NURS 3123 Exam 1 Auburn University
NURS 3123 Exam 1 Auburn University NURS 3123
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This 67 page Class Notes was uploaded by Hope Gulley on Monday September 14, 2015. The Class Notes belongs to NURS 3123 at Auburn University taught by Dr. Ramona Lazenby; Dr. Edward Campbell in Fall 2015. Since its upload, it has received 134 views. For similar materials see Nursing Pathophysiology in Nursing and Health Sciences at Auburn University.
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Module 1 Overview Cellular Biology Stress amp Nutrition This module will focus on BASIC cellular biology the effects of stress and general nutrition MODULE OBJECTIVES After reviewing this module the student should be about to Brie y describe key cellular components De ne basic pathophysiological terms Discuss the major sources of cellular energy Discuss the impact of stress and injury on the body Relate the normal cell cycle to the healing process Identify factors that impact healing and describe the impact Explain the impact of nutrition on an individual39s overall health status Distinguish the most pertinent identifying information related to selected alterations Describe clinical manifestations associated with selected alterations and relate the ndings back to the pathophysiology 10 Appreciate the impact selected alterations can have on a patient39s lifestyle QWFQP PWN MODULE CONCEPTS Stress Nutrition HealthAlterations o PTSD Overweight Obesity Malnutrition Eating disorders Anorexia nervosa Bulimia nervosa 0000 TERMS Health Disease Pathophysiology Primary prevention Secondary prevention Tertiary prevention Diagnosis Etiology Pathogenesis Clinical manifestations Signs Symptoms Diffusion Anaerobic Aerobic ATP Atrophy Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 1 Hypertrophy Hyperplasia Metaplasia Dysplasia Necrosis Apoptosis Angiogenesis Stress Adaptation Allostasis Homeostasis Malnutrition Corticotropinreleasing factor CRF Marasmus Kwashiorkor Obesity PTSD Metabolism Anorexia nervosa Bulimia nervosa Binge eating disorder BED ASSIGNMENTSREADINGS when com lete Porth Chapter 1 Porth Chapter 2 Porth Chapter 4 Porth Chapter 9 Porth Chapter 10 View Panopto Concept Pathophysiology A study of the functional changes in the body that occur as the result of disease andor injury quotpathoquot from Greek word pathos suffering quotoogyquot from Greek word logos formal study Disorder or breakdown of human body s function the study of the biologic and physical manifestations of disease as they correlate with the underlying abnormalities and physiologic disturbances Pathophysiology does not deal directly with the treatment of disease Rather it explains the processes within the body that result in the signs and symptoms of a disease pathophysiologic adj Mosby39s Medical Dictionary 8th edition 2009 Elsevier The study of structural and functional changes in tissue and organs that lead to disease Derangement of function seen in disease alteration in function as distinguished from structural defects Medical Dictionary for the Health Professions and Nursing Farlex 2012 What is psychoneuroimmunology Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 2 study of the interaction between the consciousness brain and CNS and the body s defense against external infection and abnormal cell division the assumption is that all immunemediated diseases are the result of interrelationships among psychosocial emotional genetic neurologic endocrine and immune systems and behavioral factors Learn the Underlying Principle and Apply the Principle to Understand the Disease Process use a balance of both sides of the brain left analytical right gut feeling examples pulse oximeter reading of 95 and the client is cyanotic cardiac monitor showing ventricular tachycardia but client is alert and talking Homeostasis oz dynamic balance oz changes necessary to maintain equilibrium 0 Normal response system NRS oz appropriate stimulus gt NRS good oz appropriate stimulus gt no NRS bad kt inappropriate stimulus gt NRS bad kt Example sprinkler system is stimulated by re if it is a real re the water comes out this is good someone puts a match to the sprinkler and water comes out this is bad in both cases the sprinkler system did what it was designed to do but one was good and the other was not 0 Negative vs positive feedback mechanism Pathophysiological Model oz if decreased good stuff then give more good stuff oz if too much stuff gt problem give antistuff to stop production of or block action of stuff CELL STRUCTURE AND FUNCTION Additional Resources httlowwwcell alivecom httpwwwcellsalivecomcellcyclehtm Cell cycle excellent 0 The cell is the basic functional unit of the body 0 All diseases are the result of disturbances in the environment which alter cell function Similarities among body s cells 0 most cells combine 02 with breakdown products of CHO fat or CHON to release energy for normal functioning 0 most cells can reproduce nerve cells are an exception 0 often remaining cells following destruction will regenerate until the appropriate number is restored 0 all cells are in ECF contents are precisely controlled Cell DescriptionFunction Structure Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 3 Cell oz semipermeable membrane or oz separates intracellular and extracellular environments plasma 3 functions include membrane regulates transport of materials from extracellular uid into the cell receptor for hormonesbiologically active substances assists with generation and conduction of electrical currents in nerve and muscle cells assists with regulation of cell growth and proliferation 60 proteins carry out the majority of speci c functions transpermeable proteins pass through the membrane 0 function on both sides of the membrane and carry molecules across it o peripheral proteins are bound either inside or outside and do not cross the lipid bilayer lipid bilayer impermeable to essentially everything that is not lipidsoluble oz extracellular message transduction oz outer surface of the cell that is composed of CHONs lipids and CHO 0 maintains and transmits membrane potentials 60 assists in celltocell recognition interaction 60 cellular mobility oz cellular shape maintenance oz intracellular membranes have gt of CHONs because more enzymatic activity occurs within organelles Nucleus oz control center of the cell oz largest membrane bound organelle 60 primary functions are cell division and control and protection of genetic information 60 regulation of cell type and function through control of CHON synthesis 60 the essential part of the living cell oz it oversees all cytoplasmic activity oz contains DNA genetic material necessary for synthesis of proteins needed to stay alive 60 site for RNA synthesis messenger RNA mRNA copies and carries DNA instructions for protein synthesis to the cytoplasm ribosomal RNA rRNA site of protein synthesis transfer RNA tRNA carries amino acids to site of protein 60 replication and repair of DNA 60 transcription of information stored in DNA Nucleolus oz produces ribosomal RNA Endoplasmic 0 smooth site of CHON and lipid synthesis and lipid metabolism and reticulum detoxi cation oz rough catabolism of drugsfood etc and synthesis of steroid hormones Ribosomes oz aids in production of proteins on rough endoplasmic reticulum RER and polysomes Polysome 60 site of protein synthesis Golgi complex O 60 receives newly synthesized CHONs amp lipids makes modi cations by attaching sugar molecules and then directing them to their proper destination Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 4 Secretory oz stores protein hormones or enzymes in the cytoplasm awaiting a signal for vesicles release Food vacuole oz stores ingested material and combines with lysosome Lysosome oz Contain digestive enzymes 60 60 0 0 60 Perform digestive function of the cell enzymes break down worn out cells and foreign substances Acidic environment is required for the enzymes to function hydrolytic breakdown of organic waste Lysosomes digest organic molecules ie CHONs nucleotides fats and sugars end products of lysosomal digestion are simple molecules amino acids fatty acids and sugars that can be used by the cells or secreted as waste Mitochondria 6 60 energy source of the cell Power house of the cell transform organic compounds into energy Generate energy ATP Extract energy to be used by the cell from organic compounds Aerobic metabolism requires OZ Key regulators of apoptosis Cytoskeleton 60 Microtubules micro laments intermediate laments and thick laments control cell shape and movement Cilia oz Propel materials along surface of certain cells Flagella oz Provides motive force for sperm cells Centrioles oz Helps organize spindle apparatus necessary for cell division Lysosomes digest organic molecules ie CHONs nucleotides fats and sugars end products of lysosomal digestion are simple molecules amino acids fatty acids and sugars that can be used by the cells or secreted as waste Adenosine triphosphate ATP energy source it cannot cross the plasma membrane and each cell must continuously synthesize ATP ATP is synthesized from the breakdown of glycogen and fat In order to function a cell must extract and utilize chemical energy in organic molecules As energy is lost by one molecule it is transferred to another molecule by a transferring molecule such as ATP adenosine triphosphate transfers energy from one molecule to another ENERGY METABOLISM Chemical process necessary for the conversion of ingested CHO fat and CHON to energy the body can use 0 Cell metabolism converts dietary fuels from CHO CHON and fat into ATP for the body to use 0 Adenosine triphosphate ATP 0 Major source of cellular energy 1 glycolytic pathway 0 anaerobic does not require 02 and does not produce C02 Module 1 Overview Cellular Biology Stress Nutrition Lazenby Formed through 3 major pathways Page 5 splitting of 6carbon glucose molecule into two 3carbon molecules of pyruvic acid requires 2 molecules of ATP so only there is a net gain of only 2 molecules of ATP from each molecule of glucose that is metabolized pyruvate is converted to lactic acid glycolysis supplies cells with ATP when no 02 is available 2 citric acid cycle aerobic metabolism pyruvic acid molecules from glycolytic pathway enter mitochondria and join with acetylcoenzyme to form acetylcoenzyme A acetylCo this begins the reaction which releases C02 and transfer electrons from hydrogen atom to nicotinamide adenine dinucleotide NADH or avin adenine dinucleotide FADH fatty acids and amino acid breakdown materials may also enter the citric acid cycle 0 fatty acids are oxidized by betaoxidation to acetylCoA for entry into citric acid cycle 0 at citric acid cycle end each glucose molecule has yielded 4 new molecules of ATP 2 from glycolysis and 2 from citric acid cycle 3 electron transport chain 0 main role of 1 and 2 was to make electrons from glucose and other food substances 0 oxidation of electrons carried by NADH and FADH2 is achieved through enzymatically catalyzed reactions in the mitochondria electron transport chain 0 protons H combine with 02 to form water large amounts of energy are released and used add higher energy phosphate bond to adenosine diphosphate ADP converting it to ATP Porth 2011 0 net yield of 36 molecules of ATP from 1 glucose molecule 2 from glycolysis 2 from citric acid cycle 32 from electron transport chain 0 net amount of ATP is greatest from fat then glucose then protein Anaerobic metabolism 0 Glycolysis is the liberation of energy from glucose 0 Vital source of energy for cells lacking mitochondria 0 Temporary energy source for cells deprived of 02 Aerobic metabolism 0 Requires 02 o Supplies 90 of body s energy needs 0 Occurs in the mitochondria 0 Hydrogen and carbon molecules from dietary fats CHOs and CHONs combine with 02 to form C02 and H20 as energy is released TRANSPORT OF SMALL MOLECULES Additional Resources httpwwwstolafeduDeooledianninibiolooical20anamationshtml Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 6 osmotic pressure exerted by the protein of plasma draws uid into the capillary osmolality of osmoles per kg of water or tonicity osmosis movement of water across an impermeable membrane from an area of lesser concentration to an area of greater concentration until there are equal concentrations httpfacultvalvernoedubownepsindexhtm diffusion movement of molecules from an area of greater concentration to an area of lesser concentration ex 02 and C02 exchange facilitated diffusion move down CHONs electrochemical gradient active transport must have metabolic energy riding a bike up a hill passive transport goes along riding a bike down a hill filtration transfer of water and dissolved substances from a region of increased pressure to a region of lower pressure hydrostatic pressure the force of the uid pressing outward against the vessel wall vessels have hydrostatic pressure at the arterial and venous ends this facilitates movement of uids through the capillary wall into the tissue 0 because of the force of the BP hydrostatic pressure at the arterial end of the capillary is approximately 2x the venous end 0 where there is hydrostatic pressure and osmotic pressure the net results is determined by pressure differences 0 at the arterial end of the capillaryhydrostatic pressure is gt osmotic pressure gt uid and diffusible solutes move out of the capillary at the venous end of the capillary osmotic pressure gt hydrostatic pressure gt uids and some solutes move into the capillary o excess uid and solutes in interstitial space return to intravascular space via lymph channels CELLULAR RESPONSES TO STRESS INJURY AGING STRESS J J J adaptive changes failure to maintain function to maintain function i Injury l l Maladaptive changes gt cell death Cellular Adaptation to Stress Allows the stressed tissue to survive or maintain function Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 7 1atrophy decrease in the size of a tissue or organ caused by a decreased of cells or reduction in the size of individual cells example broken leg becomes smaller as there is decreased need for the muscle to function 2hypertrophy increase in the size of cells without cell division example leg that is not broken increases due to increased need for the muscle cells to function 3hyperplasia increase in the number of cells 4 metaplasia the transformation of one cell type into another 5dysplasia abnormal differentiation of dividing cells resulting in changes in size shape appearance of cells 6intracellular accumulationsstressed cells may ll up with unused foods such as lipids or glycogen abnormal proteins pigments or calcium salts How Stress Damages Cells 0 Direct damage to proteins membranes DNA 0 ATP depletion o Aerobic metabolism stops gt decreased ATP production NaK ATPase cannot run fast enough so the cell swells with water 0 Anaerobic metabolic used gt production of lactic acid Acid damages cell membranes intracellular structures DNA 0 Free radical formation 0 Molecules with an unpaired electron in the outer neutron shell 0 Extremely unstable and reactive 0 Can react with normal cell components Damaging them Turning them into more free radicals 0 Normally removed from body by antioxidants Increased intracellular calcium 0 Cell usually maintains low intracellular calcium 0 When calcium is released into the cell it Acts as a quotsecond messengerquot inside the cell Turns on intracellular enzymes some of which can damage the cell Can open more calcium quotgatesquot in the cell membrane Allows more calcium to enter 0 quotcalcium cascadequot lnjurious Agents Hypoxia o Aerobic respiration works by breaking bonds between atoms in a molecule releasing energy electrons that made up broken bonds are passed between cytochromes to 02 and this process produces most of ATP generated ATP is then used to provide energy for cell functions a major one being the NaK ATPase pump which moves 3 Na ions out of the cell and 2 K ions into it with a net loss of cell water as osmosis draws it out of the cell with the excess Na ions this explains how a decrease in 02 supply to a cell can cause cell swelling and disruption of the cell membrane 0 Heat 0 injures blood vessels increases cell 02 needs inactivates or coagulates cell enzymes breaks cell membranes 0 Cold Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 8 o Increases blood viscosity and causes vasoconstriction freezing forms ice crystals that break the cell membrane Electricity Chemical agents Biologic agents Radiation o Damages cell molecules and forms free radicals which damage cell metabolism energy generation protein and lipid breakdown membrane lipids DNA proteins etc Nutritional imbalances Cell Death Apoptosis Programmed cell death or cell suicide Removes cells that are being replaced or have worn out Removes unwanted tissue Normal process in the body Damaged or wornout cells turn on their own enzymes inside the cell digest their own cell proteins and DNA and are then destroyed by WBCs Because the dead cells are rapidly removed before their contents leak out an in ammatory response is not elicited 0 May be caused by Signaling factor attached to quotdeath domainsquot of cell surface receptors Mitochondrial damage inside the cell Protein p53 activated by DNA damage 0 Menstruation is an example Necrotic cell death 0 Unregulated cell death caused by injuries to cells 0 Cell death and degradation 0 Cells may undergo liquefaction coagulation infarction or caseous necrosis 0 Cells swell and rupture and cell contents are often released 0 In ammation results a Gangrene 0 Large area of necrotic tissue 0 Dry gangrene lack of arterial blood supply but venous ow can carry uid out of Ussue Tissue tends to coagulate 0 Wet gangrene lack of venous ow lets uid accumulate in tissue Tissue tends to liquefy and infection is likely 0 Gas gangrene Clostridium infection produces toxins and H25 hydrogen sul de gas bubbles 00000 0 Cell Aging Cells have dif culty dividing Older cells have more DNA damage Older cells have more free radicals Cells can lose the ability to repair the end of their chromosomes telomeres lililisi Factors That Impact Healing Nutritional status Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 9 Blood supply Oxygen delivery Immune responses Infection Wound separation Stages of Wound Healing In ammatory Proliferative Contraction and remodeling Concepts of Stress How would you de ne stress situations or demands that exceed our body s ability to cope What are some sources of stress for you Is stress good or bad What is the triad of manifestations that Selye observed when rats were exposed to noxious stimuli 1 enlargement of adrenal gland cortex What is the function of the adrenal cortex secretion of glucocorticoids mineralocorticoids adrenal androgens and estrogens 2 atrophy of thymus gland and other lymphoid structures 3 bleeding ulcers of stomach and duodenal lining What are the 3 stages of the General Adaptation Syndrome 1 alarm stage ght or ight in response to stressor stressor activates pituitary gland adrenal gland and SNS 2 stage of resistance or adaptation continuation of the ght or ight begins with action of adrenal hormones cortisol norepinephrine epinephrine body tries to ght back or quotresistquot 3 stage of exhaustion compensatory mechanisms break down if stress continues and adaptation does not occur effectively may result in disease heart failure kidney failure and eventually death What are the 3 components of physiologic stress 1 exogenous or endogenous stressor 2 chemical or physical disturbance caused by the stressor 3 adaptation response to the stressor What are some examples of physiologic stressors Psychoogic media tors and speci city 0 research has demonstrated sensitivity of the pituitary gland and adrenal cortex to emotions psychologic and social in uences What are some examples of psychologic stressors What is the relationship between the psychologic state of mind and physical stressors Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 10 Homeostasis as a dynamic steady state 0 the body makes necessary adjustments based on stressors if the alterations occur in the absence of a stressor this would be considered a disease state AIostasis o ability to maintain stability through change 0 involves the person s perception of the situation and the ability to mount an appropriate response 0 perception is based on past experiences and learning 0 instability is the results of a discrepancy between what the person perceives should be and what actually is 0 also referred to as the cognitive activation theory of stress The Stress Response Psychoneuroimmunoogic Regulation What is psychoneuroimmunology study of the interaction between the consciousness brain and CNS and the body s defense against external infection and abnormal cell division the assumption is that all immunemediated diseases are the result of interrelationships among psychosocial emotional genetic neurologic endocrine and immune systems and behavioral factors Neuroendocrine regulation Stress gt SNS stimulation gt adrenal gland medulla releases catecholamines epinephrine norepinephrine dopamine into bloodstream while at the same time hypothalamic CRF corticotropinreleasing factor gt pituitary stimulation gt release of hormones ADH from posterior pituitary and prolactin GH ACTH from anterior pituitary ACTH gt release of cortisol from adrenal cortex Catecholamines 0 000000 0 epinephrine goes to liver and skeletal muscle but is quickly metabolized cannot cross bloodbrain barrier stimulates alphaadrenergic and betaadrenergic receptors epinephrine binds to and activates alpha and beta receptors norepinephrine binds to alpha receptors primarily circulating catecholamines mimic the sympathetic stimulation norepinephrine gt vasoconstriction of smooth muscle in peripheral vessels gt increased BP decreased GI activity and pupil dilation epinephrine is the primary metabolic regulator during stress esp cardiac action Cortisol hydrocotisone o the quotstress hormonequot O O O helps regulate the stress response diverts metabolism from building tissues to supplying energy for dealing with stress causes signs and symptoms of chronic stress Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 11 0 primary glucocorticoid steroid hormone released when ACTH stimulates adrenal cortex to increase adrenocortical secretion circulates as protein bound and free the unbound or free is the most biologically active mobilizes substances necessary for cellular metabolism stimulates gluconeogenesis formation of glycogen from noncarbohydrate sources such as amino or fatty acids in the liver enhances elevation of blood glucose promoted by other hormones ie epinephrine glucagon somatotropic growth hormone permissive for the action of other hormones o inhibits uptake and oxidation of glucose 0 action on CHO metabolism gt increased blood glucose 0 adaptive or destructive effect depends on intensity type duration of stressor and the length of cortisol exposure to target cells 0 Cortisol release causes increased blood glucose stronger sympathetic system effect on heart rate decrease in nonessential energyusing activities such as hormone production 0 Metabolic rate and reproductive functions decrease bone formation red and white blood cell production immune system becomes depressed 0 Bene ts of cortisol secretion during stress gluconeogenesis ensures adequate glucose source for body and nerve cells pooling of amino acids from catabolized proteins may ensure amino acid availability for protein synthesis protein is redistributed to damaged cells on a shortterm basis cortisolinduced alterations in immune cells may be adavae decreased immune cell activity may prevent immunemediated tissue secondary to prolonged cell exposure to high levels of certain cytokines o Antidiuretic Hormone ADH also called vasopressin causes vasoconstriction makes kidneys reabsorb water from urine to blood 0 Other hormones Endorphins released in response to stressful stimuli traumatic injury acute and intense stressful situation or stressinduced betaendorphins regulate ACTH secretion and inhibit hypothalamic CRF secretion Growth hormone somatotropin released from the anterior pituitary gland and affects protein lipid and carbohydrate metabolism directly affects immune cells GH receptors are located on lymphocytes prolonged stress can gt suppression of GH and other growth factors requires more intense stimuli than those leading to increases in catecholamines Prolactin released from anterior pituitary gland 0000 O Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 12 necessary for lactation and breast development directly affects immune cells receptors are located on lymphocytes requires more intense stimuli than those leading to increases in catecholamines Sex steroids testosterone regulates male secondary sex characteristics and libido levels decrease after stressful stimuli psychologic stimuli reduce levels tends to exhibit immunosuppressive activity males have a higher risk for morbidity after injury estrogen seems to be responsible for the more robust immunological pro le of females Role of the immune system 0 Stress affects the immune system by 0 decreasing immune cell production 0 decreasing thymus activity 0 changing the kind of immune cells produced nervous immune and endocrine systems communicate via common use of signal molecules and their receptors gt regulation of cellular behavior in each system during stress there are direct and indirect pathways between nervous endocrine and immune systems neuropeptides have direct effects on immune cells and indirect in uences via neurologically mediated endocrine modulation of immune function cortisol in uences neurologic cell behavior immune cell products affect nervous and endocrine cell function which re ects adaptive role for immune system as a signal organ to alert other systems of threatening stimuli other hormones are affected by stress response and include increased circulating levels of betaendorphins GH prolactin ADH testosterone decreases with stress Stress Coping and Illness StressAge Syndrome o alterations in excitability of limbic system structures and hypothalamus 0 increased blood levels of catecholamines ADH ACTH and cortisol 0 decreased testosterone thyroxine o altered opioid peptides o immunodepression o alterations in lipoproteins o hypercoagulation of blood 0 free radical damage of cells 0 while some of these changes are adaptive others may lower one39s resistance to infection and adversely impact the disease process 0 stress is perceived and responded to on a very individual basis 0 results of stress is dependent on many factors type duration adaptation intensity coping abilities etc o psychologic distress a feeling of unpleasant arousal after life events this may be predictive of psychologic physical and social outcomes manifested by physiologic emotional cognitive and behavioral changes Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 13 directly affects the central nervous system turns on the stress responses even when the body s internal sensors have not detected an imbalance list some triggering events manifestations o it is vitally important for the health care provider to collaborate with the patient and identify any stress producing factors which exist after identi cation of such factors they must be dealt with in order to have the most favorable recovery possible 0 factors which may in uence stress susceptibility age socioeconomic status gender social support religion culture spiritual factors personality selfesteem genetics past experiences positive or negative health status What are some other factors 0 social support support groups meditation biofeedback imagery relaxation exercises are useful for reducing stress in the client and the caregiver Acute stress Results of LongTerm Stress 0 chronic stress sympathetic activity and cortisol are elevated complications result from the reduced immune response 0 posttraumatic stress disorder sympathetic system is activated cortisol levels are decreased Effective coping process of managing stressful challenges that impose on the individual39s resources improves prognosis while ineffective coping may exacerbate ill effects Decreased blood flow to kidneys gt kidneys release renin into blood gt renin reacts with angiotensinogen to form angiotensin I gt angiotensinconverting enzyme in lungs converts angiotensin I to angiotensin II gt stimulates adrenal medulla to secrete aldosterone gt aldosterone activates NaK pump in distal tubules of nephrons gt Na and water reabsorption which increases blood volume and K is secreted which causes K loss Application Exercise 1 A woman is brought into the hospital after a motorcycle accident She presents with increased heart rate no urine production no bowel sounds pale and sweaty skin low blood pressure dilated pupils and elevated blood glucose Which of these is most urgent to correct and why Which organs of the body would you expect to see damaged by acute stress Why Mr P had some quothard timesquot in the Army but he quotdealt with itquot and has become a successful air traf c controller He is 50 years old overweight with increased BP and occasional tachycardia insomnia and GI discomfort He has had several colds already this year and wants a u shot What about his case might be stress related 4 His doctor has recommended relaxation therapy and Mr P is furious about his quotnew age gobbledygookquot How will you explain its physiological basis to himI UJN HEALTH ALTERATION Post Traumatic Stress Disorder PTSD DESCRIPTION quotexposure to actual or threatened death serious injury or sexual experience by directly experiencing witnessing learning that it happened to a close family member or friend Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 14 or being repeatedly exposed to the adverse details of the eventquot DSM5TR 2013 now being recognized as highly comorbid condition ETIOLOGY exposure to actual or perceived threats such as combat rape RISK assault sudden death of a loved one etc FACTORS lower cortisol levels may make a person more susceptible gene cs previous environmentalexperiential factors PATHOGENESI exposure to stressor gt heightened and sustained sympathetic s and hypothalamicpituitaryadrenal HPA axis response increased SNS activity and decreased cortisol alterations in amygdala and hippocampus lower cortisol levels may re ect PTSD vulnerability increased reactivity of amygdala and hippocampus and decreased reactivity of anterior cingulate and orbitofrontal area 0 anterior cingulate and orbitofrontal area involved in fearresponses o hippocampus involved with memory processes CLINICAL altered cortisol circadian rhythm gt sleep disturbances MANIFESTATI symptoms include ans 0 ashbacks andor nightmares intrusion o avoidance of anything that stimulates thoughts of the past experience avoidance o unable to remember portions of the event negative alterations in cognition and mood inability to feel positive emotions marked alteration in arousal and reactivity distorted beliefs about the event irritableangry outbursts hypervigilance difficulty sleeping o difficulty concentrating O 0000 DIAGNOSIS exaggerated negative feedback inhibition of cortisol release with dexamethasone suppression test Positive emission tomography PET At least one avoidance symptom Diagnostic criteria 0 Disturbances must last 2 1 month 0 HOLISTIC Comorbid condition IMPLICATIONS o Stigma and expense may prevent seeking treatment Impact on signi cant others who may not be aware of what is going on o Ongoing research is showing that benzodiazepines may not be effective and may even increase the occurrence of PTSD in trauma patients Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 15 HEALTH ALTERATION Obesity DESCRIPTION BMI 2 30 2nCI leading cause of preventable death massive obesity ETIOLOGY RISK FACTORS Genetic 30 obesity genes identi ed to date Environmental Lifestyle sedentary eating habits etc Familial Psychological factors PATHOGENESI S Adipose tissue 0 Energy storage 0 Secretes adipocytokines ie leptin tumor necrosis factor or o Produces leptin mediates body weight 0 Produces adiponectin regulates sensitivity to insulin 0 Associated with chronic in ammation increased cytokine production increased Creactive protein due to increased synthesis of acutephase reactants proin ammatory activation 0 Contains connective tissue matrix and macrophages gt in ammatory mediator production CLINICAL o MANIFESTATI ONS Upper body obesity apple 0 Central abdominal or visceral o Waisttohip ratio gt 1 in males and gt 08 in females 0 greater risk of cardiometabolic issues Lower body obesity pear 0 Peripheral or glutealfemoral DIAGNOSIS BMI 2 25 overweight BMI 2 30 obesity Childhood obesity 0 BMI 2 sex and age speci c 95th percentile obesity 0 BMI between 85th and 95th percentile overweight HOLISTIC o IMPLICATIONS Increase risk for HTN Hyperlipidemia CAD Type 2 DM Stroke Sleep apnea Cancers endometrial prostate colon uterine ovarian Thrombusembolus Metabolic syndrome Osteoarthritis GERD Gallbladder disease Fatty liver disease Psychological distress Medication complications esp with lipophilic meds 0 00000000000000 HEALTH ALTERATION Marasmus DESCRIPTION l a Loss of fat and muscle Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 16 ETIOLOGY Poor diet RISK FACTORS PATHOGENESI 0 Insufficient dietary intake of calories and CHON gt loss of S muscle and fat CLINICAL o Wasted appearance MANIFESTATI o Decreased HR temp and BP ONS Loss of subq fat Wrinkled skin 0 Thin dull dry hair diarrhea DIAGNOSIS Failure to grow HOLISTIC Compromised immune system IMPLICATIONS 0 Growth failure H EALTH ALTE RATIO N Kwashiorkor DESCRIPTION 0 Severe form of malnutrition ETIOLOGY Displacement from the breast RISK 0 High CHO low CHON diet FACTORS PATHOGENESI De ciency in dietary CHON gt loss of visceral protein S compartment gt hypoalbuminemia gt edema generalized and dependenU CLINICAL o Edema MANIFESTATI Desquamation of the skin ONS Hair discoloration Anorexia Apathy Facial extremity perineal skin lesions with a quot alq paintquot appearance Sandyred hair 0 Flag sign linear depigmentation of hair 0 Normal subq fat although massive muscle wasting Hepatomegaly Abdominal distention Cold extremities Diarrhea Decreased cardiac output Tachycardia DIAGNOSIS Mainly a clinical diagnosis Decreased serum protein 0 Other indicators of malnutrition include altered BUN BS creatinine K CBC UA HOLISTIC Dehydration IMPLICATIONS o Hypothermia Increased susceptibility to infection Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 17 HEALTH ALTERATION Anorexia Nervosa DESCRIPTION 0 Eating disorder characterized by extreme dieting and compulsive exercise 0 Some patients may purge Disturbed body image 0 Fear of becoming obese they seem themselves as quotfatquot Obsess over caloric intake ETIOLOGY Possibly genetics RISK Personalities of perfection and compulsion FACTORS Genetics environmental psychological PATHOGENESI o Alterations in medial central area of hypothalamus in uences S food intake 0 Altered activity in cerebral activity of dorsolateral prefrontal cortex inferior parietal lobule anterior cingulate gyrus and caudate nucleus Dieting begins gt pathological eating habits gt paritial or total eating disorder 0 Weight loss gt positive reinforcement gt avoidance of food and intense exercise gt low weight and starvation gt nutritional imbalances and psychological changes gt obsessive behaviors gt relief of anxiety from stressful situations the patient has some control CLINICAL MANIFESTATI ONS Abnormally low body weight Compulsive exercising Fear of weight gain Distorted body image Constipation Cold intolerance Bradycardia Lanugo Altered cognitive function due to death of white and gray matter 0 ECG changes which can result in myocardial degeneration arrhythmias heart failure and death 0 Electrolyte imbalances DIAGNOSIS Refusal to maintain appropriate body weight weight lt 85 of normal Intense fear of gaining weight Distorted perception of size shape weight Amenorrhea HOLISTIC Other psychiatric disorders may coexist such as 0CD major IMPLICATIONS depression dysthymia Decreased estrogen gt amenorrhea andor loss of secondary and increased risk of osteoporosis Requires a holistic approach to treatment as the patient is unable to grasp that there is a problem Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 18 HEALTH ALTERATION Bulimia Nervosa DESCRIPTION 0 Recurrent binge eating with vomiting fasting excessive exercise diuretic andor laxative andor enema use Subtypes based on purging or lack of purging ETIOLOGY Female RISK Age late teens or early adulthood FACTORS Biological greater risk is a rst degree relative has an eating disorder Overweight as a child or teen 0 Anxiety disorder 0 Low selfesteem Stress Social pressures Sports or artistic pressure to be perfect PATHOGENESI Possible serotonin de ciency S CLINICAL Preoccupation with weight MANIFESTATI 0 Feeling out of control about eating ONS Eating to the point of discomfort Forced vomiting or exercise to compensate for overeating Restricting calories between binging episodes DIAGNOSIS o Recurrent binge eating 2 2 xweek x 3 months Compensatory behaviors laxatives vomiting etc Obsession with body weight and shape 0 Does not occur exclusively as a part of AN 0 Body weight is typically normal HOLISTIC 0 Evidence of other psychiatric issues such as substance abuse IMPLICATIONS selfdestructive behaviors Possible complications 0 Selfinduced vomiting gt acidic exposure of teeth gt dental caries parotitis erosion of tooth enamel Esophagitis dysphagia esophageal strictures Electrolyte imbalances Aspiration pneumonia Vomiting gt loss of hydrogen potassium chloride OOOO HEALTH ALTERATION BingeEating Disorder DESCRIPTION 0 Regular binge eating without compensatory behaviors Most common eating disorder in general population ETIOLOGY Female slightly higher 60 as opposed to 40 of those with RISK BED being male FACTORS Added to DSM5 in 2013 PATHOGENESI a Not totally understood S 0 Genetic and neurobiological factors 0 Distinct familial phenotype from obesity 0 Dopamine receptor gene DRD2 polymorphisms hypersensitivity to reward o Reward center and impulsivity dysregulation structural Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 19 and functional MRI show difference relative to obesity CLINICAL Secret eating MANIFESTATI 0 Depression ONS Normal or above average weight DIAGNOSIS o Binge eating at least 2 daysweek x 6 weeks plus at least 3 of the following 0 Rapid eating 0 Eating to the point of discomfort 0 Eating excessive amounts when not hungry 0 Eating alone because of embarrassment o Disgust depression guilt due to overeating HOLISTIC 0 Increased risk for dyslipidemia type 2 DM HTN IMPLICATIONS Module 1 Overview Cellular Biology Stress Nutrition Lazenby Page 20 NURS 3123 Pathophysiology Module 2 In ammation Immunity Infection and Genech Edward Campbell MSN RNBC General Features of the Immune System 1 Know your white blood cells In order to understand the immune system it is important to be able to identify the different types of white blood cells see Figure 1 a Granuocytes Are a subcategory of WBCs that when seen under a microscope appear to be granular meaning that they have multiple pockets of enzymes that can be seen Neutrophis are the most numerous and the single most important WBC as far as the ghting common infections What makes them so important is that they contain granules of digestive enzymes that help to destroy microorganisms in the body So a person with a lowered neutrophil count is at an increased risk for an opportunistic infection Eosinophis and basophis are the least numerous of the WBCs but their role is still important These cells contain vasoactive enzymes ie histamine and heparin that are important to in ammatory responses and allergic reactions b Agranuocytes Are a subcategory of WBCs that when seen under a microscope do not have pockets of enzymes within their cytoplasm Lymphocytes are the most numerous of this category and are responsible for both cellmediated immunity and humoral immunity Lymphocytes can be further divided into Blymphocytes and TLymphocytes Monocytes are important to destruction of abnormal cells within the body For example abnormal blood cells are recognized by the spleen and sent to the liver to be destroyed by the Kupffer cells 1 Undifferentiated monocytes are released into the blood circulation until they enter a speci c body tissue In the body tissue they undergo differentiation to become a macrophage Leukocytes 96 WBC WE VE Nleutroph i is 60 Bacteria Bananas iarel LEE Lymphocytes 3390 Viruses Very Monkeys Monocytes 6 Yea st Fungi Yummy wich EGT Eosinophils 3 Parasites 1 Peanut Bananas Basophils 1 Bee Stings Buffer Allergies T Figure 1 An easy way to remember the types of cells and their primaryfunction is with mnemonics 2 Immature cells do not function as effectively as mature cells For example when neutrophils are rst produced they are less effective than neutrophils that have already matured a Younger neutrophils called banded neutrophils appear to have single large nucleus with very few granules However as they mature the nucleus separates into segments and more granules begin to appean b When the body increases neutrophil production it releases immature cells into the circulation When the body slows down neutrophil production mature neutrophils will signi cantly outnumber the immature cells This can cause shifts in cell maturity i Neutrophiic Shift to the Left occurs when there is an increased production of neutrophils And there is a resulting decrease in the average maturity of neutrophils These shifts often occur when there is an infection ii Neutrophiic Shift to the Right occurs when there is a decreased production of neutrophils And there is a resulting increase in the average maturity of neutrophils These shifts may occur when there is a lack of blood forming activity such as in severe liver disease or bone marrow suppression Two Immune Responses And Four Lines of Defense innate immunity Natural Barriers gt in ammation H Adaptive immunity Antibody Mediated I gt Cell Mediated H Figure 2 The body s immune responses include both innate and adaptive processes The innate immune system includes both natural barriers and in ammation The adaptive system includes antibodymediated AMI and cellmediated immunity CMI 1 The Innate Immune Response is the nonspeci c response to pathogens andor tissue damage It includes two lines of defense namely natural barriers and in ammation a Natural Barriers are the rst line of defense against infection These natural barriers include both physical barriers and biochemical barriers Physical barriers include tightly associated epithelial cells like those of the skin and of the membranous sheets lining the gastrointestinal genitourinary and respiratory tracts 1 The mucosal epithelial cells are highly interconnected junctions that prohibit the passage of microorganisms into the underlying tissue The normal turnover of the cells in these sites as well as mechanisms for washing the surfaces may mechanically remove many infectious microorganisms and prevent their residence on the epithelial surfaces Biochemical barriers are made by the production and secretion of substances intended to trap or destroy microorganisms Mucus sweat saliva and tears are all examples of biochemical secretions that can trap and kill potential disease causing organisms 1 A wide variety of peptides and other antimicrobial substances are derived from epithelial cells For example a Epithelial cells secrete smallmolecular weight antimicrobial peptide which can be divided into two classes based on their shape Cathelicidins have a linear ochelical shape And only one is currently known to function in humans And it is stored in neutrophils mast cells and a variety of epithelial cells Defensins have a triple stranded 3 sheet structure The ocdefensins are particularly numerous in the granules of neutrophils And the the Bdefensins are found lining the respiratory urinary and intestinal tracts as well as in the skin Both Cathelicidin and Defensins are presumed to work by inserting themselves into the membrane of potential pathogens thereby disrupting the integrity of the cell membrane b The lungs also produce and secrete collectins which facilitate recognition of microorganisms by macrophages And as a result aids in the phagocytosis of pathogens c Other epithelial antimicrobials include resistinlike molecule 3 bactericidalpermeability inducing protein and antimicrobial lectins All of which aid in the recognition and destruction of pathogens 2 Bacteria also contribute to our innate immunity because they compete with pathogens for nutrients And they prevent pathogens from attaching to the epithelium a The normal microbiome also produces chemicals such as ammonia phenols and other toxic materials that inhibit colonization by pathogenic microorganisms b As a result prolonged treatment with broad spectrum antibiotics can alter the normal microbiome decreasing its protective activity This decreased protections can lead to an overgrowth of pathogenic microorganisms such as Candida albicans or Clostridium dif cile b The In ammatory Response is generally activated when pathogens chemicals or mechanical forces damage cells or tissues And it is nonspeci c meaning it happens the same way regardless of the nature of the damaging force i The Vascular Phase of acute in ammation is characterized by changes in the small blood vessels at the site of injury 1 Vasodiation and Permeability The vascular phase begins with momentary vasoconstriction However mast cells a type of basophil that resides in tissues immediately release copious amounts of histamine causing the smooth muscles in the arterioles and venules to relax And the net result is a rapid vasodHann a In addition to histamine the mast cells also release other vasoactive amines that enhance the actions of histamine including serotonin leukotrienes and prostaglandins The net result is an increased blood ow to the capillary beds that causes pain heat and redness see Figure 3 b As the capillaries dilate endothelial cells contract and become more rounded By doing so they become permeable to both exudate and circulating white blood cells As proteinrich uid leaks out of the vasculature the osmotic pressure drops allowing uid to shift from the vasculature to the tissue The net result is swelling and pain See Figure 3 c Eosinophils play a signi cant role in the vasodilation process as well They act by releasing chemicals to degrade these vasoactive substances In essence they keep in ammation localized rather than allowing it to spread to the rest of the body Tiaaue damage Release at vaeeaetive and chemotactic factors in ii Vaaedilation Inereaaed Neutrephil permeability emigration v n Will i ll HEAT ll EHEDN39E SSI laweLlJMGl Figure 3 Tissue damage causes the release of vasoactive chemicals that cause vasodilation and increased capillary permeability The actions of these chemicals results in what some call the cardinal signs of in ammation namely pain heat redness and swelling ii The Cellular Phase of acute in ammation involves the delivery of leukocytes primarily neutrophils to the damaged tissues 1 This occurs via a fourpart process of margination transmigration chemotaXis and phagocytosis a Marynation Mast cells and injured tissues release chemotactic factors that cause endothelial cells to release adhesion molecules These molecules bind to carbohydrates on the leukocytes cell membrane to make them stick See Figure 2 b Transmigration Once a leukocyte sticks to the endothelial layer the endothelial cells separate allowing the leukocyte to migrate into the damaged tissue c Chemotaxis After the leukocyte has found its way into the tissue it follows a trail of chemicals and debris d Phagocytosis Finally phagocytic leukocytes engulf and degrade the pathogens and cellular debris 2 The net result of the cellular phase is an increase in the number of leukocytes and in ux of proteinrich exudate in the damaged tissue This purulent uid is commonly called pus 2 The Adaptive Immune Responses are two speci c responses to pathogens These responses involve the production of antibodies and the direct destruction of cells based on the recognition of foreign antigens See gure 4 a Antibody Mediated Immunity AMI also known as the humoral immunity involves antigenantibody interactions that neutralize foreign proteins and associated pathogens i The process of making antibodies begins with the introduction of a Table 1 foreign antigen That is a molecule that does not normally belong in the body These foreign substances are recognized by the phagocytic macrophages during the in ammatory process The macrophage and Thelper T4 cell process the antigen to reveal its recognition sites And after processing it the T4 cell presents the antigen to an unsensitized BPlasma cell This newly sensitized cell will then create lgM type antibodies directed at the foreign antigen These BPlasma cells will eventually mature into Bmemory cells which make lgG type antibodies in the event of reexposure to the antigen Other types of antibodies that are also made by Bmemory cell are summarized in Table 1 Various Classes ofAntibodies Produced by BCels Class Percentage Signi cance lgG lgA lgM 75 15 10 Produced primarily by Bmemory cells following an initial exposure to a pathogen They are important for longterm immunity And they help ght off pathogens during a repeat exposure lgG are also the only antibodies to cross the placental membrane passing immunity from mother to baby Primarily in bodily secretions such as saliva breast milk and respiratory secretions Helps to protect mucosal membranes Produced primarily by sensitized B Plasma cells immediately following exposure to a pathogen 10 lgD 02 Found on BCells Needed for maturation of lymphocytes IgE 0004 Bind to mast cells and basophils involved in allergic reactions ie Type1 Hypersensitivities b CellMediated Immunity CMI also known as cellular immunity involves several different kinds of TCells CD8 CD16 and Tc cells are collectively referred to as Cytotoxic Tces because they have the common ability to make perforin a substance that tears holes in a pathogen s cell walls in this response the T suppressor cells release their perforin in response to cytokines released from the activated Thelper cell LThese perforin moecues work by creating a perforin complex pore in the pathogen s cell membrane Then the Tc cell dumps enzymes into the pathogen to cause its death AntibodysMediated Immunity AMI CeiiaMediated Immunity CM Perfori39n 39 39 Figure 4 Both adaptive immune processes begin with the actions of the macrophage and Thelper cell which 11 function in conjunction with macrophages to distinguish between self and nonself antigens Hypersensitivity Disorders 1 Type 1 Hypersensitivity quotimmediatequot or anaphylactic hypersensitivity is an allergic reaction provoked by reexposure to a speci c type of antigen referred to as an allergen Such exposure may be by ingestion inhalation injection or direct contact a Macrophages and THelper cells initially recognize antigens And they stimulate B cells to produce lgE antibodies speci c to the antigen The lgE antibodies bind to receptors on the surface of tissue mast cells and blood basophils causing them to become quotsensitizedquot to the antigen b Reexposure to the same allergen activates the lgE on sensitized cells resulting in degranulation of the mast cells This causes secretion of chemical mediators such as histamines leukotrienes and prostaglandins that act on the surrounding tissues The principal effect of these products is vasodilation similar to that seen in the in ammatory process i Note An allergic reaction does not occur on the rst exposure to an allergen It is only after the mast cells have been sensitized that the hypersensitivity may occur ii Immediate phase hypersensitivity reactions may occur minutes after exposure However latephase reactions can occur 2 4 hours after exposure iii Some of the common signs of an anaphylactic reaction include 1 Wheal and Flare 2 Allergic Rhinitis 3 Asthma 12 Atopic Dermatitis UrticariaHive Angioedema Anaphylactic Shock 9 Allergen Degranuiation llistamines TYPE 1 Figure 5 Type 1 hypersensitivities are caused by rapid degranulation of mast cells and the resulting histamine release 2 Type 2 Hypersensitivity quotcytotoxicquot or quotlgG Mediatedquot hypersensitivity is the production of antibodies toward the antigens on the patient39s own cell surfaces The antigens recognized in this way may either be intrinsic quotsefquot antigen innately part of the patient39s cells or extrinsic adsorbed onto the cells during exposure to some foreign antigen possibly as part of infection with a pathogen a Once these antigens are identi ed macrophages and Thelper Cells work to identify binding sites for potential antibodies The binding sites are presented to the B Cells which proceed to make antibodies See notes for antibodymediated immunity 3 Type 3 Hypersensitivity quotImmune Complexquot occurs when antigenantibody complexes are not adequately cleared by innate immune cells These complexes accumulate in the body s tissues giving rise to an in ammatory response which causes damage to surrounding tissue 13 A antibodentige n Complex quot 9 Suriace Q G Antigens L lax Iquot Elk c x J it st it B a Neurtroplhil Autoantibodies TYPE 2 TYPE 3 Figure 6 Both Type 2 and Type 3 Hypersensitivities cause damage to selfcells In Type 2 autoantibodies attack self cells And in type 3 in ammation causes collateral damage as the body attempts to clean up antigen antibody complexes that become deposited in otherwise healthy tissue 4 Type 4 Hypersensitivity quotDelayed or quotCell Mediatedquot occurs when sensitized THelper cells release cytokines in response to an antigenallergen These cytokines activate macrophages and cytotoxic TCells which cause direct cellular damage See notes on cellmediated immunity a An example of a Type 4 reaction is a positive TB skin test On the rst exposure to mycobacteria in the active form THelper cells are sensitized to TB antigens On reexposure to these antigens via a TB skin test the THelper cells initiate the cell mediated response In this case the release of chemical mediators results in both direct damage to cells and localized in ammation 14 Antigen quot Sensitized 39li Hlel at J p P erforiln 5 Cytokines 5 ii e o G a 9 39 a Self Cell if Macrophage Tc Lymphocyte Figure 7 Type 4 reactions are a delayed cellmediated response that occurs upon reexposure to a foreign anUgen Other Problems with the Immune System 1 Autoimmune Disease occurs when there is a breakdown in the immune system s ability to distinguish between self and nonself antigens These diseases can affect almost any cell in the body And while some are tissue speci c others affect multiple organs and systems a Systemic Lupus Erythematosus SLE is an autoimmune disorder that affects nearly every cell in the body It is caused by a failure to recognize selfantigens and a resulting production of autoantibodies ie Type 2 Hypersensitivity The mass production of autoantibodies also results in deposition of antigenantibody complexes in tissues As phagocytic cells attempt to break down these immune complexes cell damage and in ammation occur ie Type 3 Hypersensitivity i Etiology The onset of the disease is most often during child bearing years 2040 years and occurs primarily in women Genetic predispositions may play a role in the development of SLE but it is not the only basis for the disease It is more likely that the disease is a combination of genetic and environmental factors 15 Signs and Symptoms Many of the initial symptoms of SLE are nonspeci c signs that do not point to a speci c cause For example weakness fatigue low grade fevers and ulike symptoms Later signs of SLE might include skin rashes cardiac and renal dysfunction joint in ammation and neurological disorders However even these symptoms are not entirely speci c to SLE Investigations Lab results often indicate wide spread in ammation due to Type 2 amp 3 hypersensitivity reactions Elevation in Erythrocyte Sedimentation Rate ESR and C Reactive Protein CRP commonly signal systemic in ammation Autoantibodies will also be present in the bloodstream Particularly antinuclear antibodies are often present These antibodies target and attack the target cells DNA andor RNA That is essentially every cell in the body Treatment Medical and pharmacological treatments are aimed at suppressing the immune system via immune suppressant therapy and removal of antibodies through plasmapheresis b Rheumatoid Arthritis RA is an autoimmune disease that affects the synovial joints as well as other tissues Similar to SLE the disease is caused by a failure of the immune system to recognize selfantigens The resulting type 2amp3 hypersensitivities cause in ammation and direct cellular damage Etiology RA affects more the 13million people And it affects those of European dissent more than other ethnic groups RA is more common in women though not as drastically so 16 as in SLE And it is seen in both children and adults ii Signs and symptoms The most persistent symptom of RA is pain caused by in ammation of the synovial joints As the disease progresses the joints tend to form scar tissue 1 Baker s cysts uid lled sacs may be seen behind the knee causing compression and pain 2 Subcutaneous nodules mobile nontender masses may appear on the ngers ulnar surfaces of the arms and the Achilles tendon iii Investigations As with SLE systemic in ammation is often present Therefore ESR and CRP levels will likely be elevated Autoantibodies will also be present in the bloodstream Particularly antinuclear antibodies are often present Rheumatoid factor RF is another autoantibody which was rst found in rheumatoid arthritis Though this antibody is common is RA it is also present in other diseases such as Sjogren s syndrome Therfore RF is used as an indicator for RA But it is not a de nitive diagnostic test iv Treatment Also similar to lupus medical and pharmacological treatments are aimed at suppressing the immune system via immune suppressant therapy and removal of antibodies through plasmapheresis 2 Immune De ciency is a general term used for insuf ciencies of immune function These de ciencies can be primary de ciencies meaning they occur because of genetic factors at birth or they may be secondary meaning they occur because of an infection or other acquired disease 17 a Acquired Immune De ciency Syndrome AIDSZ is a decrease in the adaptive immune processes that results from a marked decrease in CD4 lymphocytes This decrease in Thelper cells reduces both the antibodymediated and cellmediated immune processes And it places the patient at risk for opportunistic infections and cancen Etiology The most common cause of AIDS is infection with the Human Immunode ciency Virus HIV The virus infects CD4 cells by injecting T Cells with RNA and a protein called reverse transcriptase which recodes the TCell DNA to make new HIV virions HIV itself is passed from person to person via exposure to blood or blood contaminated uids like semen While the virus can be found in saliva tears and respiratory secretions the number of virions in these secretions are insuf cient for the transmission of the virus Thus the greatest risk is via transfusion of blood contact with blood contaminated instruments and during sexual intercourse Signs and Symptoms Common features of AIDS are associated with a decrease in adaptive immune processes These include Skin lesions Low WBC counts Dysfunction of the CNS Opportunistic Infections Cancers ex Kaposi sarcoma wewwe Investigations The standard criteria for diagnosing AIDS requires 1 Con rmation of HIV infection 2 A CD4 lymphocyte count of lt200 cellsmcL 3 Presence of one of the following 18 Opportunistic Infection Autoimmune Disease Neurological Dysfunction Cancer 1070 iv Treatment Medical and Pharmacological treatment of HIVAIDS is aimed at slowing the destruction of CD4 lymphocytes This is often done with treatment of a class of drugs called Highly Active Antiretroviral Therapy HAART Special care must also be made to prevent the spread of disease and prevent opportunistic infections 3 Transplant Immunopathology includes instances where a transplant recipient rejects hisher transplant also known as hostversusgraft disease and where a transplant rejects the recipient tissue known as graftversushost disease a Hostversusgraft Disease H VGD occurs when a transplant patient s immune system recognizes foreign antigens within a transplanted tissue or organ The adaptive immune processes then attack the transplant cells by producing antibodies antibody mediated immunity and destroying the cells directly cellmediated immunity b Graftversushost Disease G VHD occurs when macrophages and Tcells in the transplanted tissue recognize the host tissue antigens as being foreign The resulting process would be an adaptive immune response against the patient In some cases such as renal and liver transplants GVHD may result in a limited cellmediated attack However in bone marrow transplants GVDH often results in both antibodymediated and cellmediated processes 19 Genetics amp Genetic Disorders 1 Chromosomal defects are generally due to an abnormal number or alterations in the structure of one or more chromosome These abnormalities may result from errors in the separation of chromosomes during meiosis Chromosomal abnormalities occur fairly frequently But they are often lethal accounting for approximately 12 of all spontaneous pregnancy losses a Trisomy 21 Down Syndrome is a chromosomal disorder in which individuals have and extra copy of chromosome 21 It is the most common chromosomal disorder and the leading cause of mental disability occurring in 1700 live births The incidence varies among populations but increases in maternal age are associated with an increase in incidence Signs and Symptoms include Congenital heart disease Hypotonia Increased gap between lst amp 2nd toe Leukemia risks X 2 Developmental Delay Hearing problems Alzheimer s disease early onset Slanted eyes and Short neck Protruding tongue and Palmar crease Round face and Rolling eye Occiput at Brachycephaly Low set ears Epicanthal folds Mental retardation b Other Trisomies include chromosome 18 Edward Syndrome and chromosome 13 Patau Syndrome These are less common than trisomy 21 but they are more severe in nature Most affected pregnancies are lost before these children reach full term and 20 live born infants usually do not survive for more than a few days or weeks Trimomies involving 8 9 and 22 have also been observed but are extremely rare c Cri du Chat Syndrome is caused by a deletion of part of the short arm of chromosome 5 It results in a syndrome characterized by severe mental retardation round face and congenital heart anomalies And it was so named because of the characteristic cry of the affected infant which is caused by laryngeal malformation and resembles a cat crying Some children af icted with this syndrome survive to adulthood and they generally thrive better than those with the trisomies d Kinefeter Syndrome is associated with the presence of extra X chromosomes in males ie XXY XXXY XXXXY The presence of a Y chromosome means that these individuals are genetically male However the extra X chromosomes result in abnormal sexual development and increased feminine characteristics The condition usually becomes apparent during puberty and may go unnoticed until secondary sexual characteristics begin to develop e Turner Syndrome is caused by a monosomy of the sex chromosomes and is only noted in females That is there is only one sex chromosome and it is an X chromosome The absence of a Y chromosome means that the individual will be phenotypically female But their ovaries fail to develop Other characteristics of the disease include short stature webbing of the neck wide chest congenital heart defects and failure to develop secondary sexual characteristics 2 Monogenic Defects are those that involve only one gene locus and follow a predictable pattern which can be demonstrated using a Punnett square The Punnett square is based on the mendelian principle that all genes are inherited independently from each other in a random manner In a Punnett 21 square a capital letter is used for dominant alleles and a lowercase letter represents a recessive allele As the term implies a dominant allele will mask a receive allele making the associated trait apparent A recessive trait is apparent only if both alleles for the trait are recessive A pedigree may also be used to trace transmission of the disease through a family And it may be useful in determining the pattern of inheritance as recessive dominant or sex linked Codominant Expression occurs when genes are not clearly dominant or recessive resulting in a blending of associated traits Blood type for example has three distinct alleles namely A B and O The allele for Otype blood is recessive But the alleles for both A and B are codominant meaning that both may be expressed at the same time The codominant expression of these alleles results in TypeAB blood a Autosomal Dominant Disorders generally involve key structural proteins such as membrane receptors i Marfan syndrome is a disorder of the connective tissues of the body Individuals with Marfan syndrome are typically tall and slender with long thin arms and legs Although skeletal and joint deformities are problematic the cardiovascular lesions are the most life threatening The medial layer of blood vessels particularly the aorta tends to be weak and susceptible to dilation and rupture Note It is commonly suggested that President Abraham Lincoln may have had this disorder ii Huntington disease is an autosomal dominant disease that primarily affects neurologic function The symptoms of mental deterioration and involuntary movements of the arms and legs do not appear until approximately age 40 years The disease was formerly called Huntington chorea from the Greek 22 khoreia meaning quotdancequot because of the uncontrolled movements of the limbs The delayed onset of symptoms means that the disease may be transmitted to offspring before the parent is aware that he or she harbors the defective gene b Autosoma Recessive Disorders often involve abnormal enzyme functions It is estimated that nearly everyone carries several mutated recessive genes heterogeneous And related individuals are more likely to carry the same recessive genes Because recessive diseases are only expressed when both alleles for a particular gene are mutant homozygous they are often associated with consanguinity the mating of related individuals Phenyketonuria PKU results from an inability to metabolize the amino acid phenylalanine because of lack of the enzyme phenylalanine hydroxylase The symptoms of the disorder are due to the accumulation of dietary phenylalanine in the body which primarily affects the nervous system Children with PKU tend to be overly irritable and tremorous and have slowly developing mental retardation Infants typically have a musty odor because of excess phenylalanine by products in the sweat and urine The enzyme de ciency can be detected soon after birth and managed with a lowphenylalanine diet to prevent mental retardation Cystic Fibrosis CF is one of the most common singlegene disorders About 4 of Caucasian Americans harbor the defective gene and the incidence of cystic brosis is approximately 1 in 3200 live births The clinical abnormalities associated with cystic brosis have been traced to a defect in a membrane transporter for chloride ions in epithelial cells 23 The alteration in chloride transport is associated with production of abnormally thick secretions in glandular tissues The lung bronchioles and pancreatic ducts are primarily affected often resulting in progressive destruction of these organs c Sex Linked Disorders occur because of a mutation of the sex chromosomes Disorders linked to the Y chromosome are extremely rare So the terms sexlinked and X linked are often synonymous Unlike autosomal disorders affected individuals are almost always male Affected fathers will transmit the gene to all of their daughters and none of their sons i Hemophilia A is a bleeding disorder associated with a de ciency of factor VIII Individuals af icted with hemophilia A bleed easily and profusely from seemingly minor injuries Queen Victoria of England was the rst known carrier of the disease And a number of her male descendants were affected by it In fact hemophilia is prominent in European royal families due to the intermarriage of nobility 3 Polvqenic defects are those that involve multiple gene loci These traits are still heritable But predicting their occurrence is more dif cult than with monogenic traits Polygenetic traits are also commonly affected by environmental factors And for this reason they are often called quotmultifactorial traitsquot Most common diseases such as heart disease cancer and diabetes are multifactorial traits 4 Environmental factors that adversely affect the developing fetus are called teratogens Exposure to teratogens is particularly dangerous during the third to ninth weeks of gestation Known teratogens include chemicals and drugs infections and radiation The teratogenic potential of many chemicals and drugs is unknown so pregnant women are usually advised to avoid all drugs if 24 possible Of the infectious agents viruses are the most teratogenic particularly organisms of the TORCH variety toxoplasmosis others rubella cytomegalovirus herpes virus Genomic imprinting challenges the longheld belief that the parental origin of a gene does not make any difference to the cells that inherit the gene Rather maternal and paternal chromosomes are marked differentially within the cell This effect can be illustrated by considering two very different syndromes caused by the same genetic abnormality Prader Willi syndrome and Angelman syndrome both result from a deletion at the same location on chromosome 15 Prader Willi syndrome is characterized by mental retardation short stature obesity poor muscle tone and hypogonadism Patients with Angelman syndrome are also mentally retarded but they have ataxia and seizures and tend to laugh inappropriately The fact that two different syndromes result from the same mutation was puzzling until it was discovered that the Prader Willi mutation is always on the paternally derived chromosome 15 whereas Angleman syndrome is always on the maternally derived chromosome 15 25 NURS 3123 Pathophysiology Module 3 Fluid and Electrolytes Edward Campbell MSN RNBC A Look at Balancing Fluids Acids and Bases 1 A Look at Fluid Just about all major organs work together to maintain proper uid balance To maintain that balance the amount of uid gained should equal the amount lost a Fluid Losses may be both sensible and insensible lnsensibe Fluid Losses are those that cannot be seen or measured This includes losses from evaporation of sweat and moister lost during breathing And fever may cause increased sweating and faster breathing tachypnea which can cause uid losses Sensible Fluid Losses are those that can be measured These would include uid lost though defecation urination emesis blood loss and etcetera b Fluid compartments include both intracellular and extracellular Intracellular uid normally consists of approximately 40 of the person s body weight and is found inside of the cells Extracellular uid normally consists of approximately 20 of the person s body weight and is found outside of the cells 1 Interstitial uid is the uid that immediately surrounds cells and accounts for 70 of the extracellular uids 2 lntravascular uid is the uid that makes up the plasma portion of the blood and accounts for 25 of the extracellular uid 3 Transcellular uid is the uid that is found in compartments in the body including the cerebrospinial column plural cavity pericardial sac and etcetera This uid accounts for approximately 5 of the extracellular uid c Fluid Types found in the body consist of both diluted and nondiluted forms An isotonic uid is one that has the same concentration ie osmotic and oncotic pressures as the uid it is being compared to For example normal saline solution is considered isotonic because it has roughly the same concentration of sodium in the blood 09 Sodium Chloride A hypertonic uid is one that as a greater osmotic or oncotic pressure due to more dissolved particles than the one it is being compared to For example 3 Sodium Chloride solution is considered hypertonic to the blood because it has a higher osmotic pressure due to having more NaCl than the blood itself A hypotonic uid is one with less osmotic or oncotic pressure due to fewer dissolved particles than the one it is being compared to For example 045 Sodium Chloride solution is considered hypotonic to the blood because it has a lower osmotic pressure due to having less NaCl than the blood itself d Fluid and particle movement may occur in one of three different ways Passive Diffusion When two uids are separated by a semipermeable membrane that is post any membrane in our body particles will move from an area of high concentration to an area of low concentration This process happens passively with the ionic gradient because particles want to space themselves out as much as possible from each other It will also eventually equalize the osmotic gradient Active diffusion When two uids are separated by a semipermeable membrane the body may use energy in the form of Adenosine Triphosphate ATP to move particles against an ionic gradient For example cells utilize sodium potassium pumps to move sodium out of the cell and potassium into the cell However they must use ATP in the process Osmosis When two uids are separated by a semipermeable membrane especially one that does not allow the exchange of solutes or one that actively changes the ionic gradients water will move across the osmotic gradient toward the compartment with more particles Le a higher osmotic pressure Passive Diffusion Active Diffusion Osmosis Figure 1 Passive diffusion involves moving particles with the ion gradient Active diffusion involves moving particles against it And osmosis involves moving water with the osmotic gradient e Capillary Filtration is the movement of uid into and out of the capillaries which allows for exchange of uids and solutes i Hydrostatic Pressure is the pressure caused by the heart beating that pushes uids out of the capillary bed ii Oncotic Pressure also called the plasma colloid pressure is the pulling pressure that causes uid to be drawn back into the capillaries This pressure is caused by protein particles that act as a solute drawing water back to the capillaries by osmosis 1 While the oncotic pressure remains relatively stable throughout the circulatory system the hydrostatic pressure decreases drastically from the precapillary arterioles to the post capillary venuoles In effect the hydrostatic pressure is greatest in the arterioles causing water to be pushed out But it quickly becomes less than the oncotic pressure causing water to be pulled back in due to the pulling force of proteins Oncotic pressure llilydlrostatic Pressure HZO Exchange Figure 2 The balance between hydrostatic pressure and oncotic pressure allows the body to exchange uid electrolytes and waste products f Maintaining Balance The renal system and related hormones also play a signi cant role in maintaining uid balance If the kidneys do not work properly the body will have a hard time controlling uid balance i Antdiuretic Hormone ADH or vasopressin is a hormone released by the posterior pituitary This signal from the brain causes the kidneys to reabsorb water and results in concentrated urine ii ReninAngi0tensinAdoster0ne System RAAS begins with the juxtaglomerular cells which secrete an enzyme called renin when pressure in the glomerulus stops ie too little blood too little pressure The renin then undergoes several conversions as follows 1 Renin l Angiotensin Liver 2 Angiotensin l Angiotensin II Lungs 3 Angiotensin II stimulates Aldosterone release Adrenal Cortex The result is a rise in blood pressure because Angiotensin II causes vasoconstriction and Aldosterone causes the kidneys to retain more water Side Note To understand blood pressure remember three rules of thumb 1 More water More pressure 2 More constriction More pressure 3 More pumping More pressure Atrial Natriuretic Peptide ANP is stored in the cells of the atria It is released when the cells of atria are stretched by too much water volume andor increased pressure The hormone counteracts the effects of the RAAS by stopping the release of renin Atrial Vasopressin ADH Natriuretic amp Peptide Aidosterone P Urine Output L Blood Pressure L UWine Output F Blood Pressure Figure 3 Hormones acting on the kidneys can help maintain uid balance by increasing or decreasing the urine output This increase and decrease in urine output has the added effect of raising and lowering blood pressure Thus blood pressure is often closely associated with uid balance 2 A Look at Acids and Bases The chemical reactions that sustain life depend on a delicate balance between acids and bases in the body Even a slight imbalance can profoundly affect the essential body functions a Regulating Acids and Bases A person s ability to regulate their acidbase balance depends on two major systems namely the metabolic and the respiratory system The metabolic system is a complex system of chemical buffers including bicarbonate phosphate and protein buffers that bind with acids and bases to neutralize them In a medical sense the most important buffer is bicarbonate lt binds with both strong and weak acids to increase the blood s pH The kidneys assist the buffer system by controlling the production of bicarbonate ii The respiratory system regulates carbon dioxide which is a gas that combines with water to form carbonic acid Thus the more C02 that a person has in their blood the higher the acid level People can control their C02 levels by breathing faster to expel C02 or breathing slower to retain C02 The way that C02 is usually measured is through the partial pressure of the dissolved gas in the blood ie PaCOZ The Big Picture When considering AcidBase balance the most important acid in the body is carbon dioxide C02 The most important base is bicarbonate HCO3 The kidneys regulate bicarbonate and the lungs regulate carbon dioxide b Arterial Blood Gas A86 is the most common way to diagnose an acidbase imbalance They can be obtained by taking a sample of oxygenated blood from the arteries And normal results for acidbase balance should fall between the following ranges ipH 735 to 745 ii PaCOZ 35 to 45 mmHg iii HCO3 22 to 26 mEqL c Interpreting an ABG Most resources will teach a 56 step methodology for assessing ABGs but this can be simpli ed into only three steps see quotInterpreting an ABGquot d AcidBase imbalances may be caused by either the respiratory or the metabolic system They may also result in either a decrease in pH Acidosis or an increase in pH Alkalosis Respiratory Acidosis occurs when there is a buildup of C02 in the blood stream which causes a decrease pH The causes of increased C02 can include Hypoventilation Rebreathing C02 Lack of hypoxic drive Overdose of CNS depressants Obstructive Pulmonary Disease wewwe Some symptoms of respiratory acidosis include 1 Altered level of consciousness 2 Confusion 3 Shallow rapid breathing 4 Signs of increased iCa2 The kidneys will often try to compensate by increasing production of bicarbonate ions to raise the pH level We also tend to treat respiratory acidosis by increasing the ability to expel C02 such as giving medications to increase ventilation Respiratory Akaosis occurs when C02 levels get too low causing an increased pH The causes of decreased C02 can include 1 Hyperventilation 2 Hypoxia 3 Overdose of CNS Stimulant The symptoms of respiratory alkalosis include Confusion Tachycardia Kusmal s Breathing Increased iCa2 ewNH The kidneys will often try to compensate by decreasing production of bicarbonate ions to raise the pH level We also tend to treat respiratory alkalosis by having someone rebreathe C02 ex paper bag over the mouth Metabolic Acidosis occurs when there is a lack of metabolic buffers primarily bicarbonate which causes the pH to decrease Some of the causes may include 1 Increased production of acids due to metabolism of protein muscle or fat 2 Decreased production of bases due to renal failure 3 Toxic drugs or chemotherapy The symptoms are similar to those in respiratory acidosis And the treatment is to correct the underlying cause while supplementing the body s bicarbonate Metabolic Alkalosis occurs when there is too much metabolic bases primarily bicarbonate which causes the pH to increase Some of the causes may include 1 Loss of acidic GI content 2 Overdose of antacids 3 Metabolic causes The symptoms are similar to those in respiratory alkalosis And the treatment is to correct the underlying cause while supplementing the body s acids with drugs like ammonium chloride INTER PH ETING AN ABG Step 1 Cheek the pH if the pH is lew ie less than 235 the prehlern is tee nineh aeidi Therefereiwe hatre eeidesisi if the pH is high ie less than TASLthe prehlern is tee nineh easequot Therefere we have elkefesisi Step 2 Eheek fer HOME I if the PaGUZ is trending in the eppesite direetien frenn the pH then the cause ef the pureelent is respireteryn I if the BEDS is trending in an eerie direetien as the pH then the eanse ef the prehlenn is metebeiiei A ninenienie fer Step 2 is JEDME Respiraterjris Uppesite Metahelie is Equal Step 3 Eheek fer Eemeensetien I if the BEDS is geing in the same direetien as the PaCUZJ then the bed is eempenseting fer the imbalance That is either the respiraterjr system is eernpensating fer the meta helie system er V153 versai I if the HCUB is net geing in the same direetien as the Pa Ui then the bed is net eempenseting fer the imbalancequot Figure 4 Most resources will teach a 56 step methodology for assessing ABGs but this can be simpli ed into only three steps as shown above 10 Fluids and Electrolyte lmbalances 1 Sodium and Water as a 3060 deal In most cases water will follow sodium due to osmosis And sodium will follow water due to simple diffusion This is true up to the point that the body has to conserve either water or sodium Thus imbalances of sodium are also imbalances of water except in unusual circumstances a Hyponatremia or water toxicity occurs when there is too much water in the vascular system andor too little sodium lt135mEqL Think of this as dilution of CoolAid If you add more water to a cup of CoolAid then your drink will taste weak because there is not enough Cool Aid mix Excess uids tend to cause an increase in blood pressure ie more water more uid And the uid will leak out into extracellular and transcellular spaces General symptoms of hyponatremia may include i Increased Vascular Volume 1 Increased BP 2 Distended veins ii Fluid on lungs 1 Pulmonary Edema 2 Oxygen Hunger 3 Crackles on Auscultation iii Increased Intracranial Fluid 1 Decreased Levels of Consciousness 2 Increased pressure on brain 3 Confusion 4 Seizures iv Increased extracellular Fluid 1 Peripheral EdemaSwelling 2 Weight gain Treatment for hyponatremia is aimed at decreasing vascular volume by giving diuretics and increasing sodium by giving hypertonic uids b Hypernatremia or dehydration occurs when there is not enough water in the body or when there is too much sodium gt145mEqL Think of this as concentration of Cool Aid If you leave an open glass of Cool Aid out on a 11 summer day the water will evaporate and your drink will become stronger and sweeter Decreases in uid volume cause a decrease in blood pressure ie less water less pressure As water decreases in the vascular space it will also decrease in the extracellular and intracellular spaces General signs of hypernatremia tend to include i Thirst ii Decreased BP iii Weak pulses iv Decreased skin turgor v Increased HR and RR vi Loss of tissue perfusion 1 Decreased Level of Consciousness 2 Multiple organ failure 3 Confusion Treatment is generally aimed at replacing lost uids with oral uid replacement and hypotonic IV uids 2 Calcium and Magnesium as Depressants Calcium and magnesium are both cations that affect the transmission of nerve impulses by decreasing the cell s excitability In addition to action potential of nerve cells these ions also function to decrease the excitability of the sacrolemma cell membrane of muscle bers Thus increased levels of either ion will 1 depress the CNS 2 block signals in the PNS and 3 decrease muscle contraction strength a A closer look at calcium Before we can understand calcium balances there are a few basics that we need to know i How to Measure Calcium Levels Because nearly half of all calcium is bound to albumin and citrate serum protein levels can in uence serum calcium levels And thus measurements of calcium can be taken in two different ways 1 Total calcium levels are a measure of all calcium in the serum This includes calcium that is bound to 12 protein as well as calcium that is not 2 lonized calcium level measures all of the calcium that is not bound to protein or citrate This ionized form is the only form that the body has available to use in metabolic processes and is affected by the following a Protein decreases ionized calcium by binding free Ca2 ions b Citrate is a derivative of citric acid that is found in the body which also binds calcium to make calcium citrate c pH changes calcium by changing the af nity that proteins have for calcium ions An increase in pH will increase the af nity for Ca2 causing less available iCa2 And a decrease in pH will cause a decrease in af nity for Ca2 causing less available iCa2 ii How We Regulate Serum Levels The body regulates calcium by hormones of the thyroid and parathyroid 1 Parathyroid Hormone When calcium levels fall the releases parathyroid hormone which stimulates osteoclasts to degrade bone and release calcium into the blood ie PTH quotpullsquot calcium into the blood 2 Calcitonin When calcium levels rise the thyroid gland releases calcitonin to promote the actions of osteoblasts which encourages deposition of calcium into the 13 bones ie Calcitonin keeps calcium in the bone iii How we Regulate Absorption The body also regulates calcium by controlling how much calcium is absorbed through the intestines and how much is resorbed by the kidneys 1 Vitamin D has two active forms namely calcidiol and calcitriol lnitially vitamin D is converted to calcidiol by the liver which then acts on the kidney to decrease excretion of calcium and promote resorption of calcium The kidney then converts calcidiol into calcitriol which promotes absorption of calcium into the serum by the small intestine See gure 5 2 Phosphorus plays a role in serum calcium levels because it has nearly the exact opposite effect as Vitamin D That is to say phosphorus inhibits absorption of calcium by the intestines and causes a decrease in serum calcium Thus there is an inverse relationship between calcium and phosphorus So when calcium is up phosphorus is down and vice versa l Calcitriol 14 Figure 5 Vitamin D has two active forms Calcidiol acts on the kidney to increase resorption of calcium and Calcitriol acts on the intestines to increase absorption of calcium b Hypercalcemia occurs when the calcium levels get too high gt105mgdL total calcium or gt53mgdL ionized calcium Because calcium decreases the excitability of both nerve and muscle bers too much of this ion can be understood to be a problem of too much depressant Too much calcium results in the following general signs and symptoms CNS depression 1 2 Confusion Fatigue 3 Altered mental status Peripheral nervous system depression 1 2 Decreased re exes Lack of coordination ataxia Depression of skeletal cardiac and smooth muscles P P PP N General muscle weakness Slow cardiac rhythms Decreased cardiac contraction Decreased GI motility Constipation Urine retention Other signs of Hypercalcemia are often summarized by the mnemonic quotBones stones groans thrones and psychiatric 0 vertones 1 Bones refers to bonerelated complications which include pathological fractures bone pain and arthritis quotStonesquot refers to kidney stones due to formation of calcium salts in the urine 15 3 quotGroansquot refers to gastrointestinal symptoms of constipation indigestion nausea and vomiting 4 quotThronesquot refers to increased urination because of particle induced diuresis 5 quotPsychiatric Overtonesquot refers to effects on the central nervous system including lethargy fatigue depression memory loss psychosis ataxia delirium and coma Treatment includes increasing uid intake to increase calcium excretion by kidneys administering calcitonin and removing one or more of the parathyroid glands Hypocacemia occurs when calcium levels get too low lt85 mgdL total calcium or 46mgdL ionized calcium Because calcium decreases the excitability of both nerve and muscle bers too little of this ion can be understood to be a problem of too little depressant or a problem of excitability Too little calcium results in the following general signs and symptoms i CNS Excitability 1 Seizures 2 Altered mental status ii Peripheral nervous system excitability 1 Increased re exes 2 Tingling or numbness of the handsfeet iii Excitability of skeletal cardiac and smooth muscles Tetany Muscle spasms Fast cardiac rhythms Increased cardiac contraction Increased GI motility Diarrhea UnneinconUnence P P FWN 16 8 Positive Trousseau s and Chvostek s signs See Figure 6 iv Other signs of hypocalcemia may be summarized by the mnemonic quotCATS go numbquot Convulsion Arrhythmias Tetany Stridor Numbness or tingling wewwe Treatment includes administration of calcium and vitamin D supplements including IV forms like calcium guconate or calcium chloride Figure 6 Trousseau s and Chvostek s signs are symptoms of induced tetany and muscle spasms that can be caused by stimulating the brachial plexus or facial nerves d anermaanesemia is an increase of magnesium ions gt21mgdL that causes depression of the neuromuscular system That is magnesium is a neuromuscular depressant just like calcium Too much magnesium results in similar signs as too much calcium including i CNS depression ii PNS depression iii Depression of muscles Magnesium imbalances can easily be mistaken for Ca2 imbalances or K imbalances However the most signi cant features of the hypermagnesmia are decreased re exes due to 17 depression of PNS and low blood pressure due to smooth muscle dilation in arteries e Hypomagnesemia is a decrease of magnesium ions lt13mgdL that causes excitation of the neuromuscular system Too little magnesium results in similar signs as too little calcium including i CNS excitation ii PNS excitation iii Excitation of muscles Magnesium imbalances can easily be mistaken for Ca2 imbalances or K imbalances However the most signi cant features of the hypomagnesmia is increased re exes due to depression of PNS 3 Potassium and Phosphorus as Stimulants Potassium and phosphorus both affect the transmission of nerve impulses by increasing the cell s excitability And these ions function to increase the excitability of the sacrolemma cell membrane of muscle bers Thus increased levels of either ion will 1 excite the CNS 2 excite the PNS and 3 cause muscle tetanyspasms a vaerkaemia is the condition that results when serum potassium levels get too high gt5mEqL Because potassium increases the excitability of nerve and muscle bers too much potassium is a problem of excitability Too much potassium results in the following general signs and symptoms i CNS Excitability 1 Seizures 2 Altered mental status ii Peripheral nervous system excitability with paradoxical effect 1 NumbnessTingling 2 Decreased re exes 3 Flaccid Paralysis 18 4 Lack of Trousseau s and Chvostek s gtlltgtllt Special note Too much potassium has a paradoxical effect on the PNS because it causes quottoo muchquot electrical activity which shuts down the peripheral nervous system due to the inability of the nerves to repolarize In essence the electrical activity becomes so disorganized that the signal is not moving much like a traf c jam during rush hour traf c This paradoxical effect often helps us distinguish between hyperkalemia too much stimulant and hypocalcemia too little depressant iii Excitability of skeletal cardiac and smooth muscles Tetany Muscle spasmsweakness Increased GI motility Diarrhea Increased cardiac contraction causing Decreased cardiac lling Decreased cardiac output Decreased tissue perfusion Decreased urine output wewwe 1000 iv Other signs of hyperkalemia may be summarized by the mnemonic MURDER 1 Muscle weakness Muscle spasms will often lead to muscle weakness either from spasms or from paradoxical effect of PNS system 2 Urine output may be decreased due to poor cardiac output 3 Respiratory failure may occur because of accid paralysis related to paradoxical effect of PNS system 4 Decreased cardiac output is caused by decreased lling 19 increased excitability of cardiac muscles and paradoxical effect of PNS system 5 EKG Changes are caused by increased excitability of cells and paradoxical effects of the PNS system 6 Re exes are decreased due to paradoxical effect of PNS system Treatment may be aimed at binding potassium with drugs like kaexelate so it can be completely removed from the body Or when given together glucose and insulin can drive potassium back into intracellular uid while decreasing potassium in extracellular uid and serum b Hypoaemia is a condition that occurs when serum potassium gets too low lt35 mEqL causing a problem where there is not enough stimulant for the neuromuscular system Too little potassium has similar effects as too much calcium or too much magnesium including i CNS depression ii PNS depression iii Depression of muscles Other signs of hypokalemia may be summarized by the mnemonic quotSIC WAL quot i Shallow Respirations may occur due to depression of depression of CNS and PNS ii lrritability may occur due to mental confusion iii Confusion may occur due to depressed CNS iv Weakness may occur doe to depression of PNS and muscle sarcolemma 20 Summary of Electrolytes v Arrhythmias irregular rates may occur These generally begin with a slow rate But they progress to a fast rate as the body tries to compensate vi Lethargy occurs due to muscle weakness and depression of the CNS vii Thready pulses occur due to decreased heart rate and contractile force One of the most common causes of hypokalemia is the loss of potassium from gastric contents ie GI suctioning or vomiting Therefore treatment often includes either oral or IV potassium replacement Hyperphosphatemia is a problem that occurs when phosphate becomes too high gt26mEqL However because phosphate has an inverse relationship with calcium hyperphosphatemia is the same as hypocalcemia And we usually diagnose and treat the calcium imbalance Hypophosphatemia is a problem that occurs when phosphate becomes too low lt18mEqL However because phosphate has an inverse relationship with calcium hypophosphatemia is the same as hypercalcemia And we usually diagnose and treat the calcium imbalance ELEIE39T FI HEITY Proteins nfa Water Magnets Albumin 35 55 gde Mal 135 1il5 m quL 332 85 105 mgde Depressa nts MEEEl 13 21 mgfdlL H 35 5 m Eqr39L Stimulants Panes 25 45 mgde Figure 7 The most clinically signi cant electrolytes can be summarized by categorizing their effects on the body 21 Some are important for water balance Others act as stimulants And even others act as depressants 22