NUR6003 Advanced Pathophysiology Notes

NUR6003: Advanced Pathophysiology DNP: Graduate Nursing: 2017 Summer Semester Dr. Morgan Jessica L. Clement, RN BSN Unit 1 PowerPoint Presentations/Lessons Lesson 1.1: Cellular Health & Injury Chapter 1 Cellular Health & Injury • The Cell o Basic unit of health o Diseases affect cells first, then the whole body • Homeostasis o Narrow range of an intracellular environment based on physiological parameters • Cellular Stress o Adaptation o Reversible Injury o Irreversible Injury o Cell Death o • Cell Death o Normal o Pathological • Injured Cells o May be morphologically identical but function differently o For example, injured myocardium does not contract • Cellular Adaptations o Reversible changes  Size, Number, Phenotype, Metabolic Activity, Function o Physiological  For example, uterus during menstrual cycle o Pathologic • Cellular Adaptations o Due to Physiologic Stress or Pathologic Stimuli  Hypertrophy  Hyperplasia  Atrophy  Metaplasia • Additional Responses to Stress o Intracellular Accumulation o Calcification o Cell Aging • Hypertrophy o Increased cell size à Increased organ size o No increase in number of cells o Occurs where limited capacity for replication o For example, muscle cells • Examples o Physiologic  Uterus in pregnancy o Pathologic  Heart in hypertension • Limit to Hypertrophy o If cells can’t compensate à degenerative changes occurs. • Hyperplasia o Increased number of cells o Occurs in tissue capable of proliferation o May occur in isolation or in conjunction with hypertrophy • Physiologic Hyperplasia o Hormonal  Glandular breast tissue in pregnancy o Compensatory  Increased hepatocyte proliferation after resection • Pathologic Hyperplasia o Caused by excessive hormonal or growth factors o Important in the healing process o If hormones/factors are removed Hyperplasia stops o Risk factor for cancer • Atrophy o Decreased cell size à Decreased organ size o May be functionally dormant or reduced o Common causes  Disuse  Denervation  Diminished blood supply  Inadequate nutrition  Aging • Mechanisms of Atrophy o Decreased protein synthesis o Protein degradation  Ubiquitin  Proteasome o Autophagy • Metaplasia o Replacement of one adult cell type with another o Cell susceptible to particular stress replaced with one less susceptible o Thought to be changes in stem cells o Not phenotypic change of mature cell o May lead to cancer • Classic Metaplasia Examples o Barrett’s Esophagus  Stratified Esophagus à gastric columnar o Bronchial ciliated columnar cell à stratified squamous cell  More likely to survive smoke  Loss of cilia function and mucus • Cell Injury & Death o Reversible o Irreversible  Necrosis  Apoptosis • Necrosis o Severe damage to membranes o Lysosome membranes break open and digest cell from inside o Cellular enzymes leak through membrane into extracellular space  Inflammatory reaction  Clinical enzymology  Dead cells may become calcified  Always pathological • Apoptosis o May be physiologic or pathologic o Loss of growth factor o DNA or protein damage o Nuclear dissolution o Cell membrane stays intact o No inflammatory response • Injurious Stimuli o Oxygen Deprivation o Chemical agents (toxins) o Infectious agents o Immunologic Reaction o Genetic Factors o Nutritional Imbalances o Physical Agents (trauma, shock, radiation, etc.) o Aging • Cell & Tissue Damage o Reversible vs. Irreversible  Mitochondria dysfunction  Profound disruption of membrane function • Reversible Injury o Cellular Swelling  Failure of energy dependent ion pumps o Fatty Change  Appearance of lipid vacuoles • Special Cases o Smooth ER of hepatocytes o Increased P-450 enzyme activity o Increased metabolism of entire pathway o May cause interactions • Patterns of Necrosis o Coagulative o Liquefactive o Gangrenous o Caseous (cheeselike) o Fat o Fibrinoid (requires microscope) • Mechanism of Cell Injury o Cellular response depends on:  Type of injury  Duration  Severity o Consequences depend on:  Type of cell  Status (nutritional/hormonal)  Adaptability  Genetic makeup • Mechanisms of Cell Injury o Injury results from abnormalities  Ability of Mitochondria to produce ATP and ROS  Calcium Homeostasis  Plasma and Lysosome membranes  DNA  Misfolding of proteins • Review of ATP o Mitochondria produce ATP from ADP plus PO4  Aerobic • Glucose + O2 à CO2 + H2O  Anaerobic • Glucose + NO oxygen à Lactic Acid • Fun Quote of the Week o High-energy phosphate in the form of ATP is required for virtually all synthetic and degradative processes within the cell, including membrane transport, protein synthesis, lipogenesis, and the deacylation-reacylation reactions necessary for phospholipid turnover. It is estimated that in total, the cells of a healthy human burn 50 to 75 kg of ATP every day! • ATP Depletion o Usually caused by lack of O2 o Mitachondrial damage o Some toxins (e.g. cyanide) • ATP Depletion o Cell Membrane pumps stop working  Sodium influx  Water follows sodium à cellular swelling o Increase glycolysis  Deplete glycogen  Increased Lactic Acid o Decreased pH suppresses enzyme activity • ATP Depletion o Calcium pumps stop working  Influx of Calcium o Protein synthesis stops  In prolonged ATP depletion  Ribosomes detach from RER  Polysomes à Monosomes • Mitochondrial Damage o ATP Depletion o Increased numbers of ROS o Membrane Permeability Increases o Proteins released à Apoptosis • Influx of Calcium o Crytsolic Calcium – usually 10,000 times lower than surrounding fluid o Most Intracellular Calcium is sequestered ER or Mitochondria. o When cell is damaged,  ATP calcium pump stops  Influx across damaged membranes  Activate cellular enzymes  Can induce Apoptosis • Oxidative Stress o Increase in Oxygen-derived Free Radicals (ROS)