Module 1 Study Guide -Patho.pdf - N5315 Advanced Pathophysiology Altered Cellular Function and Cancer Module Core Concepts and Objectives with Advanced

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Unformatted text preview: ​ ​ ​N5315​ ​Advanced​ ​Pathophysiology Altered​ ​Cellular​ ​Function​ ​and​ ​Cancer Module​ ​Core​ ​Concepts​ ​and​ ​Objectives​ ​with​ ​Advanced​ ​Organizers Cellular​ ​Physiology 1.​ ​ ​ ​ ​ ​ ​Analyze​ ​the​ ​steps​ ​of​ ​the​ ​action​ ​potential. ● Sodium​ ​permeability​ ​increases,​ ​sodium​ ​ions​ ​move​ ​into​ ​the​ ​cell​ ​increasing​ ​positivity, depolarization​ ​is​ ​occurring,​ ​action​ ​potential​ ​threshold​ ​is​ ​reached​ ​as​ ​cell​ ​becomes​ ​more positive,​ ​potassium​ ​permeability​ ​increases,​ ​potassium​ ​ions​ ​leave​ ​the​ ​cell,​ ​repolarization​ ​is occurring,​ ​resting​ ​membrane​ ​potential​ ​is​ ​reestablished. · The​ ​action​ ​potential​ ​carries​ ​signals​ ​along​ ​the​ ​nerve​ ​or​ ​muscle​ ​cell​ ​and​ ​conveys information​ ​from​ ​one​ ​cell​ ​to​ ​another. · When​ ​a​ ​resting​ ​cell​ ​is​ ​stimulated​ ​with​ ​voltage​ ​the​ ​membrane​ ​becomes​ ​permeable​ ​to sodium. · Movement​ ​of​ ​sodium​ ​into​ ​the​ ​cell,​ ​the​ ​membrane​ ​potential​ ​decreases,​ ​moves​ ​to​ ​a negative​ ​or​ ​zero​ ​is​ ​known​ ​as​ ​depolarization​.​ ​Depolarized​ ​cells​ ​are​ ​positively​ ​charged. · To​ ​generate​ ​an​ ​action​ ​potential​ ​and​ ​the​ ​resulting​ ​depolarization​ ​is​ ​known​ ​as​ ​threshold potential​.​ ​It​ ​happens​ ​when​ ​the​ ​cell​ ​has​ ​depolarized​ ​by​ ​15-20​ ​millivolts.​ ​When​ ​the​ ​threshold​ ​is met​ ​the​ ​cell​ ​continues​ ​to​ ​depolarize​ ​with​ ​no​ ​further​ ​stimulation.​ ​This​ ​makes​ ​the​ ​sodium​ ​rush out​ ​of​ ​cell​ ​causing​ ​the​ ​membrane​ ​potential​ ​to​ ​reduce​ ​to​ ​zero​ ​and​ ​become​ ​positively (depolarization).​ ​This​ ​rapid​ ​reversal​ ​in​ ​polarity​ ​results​ ​in​ ​action​ ​potential. · Repolarization​ ​is​ ​negative​ ​polarity​ ​of​ ​the​ ​resting​ ​membrane​ ​potential.​ ​Membrane permeability​ ​to​ ​sodium​ ​decreases,​ ​and​ ​potassium​ ​increases​ ​with​ ​outward​ ​movement​ ​of potassium.​ ​This​ ​makes​ ​the​ ​membrane​ ​potential​ ​more​ ​negative. · During​ ​most​ ​of​ ​the​ ​action​ ​potential​ ​the​ ​plasma​ ​membrane​ ​cannot​ ​respond​ ​to​ ​any additional​ ​stimulus​ ​is​ ​known​ ​as​ ​absolute​ ​refractory​ ​period​.​ ​Its​ ​related​ ​to​ ​changes​ ​in​ ​sodium. · If​ ​potassium​ ​increases,​ ​a​ ​stronger​ ​stimulus​ ​can​ ​evoke​ ​an​ ​action​ ​potential​ ​is​ ​relative refractory​ ​period​. · A​ ​membrane​ ​potential​ ​more​ ​negative​ ​than​ ​normal,​ ​requires​ ​a​ ​larger​ ​stimulus​ ​to​ ​reach​ ​the threshold​ ​potential​ ​is​ ​hyperpolarized​ ​(less​ ​excitable).​ ​occurs​ ​when​ ​the​ ​membrane​ ​is repolarizing. · A​ ​membrane​ ​that​ ​is​ ​more​ ​positive​ ​than​ ​normal,​ ​needs​ ​smaller​ ​stimuli​ ​to​ ​reach​ ​threshold potential​ ​is​ ​hypopolarized​ ​(more​ ​excitable​ ​than​ ​normal). 2.​ ​ ​ ​ ​ ​ ​Discuss​ ​how​ ​the​ ​action​ ​potential​ ​is​ ​altered​ ​by​ ​calcium​ ​and​ ​sodium​ ​imbalances​ ​and​ ​the clinical ​significance · Na​ ​has​ ​a​ ​greater​ ​concentration​ ​in​ ​the​ ​ECF.​ ​When​ ​a​ ​neuron​ ​is​ ​excited​ ​by​ ​a​ ​stimulus,​ ​the stimulus-gated​ ​Na+​ ​channels​ ​open​ ​allowing​ ​Na+​ ​to​ ​move​ ​intracellularly.​ ​This​ ​moves​ ​the resting​ ​membrane​ ​potential​ ​of​ ​-70mV​ ​more​ ​towards​ ​0.​ ​Once​ ​the​ ​threshold​ ​potential​ ​is reached​ ​(-59mV)​ ​the​ ​voltage​ ​gated​ ​Na+​ ​channels​ ​open​ ​allowing​ ​for​ ​more​ ​Na+​ ​to​ ​move​ ​into the​ ​cell​ ​and​ ​complete​ ​the​ ​depolarization​ ​to​ ​a​ ​maximum​ ​of​ ​+30mV.​ ​If​ ​the​ ​depolarization​ ​does not​ ​reach​ ​a​ ​minimum​ ​of​ ​-59mV​ ​(threshold​ ​potential)​ ​the​ ​voltage​ ​gated​ ​Na+​ ​channels​ ​will​ ​not open​ ​and​ ​the​ ​cell​ ​will​ ​simply​ ​repolarize​ ​to​ ​-70mV​ ​without​ ​generating​ ​an​ ​action​ ​potential. · Hyponatremia:​ ​Cellular​ ​swelling​ ​and​ ​deficits​ ​of​ ​intracellular​ ​Na​ ​alter​ ​the​ ​ability​ ​of​ ​cells to​ ​depolarize​ ​and​ ​repolarize​ ​normally.​ ​Causes​ ​neurological​ ​changes​ ​headaches,​ ​lethargy,​ ​and seizures. · Hypernatremia:​ ​Na​ ​is​ ​largely​ ​in​ ​the​ ​ECF,​ ​increase​ ​concentration​ ​of​ ​Na​ ​causes intracellular​ ​dehydration​ ​and​ ​hypervolemia.​ ​Causes​ ​hypotension,​ ​tachycardia,​ ​thirst. · Hypercalcemia​ ​decreases​ ​cell​ ​permeability​ ​to​ ​sodium.​ ​This​ ​causes​ ​the​ ​threshold​ ​potential to​ ​become​ ​more​ ​positive​ ​and​ ​is​ ​further​ ​away​ ​from​ ​the​ ​membrane​ ​potential.​ ​It​ ​takes​ ​more​ ​of​ ​a stimulus​ ​to​ ​initiate​ ​an​ ​action​ ​potential.​ ​The​ ​cells​ ​are​ ​far​ ​less​ ​excitable​ ​and​ ​do​ ​not​ ​initiate action​ ​potentials.​ ​This​ ​leads​ ​to​ ​weakness,​ ​hyporeflexia,​ ​fatigue,​ ​lethargy,​ ​confusion, encephalopathy,​ ​a​ ​shortened​ ​QT​ ​segment​ ​and​ ​depressed​ ​widened​ ​T​ ​waves​ ​on​ ​EKG. · Hypocalcemia-​ ​calcium​ ​deficits​ ​causes​ ​partial​ ​depolarization​ ​of​ ​the​ ​nerves​ ​and​ ​muscle​ ​as the​ ​threshold​ ​potential​ ​becomes​ ​more​ ​negative​ ​and​ ​approaches​ ​resting​ ​membrane​ ​potential (hypopolarization).​ ​A​ ​smaller​ ​stimulus​ ​is​ ​needed​ ​to​ ​start​ ​the​ ​action​ ​potential.​ ​This​ ​means​ ​the cells​ ​are​ ​more​ ​excitable.​ ​This​ ​results​ ​in​ ​tetany,​ ​hyperreflexia,​ ​paresthesias,​ ​prolonged​ ​QT interval,​ ​seizures,​ ​muscle​ ​spasms,​ ​laryngospasm. Topic Describe​ ​the Action​ ​Potential How​ ​is​ ​the​ ​action potential​ ​altered​ ​by​ ​a potassium​ ​imbalance? How​ ​is​ ​the​ ​action potential​ ​altered​ ​by a​ ​calcium imbalance? Action​ ​Potential Physiology is​ ​the​ ​membrane potential​ ​of​ ​an active​ ​neuron. One​ ​that​ ​is conducting​ ​an impulse.​ ​The process​ ​of conducting​ ​an impulse​ ​(action potential) involves​ ​a stimulus​ ​that activates​ ​the neuron​ ​→​ ​the neuron depolarizes​ ​→ then​ ​repolarizes Once​ ​the​ ​cell​ ​is more​ ​positively charged,​ ​the sodium​ ​channels open​ ​and​ ​sodium flows​ into​ ​the cells.​ ​ ​Membrane potential​ ​is​ ​near zero.​ ​ ​The​ ​neuron repolarizes (becomes​ ​more negatively charged), potassium channels​ ​open. Hypokalemia​ ​causes​ ​a more​ ​negative​ ​resting membrane​ ​potential therefore​ ​the​ ​cell​ ​is​ ​more difficult​ ​to​ ​excite. Because​ ​potassium contributes​ ​to​ ​the repolarization​ ​phase​ ​of the​ ​action​ ​potential, hypokalemia​ ​delays ventricular​ ​repolarization and​ ​the​ ​frequency​ ​of action​ ​potentials Causes:​ ​weakness, smooth​ ​muscle​ ​atony, paresthesias,​ ​cardiac dysrhythmias Hyperkalemia​​ ​affects the​ ​resting​ ​membrane potential.​ ​the​ ​resting membrane​ ​potential​ ​of the​ ​cell​ ​becomes​ ​more positive.​ ​A​ ​normal​ ​RMP of​ ​-90mv​ ​may​ ​now​ ​be -80mv.​ ​The​ ​cell​ ​is​ ​said​ ​to be​ ​hypo-polarized.​ ​The cells​ ​are​ ​more​ ​excitable and​ ​conduct​ ​impulses more​ ​easily​ ​and​ ​more quickly.;​ ​therefore,​ ​the person​ ​will​ ​have​ ​peak​ ​T waves​ ​on​ ​EKG.​ ​As potassium​ ​rises​ ​the resting​ ​membrane potential​ ​will​ ​continue​ ​to become​ ​more​ ​positive Hypercalcemia causes​ ​a​ ​higher​ ​action potential​ ​threshold causing​ ​a​ ​more difficult​ ​excitable action​ ​potential. Hypercalcemia decreases​ ​the​ ​cell permeability​ ​to​ ​Na+ which​ ​makes​ ​the threshold​ ​potential more​ ​positive​ ​and further​ ​away​ ​from​ ​the membrane​ ​potential. Takes​ ​a​ ​stronger stimulus​ ​to​ ​initiate​ ​the action​ ​potential.​ ​ ​Cells are​ ​less​ ​excitable. Causes:​ ​ ​weakness, hyporeflexia,​ ​fatigue, lethargy,​ ​confusion, encephalopathy, shortened​ ​QT segment,​ ​depressed widened​ ​T-waves. When​ ​the​ ​action potential​ ​reaches​ ​the axon​ ​ending,​ ​it​ ​causes another​ ​ion​ ​(calcium, Ca++)​ ​to​ ​en ter​ ​the​ ​cell,​ ​which​ ​in turn​ ​causes​ ​the vesicles—the​ ​tiny bubbles​ ​full​ ​of neurotransmitters—to and​ ​it​ ​will​ ​eventually become​ ​equal​ ​to​ ​the threshold​ ​potential.​ ​The threshold​ ​potential​ ​is​ ​the point​ ​at​ ​which depolarization​ ​must reach​ ​in​ ​order​ ​to​ ​initiate an​ ​action​ ​potential (transmit​ ​the​ ​impulses). If​ ​the​ ​resting​ ​membrane potential​ ​equals​ ​the threshold​ ​potential,​ ​an action​ ​potential​ ​will​ ​not be​ ​generated​ ​and​ ​cardiac standstill​ ​will​ ​occur. Paralysis​ ​and paresthesias​ ​may​ ​also occur. release​ ​their​ ​content into​ ​synaptic​ ​gap Hypocalcemia​:​ ​there is​ ​an​ ​increase​ ​in​ ​cell permeability​ ​to​ ​Na+ which​ ​causes progressive depolarization. Threshold​ ​potential more​ ​negative;​ ​closer to​ ​the​ ​resting membrane​ ​potential. Cells​ ​are​ ​more excitable. Causes:​ ​tetany, seizures, hyperreflexia, dysrhythmias,​ ​and circumoral parasthesias Hyperpolarization​ ​–​ ​requiring​ ​a​ ​stronger​ ​stimulus​ ​(decreased​ ​excitability)​ ​to​ ​initiate depolarization​ ​and​ ​an​ ​action​ ​potential Cellular​ ​Adaptation​ ​Patterns 1.​ ​ ​ ​ ​ ​ ​Analyze​ ​the​ ​differences​ ​between​ ​cellular​ ​adaptation​ ​patterns. a.​ ​ ​ ​ ​ ​ ​ ​Differentiate​ ​between​ ​the​ ​etiology​ ​and​ ​the​ ​pathophysiology​ ​of​ ​atrophy, hypertrophy,​ ​hyperplasia,​ dysplasia,​ ​and​ ​metaplasia​ ​and​ ​identify​ ​an​ ​example​ ​of each. Disease Etiology Pathophysiology Example Atrophy (Adaptive decrease​ ​in cell​ ​size) Can​ ​be physiologic​ ​–​ ​as in​ ​early development​ ​or pathologic​ ​as Decreased​ ​protein​ ​synthesis, increased​ ​protein​ ​catabolism. Thymus​ ​gland decreases​ ​in​ ​size during​ ​childhood, aging​ ​brain​ ​cells Atrophic​ ​muscle​ ​cell​ ​has​ ​less endoplasmic​ ​reticulum​ ​and fewer​ ​myofilaments. Decrease​ ​or shrinkage​ ​of cell​ ​size seen​ ​in​ ​decrease in​ ​workload. Hypertrophy (Adaptive increase​ ​in cell​ ​size) Occurs​ ​as​ ​an adaptive​ ​response in​ ​striated​ ​muscle cells​ ​of​ ​both​ ​the heart​ ​and​ ​skeletal muscles. Increase​ ​in size​ ​of​ ​cell and​ ​even organs Hyperplasia (Adaptive increase​ ​in number​ ​of cells) Disuse​ ​atrophy secondary​ ​to immobilization or​ ​aging. Mechanical​ ​triggers​ ​(stretch) and​ ​trophic​ ​signals​ ​(growth factors​ ​and​ ​vasoactive​ ​agents). The​ ​increase​ ​in​ ​cellular​ ​size​ ​is associated​ ​with​ ​an​ ​increased accumulation​ ​of​ ​protein​ ​in​ ​the cellular​ ​components​ ​(plasma Physiologic: membrane,​ ​endoplasmic response​ ​to​ ​heavy reticulum,​ ​myofilaments, work​ ​load. mitochondria)​ ​and​ ​not​ ​with​ ​an increase​ ​in​ ​the​ ​amount​ ​of Pathologic: cellular​ ​fluid. associated​ ​with pressure​ ​or Hormonal​ ​stimulation​ ​or volume​ ​overload increased​ ​functional​ ​demand in​ ​disease. Man,​ ​who​ ​lifts weights​ ​regularly develops​ ​larger biceps,​ ​kidney after transplantation, Response​ ​to injury​ ​occurs when​ ​the​ ​injury has​ ​been​ ​severe and​ ​prolonged Lining​ ​of​ ​the uterus​ ​thickens after​ ​ovulation because​ ​of increased​ ​amounts of​ ​estrogen,​ ​liver post transplantation(he patocytes),​ ​bone marrow,​ ​callus. Physiologic: adaptive mechanism​ ​that enables​ ​certain organs​ ​to regenerate. Increased​ ​rate​ ​of​ ​cellular division​ ​in​ ​cells​ ​capable​ ​of mitosis​ ​(reproduction). Cells​ ​only​ ​increase​ ​in​ ​number; size​ ​of​ ​the​ ​cell​ ​remains​ ​the same. Compensatory​ ​hyperplasia​ ​enables​ ​certain​ ​cells​ ​ ​to regenerate Cardiac hypertrophy secondary​ ​to hypertension,​ ​or valvular dysfunction Dysplasia (AKA Atypical hyperplasia) Abnormal change​ ​in size,​ ​shape, and organization of​ ​mature tissue​ ​cells Pathologic hyperplasia: abnormal proliferation​ ​of normal​ ​cells​ ​and can​ ​occur​ ​as​ ​a response​ ​to excessive hormonal stimulation​ ​or​ ​the effects​ ​of​ ​growth factors​ ​on​ ​target cells Hormonal​ ​-​ ​estrogen​ ​dependent organs Strongly associated​ ​with common neoplastic growths. Not​ ​considered​ ​a​ ​true​ ​adaptive process. Abnormal changes​ ​in​ ​size, shape,​ ​& organization​ ​of mature​ ​cells. Not​ ​a​ ​true adaptive​ ​process, often​ ​called atypical hyperplasia Is​ ​classified​ ​as Mild Moderate Severe Often​ ​found​ ​adjacent​ ​to cancerous​ ​cells Cervical(pap​ ​test) and​ ​respiratory tract. Atypical hyperplasia​ ​is Strong​ ​predictor​ ​of breast​ ​cancer development. Metaplasia (Reversible replacement of​ ​one​ ​mature cell​ ​by another, sometimes less differential, cell​ ​type) Results​ ​from exposure​ ​of​ ​cells to​ ​chronic stressors,​ ​injury or ​irritations. Thought​ ​to​ ​develop​ ​from​ ​a reprogramming​ ​of​ ​stem​ ​cells existing​ ​in​ ​most​ ​epithelia​ ​or​ ​of undifferentiated​ ​mesenchymal cell​ ​present​ ​in​ ​connective​ ​tissue Bronchial metaplasia​ ​Columnar epithelium​ ​in bronchi​ ​of cigarette​ ​smoker​ ​is replaced​ ​by stratified squamous epithelium b.​ ​ ​ ​ ​ ​ ​Identify​ ​a​ ​physiologic​ ​and​ ​pathophysiologic​ ​example​ ​for​ ​atrophy, hypertrophy,​ ​hyperplasia,​ ​dysplasia,​ ​and​ ​metaplasia. Disease Physiologic​ ​Example Pathologic​ ​Example Atrophy Thymus​ ​Gland:​ ​shrinks​ ​after puberty,​ ​having​ ​already produced​ ​most​ ​of​ ​the​ ​T-cells needed​ ​for​ ​a​ ​lifetime.​ ​It eventually​ ​atrophies​ ​to​ ​nearly nothing,​ ​being​ ​replaced​ ​by adipose​ ​tissue. Disuse​ ​muscle​ ​atrophy: Bed-bound​ ​patients,​ ​disuse atrophy Hypertrophy Exercising; Changes​ ​in​ ​uterus​ ​during pregnancy Left​ ​Ventricular​ ​Hypertrophy; Cardiomegaly; Increased​ ​workload​ ​in hypertensive​ ​patients; Hyperplasia Liver​ ​regenerates​ ​after​ ​surgical removal​ ​of​ ​damaged​ ​portion Endometriosis Changes​ ​in​ ​uterus​ ​during pregnancy In​ ​the​ ​endometrium,​ ​which​ ​is caused​ ​by​ ​an​ ​imbalance between​ ​estrogen​ ​and progesterone​ ​secretion​ ​with over​ ​secretion​ ​of​ ​estrogen, causes​ ​excessive​ ​menstrual bleeding. Dysplasia Tissue​ ​changes​ ​in​ ​resp​ ​tract Cervical​ ​Ca​ ​or​ ​breast​ ​Ca Persistent,​ ​severe​ ​cell​ ​injury​ ​or irritation. Disordered​ ​cell​ ​growth. AKA​ ​pre-cancer. Epithelial​ ​tissue​ ​of​ ​the​ ​cervix and​ ​respiratory​ ​tract Metaplasia Reversible​ ​replacement​ ​of​ ​one mature​ ​cell​ ​by​ ​another sometimes​ ​less​ ​differentiated cell​ ​type.​ ​Thought​ ​to​ ​develop from​ ​a​ ​reprogramming​ ​of​ ​stem cells​ ​existing​ ​in​ ​most​ ​epithelia or​ ​of​ ​undifferentiated mesenchymal​ ​cells​ ​present​ ​in connective​ ​tissue. Change​ ​from​ ​columnar​ ​cells​ ​to squamous​ ​cells​ ​of​ ​bronchial lining​ ​in​ ​chronic​ ​smokers. New​ ​cells​ ​don’t​ ​secrete​ ​mucus or​ ​have​ ​cilia​ ​which​ ​causes​ ​a loss​ ​of​ ​a​ ​vital​ ​protective mechanism.​ ​Can​ ​be​ ​reversed​ ​if stimulus​ ​(smoking)​ ​is removed. Mechanisms​ ​of​ ​Cellular​ ​Injury 2.​ ​ ​ ​ ​ ​ ​Analyze​ ​the​ ​mechanisms​ ​and​ ​outcomes​ ​of​ ​cellular​ ​injury. a.​ ​ ​ ​ ​ ​ ​ ​Differentiate​ ​between​ ​the​ ​etiology,​ ​clinical​ ​manifestations​ ​and pathophysiology​ ​of​ ​cellular​ ​injuries​ ​caused​ ​by​ ​hypoxia,​ ​free​ ​radicals,​ ​and​ ​ethanol. Cellular Injury Etiology Hypoxic​ ​Injury HTN, hyperlipidemia,​ ​DM, ischemic​ ​heart disease,​ ​chronic​ ​heart disease,​ ​CHF,​ ​sleep apnea Lack​ ​of​ ​sufficient oxygen Lack​ ​of​ ​O2​ ​caused by​ ​↓​ ​O2​ ​in​ ​air;​ ​loss Clinical​ ​Manifestations Pathophysiology Pain,​ ​decreased​ ​pulses, change​ ​in​ ​pallor, paresthesia Anoxia MI Acute​ ​CVA ​ ​organ​ ​injury, cell/organ​ ​death inflammation of​ ​hemoglobin​ ​or hemoglobin​ ​fx;​ ​↓ RBC;​ ​cardio​ ​dzs; ischemia.​ ​From asphyxiation, drowning,​ ​Fe​ ​def anemia -poisoning​ ​of oxidative​ ​enzymes Free​ ​Radical and​ ​Reactive Oxygen Species​ ​(ROS) An​ ​atom​ ​or​ ​group​ ​of atoms​ ​having​ ​an unpaired​ ​electron. UV​ ​light,​ ​x​ ​rays,​ ​all biologic​ ​membranes contain​ ​redox systems​ ​important for​ ​cellular​ ​defense, from​ ​example inflammation,​ ​iron uptake,​ ​growth​ ​and proliferation,​ ​and signal​ ​transduction) HTN,​ ​hyperlipidemia, DM,​ ​ischemic​ ​heart disease,​ ​chronic​ ​heart disease,​ ​CHF,​ ​sleep apnea Mitochondrial oxidative​ ​stress​ ​is​ ​r/t -Heart​ ​disease -Alzheimer’s -Parkinson’s -ALS Cell​ ​injury,​ ​aging,​ ​heart dz,​ ​Alzheimer’s​ ​dz, Molecules​ ​are Parkinson’s​ ​dz, unstable​ ​and​ ​highly Amyotrophic​ ​Lateral reactive. Sclerosis,​ ​vascular damage,​ ​cancer, ROS​ ​can​ ​be sterility,​ ​GI​ ​dysfx, produced​ ​as​ ​a​ ​normal autoimmune​ ​dz byproduct​ ​of​ ​ATP production​ ​in​ ​the ROS​ ​–​ ​adverse mitochondria​ ​and​ ​by cardiovascular​ ​events migrating ·​ ​ ​Vasoconstriction inflammatory​ ​cells. ·​ ​ ​Vascular​ ​smooth muscle​ ​proliferation HTN, hyperlipidemia,​ ​DM, ischemic​ ​heart disease,​ ​chronic​ ​heart disease,​ ​CHF,​ ​sleep apnea.​ ​Pg​ ​60 ROS​ ​overwhelms endogenous antioxidant​ ​systems leading​ ​to​ ​vascular endothelial​ ​injury leading​ ​to atherosclerosis. Adverse​ ​cardiac events​ ​caused​ ​by vasoconstriction, proliferation​ ​of vascular​ ​smooth muscle, hypercoagulability and​ ​thrombosis. Overwhelms mitochondria​ ​and Ethanol A​ ​molecule​ ​with unpaired​ ​electron​ ​in outer​ ​shell,​ ​steals electron​ ​from​ ​others (usually​ ​cell membranes​ ​or nucleic​ ​acids);​ ​from absorption​ ​of extreme​ ​energy sources​ ​(eg​ ​uv​ ​rays or​ ​xrays);​ ​reactions such​ ​as​ ​redox​ ​rx, metabolism​ ​of chemicals​ ​or​ ​drugs ·​ ​ ​Hypercoagulability ·​ ​ ​Thrombosis ·​ ​ ​HTN ·​ ​ ​HLD ·​ ​ ​DM ·​ ​ ​Ischemic​ ​Heart​ ​Dz ·​ ​ ​Chronic​ ​HF ·​ ​ ​Sleep​ ​apnea Leads​ ​to​ ​vascular endothelial​ ​injury Rapid​ ​loss​ ​of​ ​the plasma​ ​membrane structure,​ ​organelle swelling, mitochondrial dysfunction,​ ​and​ ​the lack​ ​of​ ​typical features​ ​of​ ​apoptosis CNS​ ​depression, Wernicke encephalopathy, peripheral​ ​neuropathy, Korsakoff​ ​psychosis, folic​ ​acid​ ​deficiency (importance​ ​of​ ​ETOH and​ ​pregnancy).​ ​ALD, acute​ ​gastritis Substance​ ​Abuse uses​ ​all​ ​antiox; destruction​ ​of​ ​lipids (cell​ ​wall permeability); damage​ ​proteins​ ​(ion pumps​ ​and​ ​cell transport);​ ​fragment DNA;​ ​↓​ ​protein; chromatin​ ​destruction and​ ​damage mitochondria After​ ​ingestion, alcohol​ ​is​ ​absorbed unaltered​ ​into​ ​the stomach​ ​and​ ​small intestine​ ​and​ ​then transported​ ​to​ ​the liver.​ ​It​ ​is metabolized​ ​into acetaldehyde​ ​through the​ ​enzyme​ ​alcohol Liver​ ​failure,​ ​esophageal dehydrogenase.​ ​It​ ​is metabolized​ ​in​ ​the tears,​ ​Wernickeliver. Korsakoff​ ​syndrome, ​ ​Ethanol​ ​is pancreatitis,​ H ​ epatitis metabolized​ ​to and​ ​cirrhosis,​ ​Fetal acetaldehyde​ ​with​ ​the alcohol​ ​syndrome, ADH​ ​(it's​ ​an​ ​enzyme withdrawal, alcohol vitamin/mineral​ ​defic., dehydrogenase)​ ​this oral​ ​cancer, causes​ ​an Affects​ ​nutritional​ ​status incl.​ ​deficiencies​ ​of --​ ​Magnesium --Vitamin​ ​B6 --Thiamine --phosphorus --​ ​folic​ ​acid ​–​ ​decreases intestinal​ ​absorption​ ​of folate Increase​ ​in​ ​the NADH/NAD+​ ​ratio in​ ​liver​ ​will: ● Pyruvate converts​ ​to lactic​ ​acid causing​ ​lactic acidosis ● Oxaloacetate ?​ ​sleep​ ​apnea converts​ ​to hepatic​ ​and​ ​gastric malate​ ​which changes prevents gluconeogene Chronic=​ ​ald​ ​liver​ ​dz sis​ ​(glucose Fatty​ ​liver​ ​?​ ​>​ ​HCC formation) Cirrhosis​ ​>​ ​portal​ ​HTN leads​ ​to &​ ​Increased​ ​risk​ ​of​ ​HCC fasting hypoglycemia Alc​ ​hepatitis ● Triglyceride Alc​ ​cardiomyopathy formation HTN,​ ​regressive​ ​change in​ ​skeletal​ ​muscle Metabolized​ ​by​ ​ADH into​ ​acetaldehyde​ ​→ In​ ​utero​ ​exposure​ ​=​ ​FAS alters​ ​NADH/NAD+ ratio​ ​causing: Fetus​ ​has​ ​very​ ​limited ADH​ ​causing​ ​fetus​ ​to​ ​be pyruvate​ ​changes​ ​to lactic​ ​acid​ ​=​ ​lactic almost​ ​completely acidosis;​ ​oxaloacetate dependent​ ​on​ ​maternal converts​ ​to​ ​malate ADH.​ ​ ​ ​Amniotic​ ​fluid preventing holds​ ​ETOH gluconeogenesis​ ​→ --acetylaldehyde​ ​can hypoglycemia; disrupt​ ​cell ↑triglycerides​ ​and differentiation​ ​and hepatosteatosis;​ ​↓ growth;​ ​DNA​ ​and citric​ ​acid​ ​cycle​ ​= protein ketoacidosis​ ​and synth;modification​ ​of hepatosteatosis carbs,​ ​proteins​ ​&​ ​fats;​ ​& flow​ ​of​ ​nutrition​ ​across placenta FAS​ ​>​ ​growth retardation, Cognitive​ ​impairment, facial​ ​anomalies​ ​and ocular​ ​disturbances. ETOH​ ​increases apoptotic​ ​cell​ ​death b.​ ​ ​ ​ ​ ​ ​Evaluate​ ​the​ ​process​ ​of​ ​necrosis,​ ​infarct,​ ​and​ ​apoptosis​ ​and​ ​describe​ ​the implications​ ​for​ ​clinical​ ​practice. Cell​ ​Death Cellular​ ​Effect Clini...
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