NURS 5315 Advanced Pathophysiology

NURS 5315 Advanced Pathophysiology Ovarian cancer site of metastasis? Peritoneal surfaces, omentum (fold of peritoneum connecting the stomach with other abdominal organs), liver The increased NADH/NAD+ ratio in the liver from ethanol causes: 1. Pyruvate -- lactic acid, causing lactic acidosis 2. Oxaloacetate -- malate. This prevents gluconeogenesis and leads to hypoglycemia 3. Glyceraldehyde-3-phosphate -- glycerol 3- phosphate and combines with fatty acids to form triglycerides in the liver, known as hepatosteatosis 4. Decreases citric acid cycle production of NADH and leads to using Acetyl-CoA for ketogenesis and lipogenesis What can Reactive Oxygen Species cause? Heart disease, Alzheimers, Parkinsons, Amyotrophic Lateral Sclerosis (ALS), CV disease, HTN, HLD, DM, ischemic heart disease, HF, OSA. Lipid perioxidation, damage proteins, fragment DNA, less protein synthesis, chromatin destruction, damage mitochondria What is the body's defense against ROS? Antioxidants (Vitamin E, Vitamin C, cysteine, glutathione, albumin, ceruloplasmin, transferrin) How are free radicals produced? 1. Normal cellular respiration 2. Absorption of extreme energy sources (radiation, UV light) 3. Metabolism of exogenous chemicals, drugs, and pesticides 4. Transition of metals 5. Nitric oxide acting like a chemical mediator and a free radical action potential Process of conducting an impulse. Activates the neuron -- the neuron depolarizes -- then repolarizes Threshold potential Point at which depolarization must reach in order to initiate an action potential Hypokalemia and action potentials HYPERpolarized (more negative, ex. -100). Less excitable. Decreased neuromuscular excitability: weakness, smooth muscle atony, paresthesia, cardiac dysrhythmias Hyperkalemia and action potentials HYPOpolarized (more positive, ex: closer to 0). More excitable. Peaked T waves. When resting membrane potential=threshold potential, it is BAD = cardiac standstill, paresthesia, paralysis Hypocalcemia and action potentials Increased permeability to Na+. More excitable. Tetany, hyperreflexia, circumoral paresthesia, seizures, dysrhythmias. Hypercalcemia and action potentials Decreased permeability to Na+. Less excitable. Weakness, hyporeflexia, fatigue, lethargy, confusion, encephalopathy, depressed T waves Atrophy Occurs as a result of decrease in work load, pressure, use, blood supply, nutrition, hormonal stimulation, or nervous stimulation. Once the cell has decreased in size, it has now compensated for decreased blood supply, nerve supply, nutrient supply, hormonal supply, and has achieved new homeostasis. Cells are alive but have diminished function and may lead to cellular death. Atrophy examples Physiologic atrophy- shrinking of the thymus gland during childhood. Disuse atrophy- someone that ends up being paralyzed Hypertrophy Increase in SIZE of cells, which will lead to increase in size of organ. Caused by hormonal stimulation or increased functional demand. Hypertrophy examples physiologic hypertrophy- skeletal hypertrophy when a person does heavy work or weight lifting / when a kidney is surgically removed, the other kidney increases in size pathologic hypertrophy- cardiomegaly results from an increased workload in hypertensive patients / left ventricular hypertrophy Hyperplasia Increase in NUMBER of cells. Results from increased rate of mitosis. Can ONLY happen in cells that are capable of mitosis (cell division). Hyperplasia examples 1. Thickening of skin because of hyperplasia of epidermal cells. 2. Hormonal hyperplasia- occurs in estrogen dependent organs like uterus and breast. 3. Compensatory hyperplasia- liver regenerates, callus on skin 4. Pathologic hyperplasia- estrogen is unopposed by progesterone and the endometrial lining undergoes hyperplasia and increased risk for endometrial cancer Dysplasia abnormal changes in the size, shape, and organization of mature cells due to persistent, severe cell injury or irritation Dysplasia examples Pre cancer pap smears often show dysplastic cells of the cervix that must undergo treatment. Metaplasia Changed cell that is REVERSIBLE (one cell is replaced by another cell). Exposure to chronic stressors, injury or irritation, like smoking or hydrochloric acid from heart burn Metaplasia examples Most common is change from columnar cells to squamous cells (chronic smokers). Less common is change from squamous to columnar cells, like in Barrett Esophagus caused by heart burn. Carcinoma in situ Pre-invasive epithelial malignant tumors of glandular or squamous origin. Sites including cervix, skin, oral cavity, esophagus, and bronchus Hypoxic injury 1. Decrease in oxygen in the air (high altitudes, asphyxiation, drowning) 2. Loss of hemoglobin function (hemorrhage or sickle cell anemia) 3. Decrease in production of red blood cells (anemia or leukemia) 4. Diseases of cardiopulmonary systems (ischemia, blood supply loss, arteriosclerosis) Hypoxic injury clinical manifestations 1. Increased CK (muscle and heart) 2. Increased LDH (muscle, liver, lung, heart, RBC, brain) 3. Increased ALT and AST (liver) 4. Increased troponin (heart) Reperfusion injury Oxygen supply is restored to ischemic tissues. Triggers oxygen intermediates which causes cell membrane damage and mitochondrial calcium overload. Xanthine dehydrogenase -- xanthine oxidate. This makes large amounts of free radicals, superoxide, and hydrogen peroxide. Causes cell membrane damage and mitochondrial calcium overload Reperfusion injury clinical manifestations White blood cell count is impaired. Seen in tissue transplantation, ischemic syndromes of the heart, liver, intestines, kidneys, and cerebrum. Free Radical Molecules that have an unpaired electron on its outer shell. This makes the molecule unstable. Cause cellular injury, aging, and disease to occur. Reactive Oxygen Species (ROS) Produced as a normal byproduct of ATP production in mitochondria. ROS can overwhelm the mitochondria and exhaust intracellular antioxidants. Also produced by absorption of high energy sources like radiation or UV light. Ethanol Acute affects in the liver include inflammation, fatty infiltration, hepatomegaly, acute liver necrosis, suppressed fatty acid oxidation. Chronic ethanol use is mainly seen in the stomach and liver, and is caused by free radicals. Elevated anion gap and osmolar gap 10 is diagnostic Infarct Form of necrosis that is a SUDDEN insufficiency of arterial blood flow. (ie: heart attack, cold leg, MI) Apoptosis Programmed cell death (normal). Needed to prevent cellular proliferation that would result in a large body. Clinical implications: neurodegenerative disease, ischemic injury, death of virus infected cells Autophagy Autodigestion of the cell. When cells lack nutrition, autophagy is triggered. During times of metabolic stress, autophagy provides ATP and other macromolecules for energy and cell survival. When stress progresses, it leads to cell death Aging Body released more cytokines and proinflammatory substances which results in chronic inflammation What lab values are elevated as we age? Interleukin 1, tumor necrosis factor-alpha, and C-reactive protein Role of hepatocytes Acetyl CoA is processed by hepatocytes and transforms to 3 ketone bodies: 1. Acetoacetate 2. Acetone 3. B-hydroxybutyrate Role of mitochondria Ketogenesis: occurs mostly in the hepatocytes What triggers ketogenesis? Unavailability of glucose. Keto diet = no sugar. Starvation and Type 2 DM can lead to this. Role of Acetyl-CoA Returns to citric acid cycle and combines with oxaloacetate to form citrate. Also transforms into ketone bodies by hepatocytes Oxaloacetate Used in gluconeogenesis (process of getting sugars from carbs). During starvation or uncontrolled diabetes, oxaloacetate levels are insufficient because it has been completely used by gluconeogenesis. Depletion of oxaloacetate increases amount of Acetyl CoA. Normal cells Will not grow unless attached to a firm surface. Normal cells have a limited life span and divide 10-50 times. Uniform in size and shape. Cancer cells