Alt_Cell_Fcn_Class_Notes PDF

NURS 7053 Advanced Pathophysiology I for DNP Students Alterations of Cell Function - Class Notes Hypoxic Injury Lack of oxygen in the tissues leading to altered cell metabolism...

NURS 7053 Advanced Pathophysiology I for DNP Students Alterations of Cell Function - Class Notes Hypoxic Injury Lack of oxygen in the tissues leading to altered cell metabolism and function Causes Decreased oxygen content blood (hypoxemia) Decreased oxygen carrying capacity of blood (anemia) Decreased blood flow to the tissue (ischemia) Pathophysiological consequences of cell hypoxia Review of normal ATP production and cellular uses of ATP ATP production in mitochondria Uses of ATP Sodium-potassium pump Calcium pump Protein synthesis Uses for protein Repair plasma membrane & other structures Transporting lipids out of the cell 1  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations of Cell Function - Class Notes Consequences of decreased oxygen delivery to the cell and anaerobic metabolism 2  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations of Cell Function - Class Notes Reperfusion injury If the hypoxic tissue is reperfused cell injury occurs due to several factors: Oxidative stress: Introducing oxygen to tissue that has been hypoxic for > 60 min causes the formation of reactive oxygen species (ROS) (i.e., free radicals) Ca2+ release: Oxidative stress further damages the sarcoplasmic reticulum where Ca 2+ is stored in muscle tissue. Excess intracellular Ca2+ causes cell injury. Inflammation: WBCs that are reintroduced to the tissue release a myriad of inflammatory mediators, some of which can cause cell injury (NO, IL-1, TNF, etc), and ROS Free Radical Injury Free radicals are molecules that have an unpaired electron Causes of Free Radical Formation Absorption of extreme energy sources Endogenous, usually oxidative, reactions from normal metabolic processes Inflammation Enzymatic metabolism of exogenous chemicals or drugs Other sources – cigarette smoke, alcohol, pollution, transfats, heavy metals, etc. 3  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations of Cell Function - Class Notes Types of Free Radicals Reactive oxygen species (ROS): Hydroxyl radical (OH-), superoxide radical (O2-), nitric oxide- derived peroxynitrite (ONOO-), hydrogen peroxide (H2O2) Reactive nitrogen species (RNS): Nitrogen dioxide (NO2), nitric oxide (NO) Effects of Free Radicals Low/moderate levels – essential for cell metabolism and immune function High levels – causes ‘oxidative stress’ and cell injury DNA damage Fragmented proteins Lipid peroxidation Clinical Examples Free radical injury and aging Free radical injury causes disease Cancer Cardiovascular disease 4  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations of Cell Function - Class Notes Clinical Examples (continued) Pulmonary disease Neurodegenerative diseases Ocular disease Molecules that Inactivate Free Radicals Endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, peroxiredoxins) Non-enzymatic Antioxidants Vitamin A* Vitamin C* Vitamin E* Glutathione *dietary 5  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations of Cell Function - Class Notes Cell Death Apoptosis Programmed cell death Signals that induce apoptosis Extracellular signals (‘death ligands’, withdrawal of hormones/growth factors, toxic agents, etc.) Intracellular signals (decreased number of anti-apoptotic proteins + production of pro- apoptotic proteins) Mechanisms of apoptosis Nucleus condenses and cell shrinks Activation of intracellular enzymes (i.e., caspases) that breakdown structural proteins and DNA Apoptotic bodies are ingested by neighboring cells and local phagocytes (white blood cells), or just degenerate Note: No activation of the inflammatory response Clinical Examples Apoptosis during embryonic development Apoptosis in cancer cells 6