s named for B-Cell Lymphoma – too much BCL-2 protein prevents B-cells from dying, leading to a form of lymphatic blood cancer Necrosis  Inflammation  Cell Swelling  Rupture of membrane Mechanism is determined by type of injury & type of Gangrene tissue  Dry gangrene – lack of arterial blood supply but  Types venous flow can carry fluid out of tissue - A. Liquefaction (undergoes liquefaction) - Tissue tends to coagulate o Some of the cells die but their  Wet Gangrene – lack of venous flow lets fluid catalytic enzymes are not accumulate in tissue destroyed - Tissue tends to liquefy & infection is likely o Example: softening of the cancer of  Gas Gangrene: Clostridium infection produces an abcess; commonly seen in brain toxins and H2S bubbles tissue - B. Coagulation (firm, gray mass) o Acidosis develops & denatures the enzymatic & structural proteins of the cell o Characteristics of hypoxic injury; commonly seen in cardiac muscle tissue