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Pathophysiology I

by: Mr. Holden Maggio

Pathophysiology I NU 231

Mr. Holden Maggio
GPA 3.52

Mary Wallace

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Mary Wallace
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This 123 page Class Notes was uploaded by Mr. Holden Maggio on Thursday October 15, 2015. The Class Notes belongs to NU 231 at Northern Michigan University taught by Mary Wallace in Fall. Since its upload, it has received 77 views. For similar materials see /class/224049/nu-231-northern-michigan-university in Nursing and Health Sciences at Northern Michigan University.

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Date Created: 10/15/15
NU 231 PATHOPHYSIOLOGY Cardiovascular Disorders TOPICS Coronary Heart Disease CHD 0 Chronic Ischemic Heart Disease I Stable Angina I Variant 0r Prinzmetal s Angina I Silent Myocardial Infarction 0 Acute Coronary Syndrome ACS I Unstable Angina I Myocardial Infarction o NSTEMI NonST Segment Elevation MI Non QWave MI 0 STEMI ST Segment Elevation MI QWave MI Heart Failure 0 Systolic vs Diastolic Failure 0 Left vs RightSided Heart Failure Bacterial Endocarditis Rheumatic Heart Disease Shock 0 Cardiogenic o Hypovolemic o Obstructive Distributive O I Neurogenic I Anaphylactic I Septic Shock CHD CORONARY HEART DISEASE o Describes heart disease due to blockage of coronary arteries usually caused by atherosclerosis o Blockage of coronary arteries can lead to o Angina o Myocardial Infarction MI 0 Heart Failure 0 Cardiac Arrhythmias Conduction Defects 0 Statistics CHD CHD most common type of heart disease Leading cause of death and disability for both men amp women in US About 15 million MI s occur per year About 30 of pts die before they reach the hospital Costs 14 billion in direct and indirect costs Coronary Artery Circulation Coronary arteries are the major blood vessels that supply myocardium with OZNutrients Two Main Coronary Arteries 0 Left Coronary Artery LCA o Circum eX 0 Left Anterior Descending LAD 0 Right Coronary Artery RCA 0 Posterior Descending Artery Collateral Circulation New outgrowths of small vessels Diverts blood around blocked artery to myocardial tissue Develops when there is a gradual occlusion of coronary arteries Develop at the same time the atherosclerotic changes are occurring Pathogenesis of Most have atherosclerosis of coronary arteries Athero can affect one or all of the coronary arteries LEFT is most often affected Types of atherosclerotic lesion include Stable Fixed a Thick cap with small lipid core a Associated with stable angina Plaque a Angina occurs when demand for 02 exceeds supply 0 Physical Activity Emotional Stress Etc Unstable a Progression of stable plaque VUInerable a Thin cap with large lipid core Plaque a Tends to rupture causes platelet adhesion and thrombus formation blood clot a Rupture causes platelet adhesion and thrombus formation a Associated with Unstable Angina and MI CHD CORONARY HEART DISEASE Risk Factors Mechanism of atherogenesis is poorly understood One hypothesis suggests that atherosclerotic plaque formation is initiated by injury or damage to the endothelial lining inner lining of the blood vessel which produces an in ammatory response However there are a number of risk factors that may predispose to atherosclerosis and CHD See Text Atherosclerosis p 351354 NonModifiable 0 Age Risk factors 0 Gender MgtF Males risk increases after 45 yo Females after 55 yo Family History Modi able Risk 0 Obesity Apple vs Pear Shape Factors 0 Physical Inactivity exercise is good for lipid levels Cigarette Smoking Hypertension Diabetes Mellitus Hyperlipidemia Other Risk Hyperhomocysteinemia Factors 0 amino acid that occurs naturally in the body believed to promote atherosclerosis and thrombus formation 0 Folate is given to treat CReactive Protein CRP 0 measures in ammation in the body 0 unclear whether CRP plays a direct role in athero Periodontal Disease Classi cation of Chronic 0 Stable classic Angina ISChemiC Heart 0 Prinzmetal s or Variant Angina Disease 0 Silent Myocardial Ischemia Acute Coronary o Unstable Angina Syndrome o Myocardial Infarction A03 0 NSTEMI Non ST Segment Elevation MI Non QWave MI 0 STEMI ST Segment Elevation MI Q Wave MI CHRONIC ISCHEMIC HEART DISEASE STABLE CLASSIC AN GINA Angina Pectoris Chest pain pressure squeezing sensation caused by inadequate blood ow and oxygenation to heart muscle Caused by stable xed atherosclerotic plaque Produces transient myocardial ischemia when 02 demand exceeds supply Angina sx remain predictable fixed 0 No change in frequency severity duration SS o No change in precipitating events 0 Onset Sudden or gradual Quality 0 Pressure heaviness tightness or sensation Location 0 Precordium area on anterior surface of body overlying the heart o Substernal area Radiation 0 Most often left arm but also jaw neck and right arm 3 Duration Usually 25 minutes Occasionally 515 minutes Provoked by Physical activity or emotional stress Relieved by Rest or Nitroglycerin PRINZlVIETAL S OR VARIANT ANGINA o Caused by coronary artery spasm 9 restricts blood ow to heart muscle 0 May occur with or without atherosclerosis Etiology 0 Unknown Several Theories o Hyperactive SNS o Decreased Nitric Oxide NO release by endothelium I NO dilates blood vessel allowing blood to ow freely SS Quality of Pain Squeezing tightness pressure or crushing type chest pain Timing Occurs same time each day main thing differentiating from classic angina Occurs at rest or during sleep Usually between 12 midnight and 800 am Complication Increased risk of arrhythmias and sudden death SILENT MYOCARDIAL ISCHEMIA o Goes unde1 o 25 of all MI s are silent 0 Most have atherosclerosis 9 decreases blood ow thru coronary arteries 9 Ischemia 0 However the ischemia occurs WITHOUT chest pain ected because pt may be asymptomatic or may have agypical presentation S S Atypical Presentation Anginal Equivalent o SOBDyspnea o Weakness o Lightheaded o Exerciseinduced pain in neck jaw ear upper abdomen and back but without the chest pain Who s at Risk Women Diabetes Mellitus DM Elderly Pathogenesis Pathogenesis is unclear May have increased pain threshold high endorphin levels May have defect in pain transmission May have sensory defect autonomic neuropathy often seen in Diabetes Mellitus DM ACS ACUTE CORONARY SYNDROME UNSTABLE ANGINA Caused by unstable plaque Severity Intermediate severity between Stable Angina and MI Referred to as Preinfarction Angina Provoked by minimal activity rest Progressive worsening of sx T frequency T severity T duration Duration gt 20 minutes Serum Cardiac Markers Normal MYOCARDIAL INFARCTION 0 Loss of heart muscle as a result of coronary artery occlusion 0 Usually occurs when an atheromatous plaque in a coronary artery ruptures and the resulting clot obstructs blood ow 0 Most infarcts involve LEFT VENTRICAL which is thicker because it has to eject blood into the entire body NSTEMI o Produces a small infarct NODST o Heralds onset of a larger infarct EleVation MI 0 Infarct limited to subendocardial layer 118 Q39WaVe 0 Serum Cardiac Markers Elevated STEMII 0 Most common type 70 of cases ST EleVatiOH M1 0 Triggering Event Unstable plaque ruptures Q39WaVe MI Platelets stick to exposed tissue Forms a blood clot that may completely occlude vessel Myocardial cell death occurs from prolonged ischemia gt 2040 min 0 Involves full thickness infarct Transmural Infarct involves full thickness of heart 0 ECG ST Segment Elevation QWave 0 Serum Card ac Markers Elevated S S Onset o Gradual onset of pain pressure Quality 0 More severe than stable angina o quotCrushingquot Suffocating sensation 0 Like an elephant sitting on my chest Location 0 Precordium o Substemal Radiation 0 Mostly left arm but can also radiate to jaw neck right arm back and epigastric region mimics healtburn Duration 0 gt 20 minutes 0 Duration distinguishes classicstable angina vs MI Provoked by 0 May occur at rest 0 Usually 600 am to 1200 Relieved by 0 Not relieved by restnitroglycerin o Morphine vasodilates often required Other Assoc SK 0 Weakness Lightheaded o Restless Anxious feeling of impending doom 0 Skin is pale cool clammy diaphoretic Most often due to massive surge of catecholamines o A N V o SOB Heart Palpitations MYOCARDIAL INFARCTION MI Pathologic Changes 0 i 02 9 shift from aerobic and anaerobic metabolism 9 T lactic acid 0 i cardiac contractility o i CO 0 i ejection fraction 0 T LVEDP left ventricular end diastolic pressure T Preload distention of ventricle because blood isn t being ejected so it s just staying building up in the LV Tissue Changes After MI 0 gt 2040 minutes 9 irreversible cell death 0 Necrotic tissue replaced with scar tissue 0 Takes about 8 weeks to heal Serum Cardiac Markers for Detecting MI Troponin I amp T Gold standard for detecting MI Enzyme released with myocardial injury Serial sampling 0 4 8 12 and 24 hours Troponin I Detectable in serum 36 hrs after infarction Remains elevated for 710 days Troponin T Remains elevated for 14 days Creatine Kinase CK Three isoenzymes CK MB Heart CKMM Skeletal Muscle CKBB Brain Rises Within 4 hours of infarct Peaks 1825 hours Normalizes 34 days ECG Changes EKG Three zones of tissue damage Zone of Ischemia T Wave Inversion Zone of Hypoxic Injury STSegment Elevation Zone of Infarction Prolonged Q Wave MYOCARDIAL INFARCTION Complications Arrhythmia o Irregularity or loss of rhythm 0 Some may be fatal and cause sudden death 0 Occurs in 80 of MI pts 0 Usually occurs lSt wk after MI Heart Failure 0 Failure of the heart as pump 0 iCO o iPerfusion Cardiogenic Shock 0 Profound failure of the heart as a pump Pericarditis 0 In ammation of pericardium o Pericardial sac encloses the heart 0 Visceral layer inner o Parietal layer inner o Pericardial cavity lled with small amt of uid 0 S S o Appear 23 rd day after MI 0 Sharpstabbing pain aggravated with deep inspiration or position changes 0 Usually transitory and resolves uneventfully Thromboembolism 0 Blood clot thrombus that detaches embolism 0 MI i CO leads to sluggish blood ow 0 Most blood clots originate in LE 0 Detached blood clot travels to right side of heart 0 Heart pumps it to lungs pulmonary embolism PE 0 Prevention Elastic stockings ActivePassive ROM anticoags Health Control Risk Factors Promotion and HTN Disease High Cholesterol Preventron DM Cigarette Smoking Obesity Sedentary lifestyle Diet 0 Folic acid to decrease homocysteine levels o ASA aspirin anticoagulant HEART FAILURE CONGESTIVE HEART FAILURECHF 0 Failure of heart to pump sufficient blood to meet metabolic needs of the body 0 i CO i Tissue Perfusion 0 CHF Cong stion in pulmonary circulation Anatomy of o Circulation through the Heart Heart 0 Right Side Pumps blood to lungs to become oxygenated 0 Left Side Pumps oxygenated blood out to systemic circulation 0 Heart Valves 0 Right Side Tricuspid amp Pulmonic Valve 0 Left Side Mitral amp Aortic Valve 0 Heart Sounds 0 S1 Lub Closure of mitral amp tricuspid valve 0 S2 Dub Closure of aortic amp pulmonic valve Heart 0 See HTN notes CO Stroke Volume Preload Afterload Cardiac Contractility Physiology HF Stats 0 US 550 new cases dX each year 0 Nearly 5 million adults have HF 0 Most common cause of hospitalizations 0 Cost 28 billionyear Pathogenesis o Involves the interplay between two factors Inability of heart to maintain CO Recruitment f compensatory mechanisms designed to maintain CO Frank Starling The greater the stretch the greater the force of contraction MeChanism o Kidneys compensate and conserve Na Water which increases volume amp T preload 0 Has and effects Sympathetic NS 0 Release of catecholamines Epi amp Norepinephrine 0 Effects of Catecholamines Increases HR Increases force of contraction Vasoconstricts blood vessels 0 Has and effects TCO and tissue perfusion Twork of heart RAA Mechanism 0 Activated because of low blood volume or low BP ReninAngiotensin Has and effects A Myocardial 0 Long term compensatory mechanism Hypertrophy 0 Cardiac muscle responds to increased work demands 0 Usually involves left ventricle Hypertrophies 0 Left Ventricular Hypertrophy LVH 0 Has 2 and effects HEART FA ILURE Causes of HF 0 Most common MI and Hypertension o Other Causes Hypertrophic Cardiomyopathy Heart Valve Damage Stenotic or Regurgitant Valves Hquotperthyroid Anemia Volume Overload Congenital Heart defects Types of HF Systolic Failure Accounts for 7000 of cases Caused by CHD MI Characterized by impaired ejection of blood from heart during systole 0 Effects L CO amp Tissue Perfusion O L Ejection Fraction lt3540 Diastolic Failure Accounts for 30 40 o of cases Caused by HTN most common Characterized by impaired lling ofventricles during diastole Decreased chamber size 2 d to LVH Ventricles stiff decreased ventricular compliance Effects 0 Pressure in heart increases T to force enough blood into LV to maintain CO 0 Normal or minimally subnormal ejection fraction Left Sided Failure Most common type Forward Failure LV unable to pump blood into systemic circulation blood dams up Backward Failure Blood accumulates in LV LA Lungs Results in pulmonary SS General 0 Easy fatigability hypoxia Resp SOB Dyspnea on Exertion DOE RalesCrackles Cough Orthopnea SOB in supine position Paroxysmal Nocturnal Dyspnea Sudden SOB that occurs during sleep 11 pt feels like they are CV 0 S3 gallop earliest sign of CHF Renal o Nocturia Supine position T venous return 9T renal perfusion o Fluid that accumulates in LE lower extremities during day upright position gets reabsorbed in supine position and returned to Right Sided Failure Causes Left Heart Failure and COPD chronic obstructive pulmonary disease Forward Failure RV unable to pump blood to lungs blood dams up Backward Failure Blood accumulates in RV RA Systemic Venous Circ Results in edema Fatigue Weakness Edema Weight gain due to uid accumulation JVD jugular venous distention Liver Enlargement Hepatomegaly Cyanosis late sx HEART FAILURE Health 0 Promotion Disease Prevention Control Risk Factors OOOOOOO Hypertension High Cholesterol DM Smoking Obesity Lack Of Physical Activity Diet Decrease saturated fats increase folic acid BE BACTERIAL ENDOCARDITIS 0 Infection of the endocardial surface of the heart including heart valves 0 Bacteria mot common infecting organism PathogeneSiS 0 Two factors contribute to the development of BE Damaged endocardial surface Portal of entrance by which organism gains access to blood stream 0 P quot 39 factors unknown in 2030 of pts Damaged High Risk Prosthetic Heart Valve Endocardial Prior episode of BE Surface Congenital Heart Defect Mod Risk Mitral Valve Prolapse MVP with Regurgitation 39 39 Heart Disease Negligible MVP without Regurgitation Risk Functional Innocent Murmur Cardiac Pacemaker P011311 0f Entry 0 Dental Procedures 0 GIGU Respiratory Procedures 0 IV Drug Use IVDU 0 Indwellin Catheters 0 Pathogens gain access to blood stream 0 Pathogens colonize damaged endocardial surface and proliferate 0 Form bulky friable vegetative lesions composed of pathogens amp cellular debris 0 Vegetation loosely attached 0 Fragments of lesionpathogen break off 0 Form emboli and travel in blood stream 0 Cause distant systemic effects SS Clinical course depends on eXtent of heart damage type of pathogen amp site of infection H9311 0 90 present with heart murmur 0 Either new murmur or change in preeXisting murmur 0 Usually involves Mitral Valve 0 IVDU Tricuspid Valve Skin 0 Petechial Hemorrhage LeSionS 0 Found on skin nail beds mucous membranes 0 Caused by emboli that lodge in small blood vessels 0 Janeway Lesions o Macules at lesions found on palms amp soles of feet 0 Nontender e1 thematous macules 0 Osler s Nodes 0 Tender peasize purplish nodules found on ngers amp toes Nails 0 Splinter Hemorrhages 0 Dark red lines under nails of ngers and toes o A 39 d with minute emboli Resp SX o IVDU IV Drug Use associated with right sided endocarditis 0 Emboli travel to lung PreVentiOIl 0 Antibiotics prior to dental or other invasive procedures RHEUMATIC FEVER RHEUMATIC HEART DISEASE 0 RF is a multisystem immunologically mediated in ammatory disease 0 Follows Gro p A Beta Hemolytic St GABHS throat infection PrediSPOSing 0 Usually develops 14 weeks after untreated strep throat must give antibiotics within 1st 9 days after F2 me infection to prevent RHD only 3 with strep throat will develop RHD 0 Mostly affects kids 5 15 YO PathogeneSiS 0 Immunological reaction Form antibodies against antigen present in strep pathogen 0 Antibodies cross react with similar antigens in individual s own tissue 0 Leads to in ammation of Heart Joints Skin CNS 0 Individuals who have had one attack of RF are more susceptible to recurrent attacks of RF after 39 strep throat infections SSi carditis 0 In ammation of endocardium amp heart valves Hea 0 Repeated attacks produce scarring amp deformity of heart valves 0 Mitral and aortic valves most commonly affected 0 Earliest sx New murmur or change in pre existing murmur Migratory 0 Arthritis In ammation of synovial membrane POIya h tis 0 Affects large joints such as knees ankles elbow wrist bun 0 Joints appear red warm swollen and tender 0 Duration Last few days and then goes away migrates to another joint 0 UntX it goes away in 4 weeks almost never results in nermanent damage Sydenham S 0 Neurological Movement Disorder Chorea 0 Onset Begins gradually progressively worsens over few weeksmonths OR 0 Characterized by irregular abrupt rapid jerky movements chorea of muscles St Vitus Dance 0 Affects face neck trunk arms and legs CNS 0 Additional Findings 0 Diminished muscle tone muscle weakness 0 Emotional behavioral disturbances esp obsessivebehavioral disorder 0 t 39 resolves within 9 months to 2 years Erythema 0 Rare Occurs 10 of pts with RF Mafginatum 0 Lesions develop on trunk inner thigh or upper arm Skm 0 Red macular nonpruritic lesions 0 Transitory disappear during course of the disease SQ Nodules 0 Rare sub39Q 0 Associated with severe carditis 0 Painless hard movable nodules 0 Found on eXtensor surface of j oints PreVentiOIl 0 Treat strep throat infection with antibiotics must be given wi 9 days of infection 0 Antibiotic prophylaxis to prevent recurrent attacks SHOCK 0 Life threatening Lead to multipl Inadequate tissue perfusion cell hypoxia Cells are quickly and irreversibly damaged 3 organ damage MOD and death Stages of Shock C y Stage 0 Body attempts to reverse the condition 0 Activates compensatory mechanism to maintain CO amp C 39 39 SNS 39 39 perfusion of vital organs 0 RAA ADH Progressive Stage o Occurs when compensatory mechanisms fail to maintain CO Tissue becomes hypoxic due to inadequate tissue perfusion Cells switch from aerobic to anaerobic metabolism Lactic 39 producing metabolic acidosis Irreversible Refractory Stage 0 Shock no longer reversible Vital organs fail Death occurs quickly Types of Shock Cardiogenic Hypovolemia Obstructive Distributive o Neurogenic o Anaphylactic 0 Septic CARDIOGENIC SHOCK Profound failure of the heart as a pump L Cardiac Output L Tissue Perfusion Cause 0 Results from heart failure from any cause 0 Myocardial infarction most common 0 Cardiac arrhythmias 0 Valve Dysfunction o Congestive Heart Failure Mortality rate 5000 Compensatory Mechanisms SNS RAA ADH Short term effective Long term worsens shock HYPOVOLENHC SHOCK o Inadequate Blood Volume Hypovolemia Causes 0 Hemorrhage Blood Loss 0 Dehydration o Vomiting Diarrhea o Diuresis Diuretics DM Diabetes Insipidus Compensatory o Hypothalamus stimulates thirst mechanism Mechanisms o o SNS o ADH SS Severity Volume Lost SS Mild 7501250 ml Thirst 1525 L in blood volume Mild Tachycardia S1 L BP Cool handsfeet Moderate 12501750 ml Thirst 2535 L in blood volume Restless Pallor pale skin Tachycardia 100120 BPM SBP 90100 mm Hg Severe 2500 ml Confusion 50 of blood volume Unconscious EXtreme Pallor Tachycardia gt 120 BPM SBP lt 60 mm Hg Cold EXtremities Anuria OBSTRUCTIVF SHOCK 0 Results from obstruction of blood flow through central Circulation 0 Central circulation heart lungs great veins superiorinferior vena cava pulmonary veins Etiology Pulmonary Embolism PE most common cause Dissecting Aortic Aneurysm Cardiac Tamponade 1 Pathogenesis Results in T right heart pressure Impairs venous return L CO amp Tissue Perfusion SS Right Heart Failure 0 JVD o Edema 0 Weight Gain 0 LiverSEleen enlargement DISTRIBUTIV SHOCK De nition 0 Widespread and massive vasodilation o Normovolemic Shock 0 Vascular expands so that normal blood volume does not ll circulatory system Types 0 Neurogenic Vasogenic Shock Anaphylactic Septic Shock N EUROGEN IC VASOGENIC SHQC K Cause Brain Injury Spinal Cord Injury General Anesthesia Hypoxia Lack of Glucose insulin reaction Fainting due to emotional stress may cause transient form of neurogenic shock Patho Widespread and massive vasodilation Results from SNS Inhibition o PNS Stimulation Produces L CO L PVR L Tissue Perfusion Impaired cellular metabolism 0 ANAPHYLAC IC SHOCK Patho Severe whole body allergic reaction Occurs in previously sensitized persons Antibody IgE AntibodyAllergen Drugs Insect bites lateX allergy foods Mast cells release histamine and other mediators resulting in massive vasodilation capillary permeability and smooth muscle constriction Produces L CO L PVR L Tissue Perfusion Impaired Cellular Metabolism SS Onset 0 Usually sudden death may occur in minutes Depends on sensitivity of person amp rate amp qty of antigen eXposure Mental Status A u 39 e Restless AnXious Skin Burning warm sensation Urticaria hives itchy Throat Tongue swells Laryngeal Edema Airway obstruction Resp SOB Chest tightness Wheezing cough Respiratory Arrest CV Decrease BP Weak pulse Cardiac arrest Topics 0 NU 231 Pathophysiology Endocrine Disorders Diabetes Mellitus Type 1 and Type 2 Hypothyroid Hyperthyroid Cushing Syndrome DM DIABETE gt MELLITUS Classi cation of DM See text p 706 Diabetes Mellitus Type 1 Diabetes Mellitus Type 2 Gestational Diabetes Mellitus GDM Other Speci c Types De nition Chronic disorder of carbohydrate fat and protein metabolism Primarily the result of o De ciency or complete lack of insulin secretion by beta cells of pancreas 0 OR Insulin Resistance 0 OR Both 1 2 3 4 O O GLUCOSE FA amp PROTEIN METABOLISM Glucose I Primary fuel source provides 4 kcalgram Brain amp NS rely almost exclusively on glucose as a fuel source 0 Only stores enough glucose to last few minutes 0 Prolonged amp severe hypoglycemia can result in brain death Liver maintains glucose 39 39 by 39 39 39 39 glucose has an effect on the NS can cause death u u u 0 Glycogenesis I Liver converts excess glucose to glycogen which is stored in liver amp muscle tissue Glycogenolysis I Liver converts glycogen back to glucose when blood glucose levels fall Gluconeogenesis I Liver synthesizes glucose from non carbohydrate sources 0 Amino Acids Lactic Acid Glycerol Most ef cient fuel source provides 9 kcalgram Excess CHO converted to triglyceride and stored in adipose tissue Triglyceride consists of 3 fatty acids and a glyceride Lipase breaks down triglycerides into fatty acids amp glycerol which can be used as energy source Almost all cells with the exception of brain tissue and RBC can use fatty acids interchangeably with glucose for energy When large amounts of fatty acids used as energy source fasting DM liver converts fatty acids into ketones amp releases them into the blood 0 Ketones are acid waste product of fat metabolism 0 Increased ketones lead to 39 39 39 39 metabolic acidosis Protein Provides 4 kcalgram Proteins are made up of amino acids Amino acids in excess of those needed for protein synthesis are converted to fatty acids ketones or glucose and are stored or used as metabolic fue When metabolic need exceeds intake liver uses the amino acid as a major substrate for gluconeogenesrs GLUCOSE REGULATING HORMONES o Endocrine portion of the pancreas made up of Islet of Langerhans o Islet cells composed 0 Beta Cells Secrete Insulin 0 Alpha Cells Secrete Glucagon 0 Delta Cells S quot inhibits release of insulin amp olucaoom Insulin i BS 0 Only hormone that i BS blood sugar 0 Promotes glucose uptake by target cells 0 Insulin receptors on cells recognize insulin amp allow glucose to be transported into cell where glucose is converted to energy 0 Receptor amp Insulin Lock amp Key Effect 0 Acti n of insulin on glucose fats and proteins Glucose o Promotes glucose uptake by target cells Facilitates storage of excess glucose as glycogen in the liver Inhibits breakdown of stored glycogen Fats Facilitates triglyceride synthesis from glucose Promotes transport of fatty acids into adipose tissue Inhibits breakdown of stored fat Proteins Increased protein synthesis by transporting amino acids into body cells Inhibits protein breakdown by enhancing use of glucose and fatty acids as fuel source Glucagon T BS 0 Maintains BS between meals and during fasting and starvation states by T hepatic glucose production C39 39J 39 C39 39 COUNTER REGULATORY HORMONES Cate T BS 0 Epinephrine amp Norepinephrine Adrenal Medulla Stress hormonesquot cholamines o T BS during periods of stress by 0 Decreases release of insulin from beta cells 0 Promotes conversion of glycogen to wcose Glyco enolysis Gluco T BS 0 Cortisol is the major glucocorticoid Adrenal Cortex Stress hormonequot COITiCOid o T BS during stress fastingstarvation by T hepatic wcose production Growth T BS 0 Secreted by anterior pituitary Hormone o T BS by decreasing cellular uptake and use of glucose DIABETES M ILLI TUSTYPE 1 Names New Name Diabetes Mellitus Type 1 use Arabic rather than Roman numerals Old Names Juvenile DM or Insulin Dependent DM IDDM Frequency Accounts for 510 of all cases of diabetes mellitus Occurs at any age Peak age 812 YO DIABETES M o ITI TUS TYPE 1 Etiology Pathophys Results from autoimmune destruction of pancreatic beta cells 0 Genetic Susceptibility o Hypothetical Environmental Agent that triggers autoimmune process 0 39 Response Destroys Beta Cells Genetic Factors 0 Associated with Human Leukocyte Antigens HLADR3 amp HLADR4 O 90 of persons have one or both of the these molecules 0 Inheriting alleles T susceptibility to altered immune response Family History The frequency of DMl developing in children with 0 Diabetic Mom 23 Diabetic Dad 56 0 Both Parents 30 Trig Environmental Precise mechanism is unknown Monozygotic Identical Twin Study 3050 concordance rate Potential Triggering Agents 0 Viral Infections Coxsackie Mumps Rubella Cytomegalovirus o Cow s Milk gering Agent 0 Autoimmune Response Markers of immune destruction include o Islet cell autoantibodies o Autoantibodies to insulin Autoantibodies are usually present in 8590 of persons with DMl Pathophys O o Destruction of beta cells leads to absolute lack of insulin 9T BS HYPERGLYCEMIA 0 Unable to use glucose as energy source 0 Breakdown fats and proteins for use as energy source Rate of beta cell destruction can vary 0 For infantschildren rate of destruction can be rapid o For adults rate of beta cells destruction is usually slower SS Symptoms appear when 90 of beta cells destroyed Usually body type thin Peak age 812 although may occur any age Glucose accumulates in blood amp spills in urine as renal threshold is exceeded 0 Glucose normally totally absorbed by renal tubules 0 When plasma glucose is 3 180 mgdl glucose spills into urine glucosuria Fatigue Listlessness Polyuria Polydipsia Polyphagia Weight Loss Glucosuria V 39 39 39 T Ketones 2quot01 to burning fats See acute TX NO cure Insulin Replacement Therapy by insulin injection or insulin pump Dietary Management Monitor BS using glucose meters DIABETES MELLITUS TYPE 2 Names 0 New Name Diabetes Mellitus Type 2 use Arabic rather than Rom an numerals 0 Old Names Adult Onset DM NonInsulin Dependent DM NIDDM Frequency 0 Accounts for 90 of all cases of diabetes mellitus Risk Factors Age Mostly affects adults 3 40 YO Although incidence is increasing in adolescents and young adults 2quotd to obesity Race African Americans Native Americans Hispanic Latino Asian Americans Family HX Very strong genetic connection esp if you have lSt degree relative Genetics Monozygotic twin study 90 concordance rate No association with HLA Antigens No evidence of autoimmunity Obesity 90 are obese Risk of DM increases as BMI body mass index increases Obesity associated with Insulin Resistance see pathophys Centralabdominal obesity is most closely linked to insulin resistance vs peripheral obesity thighsbuttD Weight loss improves insulin resistance HX of previous IFG Impaired Fasting Glucose Prediabetes often precedes overt DMType 2 De ned as o IFG Fasting Plasma Glucose FPG level 100125 mgdl o IGT Oral Glucose Tolerance Test OGT 140199 mgdl Most will eventually develop DM2 within 510 years IGT Impaired Glucose Tolerance GDM Hyperglycemia that is rst detected during pregnancy Gestational Due to combination of insulin resistance and impaired insulin Diabetes Mellitus secretion Occurs in approximately in 214 of all pregnancies in US BS usually returns to normal after delivery About 4060 eventually develop DM2 in 510 years Often occurs in women with o family history of DM 0 Obese 0 Advanced maternal age DIABETES MEL LITUS TYPE 2 Pathophys 0 Three metabolic abnormalities that result in hyperglycemia ltgt Insulin Resistance 0 T Insulin Secretion O T Hepatic Glucose Production C39 39 39 C39 39 IR a Normal amounts ofinsulin are inadequate to regulate BS levels Insulin o IR 9 Leads to T cellular uptake of glucose 9 T BS Hyperglycemia Resistance o Initially I l for Lyr 39 39 by T insulin secretion hyperinsulinemia o Obesity central abdominal is the most common cause of IR Several proposed mechanism linking obesity amp IR 0 Defect in insulin receptors on cell membrane o Intracellular Postreceptor Defect Glut l 2 3 4 0 Increase in Free Fatty Acids o Decreased levels of Adiponectin hormone secreted by adipose tissue T Insulin o Hyperinsulinemia leads to beta cell eXhaustion Secretion a Beta cells eventually poop ou T Hepatic o Insulin de ciency 9 Cells unable to use glucose as energy source Glucose o Cells starving 9 Liver converts glycogen to glucose Glycogenolysis Production 0 Worsens hyperglycemia S S o Asymptomatic 7 go undetected for years 0 3 Polys Polyuria Polydipsia Polyphagia 0 Recurrent Infections 0 Urinary Tract Infection 0 Vaginal Infection Yeast Infection Candida 0 Skin Infections Boils Carbuncles Cellulitis 0 Other signs and symptoms of hyperglycemia 0 Fatigue 0 Blurred Vision 0 Paresthesia o No weight loss often have problems with obesity 0 No 39 39 39 39 METABOLIC SYNDROME Syndrome X Insulin Resistance Syndrome o Cluster of clinical traits that when occurring together increase the risk for the development of atherosclerosis and CV disease 0 Affects about 24 of the population in US between ages 2070 YO 0 Criteria for dX Metabolic Syndrome NCEP ATP III 2001 Any three of the following Abdominal Obesity 0 Male Waist Circumference gt 40 inches 0 Female Waist Circumference gt 35 inches Triglyceride o 3 150 mgdl 0 OR tX for elevated triglycerides HDLC 0 Men lt 40 mgdl 0 Women lt 50 mgdl 0 OR tX for low HDLC Blood Pressure gt 13085 mm Hg 0 OR tX for elevated BP FPG Fasting Plasma Glucose 3 100 mgdl OR previously dX DM type 2 CRITERIA FOR DIAGNOSING DIABETES Lab Test Test Info Normal Prediabetes Diabetes FPG Fasting No food or drink for at 7099 mgdl 100125 mgdl 3 126 mgdl Plasma least 8 hrs Glucose IFG Impaired Fasting Glucose 2 HI Oral No food or drink for at lt 140 140199 2 200 Glucose least 8 hours Tolerance Initial BS level is drawn 2hr post 2hr post glucose 2hour post Given g1ucose 1oad 75 glucose load load glucose load grams of glucose dissolved in water IGT Impaired Oral Measure glucose level at Glucose Tolerance different interval levels to see how well pancreas can handle glucose load Random N0nfasting test 3 200 mgdl PLUS Blood Sugar presence of classic sx 3 polys OTHER TESTS Hemoglobin 0 Not used to ix DM AIC o Determines how well DM is being managed o Re ects average glucose for the preceding 612 week period 0 Not affected by food intake stress or exercise 0 Normal 46 0 Goal for DM lt7 DM COMPLIC ITIONS Acute Complications DKA Diabetic Ketoacidosis Hypoglycemia HHS Hyperglycemia Hyperosmolar State Somogyi Phenomenon Dawn P39 Chronic Complications Microvascular Disorders Macrovascular Disorders Foot Ulcers DKA DIABETICKETOACIDOSIS Those at Risk Occurs in DMl Predisposing Factors Individuals at Risk 0 Undiagnosed before diagnosed o Omit insulin or insufficient dose 0 Individuals with severe physical emotional stress illness accident trauma etc 9 T BS 2quotd to TIncrease Counter Regulatory Hormones Pathophys Two major metabolic abnormalities 0 Increased BS 300 750 9 TOsmolality No insulin T Counter Regulatory Hormones T Hepatic Glucose Production 0 Metabolic Acidosis Use fatty acids for energy 9 Increased ketones KetoacidosisMetabolic Acidosis SS Slow onset T BS 9 Osmotic Diuresis 9 Polyuria Dehydration Hypovolemia 9 Polydipsia 0 Dry mouth 0 Poor Skin Turgor 0 Weight loss 0 Tachycardia o Hypotension T RR Kussmaul Respirations 9 compensate for metabolic acidosis GI Abdominal Pain N V CNS Depression Fatigue lethargy coma Odor of ketones fruity odor on breath ABG Metabolic Acidosis pH lt 735 HCO3 lt 15 mEqL Urine for Ketones HYPOGLYCEMIA Synonyms Insulin Shock Insulin Reaction Those at Risk Individuals with DMl or DM2 Predisposing Factors Too much insulin or hypoglycemic agent Sulfonylureas Too little food intake in rs to insulin missing delaying meals Exercise exercising muscles more permeable to glucose even in absence of insulin Alcohol occurs in people who consume large amounts on empty stomach Alcohol decreases 001160 enesis Pathophys BS lt 50 mgdl SS Rapid Onset Wide variations in presentation more variable in children amp elderly SS Irritable Weak Hungry Shaky HA Mental confusion Difficulty problemsolving Slurred speech Impaired motor function Convulsions Seizures o Coma OOOOOOOOO TX Conscious Ingest Sugar 0 OJ add sugar 0 Coke nondiet 0 Hard Candy Unconscious Hospitalize o Glucagon SQ injection 0 Glucose Gel squeeze bottle 0 IV with glucose HHS HYPERGLYCEMIC HYPEROSMOLAR STATE Those at Risk DM2 Predisposing o Elderly who have comorbidities infection CV disease renal disease FaCtOTS 0 High carbohydrate diets eg tube feedings TPN Pathophysiology o Glucose levels 5002000 mgdl 0 Increased Osmolality gt 350 mOsmL 9 Osmotic Diuresis 0 Not ketosis prone produce enough insulin to prevent lipolysis S S o Osmotic Diuresis 9 Polyuria Dehydration Hypovolemia 9 Polydipsia 0 Dry mouth 0 Poor skin turgor 0 Weight loss 0 Tachycardia o Hypotension SOMOGYI PHENOMENON Who s at Risk DMl newly 139 J trying to regulate insulin dose Pathophys Morning hyperglycemia 2quotd nocturnal hypoglycemia Nocturnal hypoglycemia Occurs because evening dose of insulin too high Morning Hyperglycemia Compensatory response 0 T counter regulatory hormones o T Hepatic glucose production Tx Con rm Somogyi effect by measuring BS 2300 am Decrease evening insulin dose DAWN PHENOMENON Who s at Risk 0 DMl or DM2 Pathophys Morning hyperglycemia without nocturnal hypoglycemia o Caused by nocturnal elevation of growth hormone 9 i cellular uptake and use of wcose TX 0 Increase PM insulin dose Switch evening NPH to HS CHRONIC COMPLICATIONS Microvascular Disorders he Microcirculation Disorders of t Retinopathy Occurs in all DMl and approx 60 of DM2 Damage amp rupture small blood vessels of the eye Leading cause of blindness in US Nephropathy o DMl present after 15 years 0 DM2 present at time of dx 0 Affects blood vessels that supply glomeruli 0 Leading cause of ESRD 0 First sign of diabetic nephropathy is an T urinary albumin excretion microalbuminuria Neuropathy o Occurs in both DMl and DM22 0 Classi cation of Peripheral Neuropathies See text p 718 Somatic Involves sensory and motor nerves Neuropathies Most commonly affects lower extremities 0 Loss of sensation o Numbness and tingling 0 Can lead to serious injuries Two Pathologic Changes 0 Endothelial thickening of blood vessels that supply nerves 9 nerve ischemia 0 Demyelinization of Schwann cells 9 slows down nerve Autonomic Neuropathy Postural Hypotension Impaired CV Function Impaired GI Function Impaired GU Function Cranial Nerve Involvement MACROVASCULAR DISORDERS 0 Who s at Risk 0 DMl Onset depends on age amp duration of DM 0 DM2 Present at time of diagnosis 0 Types of Macrovascular Disorders 0 Coronary Artery Disease angina MI 0 Cerebral Vascular Accident Stroke 0 Peripheral Arterial Disease DIABETIC FOOT ULCERS Most common complication 6070 of people with foot ulcer have neuropathy 1520 have vascular disease 1520 have neuropathy vascular disease Unaware of trauma of feet leads to amputations TREATMENT Dietary management Exercise Control CoMorbidities HTN Lipids etc Glucose Monitoring Insulin injection or pump PO Oral Meds only used for DM2 o Sulfonylureas o Biquanide Metformin THYROID GLAN Thyroid Anatomy Consists of two lateral lobes connected by an isthmus Covered by sternomastoid muscle Normal thyroid gland is usually NOT palpable Thyroid Gland Follicular Cells functional unit of the thyroid gland Physiology 0 Synthesizes thyroid hormones 7 T3 T 4 0 T3 Triiodothyronine 0 T4 Thyroxine Parafollicular Cells C Cells 0 Secretes Calcitonin ltgt Calcitonin decreases Ca level 0 Moves calcium from plasma to bone Hypothalmic Secretion of thyroid hormones regulated by HypothalmicPituitaryThyroid Pituitary Feedback Loop Thyroid O Hypothalamus secretes TRH Thyroid Releasing Hormones System 0 Anterior Pituitary secretes TSH Thyroid Stimulating Hormone o Thyroid Gland secretes T3 T4 Acts on target cell Action of Thyroid Acts on nearly every cell in the body Hormones 0 Increase basal metabolic rate BMR o Affect body temperature 0 Increase carbohydrate CHO fat and protein metabolism 0 Increases vitaminmineral metabolism 0 Increase heart rate and force of contraction o Increases GI Function 0 Increases SNS activity 0 Increases skeletal muscle contraction Alterations in Hypothyroid Thyroid Function Hyperthyroid Goiter enlarged thyroid gland ltgt Hypothyroid ltgt Hyperthyroid ltgt Euthyroid HYPOTHYRO D De nition 0 i Thyroid hormones o l BMR o Slows dovs n all body activity Classi cation Congenital o Affects approx 1 of 5000 births Hypothyroid o Caused by 0 Absent thyroid gland o Inadequate thyroid hormone production 0 De cient TSH o Cretinismmanifestations of untX congenital hypothyroidism 0 Growth retardation 0 Mental retardation o TX Hormone 39 Acquired 0 Primary Hypothyroid Thyroid Gland Dysfunction Hypothyroid 0 Secondary Hypothyroid Pituitary Gland Dysfunction rare 0 Tertiary Hypothyroid II Jr quot 39 39 Dysfunction grare Etiology Hashimoto s 0 Most Common Causes Thyroiditis o FM Ratio 51 ratio 0 Autoimmune Disorder Form autoantibodies which destroy gland Surgical o Thyroidectomy Induced 0 Complete or partial removal of thyroid gland Radiation o Radioactive iodine RAI used to tX hyperthyroid Induced o Thyroid gland concentrates RAI o Destroys gland Hypothyroid Medication o Hyperthyroid Propylthiouracil PTU Methimazole Tapazole Induced o Bipolar Disorder Lithium o Arrhythmia Amiodarone o Iodinecontaining radiographic contrast media dX tests Iodine 0 Rare in US De ciency S S 0 Related to two factors 0 Hypometabolic State 0 Collection of Myxedema Fluid I Causes hard nonpitting edema l 39 inn of 39 J 39 39 39 interstitial spaces Most obvious in face but also collects in interstitial spaces of almost any I I J ide that traps water in 1 organ heart and other areas HYPO THYROJD SS Behavior Mentally Sluggish Physically Sluggish Skin Hair Skin CourseDry Hair CourseBrittle Loss of lateral 13 of eyebrows Cold Thermostat Sign Face Neck Myxedema Fluid Puffy appearance Dull expression Thickening of tongue Speech is slowslurred Voice hoarsehusky Mildtomoderate goiter OOOOO CV Function Bradycardia Decreased cardiac output Heart Failure Resp Function Decreased respiratory rate Hypoventilation GI System 0 Decreased Appetite 0 Weight Gain 0 Decreased bowel activity 0 Consth on GU System 0 Anovulation o Menorrhagia heavy period MS 0 Decreased muscle tone Nervous o Decreased DTR s SyStem o Paresthesia Other 0 Severely hypothyroid pts may have dif culty metabolizing o Sedatives 39 39 esthetic Drugs Lab Tests 0 i T3 T4 T TSH o T hnlesternl TX 0 Thyroid Hormone Replacement e g Synthroid HYPERTHYROID THY ROTOXICOSIS De nition 0 Excess thyroid hormones o T BMR 0 Accelerates all body activity ClaSSi catiOIl 0 Primary Hyperthyroid Thyroid gland dysfunction 0 Secondary Hyperthyroid Pituitary Dysfunction Rare 0 Tertiary Hyperth roid I 39 39 D sfunction Rare Causes Of 0 Graves Disease most common cause Hype hymid 0 Several other causes of hyperthyroid will not discuss GRAVES DISEASE 0 Overproduction of thyroid hormones 0 Onset 2040 YO 0 F gt M 51 ratio 0 Graves often accompanied by Exophthalmos amp Goiter 0 Accounts for l l 39 6090 of cases of hyperthy 39 39 Etiology 0 Autoimmune Disorder Pathophysiology o Thyroid Stimulating Immunoglobulins TSI bind to TSH receptor sites on thyroid gland o TSI competes with TSH T T3T4 0 Do not know what triggers autoimmune response 0 Genetic Susceptibility Familial Clustering 0 1520 of pts have close relative with the disorder 0 Associated with HLADR3 HLABS o A 39 d with other disorders SSi Skin 0 Skin smooth velvety skin Half 0 Hair Thin ne silky Nalls o Nails Brittle Break easily Heat 0 Thermostat Sign IntOICTance 0 Excessive Sweating NeCk 0 Goiter 0 Diffuse amp symmetrical enlargement o Bruit use bell of stethoscope Eyes 0 Exophthalmos o Occurs in 13 of pts with Graves o Eyeballs protrude bulge o Lids don t close over eyeball eye irritation dry eyes corneal ulcers 0 Photophobia 0 Double Vision 0 EOM weakness CV 0 Increased CO 0 Tachycardia 100 120 o Irregular Heart Beat 0 Hypertension o Angina 0 CHF Resp 0 SOB with exertion GRAVES DISEASE SS GI Increased appetite Weight loss Increased GI Motility Bowel Sounds Abdominal cramping Diarrhea GU Lighter menstrual period Oligomenorrhea Amenorrhea Infertility Difficulty conceivin MS Muscle weakness Fatigue Muscle protein breakdown Osteoporosis NS Increased energy Restless Anxious Nervous Insomnia Difficulty concentrating Find hand tremors Hyperactive DTR s Graves Dermopathy Also called Pretibial Myxedema Rare 7 almost always assoc with Graves Cause is uncertain S S Pinkingred lesions located on anterior and lateral aspect of legs Produces nonpitting edema Hair follicle may be prominent orange peel appearance Lab Tests T T3 T4 1 TSH L Cholesterol TX Surgery Medications PTU Tapazole RAI radioactive Iodine Therapy ADRENAL GLAND DISORDERS Anatomy and o Physiology 0 Adrenal glands located on top of each kidney Composed of Adrenal Medulla amp Adrenal Cortex Adrenal Medulla Catecholamines Epinephrine Norepinephrine 0 Stress Hormones 0 Action T BP HR Respiration T Peripheral vasoconstriction T Sweating Adrenal Cortex Mineralocorticoid Aldosterone o Regulated by ReninAngiotensinAldosterone Mechanism 0 Regulates Na and Water Balance Glucocorticoid Cortisol o Regulated by HypothalamicPituitaryAdrenal HPA System Hypothalamus CRH Corticotropin Releasing Hormone Anterior Pituitary ACTH Adrenocorticotropic Hormone Adrenal Cortex Cortisol o Diurnal Variation in Cortisol Secretion Morning 68 am Increased Evening 46 pm Decreased o Protects against Stress o Cortisol Action T BS T Protein break down T Use of fatty acids instead of glucose Antiin ammatory effect Suppressed immune response Sex Hormones o Adrenal cortex produces small amounts of androgens in both males and females 0 Main source of androgen in females 0 In males exerts little effect on sexual function because testes produce most of the androgen Adrenal Cortex Disorders Hyperfunction Cushing s syndrome Hypofunction Primary Adrenal Insufficiency Addison s Disease NU 2 3 1 Pathophysiology GENETICS Outline H 0 l 01th Terminology DNA Chromosome Genes Gene ric Mu ra rion 0 Acquired Mu ra rions o In heri red Mu ra rions Classifica rion of Gene ric Disorders 0 Single Gene Disorders 0 Au rosomal Dominan r o Au rosomal Recessive o XLinked Recessive 0 Chromosomal Al rera rions o Al rera rions in S rruc rure o Al rera rions in Number 0 Mul rifac rorialInheri rance Disorders due ro Environmen ral Influence NU 2 3 1 Pathophysiology TERMINOLOGY Allele AlTernaTe forms of a gene one from each parenT ThaT occupy The same posiTion locus on paired chromosomes CongeniTal Disorder SomeTimes called a birTh defecT DefecTs ThaT are presenT aT birTh wheTher The resulT of geneTic or nongeneTic facTors eg drugs Taken during pregnancy GenoType o ComposiTion of genes aT a given locus KaroType o Orderly display of chromosomes arranged according To The lengTh and locaTion of cenTromere PhenoType o The expression of a genoType The ouTward physical appearance eg blue eyes NU 2 3 1 Pathophysiology DNA DEOXYRIBONUCLEIC ACID Contains genetic information that controls inheritance amp dayto day cell function Resembles a spiral staircase Double Helix o Handrails composed of Sugar Molecule Si Phosphate Molecule 0 Stairs composed of four nitrogenous bases Adenine Thymine Cytosine Guanine Complementary Base Paring o Bases pair up with each other Adenine binds withThymine Cytosine binds with Guanine 0 DNA molecule consists of approx 3 BILLION BASE PAIRS DNA Replication 0 During cell division two DNA strands separate 0 Each strand serves as a template for duplicating the sequence of bases 0 Based on complementary base pairing AT CG 0 Each new cell gets exact copy of the DNA present in the old cell DNA Genetic Code 0 Genetic code is written in groups of three letters triplet code or codon o The letters are the four bases A T C G When code gets transcribed from DNA to mRNA T Thymine is replaced with U Uracil 0 Each codon specifies a single amino acid which are the building blocks of PROTEIN 0 Protein play critical role in the body and do most of the work in cells Every cell in the body contains the SAME DNA 0 Liver cells contain the same genetic info as skin and skeletal muscle cells 0 Each cell type selectively uses only a portion of the info depending on the structure and function of the cell 0 This is what makes brain cells look and act differently than liver cells NU 2 3 1 Pathophysiology CHROMOSOMES F0 0 0 EA O 0000 CH 0 00000 CH O 0000 UND IN THE NUCLEUS OF EVERV CELL OF THE BODY Made up of tightly coiled DNA Structure of Chromosome J Centromere J Short Arm P Arm J Long Arm Q Arm CH HUMAN CELL CONTAINS 46 CHROMOSOMES Arranged in pairs 2 23 pairs One member of a pair comes from mom the other from dad Paired chromosomes are referred to as HOMOLOGOUS CHROMOSOMES 22 pairs are AUTOSOMES 1 pair are SEX CHROMOSOMES J Sex Chromosomes X and Y J Females XX J Males 2 XY J Mom can y contribute an X J Dad contributes either X or Y ROMOSOMES SOMATIC CELLS Somatic Cells 2 All body cells except for germ cells gametes 2 egg Si sperm All body cells contain 46 chromosomes Full complement DIPLOID NUMBER Human cells are subject to wear Si tear and do not last a lifetime Replacement of somatic cells involves MITOSIS Each new daughter cell receives an identical and full set of 46 chromosomes ROMOSOMES GERM CELLS Germ cells 2 gametes egg and sperm Contain 23 single chromosomes complement HAPLOID NUMBER Cell division MEIOSIS Meiosis is the process by which haploid cells are formed from diploid stem cells When sperm ovum unite produce zygote with 46 chromosomes NU 2 3 1 Pathophysiology GENES BASIC UNIT OF HEREDITY o A gene is a segmenT of DNA 0 Range in size from a few hundred To gt1 million base pairs 0 2500030000 genes EACH PERSON HAS TWO COPIES OF EACH GENE 0 One inheriTed from each parenT 0 Each gene occupies a cerTain locaTion locus on a chromosome 0 HerediTary TraiTs are conTrolled by pairs of genes locaTed in The same posiTion on paired chromosomes GENETIC MUTATIONS o PermanenT change in The DNA sequence ThaT makes up a gene Bases can be added deleTed or rearranged MuTaTions range in size from a single base To a large segmenT of a chromosome AlTers The geneTic message carried by a gene GeneTic muTaTions can eiTher be acquired or inheriTed OOOO ACQUIRED MUTATION o Occur in DNA of somaTic cells Are NOT TransmiTTed from parenT To offspring However They are imporTanT causes of cancer Tumors Caused by EnvironmenTal agenTs ThaT damage DNA AccidenTal Errors in DNA DuplicaTion OOO INHERITED MUTATIONS o MuTaTions presenT in germ cells Sperm Si Egg C ARE TransmiTTed from parenT To offspring NU 2 3 1 Pathophysiology CLASSIFICATION OF GENElTC DISORDERS 0 Single gene disorders 0 Chromosomal disorders 0 Multifactorial inheritance SINGLE GENE DISORDERS SGD o CAUSED BY A MUTATION IN A SINGLE GENE o Mutation may be present on ONE member of a pair of genes or BOTH members of a pair of genes Mutation may be on an on AUTOSOME or SEX CHROMOSOME Hereditary traits are controlled by pairs of genes located in the same position locus on paired chromosomes Clear pattern of inheritance Use Punnet square to predict the distribution of specific traits for each pattern Capital letters 2 Dominant Allele 0 Lower case letters 2 Recessive Allele O O O O O GENE PAIRS MAY 0 both be dominant 9 AA 0 both be recessive 9 aa or consist of one dominant and one recessive 9 Aa Identical Gene Pairs 9 HOMOZYGOUS Both dominant 2 AA Both recessive 2 aa Different Gene Pairs 9 HETEROZYGOUS One dominant one recessive Aa O O O o EXPRESSION OF A RECESSIVE TRAIT o Recessive gene is expressed ONLY in a homozygous state 9 need 2 copies aa 0 One copy 2 CARRIER o Carriers DO NOT express the trait o EXPRESSION OF A DOMINANT TRAIT 0 Dominant gene is expressed either Homozygous 9 AA Or Heterozygous 9 Aa NU 2 3 1 Pathophysiology SGD THREE PATTERNS OF INHERITANCE o Au rosomal Dominan r o Au rosomal Recessive o XLinked Recessive AUTOMSOMAL DOMINANT DISORDERS Usual Pa r rern of In heri rance Abnormal allele is DOMINANT T He rerozygo re T r ma ring wi rh normal person H T T l39 T l ff 139 T l l39f Resul r Al rerna re Pa r rern He rerozygo re T r ma ring wi rh a He rerozygo re T r of Inheri rance T r T TT T r l39 T l l39f Resul r General Principles of Au rosomal Dominan r In heri rance Those wi rh The disorder have an affec red paren r Ei rher sex can be affec red because if involves AUTOSOMES Trai r is expressed ei rher o Heferozygo re 1 copy of gene TT 0 Homozygo re 2 copies of gene TT Offspring L rh mu ran r gene will have disorder and may rransmi r To Their offspring Offspring wi rhou r mu ran r gene will NOT have disorder and canno r rransmi r To Their offspring Examples of Au rosomal Dominan r Disorders Achondroplasia Dwarfism Adul r Polycys ric Kidney Familial Hypercholes rerolemia Marfan39s Syndrome Neurofibroma rosis von Recklinghausen disease Hun ring ron39s Chorea NU 2 3 1 Pathophysiology AUTOSOMAL RECESSIVE DISORDERS Usual PaTTern of o Abnormal allele is RECESSIVE T InheriTance o BoTh parenTs have a single copy of The abnormal allele 0 BoTh parenTs are CARRIERS 0 Carry The gene buT do noT express iT T T T TT TT T TT TT RESULTS General Principles 0 AffecTed persons have 2 copies TTof The abnormal allele of AuTosomal Homozygous Recessive 0 Those who have 1 copy of The abnormal allele TT are CARRIERS Si InheriTance are noT affecTed o EiTher sex may be affecTed AuTosome Examples of o CysTic Fibrosis AuTosomal o PKU PhenylkeTonuria Recessive o Tay Sachs Disease Disorders 0 Albinism o Sickle Cell Anemia NU 2 3 1 Pathophysiology X LINKED RECESSIVE DISORDERS o Mu ra rion is on The Xchromosome o Inheri rance pa r rern is recessive o Abnormal X may be rransmi r red by mom or dad 0 Mom XX rransmi rs ro daugh rers XX or sons XY 0 Dad XY rransmi rs ro daugh rers XX Females wi rh o Carriers he rerozygous XX 2 1 copy of abnormal gene Abnormal X 0 Disease is NOT eXpressed o Mu ran r gene ma rched by normal gene 0 Normal gene quothidesquot The recessive gene 0 Carrier female XX rransmi rs abnormal X To daugh rers XX or sons xv Males wi rh o Hemizygous XY 1 copy of abnormal gene Abnormal X 0 Disease IS expressed o Abnormal gene has no coun rerpar r on Y chromosome 0 Affec red male rransmi rs defec rive X To all daugh rers XX Usual Pa r rern 0 Normal male XV ma ring wi rh female carrier XX of Inheri rance Mu ra rion is on Xchromosome o Inheri rance pa r rern is recessive X y x XX Xy X XX XV RESULTS Examples of o Fragile X Syndrome XLinked o Hemophilia Disorders 0 Duchenne Muscular Dys rrophy NU 2 3 1 Pathophysiology CHROMOSOMAL DISORDERS o AlTeraTions in Chromosome Number 0 AlTeraTions in Chromosome STrucTure ALTERATIONS IN CHROMOSOME NUMBER Aneuploidy Refers To an abnormal number of chromosomes Usually 45 or 47 May occur in eiTher auTosomes or sex chromosomes Causes of Anuploidy NondisjuncTion Failure of homologous chromosomes To separaTe during oogenesis or spermaTogenesis Gives rise To germ cells wiTh an even number of chromosomes 22 or 24 0 Normal gameTe 23 chromosomes haploid uniTes wiTh abnormal gameTe 23 22 45 chromosomes 23 24 47 chromosomes Types of Anuploidy o Trisomy Have Three chromosomes in a seT o Monosomy One chromosome in a pair 0 O AuTosomal Aneuploidy Down39s Syndrome Trisomy 21 o Trisomy 2 Three chromosomes in a seT o More common in women gt 40 possibly due To aging oocyTes o CharacTerisTics of Down39s Mild To moderaTe reTardaTion Small squarish head Upward slanTing eyes LowseT ears Hands are shorT and sTubby Single palmar crease simianquot crease xxxx Sex Chromosome Aneuploidy Turner39s Syndrome Monosomy of X o KaroType 45 XO o No homologous X or Y chromosome 0 AffecTs approx 1 of every 2500 live birThs o VariaTions in The syndrome wiTh various abnormaliTies o CharacTerisTics Female body configuraTion ShorT STaTure buT body proporTions are normal Ovaries are absenT imperfecT does noT mensTruaTe No 2quotd sex characTerisTics NU 2 3 1 Pathophysiology O O Klinfel rer39s Syndrome Polysomy of X Kar o rype 47 XXV Fea rur es usually become apparen r during puber fy Charac rer is rics J Tall s ra rur e Lower par r of body longer Than upper par f Sparse facialbody hair Enlarged breas rs gynecomas ria Tes res are small InferTHe Mildly impaired IQ NU 2 3 1 Pathophysiology ALTERATIONS IN CHROMOSOME STRUCTURE o Chromosome segment breaks off or is duplicated o The effects depend on the size and location of the structural change 0 Usually occurs in MEIOSIS germ cell 0 Can also occur during MITOSIS somatic cells 0 Risk Factors exposure to radiation chemicals viral infections Types of Structural Abnormalities Deletion 0 Piece of chromosome segment breaks off and gets deleted 0 The union of a normal gamete Si gamete that carries the deletion produces zygote that has one chromosome with the normal complement of genes and one with missing genes 0 Example Cri du chat syndrome French means cry of the cat 0 Caused by deletion of short arm of chromosome 5 0 Characteristics Distinctive cry microcephaly mental retardation and low birth weight Duplication 0 Piece of DNA is abnormally copied one or more times 0 Usually less serious consequences Inversion 0 Two breaks on a chromosome 0 Reinsertion of missing fragment at its original site but in inverted order 0 No loss or gain of genetic material 0 Inversion carriers are usually normal but offspring may be abnormal Translocation Reciprocal Translocation 0 Break in two nonpaired chromosomes 0 Exchange parts no genetic material is lost 0 Translocation carriers are usually normal but offspring may be abnormal Robertsonian Translocation o Chromosomes 14 Si 21 most often affected 0 Break in two non paired chromosomes near centromere center 0 Long arms fuse at centromere 0 Short arms fuse o Carriers of Robertsonian Translocation are normal their offspring however may have serious monosomies or trisomies NU 2 3 1 Pathophysiology MID MULTIFACTORIAL INHERITANCE DISORDERS o MID Many facTors mulTifacTorial are involved in causing birTh defecTs o Disorders are caused by The effecTs of mulTiple genes in combinaTion wiTh environmenTal facTors lifesTye o ExacT number of genes conTribuTing To MID is noT known 0 DOES NOT have clear paTTern of inheriTance like single gene disorders 0 MID Tend To cusTer in families 0 DefecTs usually involve same or similar defecTs 0 Example ParenTs of an offspring wiTh cefT lip have an increased risk of having anoTher chid wiTh cefT lip vs spina bifida o The greaTer The number of affecTed offspring The higher The recurrence risk Examples of MulTifacTorial InheriTance Disorders DefecTs PresenT aT o Spina Bifida BirTh o ClefT Lip Si PalaTe 0 Hip Dysplasia 0 Club FooT DefecTs may be 0 LifesTyleEnvironmenTal facTors play key role in MID in adulThood expressed during 0 Coronary HearT Disease aduT life 0 HyperTension 0 Cancer 0 ObesiTy o DiabeTes MeiTus Type 2 o PsychiaTric Disorders 0 Depression 0 Schizophrenia o Bipolar Disorder Topics NU 231 PATHOPHYSIOLOGY FLUID ELECTROLYTES amp ACID BASE BALANCE Revised 12010 0 Fluid amp Electrolytes Body Fluid Compartments ECFICF Electrolyte Concentration Osmotic Activity of a Solution 0 Isotonic o Hypertonic o Hypotonic Edema Sodium and Water Balance gt Alterations in Sodium amp Water Balance 0 Proportionate Changes in Na amp Water Balance 0 Disproportionate Changes in Na amp Water Balance Potassium Calcium 0 Acid Base Balance Handouts bring to class Arterial Blood Gas ABG Summary ABG Disorders Chart Steps in ABG Interpretation Examples of ABG Interpretation ABG Case Studies Body Fluid Compartments o ICF Intracellular Fluids 0 Fluids inside cell 0 28 Liters o 40 ofbody weight 0 ECF Extracellular Fluids 0 Fluids outside the cells 14 Liters 20 of body weight 0 Interstitial 10 Liters I Fluid between cells 0 Vascular 3 Liters has more protein than the interstitial compartment to keep uid inside vascular compartment I Fluid within blood vessels I Use this uid for lab tests eg electrolytes I Use the term Serum or Plasma in reference to lab values 0 Transcellular 1 Liter I Synovial GI CSF Pleural Pericardial Fluid ECF amp ICF ELECTROLYTE CONCENTRATION Electrolyte ECF ICF Interstitial amp Vascular Na 135 145 mEqL 10 14 mEqL K 35 50 mEqL 140 150 mEqL Cl 98 106 mEqL 3 4 mEqL HCO3 21 28 mEqL 7 10 mEqL Ca 85 105 mgdl lt 1 mEqL PO4 2545 mgdl 4 mEqkg 2030 nEdl 40 n kg OSMOTIC ACTIVITY OF A SOLUTION 0 Normal serum osmolality osmolarity 280295 mOsmkg of H20 determined by Na and it s anions o Osmosis Movement of uic from area of lesser to greater solute concentration Body cells Isotonic o ECF amp ICF has same osmolality exposed 10 o No concentration gradient different 0 No uid shift across cell membrane type 0f Hypertonic o ECF has greater osmolality than ICF SOlunonS 0 Concentration gradient 0 Fluid shifts from ICF to ECF Cells Shrink Hypotonic o ECF has lower osmolality than ICF 0 Concentration gradient 0 Fluid shifts from ECF to ICF Cells Swell 0 Types edema Causes of Edema Fluid shifts from vascular compartment to the interstitial compartment amp Due to Fluid accumulates in dependent areas Edema Read text T Capillary Hydrostatic Pressure 109 113 l Colloid Osmotic Pressure Membrane SODIUM 135 145mEqL VALUE IS ALWAYS THE ECF o ECF 135145 mEqL o ICF 10 l4mEqL SODIUM FUNCTION Water Balance Major ECF Cation Provides most of the osmotic activity in ECF Changes in Na are normally accompanied by proportionate changes in water volume Regulates AcidBase Balance Sodium combines with bicarbonate NaHCO3 Facilitates Impulse Na amp K transported across cell membrane Transmission in Causes depolarization of cell membrane MuscleNerve Fibers Creates action potential Generates nervemuscle activity SODIUM REGULATION Kidney Major regulator of Na Retains or Excretes Na Aldosterone Acts on kidney to promote Na H20 Reabsorption ANP Atrial Secreted by atrial tissue of the heart in response to increased BP Natriuretic Peptide Acts on kidney to promote Na H20 Excretion thereby lowering blood volume and BP SODIUM GAINS amp L DSSES Gains Diet Minimum reguirements 2 gramsday g 1 tsp Losses Kidney Urine GI Vomiting Diarrhea Skin Perspiration GISkin losses lt 10 of Na intake WATER WATER GAINS amp LOSSES Fluids Gained Fluids Lost 0 Gain 2500 cc FoodFluid 0 Lose 2500 cc Urine Stool Skin Lungs Obligatory Urine Output UO 300500 ml day 0 U0 needed to eliminate waste products WATER REGUI ATION Thirst Thirst center in hypothalamus Thirst stimulated when i blood volume Q T ECF osmolality ADH Synthesized in Hypothalamus stored in posterior pituitary Released in response to i in blood volume or T in ECF osmolality Antidiuretic Acts on kidneys to reabsorb water Hormone OR o T ADH i UO ADH acts on kidneys to T reabsorption of water Vasopressin o i ADH T UO ADH acts on kidneys to i reabsorption of water Two Types of ADH Disorders 0 Diabetes Insipidus has NOTHING to do with Diabetes MellitusiADHTUO o Syndrome of Inappropriate ADH Release TADHiUO ALTERATIONS IN SODIUM amp WATER BALANCE o Proportionate changes in Na amp Water Balance 0 Isotonic Fluid De cit Hypovolemia No changes in proportion of NA to H20 0 Isotonic Fluid Excess Hypervolemia No changes in proportion of NA to H20 o Disproportionate Changes in Na amp Water Balance 0 Hyponatremia o Hypematremia ISOTONIC FLUID VOLUME DEFICIT HYPOVOLEMIA o Losses are isotonic o Proportionate losses of Na amp Water 0 Contraction of ECF Interstitial amp Vascular o No change in osmolality o No Fluid Shift CAUSES G1 0 Vomiting Na Water K HCL Diarrhea Na Water K Bicarbonate MEDS o Diuretics LasiX 9 T Urine Output Na Water K Osmotic Diuresis 0 Diabetes Mellitus Diuresis T Urine Production Polyuria DM T Blood Sugar 9 T Serum Osmolality Pulls water from ICF to ECF 9 Dilutes Glucose Polyuria Excrete Na Water amp Glucose Decreased o Addison s Disease or Adrenal Insuf ciency Aldosterone o Excrete NaWater Retain K SIGNS amp General 0 Thirst SYMPTOMS o WeiLht Loss Skin 0 Dry Mucous Membranes Poor Skin Turgor Poor ca lary re ll time prolon ed re ll time CV o i BP Weak rapid pulse Postural Orthostatic Hypotension position changes going from supine to sitting position pass out when they get up Renal o Decreased UO except in osmotic diuresis ISOTONIC FLUID VOLUME EXCESS HYPERVOLEMIA o Losses are isotonic o Proportionate gain in sodium amp water 0 Expansion of ECF interstitial amp vascular o No change in osmolality o No Fluid Shift CAUSES T Sodium amp o Congestive Heart Failure CHF inadequate pump Water Retention Decreased renal perfusion increased Na and H20 Renal Failure Decreased UO Liver Failure Increased Aldosterone Cushing s Disease Increased Cortisol SIGNS amp General 0 WeiLht gain SYMPTOMS Skin 0 Edema CV 0 Increased BP Full bounding pulse JVD Guglar venous distention Respiratory 0 Pulmonary Edema SOB Dyspnea Crackles Cough Renal 0 Increased UO DIDPROPORTIONATE CHANGES IN SODIUM amp WATER NORMAL Na135 145n 1EqL o Hyponatremia o Hypematremia HYPONATREMIA lt 135 mEqL o Caused by either a Sodium Loss or Water Gain 0 Most often due to Water Gain Dilutional Hyponatremia o ECF Hypotonic i Serum Osmolality o Fluid Shift from ECF to ICF Cells Swell CAUSES Water Gain Psychogenic Polydipsia Syndrome of Inappropriate ADH Secretion T ADH i UO Using tap water to replace Na losses during heavy exercise or vomiting amp diarrhea SIGNS amp SYMPTOMS Abdominal CrampsPain A N V D anorexia nausea vomiting diarrhea Renal Increased UO except in SIADH i UO MS Muscle cramps and weakness Muscle Twitching i DTR CNS Brain and NS most seriously affected due to cells swelling Lethargy HA Confusion Disorientation Seizures Coma HYPERNATREMIA gt 145 MEQL 0 May be caused by Sodium Gain or Water Loss 0 Most often due to Water Loss Hemoconcentration o ECF Hypertonic T Serum osmolality o Fluid Shift ICI to ECF cells shrink CAUSES Sodium 0 Rapid ingestion or infusion of Na Gain 0 Administration of NaHCO3 during CPR Water Loss 0 Decreased Water Intake 0 Defect in Thirst Sensation o Inability to obtain or drink water Water Loss 0 Diabetes Insipidus i ADH T UO SIGNS amp General 0 Thirst SYMPTOMS Skin 0 Dry Mucous Membranes Poor Skin Turgor CV o Decreased BP Tachycardia Weak Pulse Renal o Oliguria except in Diabetes Insipidus CNS 0 Headache Restless Agitated Confusion Disorientation i DTR Seizures Coma POTASSIUM 35 50 MEQL 0 Major ICF Cation Provides most of osmotic activity in ICF o ICF 140 150 mEqL o ECF35 50 mEqL POTASSIUM GAINS amp LOSSES Gains Diet 50100 mEq day Found in variety of fruits amp vegies o Bananas oranges peaches apricots cantaloupe o Broccoli potatoes sweet potatoes Losses Kidneys Main source of K loss excrete 8090 of K in urine GI amp Skin Approx 1020 lost in stool amp sweat POSTASSIUM REGULATION Kidneys RetainsExcretes K Aldosterone T Aldosterone 9 T Na amp Water i K i Aldosterone 9 i Na amp Water T K Shift of K Exchange between H amp K between Factors that affect ICFECF Distribution of K ECF amp ICF o AcidBase Balance 0 Insulin o Epinephrine Repeated muscle contraction o POTASSIUM FUNCTION Facilitates impulse transmission in Nerve amp Muscle Tissue o Affects cardiac skeletal and smooth muscles 0 Na amp K transported across cell membrane 9 Creates action potential 0 Generates musclenerve activity i K i NerveMuscle Activity Cells become hyperpolarized 9 Moves RMP further away from threshold Takes GREATER stimulus to reach threshold 9 More difficult to achieve action potential T K o T NerveMuscle Activity Cells become hypopolarized 9 Moves RMP closer to threshold Takes LESS stimulus to reach threshold 9 Less difficult to achieve action potential Although initial effects may T musclenerve activity persistent depolarization inactivates sodium channels and become refractory increasing the threshold to generate an action potential Over the long haul produces decrease in nervemuscle activity HYPOKALEMIA lt 35 MEQL CAUSES i Intake 0 Low K Diet Anorexia Fasting o NPOn0thing by mouth Fail to replace losses especially after surgery Meds o Diuretics cause an increase in urine output Lasix Thiazide 9 Excrete Na H20 amp K T Aldosterone o Hyperaldosteronism Retain Na amp Water Excrete K T Cortisol Cushing s Syndrome Retain Na amp Water Excrete K GI Losses Vomiting Diarrhea Laxative abuse Excrete Na H20 amp K Compensatory Response to Fluid LossT Aldosterone Shift of K from ECF to ICF Exchange between K amp H o H ECF o K ICF Factors that Shift K to ICF o Alkalosis i H 0 Excess Insulin o Epinephrine SIGNS amp SYMPTOMS Bradycardia Weak irregular pulse Postural Orthostatic Hypotension ECG Changes Arrhythmias Cardiac Arrest Neuro muscular Fatigue Muscle Weakness Muscle Cramps amp tenderness esp with exercise Paresthesia PanLlLsis severe hypokalemia CNS Confusion Depression GI i Peristalsis i Bowel Sounds Abdominal Distention A N V anorexia nausea vomiting Constipation Renal Interferes with the ability to concentrate urine Polyuria i Specific Gravity not very concentrated dilute Thirst HYPERKA LEMIA gt 50 ME QL CAUSES Excess Intake Dietary excess uncommon as long as kidneys function Excess IV 39 too much K in an IV or too fast 1 Renal Failure Most common cause Kidneys unable to remove K from body i Aldosterone Addison s Disease Excrete Na amp Water Retain K Medications Potassium Sparing Diuretics ACE Inhibitors Angiotensin Converting Enzyme Shift of K from ICF to ECF Exchange between H amp K o K ECF o H ICF Factors that shift K into ECF 0 Metabolic Acidosis T H Tissue injury that causes cell death crushing injuries or burns releases K into ECF Strenuous exercise causes K to be released into ECF O O SS CV ECG Changes Arrhythmias Cardiac Arrest with severe hyperkalemia GI T Peristalsis T Bowel Sounds Abdominal Cramps N V nausea vomiting Diarrhea Neuromuscular Paresthesia lSt symptoms Muscle Cramps Spasm Muscle weakness Paralysis severe hyperkalemia CALCIUM o ECF 85 105 mgdl ICF lt 1 mEqL o 99 found in bones amp teeth 0 1 found in ICF amp ECF ICF 07 ECF 0203 CALCIUM GAINS amp LOSSES Gains Milk amp Milk Products Need 1000 1500 mgday If diet insufficient bones act as reservoir Calcium should be paired with Vitamin D Losses Kidneys Urine GI Stool O ECF CALCIUM EXISTS IN THREE FORMS Ionized o FreeIonized Calcium Calcium 0 Carries out physiologic function 50 0 Plays essential role in nerve amp muscle activity 0 Essential for contraction in skeletal cardiac amp smooth muscle 0 Plays role in blood clotting process ProteinBound 0 Calcium bound to plasma protein primarily albumin 40 Complexed 0 Calcium bound to anions citrate phosphate sulfate carbonate 10 CALCIUM REGULATION PTH o Increases ECF Ca level Parathyroid o Releases Ca from bone Hormone o Increases kidney reabsorption of Ca o Increases GI small intestine absorption of Ca under the in uence of Vitamin D Vitamin D o Increases Ca level 0 Classified as vitamin but functions like hormone 0 Liver amp Kidney metabolize precursor Vitamin D to active form calcitriol 0 Active form of Vitamin D PTH work together to T GI absorption of Ca Calcitonin o Decreases Ca Level 0 Inhibits bone resorption of Ca 0 Only hormone that decreases Ca level Phosphate o Inverse relationship between Ca amp P04 one goes down the other goes up Serum pH 0 Inverse relationship between Ca amp pH acidodicmore calcium One is up the other is down HYPOCALCEMIA lt 85 I lGDL CAUSES i Dietary Intake 0 Exerts its effect on bone stores rather than on ECF calcium levels i PTH o Hypoparathyroidism Most common cause 0 Usually occurs after thyroidectomy due to thyroid cancer i Magnesium Inhibits PTH Release 0 i Magnesium results from intestinal malabsorption or i dietary intake Renal Failure o Decreased production of activated Vitamin D must be paired with Ca so Ca also decreases Renal failure 0 Excrete Ca and retain P04 0 Inverse rs between Ca amp P04 Alkalosis o Inverse rs between pH amp Ca T pH 0 Alkalosis T pH i Ionized Ca o T binding of Ca to protein SS CV o i Cardiac Output Hypotension Arrhythmias ECG Changes Skeletal o Osteoporosis loss of bone mass if the Ca is being pulled from the bones Pathologic Fractures bones can fracture while only walking or standing bones are very fragile Neuro o Paresthesia tingling around mouth hands feet muscular 0 Muscle Twitching Muscle SpasmsCramps Hyperactive DTR s deep tendon re exes Tetany muscle spasms of muscles of face hands amp feet Tests used to Assess Tetany o Chvostek vos teks Sign 0 Tap facial nerve in front of ear 0 twitching of lips nose amp facial muscles 0 Trousseau Sign 0 Apply BP cuff to upper arm amp in ate 20 mm Hg above systolic pressure o Carpopedal spasm spasm of hand amp wrist NU 231 Pathophysiology GI Disorders Topics 1 GERD Gastroesophageal Re ux Disease 2 PUD Peptic Ulcer Disease Duodenal Ulcer Gastric Ulcer Stress Ulcer Curling s Ulcer Cushing s Ulcer Zollinger Ellison Syndrome 3 IBD In ammatory Bowel Disease Crohn s Disease Ulcerative Colitis 4 Diverticular Disease 5 Colorectal Cancer 6 Appendicitis GASTROES OPHAG EAL REFLUX DISEASE GERD De nition 0 Refers to backward movement re ux of gastric contents into the esophagus through the lower 1 39 39 sphincter LES which leads to heartburn Etiology 0 Caused by weak or incompetent LES that fails to close tightly after swallowing food PathophySiOIOgy 0 LES Dysfunction may be due to Transient Relaxation of LES Most Common Increased intraabdominal pressure Permanent Relaxation of LES Hiatal Hernia 0 Transient Relaxation of LES Common after meals Certain foods beverages can increase relaxation of LES Foods High Fat Fruit Chocolate Peppermint TomatoBased Foods Onions Garlic Beverages Coffee Alcohol Citrus drinks Smoking can also cause relaxation 0 Increased intraabdominal pressure Obesity Pregnancy Supine position or bending forward 0 Hiatal Hernia Stomach protrudes thru the diaphragm into the thorax Pts with moderate to severe re ux often have hiatal hernia GERD GASTROESDPHAGEAL REFLUX DISEASE 55 0 Heartburn caused by regurgitation of gastric contents Burning sensation in epigastric region Sour Taste Occurs 3060 min after eating esp large fatty meal Worse in supine position or bending forward Often occurs at night Epigastric discomfort may be confused with angina because of the location of the pain 0 Asthma Type Symptoms Cough Wheezing 0 Chronic Sore Throat Complications 0 Erosive Re ux Esophagitis Acidity of stomach irritates amp in ames the esophagus 0 Barrett s Esophagus Occurs if re ux is severe and untreated Results in 39 increased risk of 39 39 cancer Counseling Avoid foods that cause sx to prevent or decrease Eat small frequent meals symptoms Decrease fatty meals Avoid eating at HS Avoid supine position x 3 hours after meal Elevate head of the bed HOB on blocks Stop smoking Reduce alcohol intake Weight Loss PUD PEPTIC U JCER DISEASE De nition Erosion ulceration in the lining of the stomach or duodenum Two Types of PUD DU Duodenal Ulcers 5X more common than gastric ulcers GU Gastric Ulcers Other Types of Ulcers Stress Ulcers Curling s Ulcer occurs with severe physiologic stress Burns Trauma Sepsis Major Surgical Procedures Caused by ischemia tissue acidosis amp bile salts entering stomach in critically ill patients Cushing s Ulcer occurs in pts with head injury operations or tumors Caused by hypersecretion of gastric acid resulting from stimulation of vagal nuclei by increased intracranial pressure Zollinger Ellison Syndrome o Rare condition caused by gastrinsecreting tumor Gastrinoma Most commonly located in pancreas Most are malignant Gastric Mucosal o Protects against corrosive action of stomach acids Hydrochloric Acid HCl and Barrier GMB Pepsin 0 Several mechanisms contribute to the protection of the gastric mucosa and are collectively referred to as the GASTRIC MUCOSAL BARRIER o Gastric Mucosa protected by Epithelial Cells EC impermeable to acids because EC connected by tight cellular junctions EC covered by impermeable hydrophobic lipid layer EC secrete thick layer of alkaline mucus Prostaglandins chemical messenger exert their effect by Improved blood ow Increased bicarb ion secretion Increased mucus production PathophyS o PUD can affect one or all layers of stomach or duodenum Layers include Mucosa Submucosa Muscle layer oblique circular longitudinal Serosa Loss of mucosal layer exposes the area to gastricjuices HCl amp Pepsin PUD PEPTIC U JCER DISEASE Etiology LICOBACTER PYLORI HE 0 Most common cause of PUD First identi ed in 1982 by two Australian researchers Spiralshaped gram rod Mode of Transmission FecalOral Route 0 Ingest foodwater contaminated with feces of infected individual Causes ulcers by producing enzymes and toxins that increase permeability of mucosal layer which allows acids to penetrate GMB US Approx 50 of adults 3 60 YO carry H Pylori but only 1020 who harbor pathogen develop ulcers Unclear why H Pylori doesn t cause ulcer in every infected person Complication Chronic Gastritis Gastric Cancer 0 90 of pts with gastric cancer are seropositive for HP NSAIDs NON STEROIDAL ANTI INFLAMMATORY DRUGS o 2quotd most common cause of PUD o ASA Ibuprofen Advil Motrin Naproxen Aleve Anaprox o Inhibits prostaglandin synthesis 0 Damages gastric mucosal barrier so that acids able to diffuse across the lipid layer DUODENAL ULCER STRIC ULCER Cause 0 95 caused by H Pylori 75 infected with HP 0 25 caused by NSAIDs 1020 caused by NSAIDS Peak Age 0 3555 5570 Clinical Course 0 Relapses amp remissions Relapses and remissions Location of the Ulcer o 90 located in first portion of duodenum Occurs most o en in lesser curvature of the stomach Classic SX Intermittent heartburn Burning gnawing sensation in epigastric region Intermittent heartburn Burning gnawing sensation in epigastric region Timing of Pain Occurs when stomach is empty 13 hours after a meal 0 12 am Varies Occurs when stomach is empty OR when stomach is full Pain Relief Relieved by food amp antacids May be relieved by foodantacids OR food may worsen the pain PEPTIC ULCER PUD Complications DISEASE PUD GI Bleed AcidUlcer ruptures blood vessel Onset may be sudden and without warning OR onset may be insidious producing only occult blood in stool Weak Dizzy Fatigue Black Tarry Stools Melena Hematemesis coffee ground emesis Perforation with Ulcer erodes through all layers of the stomach or duodenum PeritonitiS 0 GI contents enter peritoneum causing PERITONITIS o S S Sudden severe sha1p pain Usually pt lies very still movement aggravates pain Rigid boardlike abdomen due to muscle guarding Rebound Tenderness Absent Bowel Sounds Fever Increased WBC Obstruction o Caused by edema spasm scar tissue Blocks passage offood SS Crampy Pain Abdominal Distension A N V Highpitched rumbling BS INFLAMMATORY BOWEL DISEASE IBDD De nition 0 Includes in ammatory intestinal disorders 0 CD Crohn s Disease 0 UC Ulcerative Colitis Etiology 0 Unknown 0 Autoimmunity o Genetics may predispose to autoimmunity 0 Environmental triggering factor viruses or bacteria dietary antigen 0 Stress DOES NOT cause IBD although mav 39 symptoms Risk Factors 0 Age 0 May occur at any age 0 Peak age 2030 s 0 Race Ethnicity o Caucasians amp Ashkenazi Jewish Descent 0 Family HX 0 Increased risk if you have a parent or sibling 0 Cigarette Smoking 0 Smokers are 3X more likely to develop Crohn s 0 May lead to more severe disease 0 Where you live 0 Crohn s occurs more often among people living in cities and industrial nations 0 People living in Northern climate a so have higher risk CROHN S DISEASE ULCERATIVE COLITIS Age 0 2030 s 0 Peak Age 2025 0 May present before age 15 YO 0 Bimodal 1540 YO 5560 YO Sex 0 FgtM o F gt M Clinical Course 0 Varies o Varies 0 Relapses and Remissions 0 Relapses and Remissions 0 Slowly pro ressive amp relentless Type of o Granulomatous Lesions 0 Ulcerative and Exudative LeSionS 0 Lesions are sharply 39 39 Appearance 0 Cobblestone Appearance 0 Produces pinpoint mucosal hemorrhages which in time suppurate and develop into crypt abscesses 0 Crypt abscesses may become necrotic and ulcerate DiStI ibUtiOH 0 Can affect any area from mouth to anus 0 Limited to the COLON 0 35 Distal Ileum 0 Always begins in the rectum left side and o 35 Proxima1 C010n eXtends proximally upwards o 20 C010n A101 0 May involve rectum alone rectum amp sigmoid or 0 5 Small Intestine alone entire 0010 PamOIi S o 5 C 39 39 39 EXtent 0f 0 Produces skip lesions 0 In ammatory process is continuous InVOIVemem 0 Normal bowel interspersed between lesions CROHN S DISEASE ULCERATIVE COLITIS Level of 0 May affect ALL layers of intestine from o Affects mucosal and submucosal layer Involvement mucosa to serosa although mostly mucosal 0 Although submucosal layer affected to the greatest extent 3 S o Varies depending on severity o LLQ Colicky Abdominal Pain 0 RLQ Colicky Abdominal Pain 0 Bloody Mucopurulent Diarrhea o Nonbloody diarrhea 0 Frequency varies according to 0 Low Grade Fever severity of disease 0 Malaise 0 Fatigue and weakness 0 Anorexia amp Wt Loss 39 AHOTeXia o Nutritional De ciencies 0 Fecal incontinence o F amp E Imbalances 0 Children may present w growth retardation Complications o Colon Cancer relatively uncommon o Colon Cancer Relatively Common 0 Fistula Formation 0 Those with pancolitis for 10 yrs or more 0 Abscess Formation are 2030x greater risk than general 0 Perianal Ulcers POPUIation Toxic Megacolon colon swells requires immediate treatment DIVERT ICUL Statistics AR DISEASE Most common in Western Society Affects approx 10 of population older than 40 YO Affects about 50 ofthose older than 60 YO De nition Intestinal lining balloons out through weak area of the intestinal wall Produces saclike outpouching of the intestinal wall Etiology Age Lack of Dietary Fiber Lack of Physical Activity Poor Bowel Habits Neglecting urge to defecate Pathophys Weak areas in the intestinal wall T intracolonic pressure causes mucosal and submucosal layers to herniate push outward through the muscularis layer Produces saclike protrusions Can occur anywhere however most occur in descending amp sigmoid colon Two Clinical Forms Diverticulosis Diverticulitis Diverticulosis Asymptomatic OR Mild Symptoms Usually found incidentally gxray Diverticulitis Complication of Diverticulosis In ammation and infection caused by stool undigested food amp bacteria trapped in saclike hemiations Fever LLQ Abdominal Pain Severity depends on extent of the infection Pain is a steady colickycrampy type pain Worse after meals relieved by BM Other sx N V constnamption or loose stools T WBC Prevention Increase Fiber Intake Fruits Vegies Whole Grains Beans Promotes regular defecation T colonic contents and colon diameter thereby i intracolonic pressure Increase uid intake 8 cupsday Bulk forming laxatives Metamucil o COLORECT AL CANCER Statistics 0 3rd most common cancer site M amp F 0 3rd most common cause of cancer death M amp F 0 Death rates have been dropping for the past 15 years De nition 0 Cancer that develops in the colon or rectum o Collectively known as colorectal cancer Patho 95 are Adenocarcinomas PhySiOIOgy o Occurs in the glandular cells that line the inside layer of the wall of the colon and rectum 0 Slow growing has long preinvasive period Etiology 0 Unknown 0 Most likely a multistep process All cancer begins with DNA mutation Mutations occur in oncogenes turn on cell division OR tumor suppressor genes turn off cell division Leads to uncontrolled growth amp proliferation of abnormal cells 0 Mutation may be inherited or acquired Acquired mutations most likely caused by exposure to environmental carcinogens Abou 510 of colorectal cancers are caused by inherited gene mutation Inherited form of colon cancer FAP Familial Adenomatous Polyposis Accounts for 1 of all colorectal cancers Mutation is in the APC gene APC gene normally is responsible for slowing growth of cells However for those who inherit the abnormal APC gene the brake on cell growth is turned off Develop hundreds of polyps in colon amp rectum By 40 almost all with this disorder will have developed cancer HNPCC Hereditagy Nonpolyposis Colon Cancer Accounts for 34 of all colorectal cancers Also have polyps but only a few Mutation is in DNA repair gene When DNA replicates itself DNA repair gene normally acts as proof reader or spell checker to make sure DNA was copied correctly Mutation in DNA repair gene allows errors to go uncorrected These errors will sometimes affect growthregulating genes COLORECT AL CANCER Risk Factors Age 0 90 are dX after 50 YO Ethnicity c European Jews have highest rate of any ethnic group Race 0 African Americans have highest rate of all racial groups Personal HX of o If you have had colorectal cancer even though completely removed Colorectal you are more likely to develop new cancers in other areas of the colon Cancer and rectum Personal HX of o IBD causes chronic in ammation of the colon IBD o Leads to Dysplasia Abnormal cells that may progress to cancer esp UC Diet 0 Increased fat red meat processed meat 0 Low ber intake research mixed Frying grilling cooking meat at high temp creates chemicals that increase risk Lifestyle Factors 0 Smoking 0 T Alcohol 0 Physical inactivity o Obesity Diabetes 0 People with DM have a 3040 increase risk of colorectal cancer Mellitus Type 2 o Tend to have a higher death rate after diagnosis Adenomatous o Growths which develop in colon Polyps 0 Most are benign 0 However polyps gt 1 cm have greater cancer risk 3 S o Asymptomatic for years before sx develop usually slow growing cancer 0 Rectal bleeding is an early sx o A change in bowel habits such as diarrhea or constipation o Pencilthin stools that lasts for more than a few days 0 A sense of urgency to have a BM 0 A feeling that bowel doesn t empty completely 0 Cramping or steady abdominal pain 0 Weakness and fatigle usually 2quotd to iron deficiency anemia due to bleeding ACS 0 Screen men amp women 3 50 YO Screening 0 Start screening earlier if strong family history Guidelines 0 Screening Methods for Early Fecal Occult Blood Test FOB Q Year Detection Sigmoidoscopy every 5 years Colonoscopy every 10 years J J Colorectal 0 Once cancer dX need to determine the extent or STAGE of disease Cancer 0 Stage 0 CIS Carcinoma in situ Stages 0 Stage 1 Has not spread beyond colon wall Stage 2 Has grown into or thru colon wall Stage 3 Has invaded nearby lymph nodes Stage 4 Metastatic spread NU 231 PATHOPHYSIOLOGY PERIPHERAL VASCULAR DISORDERS TOPICS 0 Lab Test Lipid Pro le 0 Hypertension 0 Peripheral Arterial Disease PAD o Buerger s Disease 0 Raynaud s o Raynaud s Disease primary 0 Raynaud s Phenomenon secondary o Aneurysms o Abdominal Aortic Aneurysm AAA 0 Thoracic Aortic Aneurysm TAA o Cerebral Berry Aneurysm o Aortic Dissection o Varicose Veins o Venous Thrombosis o Super cial Thrombophlebitis 0 Deep Venous Thrombosis DVT 0 Chronic Venous Insuf ciency CV I LAB TEST LIPID PROFILE CORONARY RISK PROFILE 0 Adults 2 20 YO need a fasting 9 12 hours lipid pro le Q 5 years 0 Lipid Pro le includes Total Cholesterol HDL LDL Trigly eride Total Cholesterol 0 lt 200 Desirable 0 200 239 Borderline High 0 Z 240 High LDL Cholesterol 0 lt 100 Desirable o Sticks to arterial walls 0 100 129 Near Optimal 0 130 159 Borderline High 0 160 189 High 0 Z 190 Very high 0 Persons with ven high risk factors lt 70 HDL C Males Females 0 Low Level lt 40 mg d1 lt 50 13 d1 0 Average Level 4050 5059 0 High Level 2 60 Z 60 Triglyceride o lt 150 Desirable 0 150 199 Borderline High 0 200 499 High 0 Z 500 Very HYPERTENS ION HTN o Is a persistent elevation in systolic and diastolic pressure 3 14090 0 Called Silent Killer Usually NO symptoms until blood pressure BP reaches advanced stage 0 BP is the measurement of force applied to arterial wall 0 Systolic BP SBP is the pressure exerted on the arterial wall during systolecardiac contraction o Diastolic BP DBP is the pressure exerted on the arterial wall during diastolecardiac relaxation PHYSIOLOGY OF BP 0 BP is determined by the amount of blood your heart pumps and the amount of resistance to blood ow in your arteries The more blood your heart pumps and the narrower constricted your arteries the higher BP 0 BP C0 X PVR Any factor producing an alteration in CO cardiac output or PVR peripheral vascular resistance or both will affect BP PVR o Determined by blood vessel diameter 0 Constricted vessels T BP 0 Dilated vessels lBP CO 0 CO is the amount ofblood ejected by the heart in 1 minute 0 Average 4 8 liters minute depends on body size amp metabolic need 0 CO determined by HR amp Stroke Volume Heart 0 Determines how often ventricles contract amp eject blood Rate 0 Sympathetic Activity THR o Parasympathetic Activity lHR Stroke 0 Amount of blood ejected by heart with each beat V0111II1e 0 Approximately 60100 ml 0 Depends on Preload Afterload amp Contractility PRELOAD 0 As ventricles ll with blood during diastole it exerts stretching force on myocardial bers The greater the volume the greater the stretch the greater the force of contraction Frank Starling Law Left Ventricular End Diastolic Pressure LVEDP Greatest stretch on cardiac muscle bers is at the end of diastole 0 Main source of preload on riLht side of heart venous return AF TERLOAD 0 Force pressure the heart must generate to move blood out of the ventricles and into the aorta o The resistance against which the left ventricle must eject its volume of blood during contraction 0 Main source of afterload on left side of heart HTN amp Aortic Stenosis CARDIAC CONTRACTILITY Refers to the ability of the heart to change its force of contraction Various factors can increase or decrease the force of contraction Inotropic Effect Inotropic Effect EjectiOIl o Represents the of diastolic volume that is ejected from the heart ventricle during systole Fractlon o Normal EF 55 70 0 Ventricles never eject 100 HYPERTENSION Short Term o Corrects temporary imbalances Regl anon Of BP 0 Occurs over minutes and hours and involves SNS o Prepares the body to cope With stress Fight or Flight 0 Secretion of Catecholamines Epinephrine amp Norepinephrine o Increases BP HR Cardiac Contractility 0 Va soconstricts blood vessels PNS o Decreases BP HR Cardiac Contractility Baroreceptors 0 Located in aortic arch and atria of heart 0 Allow physiologic adjustment to changes in BP 0 Example moving from supine to upright position Chemoreceptors 0 Located in carotid arteries amp aorta Sensitive to changes in PC02 o Signals to respiratory center in brain to either increasedecrease ADHVaSOPreSSin o Regulates water 0 Released in response to Decreased BP Decreased Blood Volume or Increased Serum 0 mnlalitv of body ui Long TQFIH o Regulates BP on daily weekly or monthly basis Regl anon Of BP 0 Regulates BP through Renin Angiotensin Aldosterone System RAA KIDNEY o RAA activated With l BP l blood volume Types Of BP 0 Primary Essential HTN 0 Secondary HTN o HTN in Special Populations o Elderly 0 Kids 0 Pregnant Women PRIMARY ESSENTIAL HTN 0 Chronic elevation in BP 3 14090 0 Constitutes about 90 95 of cases o No identi able cause 0 Likely due to genetic r quot ili amp lifestyle factors multifactorial pattern of inheritance Risk Factors 0 NonModi able Risk Factors 0 Age 0 Gender MgtF 0 Race African Americans gt Caucasians African Americans have much higher death rate from HTN 0 Family History multifactoral genetics and lifestyle factors Modi able Risk Factors 0 Obesity The more you weigh the more blood you need to supply 02 amp nutrients to tissue As volume increases the pressure in arteries also increases 0 Sedentary Life Style People who are inactive have higher heart rates With higher HR heart must work harder with each contraction and the stronger the force on arteries 0 Tobacco Use Nicotine vasoconstricts which temporarily T BP Chemicals in cigarettes damage lining of arteries making it more susceptible to the development of atherosclerosis 0 Alcohol Heavy drinking can damage heart 3 2 3 drinks day can temporarily raise BP by increasing HR Affects systolic pressure more than diastolic pressure 0 T Salt Intake Increases vascular volume by increasing uid retention 0 l Potassium K helps balance the amount of Na in cells Iftoo little K may too much Na S S Usually asymptomatic Sustained HTN causes wear and tear on blood vessels and leads to Target Organ Damage Target organs incl de Brain 0 Stroke 0 TIA transient ischemic attack Heart 0 Left ventricular hypertrophy LVH o Angina 0 MI 0 HF Eyes 0 L r hv Kidneys 0 Renal Failure Lower Extremities 0 Peripheral Arterial Disease Diagnosing Method for taking BP HTN 0 Quiet room 0 No eating smoking exercise or caffeine 30 min prior to taking BP 0 Use correct BP cuff size 0 Position Sitting or supine 0 Arm at heart level with palm up 0 Choose extremity Wo IV injury or tight clothing 0 Con rm elevated rea ing in other arm but wait 5 minutes before taking it Joint National Category Systolic Diastolic Commission J NC mm Hg mm Hg V11 2003 Normal lt 120 lt 80 BP Classi cation for Adults 2 18 Pre Hypertenslon 120 139 80 89 Hypertension Stage 1 140 159 90 99 Hypertension Stage 2 Z 160 3 100 Health Promotion Lifestyle Modi cation Disease Prevention Exercise Maintain normal BMI Body Mass Index 185 249 Stop Smoking Manage Stress Eat Healthy Diet 0 FruitsVegiesFiber 0 Limit Sodium to 2400 mgday for healthy person 0 Limit saturated fats meat dairy eggs 0 Moderate alcohol consumption SECONDARY HTN 0 BP elevation from an identi able cause 0 Cnnsttntes about 5 10 of cases Causes of Kidney Disease Renal Failure RF 2nd HTN Glomerulonephritis Renal Artery Stenosis Coarctation of the Aorta Narrowing of aorta Decreases blood ow to LE and kidneys o UE T BP 0 LE l BP Hyperthymidism Hypermetabolic state THR amp Force of Contraction Primary Aldosteronism T A t T Na Water 39 T K Cushing s Syndrome T Glucocorticoid Cortisol TNa H20 Retentinn39 T K Pheochromoc oma Tumor of adrenal medulla secretes epinorepi Sleep Apnea Upper airway occlusion 2nd to obesity Hypoxia Meds Oral Contraceptives NSAIDS Steroids Illegal Drugs Cocaine A I Malignant HTN Accelerated and potentially fatal form of HTN DBP 3120 mm Hg Occurs in small of persons with 2nd HTN Occurs in younger persons especially African Americans women with HTN of Pregnancy and persons with kidney disease HTN IN Sl ECIAL POPULATIONS Elderly 0 Isolated Systolic Hypertension o Systolic BP Z 140 o Diastolic BP lt 90 o tiffrigid aorta and peripheral arteries HTN in Infants amp 0 Mostly due to 2nd HTN Children Children 0 75 80 of cases caused by kidney abnormalities 0 Chronic Pyelonephritis o Glomerulonephritis 0 Renal Artery Stenosis o C 39 of Aorta J Most often due to obesity HTN in o Occurs in 5 10 of pregnancies Pregnancy 0 2nd leading cause of maternal death 0 Risk Factors 0 First pregnancy 0 lt 18 or gt 35 YO 0 Multiple fetuses o Obesity 0 DM 1 or 2 o Co existing renal disease 0 More common in African American women PERIPHERAL ARTERIAL DISEASE PAD Narrowing of arteries in lower extremities LE caused by atherosclerosis Leads to inadequate oxygenation of tissues Most common arteries Femoral and Popliteal Arteries Other Names 0 Arterial Insuf ciency o Atherosclerotic Peripheral Arterial Disease 0 Poor Circulation Statistics 10 12 million persons in US Affects older age group 60 70 s F Risk Factors 0 Age 0 Gender MgtF except after menopause 0 Family History M gt Non Modi able Risk Factors Cigarette Smoking most signi cant risk factor increases risk 4 5x higher Diseases 0 Diabetes Mellitus o Hyperlipidemia o Coronary Heart Disease 0 Hypertension SS Sx occur gradually Z 50 narrowing of blood vessel Classic Sx Intermittent Claudication SignsSymptoms 0 Pain in Calf Thigh or Buttock o Described as Muscle Cramp or Tightening o Accompanied by numbness tingling sensation Provoked by Activity Exercise Relieved by Rest Skin Temp Cool to touch Skin Color PaleWhite if extremity elevated above heart level Pulses Dependent Rubor if extremity in dangling position Weak or absent pulses distal to the occlusion o DPDorsalis Pedis Pulse 0 PTPosterior Tibial Pulse Trophic Changes Skin thin shiny smooth Hair absent Toenails thickyellow Ulcers Occur in areas of minor trauma Heal poorly due to poor 39 Gangrene Tissue becomes necrotic Often leads to amputations Health Promotion Disease Prevention I Risk Factor Reduction Smoking Cessation Lipids DM HTN Hydration decreases blood viscosity Walking slowly to increase collateral circulation O O O O Protect feet from injury BUERGER S DISEASE Other Name 0 Thrombangitis Obliterans De nition 0 In ammatory arterial disorder that causes thrombus formation 0 Affects medium sized arteries 0 Usually lower leg and foot EtiOIOgy 0 Unknown 0 Usually affects men between 20 40 biggest difference from PAD who are heavy cigarette smokers or use other forms of tobacco eg chewing tobacco 0 Rare in US but increased rates found in Middle East or Far East where heavy smoking is common 55 Pain 0 Intermittent Flandim nn Skin Temp 0 Cool to touch Skin COIOF o Reddish blue cvanotic PUISBS 0 Weak Absent Peripheral Pulses PareStheSia o Numbness prickly or burning en atinn Trophic Changes 0 Skin thin shiny smooth 0 Hair absent 0 Toenails thickyellow Skin Ulcers amp Gangrene 0 May be present Buerger s 0 Control Risk Factors Treatment 0 Smoking Cessation is the ONLY way to stop progression of disease 0 Exercise 0 Protect feet from injury 0 Maintain Hydration o Medications that vasodilate or dissolve blood clots o Amputation if gangrene RAYNAUD S Two Types Primary Raynaud s Raynaud s Disease Secondary Raynaud s Ravnaud s P Etiology Brief episodes of intense vasospasm narrowing of arteries and arterioles Usually affects ngers Less often toes nose ears lips Primary Raynaud s More common but less severe than 2nd Raynaud s Gender FgtM 41 ratio Age Affects healthy women 20 40 YO More common in colder climates Etiology Cause of vasospasm unknown idiopathic o Vasospasm precipitated by cold temperatures or stressful emotions 0 May be rt hyperactivity ofSNS T t T tone Secondary Raynaud s 2nd to another disease process Vasospasm associated with o Vessel injury I Frostbite I Use of heavy vibrating tools jackhammer I Repeated exposure to hotcold temperature butchers o Repetitive Action Typing Playing Piano 0 Autoimmune Diseases Scleroderma Systemic Lupus Erythematosis SLE 0 Drug Induced Beta Blockers Signs amp Symptoms S S may be more severe with 2nd Raynaud s Starts in ngertips and progresses to distal phalanges Color Changes 0 White Pallor 0 Blue Cyanosis 0 Red Hyperemia Digits may also feel cold numb Digits may throb and swell as blood returns to affected area Usually lasts about 15 minutes although may be longer Complications Most often occurs with 2nd Raynaud s Ulceratinn and Gangrene Health Promotion Disease Prevention Avoid exposure to cold stressful situations Use gloves hat No Smoking No Caffeine Avoid OTC meds that vasoconstrict No prescription drugs that vasoconstrict AN EURYSMS De nition 0 Abnormal localized dilation of blood vessel Location 0 Most aneurysms involve the AORTA o Abdominal Aortic Aneurysm AAA 75 of cases 0 Thoracic Aortic Aneurysm TAA 25 of cases 0 Cerebral Berry Aneurysms rare Shapes Saccular Dilates on one side Aneurysm Appears like a sac Usually result from trauma or I malformation Involves entire circumference of vessel Balloons out on all sides Fusiform Aneurysm AOrtiC Etiology o Weakness in arterial wall which may be caused by several factors Aneurysm Atherosclerosis most common cause Hypertension Heredity Congenital Defects Trauma o Infections OOOO Risk Factors smoking Gender M gt F Race Caucasian Family History Marfan s J Affects 60 0 YO Men are 5 10x more likely to have AAA than women Most are fusiform Z 90 located below renal artery Most are slow growing Signs Symptoms 0 Most are asymptomatic 1st symptom Pulsating bulge in epigastric area Often discovered during routine PE or x ray of abdomen Pain varies may be located in abdomen or may cause back pain Bruits Blowingswishing sound caused by turbulent blood ow Extremities are cool to touch 0 Thrombus formation 2nd to blood stasis Complication Rupture 0 Mortality rate after rupture gt 90 AAA Abdominal Aortic Aneurysm OOOOO May result from injury to chest Dif cult to diagnose usually no sx even when large Most discovered 39 39J t when pts undergo chest x ray or other tests TAA Thoracic Aortic Aneurysm Cerebral Berry Aneurysm Often found in Circle of Willis Often size of a small berry More likely to occur in 35 60 YO Most produce no sx until they become large begin to leak or rupture Rupture causes bleeding into subarachnoid space Subarachnoid hemorrhage 0 Severe HA worse headache of my life 0 N V o Stiff Neck 0 Seizures AN EURYSMS Aortic Dissection False Aneurysm Life threatening Caused by tear in intimal layer Blood accumulates between medial and intimal layer creates a blood lled cavitychannel Caused by any condition that weakens elastic smooth muscle layer of aorta o 90 of cases occur in men 40 60 YO with hx of hypertension 0 2nd most common group patients with Marfan s Syndrome Majority of cases involve ascending aorta Signs and Symptoms o Abrupt onset of excruciating pain Pain described as tearing or ripping sensation If it involves ascending aorta pain occur in anterior chest If it involves descending aorta pain occur in the back Initially BP elevated 0 Later B 39 OOOO Aortic Aneurysm Treatment Small lt 4 cm in diameter watchful waiting Medium 45 50 cm in diameter weigh risk benes of surgery Large 3 55 cm in diameter Surgery to remove damaged section VENOUS SYSTEM AampP Super cial Vein Located in SQ tissue Perforating Vein Connects super cial and deep veins Deep Vein Located in deep muscle compartment Blood shunted from super cial veins to perforator veins to deep veins and then back up to heart via the inferior vena cava Veins equipped with one way valve that prevents backward retrograde blood ow Veins rely on pumping action of skeletal muscles to move blood up to heart against gravity VARICOSE VElNS De nition Enlarged dilated super cial vein of lower extremities Due to valve incompetence Allows re ux of blood retrograde blood ow Results in vein en or ement venous pooling Classi cation Primary Varicose Veins Originate in super cial saphenous vein Predisposing Factors Age gt 50 YO Obesity Gender F gt M Pregnancy hormones dilate veins uterus prevents venous return Family History Prolonged Standing Unsightly appearance Dull ache occurs at end of day or after prolonged standing Edema improves with rest leg elevation 1 lEOOOOOO y Varicose Veins 2nd to another condition that impairs blood ow in deep veins Most common cause DVT Deep Vein Thrombosis o Damages Valves Leads to Venous Pooling SS Discomfort tends to be more severe than primary varicose veins Complication Leads to chronic venous 39 r 39 CVI Prevention of Varicose Veins o Prevent Blood Poolin 0 Avoid Prolonged Standing 0 Leg Elevation 0 Support Hose Compression Stockings 0 Avoid sitting too long 0 No crossing legs 0 Avoid tight clothing 0 WeiLht Loss Varicose Veins surgery TX VENOUS THROMBOSIS Types o Super cial Thrombophlebitis 0 Deep Vein Thrombosis DVT Primary Mechanism Virchow s Tri ad for Venous Venous Stasis o sluggish blood ow Thromb05i51 0 Bed Rest Immobility 0 MI CHF 0 Long plane or car trips gt 4 hours TBIOOd o Inherited Protein C or S De ciency coagulation disorder coagl atlon 0 Pregnancy Early postpartum period 0 Cancer 0 Previous DVT o Dehydration 0 Oral Contraceptives 35561 Wall 0 Injury triggers in ammation results in platelet adhesion InJuW 0 IV Catheters 0 Surgery Gynecology Orthopedic surgery 0 Lower extremity fracture 0 Massive trauma or infection Super cial 0 In ammation of super cial veins caused by blood clot ThrombPPhIBbitiS o I ocation39 upper or lower extremities Phleb1t1s 55 0 Red amp Warm o Tenderness along super cial vein 0 No signi cant swelling of limb o Veins feels hard or cord like o Complication 0 Many pts also have an occult DVT 0 Always assume there is a DVT until proven otherwise Deep VBiIl 0 Blood clot in deep veins Thrombosis DVT o Affects mostly lower extremity LE occasionally upper extremity UE DVT U U S S related to degree of obstruction May be asymptomatic if vein not totally occluded Low grade fever Red Warm Unilateral swelling Pain Tenderness along vein Elevated WBC Sed Rate Walking aggravates pain Homan s Sign not very accurate Calf Pain on Dorsi exion present in lt 30 of pts with DVT DVT Illll PE Pulmonary Embolus 0 Life threatening 0 Blood clot dislodges and travels to lung 0 Occurs in 30 of pts with DVT Recurrent DVT 0 Acute episode of DVT predisposes to recurrent episodes CVI Chronic Venous Insuf ciency 0 35 50 of pts with DVT develop CV1 0 May occur monthsvears after initial episode Early ambulation after childbirth surgery Exercise legs Support hose Compression stockings Avord o Crossing legs Standing for long periods Avoid constricting clothing No smoking OOO Treatment Hospitalize ER with leg elevated Support Hose Compression stockings Anticoagulants NU 231 Pathophysiology Respiratory Disorders TOPICS 0 Asthma o COPD Chronic Obstructive Pulmonary Disease 0 Pneumonia o Tuberculosis 0 Lung Cancer 0 Pneumothorax ASTHMA Statistics 0 Affects people of all ages but most often starts in childhood 0 Affects more than 22 million people in US 0 Nearly 6 million of these people are children De nition 0 Chronic longterm lung disease 0 Characterized by narrowed airways caused by 0 Bronchospasm 0 In ammation Categories 0 Extrinsic Atopic Asthma 0 Most have a personal andor family history of allergies o Initiated by Type I Hypersensitivity Response 0 Intrinsic Nonatopic Asthma o Initiated by diverse nonimmune 39 Asthma EXTRINSIC ATOPIC ASTHMA Triggers Allergens 0 Outdoor Allergens o Pollen Trees Grasses Weeds 0 Indoor Allergens 0 Dust Mites o Cockroach Allergen 0 Pets 0 Mold INTRINSIC NONATOPIC ASTHMA Viral URI 0 Colds amp Sinus Infections Airborne 0 Tobacco smoke Pollutants 0 Air Pollution 0 Strong Odors perfumes cleaning agents 0 Occupational Irritants gChemicals dust gases fumes Exercise 0 Cause unclear 0 Thought to be due to loss of heatwater from lungs o Worse in cold weather Drugs 0 ASA NSAID Beta Blockers ACE Inhibitors o Mechanism not fully understood Chemicals 0 Sul tes food preservative Others 0 Emotional Factors laughing crying anger 0 Sex Hormones 40 of women experience worsening of asthma sx premenstrually o GERDEsophagus amp bronchial tree share vagal innervation ASTHMA Etiology 0 Most likely due to genetic and environmental factors 0 Common denominator of ALL forms of asthma is an exaggerated hypersensitivity response to a variety of stimuli Pathogenesis Two Primary Airway Problems Bronchospasm Smooth muscles surrounding the bronchioles tighten Narrows airways Bronchospasm triggered by 0 Release of chemical mediators from IgE sensitized mast cells Histamine Leukotrienes Interleukins Prostaglandins o Bronchioles innervated by PNS PNS via the vagus nerve produces bronchoconstriction SNS via beta 2 adrenergic receptors T bronchodilation Airway In ammation Plays major role Airway in ammation results in o Injures Epithelial Cells 0 Edema Swelling narrows airways o Impairs mucociliary function 0 Increases airway hyperresponsiveness Two Phases Early Phase Produces bronchospasm upon exposure to inhaled allergen Sx develop in 1020 min Usually subside 12 hours Late Phase Involves airway in ammation Develops 48 hours after exposure to asthma trigger Lasts for several days to weeks SS Severity Varies Mild to Severe see text p 499 General Fatigue easily Activity exercise limitations Skin Bluish color of facelips severe Resp Chest tightness SOBDyspnea Wheezing Cough worse at night and early am Sputum production Increase respiratory rate with prolonged expiration Auscultation Distant breath sounds Use accessog muscles severe Tachycardia DX o Pulmona Function Test Spirometer Prevention 0 Environmental Control TX 0 Quick Relief Meds o LongTerm Control Meds COPD EMPHYSEMA AND CHRONIC BRONCHITIS Statistics Affects about 11 million persons in US 43911 leading cause of death Cost 37 million year in direct and indirect costs De nition COPD includes 0 Emphysema 0 Chronic Bronchitis o Unremitting Asthma Characterized by chronic air ow obstruction 0 Difficulty inspiring air narrowed airways 0 Difficulty expiring air airways collapse on expiration As COPD progresses pts often have some degree of both emphysema and chronic bronchitis COPD Risk Factors Tobacco Smoke 0 Causes 8090 of cases 0 Cigarette smoke is an irritant o Stimulates movement of in ammatory cells neutrophils macrophages into lung tissue 0 Releases Elastase protease which destroys lung tissue Passive Second Hand Smoke Air or occupational pollution Emphysema Genetic Risk Factor Alphal Antitrypsin AlAT Deficiency 0 Causes lt 5 of cases of Emphysema o AlAT is produced by liver that inhibits the action of proteolytic enzymes that destroys lung tissue AlAT is a lung protector 0 May cause emphysema in nonsmoker EMPHYSElV A Pathologic Features Enlargement of airways distal to terminal bronchiole Destruction of alveolar walls and capillary bed Loss of lung elasticity SS Bronchioles col Onset la se durin ex iration traps air hyperin ation Age 4050 s Disease far advanced by the time sx appear General Thin and Emaciated Sit Tripod Position allows for maximum chest expansion Skin N ails Pink Puffer o Cyanosis absent even late in disease 0 Proportionate loss of ventilation and perfusion areas 0 Compensate by T RR Finger Clubbing Respiratory Barrel Chest SOB most common sx No Cough or Mild Cough Sputum minimal or no sputum production Percussion Hyperresonant Auscultation o Decreased Breath Sounds BS 0 No wheezing Use accessory muscle to breath Use pursed lip breathing Slow controlled expiration o Decreases bronchiolar collapse 0 Decreases trapped air volume ABG Relatively normal until late in disease i P02 T PC02 Hypoxic drive to breath Hemoglobin Increased Hgb level Increased RBC 0 Compensatog mechanism related to hypoxia CHRONIC BRONCHITIS Pathologic Airway obstruction caused by airway in ammation Features Excess mucus produced 2quotd to hypertrophy amp hyperplasia of mucus secreting glands Loss of cilia function 9 Increases incidence of respiratog infections SS Onset 3040 years of age General Normal or overweiat Skin Nails Blue Bloaters o Cyanotic Appearance 0 Disproportionate loss of ventilation amp perfusion areas Impaired Ventilation with normal perfusion Impaired Perfusion with normal ventilation Finger Clubbing Respiratory Barrel Chest SOB early sx Chronic Cough Copious amounts of sputum Percussion Hyperresonant Auscultation Expiratory wheezing and rhonchi Use pursed lip breathing Slow controlled expiration o Decreases bronchiolar collapse 0 Decreased trapped air volume ABG s Respiratory Acidosis i P02 T PC02 Hemoglobin Increased Hgb level Increased RBC 0 Compensatory mechanism related to hypoxia COPD Cor Right heart failure from lung disease and pulmonary Complications Pulmonale hypertension 0 Hypoxemia i P02 causes vasoconstriction of pulmonary capillary bed 9 Pulmonary HTN 0 RV has to pump against high pulmonary pressure 0 RV hypertrophies 9RHF S S of RHF o JVD o Edema o Wt Gain 0 Enlargement of Liver Spleen 0 GI N V Respiratory Occurs with acute exacerbation Failure Defined o i P02 lt 50 Normal80100 o TPCOZ gt 50 Normal 3545 I S S o Hypoxic 9 Confused restless anxious Lung Cancer Linked to smoking DX Pulmonary Function Test Spirometer TX No Cure Stop Smoking Meds PNEUMONIA Statistics Affects 4 million people in US 63911 leading cause of death in US Most common cause of death due to infectious disease Cost 23 billionyear De nition Acute in ammation of the lung structures bronchioles amp alveoli caused by infection 0 Bacteria most common 0 Viruses o Fungi Bronchioles and alveoli become plugged with exudate o Exudate uid cellular debris and pus 0 Areas consolidate Solidi es 0 Gas exchange cannot occur in areas of consolidation hypoxemia High Risk Groups Very young very old Cigarette Smokers Malnourished Have underlying lung disease asthma COPD cystic brosis Underlying medical problem DM Cancer HD Have weakened immune system HIVAids Organ transplant steroid use Have dif culty coughing due to stroke limited mobility sedating drugs Have had a recent URI Classi cation of Pneumonia Community Acquired Pneumonia CAP Hospital Acquired Pneumonia Aspiration Pneumonia CAP Community Acquired Pneumonia Bacteria 0 81 Organisms found in the community rather than hospital or nursing home DX within 48 hours after admission to the hospital 39 P Haemophilus In uenza Moraxella Catarrhalis Stapiylococcus Aureus Atypical Pneumonia Mycoplasma Pneumonia Legionella Pneumonia Chlamydia Pneumonia Viruses In uenza Virus Adenovirus RSV Respiratog Synctial Virus gt RR gt 20 Dullness to Percussion RalesCrackles Cough Sputum changes from watery to blood tinged or rust colored to purulent Less to are q year Pneumococcal Vaccine protects against 23 types of pneumococcal bacteria 0 Recommended for persons 3 65 years amp persons 265 YO with chronic illness andor I Gram among 34 most common causes CAP I Found in warm standing water air conditioning system I Pathogens gt 5 lt 25 YO Outbreaks occur in crowded military and institutional settings Persontoperson transmission by contact with respiratory secretions Sore Dry Hacking Nonproductive Cough may persist for gt 6 weeks PNEUMONIA Hospital Acquired Pneumonia Nosocomial Infection Infection acquired in the hospital Occurs 3 48 hours after admission to hospital Mortality rate 2050 High Risk Persons 0 Mechanical ventilators o Compromised immune system 0 Chronic lung disease 0 Airway instrumentation endotracheal intubation or tracheotomy Pathogens 90 are bacterial o Pseudomonas Aeruginosa o Staph Aureus o Klebsiella o E Coli Many are antibiotic resistant and difficult to treat TUBERCULOSIS Statistics US In 2008 atotal of 12898 cases were reported MMWR March 20 2009 0 Lowest rate recorded since national reporting began in 1953 o More TB cases were reported among Hispanics than any other racial ethnic group followed by Asians and African Americans Worldwide 0 About 9 million new cases in 2008 0 Most cases occurred in SE Asia and Africa De nition Infectious disease caused by Mycobacterium tuberculosis o Mycobacterium also called tubercle bacillus o Mycobacterium is an acid fast bacillus 0 Slow growing 0 Resistant to destruction Infects Mostly lung tissue Pulmonary TB Infection can become disseminated Miliary TB 0 Spread thru blood stream hematogenous spread 0 Can infect any organ Mode of Airborne infection Transmission Spread by minute particles called droplet nuclei 0 Persons with ACTIVE TB emit droplet nuclei as they talk cough sneeze o Droplet nuclei circulate in air 0 Another person can inhale organism into lung Upper airway prevents most inhaled organisms from reaching lungs Persons who are exposed to ACTIVE TB 0 75 DO NOT become infected o 25 become infected 0 Of the 25 who are infected only about 10 develop ACTIVE TB More easily transmitted in closedconfined spaces with poor ventilation Predisposing Living in crowded and confined conditions increases risk of spread Factors for TB Close contacts of persons with active TB Immigrants from countries with high rates of TB Immunosuppressed HIVAIDS Chronic Disease COPD DM Cancer ESRD EmployeesResidence of high risk settings 0 Correctional facilities 0 Nursing Homes 0 Homeless Shelters 0 Drug Treatment Facilities Health care workers who serve high risk clients Poorly nourished TUBERCULOSIS Two Types 0 Latent TB Infection 0 Active TB Disease Latent TB Infection Person is infected with TB but is NOT sick Pathogen is dormantwalled off Cell mediated immunity T lymphocytes keep pathogen under control May harbor pathogen for life and may never develop active TB However about 510 of people infected with TB go on to develop active TB especially if immunocompromised HIVAIDS S o PPD o Sputum Cultures o Chest Xray 0 NO symptoms 0 NOT CONTAGIOUS TX 0 Isoniazid INH X 69 months to prevent development of active TB Active TB Disease 90 of cases result from progression of latent TB Infection Most often occurs due to impaired immune system However some may develop Active TB soon after infection SS of Active TB Disease 0 PPD o Sputum Culture 0 Chest Xray o CONTAGIOUS Other Symptoms include Low Grade fever Night sweats Fatigues easily Loss of Appetite Unintended weight loss Cough that lasts 3 3 weeks Hemoptysis Pain with breathing or coughing 00000000 0 Use multiple drugs due to drug resistance Isoniazid IHN Rifampin Pyrazinamid PZA Ethambutol EMB TX for 612 months Usually no longer contagious after 2 wks of antibiotic therapy Drug Resistance 0 MDR TB Multi Drug Resistant TB Resistant to INH and Rifampin o XDR TB Extensively Drug Resistant TB Resistant to INH amp Rifampin to 3 3 of the 2 line TB drugs 00 TUBERCULOSIS Patho Inhale droplet nuclei into lungs physiology Alveolar macrophages surround and engulf bacilli 0 Unable to kill all bacilli some bacilli survive within macrophage o Macrophages initiate a cell mediated immune response TLymphocytes o CellMediated Immune Response Usually occurs about 212 weeks after infection Develop Sensitized T Cells TB skin test becomes positive Macrophages and TLymphocytes surround the organism in GRANULOMAS o Granulomas are a distinctive chronic in ammatory response 0 Ghon Focus Graywhite circumscribed granulomatous lesion Contain tubercle bacilli macrophages and other immune cells 0 Ghon Complex Combination of Ghon Focus lymphatic lesion The destructiveness of the disease is due to cellmediate immune response 0 Sensitized T Cells Attack Ghon Focus Forms soft yellow cheesy mass called caseous necrosis Caseous necrosis eventually calcifies amp scars over Bacilli are walled off Contained within calcified lesion Can harbor organism for life However organisms may be reactivated Active Disease DiagnOSiS 0 TB Skin Test PPD Puri ed Protein Derivative 0 Chest Xray o S utum Culture PPD Used to screen for TB exposure Measure delayed hypersensitivity reaction TYPE IV Usually takes 2 12 weeks to develop Sensitized T Cells Measure area of induration swelling NOT area of redness PPD 0 Been exposed to pathogen and have sensitized T Lymphocytes 0 Does NOT differentiate between Latent vs Active TB disease 0 Positive for LIFE 0 No need to repeat PPD in person with known 0 False and False reactions can occur TUBERCULOSIS PPD Interpretation 04 mm of induration NEGATIVE 59 mm of induration POSITIVE FOR HIGH RISK GROUPS SUCH AS 0 Exposed to someone with ACTIVE TB 0 HIV infection 0 Immunocompromised 10 l 5 mm of induration POSITIVE FOR THE FOLLOWING 0 IV drug users HIV neg 0 Recent immigrant within last 5 years from country with high TB prevalence Resident employee in high risk settings prison 0 longterm care facility hospitals homeless shelter Medical Risk Factors DM ESRD COPD Cancer 0 gt 15 mm of induration POSITIVE FOR PERSONS WITH NO KNOWN RISK FACTORS LUNG CAl CER Statistics 1 cause of cancer death in both men and women 2quot most common cancer site in both men amp women More Americans die each year of lung cancer than from breast prostate and colon cancer combined Overall 5year survival rate is 1315 Etiology Unknown Cancer cells develop because of damage to DNA Most likely cause by repeated exposure to environmental carcinogens eg smoking radon Results in malignant neoplasm TUMOR marked by uncontrolled growth and proliferation of cells Types 95 of all lung cancers are BRONCOGENIC CARCINOMA o Originate in Epithelial lining of major bronchi 0 May also begin in trachea bronchioles and alveoli o Subdivided into two major categories based on microscopic appearance Small Cell Lung Cancer SCLC Non Small Cell Lung Cancer NSCLC Adenocarcinoma Squamous Carcinoma Large Cell Carcinoma Small Cell Lung Cancer Represents about 1015 of cases Also referred to as oat cell carcinoma because cells resemble oats under microscope Almost always caused by SMOKING Grows quickly Metastasizes early Poor Prognosis Associated with secretion of ectopic hormones o ACTH Adrenocorticotropic hormone o ADH Antidiuretic hormone o Parathyroidlike hormone Hypercalcemia Adenocarcinoma Most common type found in women and nonsmokers Tends to be located in peripheral portions of lung bronchiolar and alveolar tissues Squamous Cell Carcinoma Found mostly in men Closely correlated with smoking history Originated in central bronchi as an intraluminal growth Large Cell Carcinoma Highly anaplastic Grows rapidly Spreads quickly Poor prognosis LUNG CANCER Risk Factors Cigarette Responsible for 90 of cases Smoking Contain gt 4000 carcinogens Risk correlates with of cigarettes smoked Risk gradually decreases in persons who quit Risk decreases to level of someone who has never smoked after about 15 years Passive Second Responsible for approx 3000 deathsyear Hand Smoke Nonsmoker who lives with a smoker has about 2030 greater risk of developing lung cancer Workers who are exposed to tobacco smoke in workplace are also more likely to get lung cancer Some evidence suggests that certain people are more susceptible to cancer causing effects of tobacco smoke than others Cigars and Also increases risk of lung cancer but not as much as smoking Pipe Smoking cigarettes Radon 2quotd leading of cause of lung cancer Leading cause of lung cancer in nonsmoker Present in indoor and outdoor air Natural radioactive gas that results from the breakdown of uranium in soil and rock Seeps into houses through cracks in the foundation or insulation Asbestos Exposure increases risk of developing MESOTHELIOMA a type of cancer the starts in pleura Air Pollution Raises risk slightly Risk is far less than risk caused by smoking CER LUNG CAD S S o Varies o Clinically silent for many years 0 SK often ignored Due to involvement of lung and adjacent structures Earliest sx 0 Chronic cough 0 SOBWheezing Hemoptysis Chest pain Repeated respiratog infections Due to Local Spread Difficulty swallowing due to compression of esophagus Pleural Effusion if tumor adjacent to visceral pleura Superior vena cava syndrome caused by compression of superior vena cava Due to Metastatic Spread Occurs by way of lymph channels and bloodstream Mets exist in 50 of pts with lung cancer and eventually develops in 90 of pts Most common sites 0 Brain 0 Bone 0 Liver Due to Paraneoplastic Syndrome Unrelated to metastasis Often precedes other signs and symptoms of lung cancer Seen most often in Small Cell Lung Cancer SCLC Small cell has the ability to synthesize hormones o ACTH Cushing s o ADH SIADH o Parathyroidlike hormone hypercalcemia Other Paraneoplastic manifestations o Neurologic sx o Muscular sx o 1 39 39 disorders Nonspecific Symptoms Weakness Fatigue Anorexia Weight Loss Topics NU 231 PaThophysiology ImmuniTy I 13 Immune Response I 14 InflammaTion and Tissue Repair I 15 AlTeraTions in Immune Response IMMUNE RESPONSE TWO MAJOR DIVISIONS OF THE IMMUNE SYSTEM NonSpecific Immune SysTem Also called INNATE OR NATURAL IMMUNITY FirsT line of defense I C r of nonspecific immuniTy Physical Barriers I Skin mucous membranes Chemical Barriers I AnTibacTerial subsTances inhibiT growTh FaTTy acid Lysozyme Cellular Barriers I NeuTrophils and macrophages major phagocyTic cells I NaTural Killer Cells NKC Physiologic Barriers I Fever I Low pH skin sTomach vagina inhibiT growTh ComplemenT SysTem I I Produces inflammaTory response PromoTes phagocyTosis and cell lysis CharacTerisTics o No specificiTy broad specTrum acTs on many organisms unable To differenTiaTe beTween organisms o No memory response Thus no lasTing immuniTy o Able To quot 39 39 39 self from nonself Specific Immune SysTem Also called ACQUIRED OR ADAPTIVE IMMUNITY 2quot Line of Defense acquired Through previous exposure Key Players LYMPHOCYTES B amp T LymphocyTes CharacTerisTics o SpecificiTy Have specific cell membrane recepTors ThaT TargeT specific anTigens 0 Memory Response Remembers exposure To anTigen and quickly responds on subsequenT exposure RecogniTion of Self from NonSelf PrevenTs reacTion againsT own Tissue Self AnTigens O IMMUNE STRCTURES CenTral Immune STrucTures Bone Marrow Produces B amp T LymphocyTes from precursor cells in bone marrow B cells maTure in bone marrow B Cells provide humoral or anTibodymediaTed immuniTy Thymus T Cells maTure in Thymus Made in The bone marrow T Cells provide cellmediaTed immuniTy O O O O O O Peripheral Immune STrucTures Lymph Nodes Tonsils Spleen Appendix Peyer39s PaTches in inTesTines MucosaassociaTed lymphoid Tissue in RespiraTory GI amp 6U TracTs FuncTion Traps and processes The anTigen PromoTes inTeracTion wiTh maTure immune cells 0 ANTIGENS IMMUNOGENS AnTigens Immunogens I Foreign subsTance ThaT can sTimulaTe The producTion of anTibodies immunoglobulins Also a subsTance ThaT can INITIATE an immune response Foreign AnTigens PaThogens bacTeria viruses proTozoa fungi parasiTes PlanT Pollen Poison Ivy Resin TransplanTed Organ IncompaTible Blood Transfusion I O O O O O MHC Major HisTocompaTibiliTy Complex MHC is clusTer of genes locaTed on chromosome 6 Codes for HLA Human LeukocyTe AnTigens o FirsT deTecTed on WBC because of Their role in organ TransplanTs o HLA found on surface of nearly every cell in The body 0 Self AnTigensquot 0 ONLY idenTical Twins have The same HLA ThaT39s why organs are ofTen rejecTed o Allows immune sysTem To disTinguish self from nonselfquot Proper ries of MCH Class I and II Molecules Properfy MHC Class I MHC Class II HLA HLAA HLADR HLAB HLADP HLAC HLADQ Dis rribufion Vir rually all cells of body no Macrophages on RBC39s An rigen Presen ring Cells BCells Func rion Presenf processed an rigen To Presenf processed an rigen fragmen rs CD8 T Lymphocyfe To CD4 T Helper Cells Resfric rs cyfolysis To virus Necessary for effec rive inferacfion infec red cells rumor cells and among immune cells Transplan red cells Defec rs in MCH Genes I May lead To au roimmune diseases if defec red I Presence of HLA Type may indica re a PREDISPOSITION To cer rain au roimmune disorders I HLADR3 and HLADR4 Diabefes Melli rus I HLADRZ Mul riple sclerosis IMMUNE CELLS Whi re Blood Cells WBC originafe in bone marrow from a s rem cell I To ral WBC Coun r 5000 To 10000 per cubic mm of blood I Granulocyfes o Neu rrophils 6070 0 Eosinphils 1 0 Basophils 14 I Agranulocyfes o Monocyfes Macrophage 2670 0 Lymphocyfes 2040 Nafural Killer Cells 10 B Lymphocyfes 1020 T Lymphocyfes 70 GranulocyTes NEUTROPHILS 0 Primary phagocyTic cell 0 Also known as PMN Polymorphonuclear NeuTrophil Segs SegmenTed NeuTrophil Bands or STabs ImmaTure NeuTrophils 0 Increase during bacTerial infecTion LeukocyTosis T WBC gt 10000 15000 To 20000 ShifT To The lefT Increase in immaTure neuTrophils STabsBands o FirsT To arrive aT injury siTe wiThin 90 minuTes o Lifespan 45 days BASOPHILS o ConTains hisTamine and oTher chemical mediaTors EOSINPHILS o Increases during an allergic reacTion or parasiTic infecTion Ag ranulocyTes MONOCYTES MACROPHAGES 0 Primary phagocyTic cell MonocyTes maTure inTo macrophages as iT migraTes To injured siTe Arrives wiThin 24 hours Engulfs and desTroys foreign subsTance Found in large quanTiTies in spleen lymph nodes Tonsils Liver Kupffer Cells Skin Langerhans Cells Lung alveolar macrophage Brain Microglial Cells 0000 NATURAL KILLER CELLS NKC o ImporTanT in NonSpecific ImmuniTy o Kills cancer cells and virus infecTed cells 0 Does noT have abiliTy To disTinguish one anTigen from anoTher NK cells don39T care whaT kind of anTigen iT is Kills cancer cells and virus infecTed cell O B LYMPHOCYTES Responsible for specific immune response Formed from sTem cells in bone marrow maTure in The bone marrow Less Than 1 enTer circulaTion Acquire specific membrane recepTor for a specific anTigen Provide HUMORAL IMMUNITY or anTibody mediaTed immuniTy When B LymphocyTes encounTer complemenTary anTigen They differenTiaTe inTo Plasma Cells Produce anTibodies Memory Cells Remember exposure To anTigen 0 00000 Five Clc sses of AnTibodies T 39 39 quot IgA Found in body secreTions Tears Saliva Resp GI Vagina ProsTaTe and ColosTrum 1quot milk of nursing moThers PrevenTs aTTachmenT of viruses and bacTeria To epiThelial cells Considered primary defense againsT local infecTions in mucosal Tissue IgD Found primarily on The cell membranes of BLymphocyTes Serves as anTigenrecepTor for iniTiaTing differenTiaTion of B Cells IgE Involved in inf39 39 and allergic responses amp parasiTic infecTions IgG MosT abundanT immunoglobulin ProTecTs againsT bacTeria viruses Toxins in body fluids AcTivaTes complemenT sysTem Crosses placenTa Transfers immuniTy from moTher To feTus 0 Provides PASSIVE IMMUNITY ShorTlived 36 monThs o LargesT amounT crosses placenTa during lasT weeks of pregnancy SynThesized during SECONDARY RESPONSE which suggesTs pasT infecTion IgM LargesT immunoglobulin SynThesized during PRIMARY RESPONSE which suggesTs currenT infecTion FirsT anTibody made by newborn 0 Presence of IgM raTher Than maTernally Transferred IgG is indicaTive of newborn infecTion PRIMARY RESPONSE I Occurs when anTigen firsT inTroduced inTo body I Lag Time Takes a few days before anTibodies deTecTed in blood I IgM PredominanT anTibody suggesTs currenT infecTion SECONDARY RESPONSE I Occurs on 2quot exposure To same anTigen I No Lag Time Rapid rise in anTibody produced I Memory Cells remember pasT exposure To anTigen I IgG predominanT anTibody suggesTs pasT infecTion Ag ranulocyTes T LYMPHOCYTES o Responsible for specific immuniTy Have noThing To do wiTh anTibodies Acquire specific membrane recepTor for a specific anTigen Provide CELL MEDIATED IMMUNITY FuncTion AcTivaTes oTher T amp B cells ConTrols viral replicaTion RejecTs foreign Tissue grafTs AcTivaTes delayed hypersensiTiviTy reacTions RegulaTes selfrecogniTion Two PopulaTions of TCells T Helper Cells CD4 OOOO MasTer swiTchquot for The immune sysTem Turns on The immune sysTem Two subpopulaTions TH1 and TH2 SecreTe CyTokines funcTion as inTracellular signals ThaT acTivaTe oTher immune cells CyToToxic T Cells CD8 DesTroys TargeT cells by releasing cyTolyTic enzymes Toxic cyTokines perforins TWO TYPES OF IM AcTive ImmuniTy MUNITY Acquired by having The disease or by immunizaTions DPT MMR Polio HBV Body synThesizes own anTibodies Long lasTing may need a boosTer Passive ImmuniTy I Acquired by The Transfer of anTibodies from one source To anoTher ShorTTerm usually lasTs weeks To monThs Examples 0 Transfer of anTibodies from mom To infanT IgA BreasT milk IgG Crosses placenTa largesT amounT cross lasT few weeks of pregnancy AnTiserum conTains anTibodies for specific anTigen Gamma Globulin conTains pool of anTibodies for many infecTious diseases eg O O HepaTiTis A B Measles DiphTheria INFLAMMATION Complex biological response of Tissue To harmful agenTs CausaTive AgenTs o Microbial AgenT BacTerial Virus Fungi ProTozoa o Nonmicrobial AgenT Physical injury surgery burns chemical agenTs eTc Named by adding suffix iTis To The affecTed organ or sysTem o TonsiIIiTis o AppendiciTis o HepaTiTis InflammaTion is a prereguisiTe To healing o WiThouT inflammaTion wounds would noT heal minor infecTions would become overwhelming 0 However some forms of inflammaTion eg RheumaToid ArThriTis are noT beneficial Purpose of InflammaTion o DesTroys amp neuTralizes harmful agenTs o LimiTs spread of Tissue damage 0 Prepares damaged Tissue for repair Types of Inf39 39 AcuTe and Chronic Inf39 39 ACUTE INFLAMMATION IniTial response of body To harmful sTimuli Rapid OnseT LasTs lt 2 weeks Local signs and sympToms o Redness o HeaTWarmTh o Swelling 0 Pain 0 Impaired FuncTion SysTemic signs and sympToms o Fever Enlarged lymph nodes ElevaTed WBC CounT ElevaTed EryThrocyTe SedimenTaTion RaTe ESR CReacTive ProTein CRP Loss of AppeTiTe 0 Increased Sleep Three Responses 0 Vascular Response Cellular Response and InflammaTory MediaTors OOO Vascular Response CharacTerized by small changes in blood vessels aT siTe of injury Begins almosT immediaTely afTer injury LasTs a few seconds To minuTes TransienT vasoconsTricTion VasodilaTion Increases blood flow 9 increases warmTh amp redness Capillary PermeabiliTy O Fluids move ouT of capillary and inTo inTersTiTial space 0 Leads To swelling 9 irriTaTes nerves 9 Pain 9 Loss of FuncTion O Fluid diluTes Toxic agenT amp brings chemoTacTic subsTances To area Cellular Response MovemenT of WBC To injured siTe STeps o MarginaTion amp Adhesion o EmigraTion aka diapedisis o ChemoTaxis o PhagocyTosis InflammaTory MediaTors Injury paThogen causes The inflammaTion buT inflammaTory mediaTors enhance The inflammaTory response redness heaT swelling pain loss of funcTion InflammaTory MediaTors include The following HisTamine I Sources 0 MasT cells major source 0 Basophils amp PIaTeIeTs I Released in response To allergic amp anaphylacTic reacTion I AcTion VasodilaTion 9 Redness warmTh Capillary PermeabiliTy 9 Swelling AnTihisTamines ClariTin Clarinex Zerec Allegra Benadryl ChlorTrimeTon O O I Meds O O Leuko rriene Hisfamine and leukofriene has similar func139ion bu139 leukofriene is more powerful Ac rion 0 Powerful vasodila139or o Capillary permeabili ry 0 Powerful bronchocons rricfion As rhma Medicafions Leuko rriene ModifiersAn ragonis rs o Accola139e Zafilukas r o Singulair Monfelukasf Sodium o ny lo Zi le u139on Prosfag landi n Several Types Ac rion o Vasodila139ion o Capillary permeabili ry o PAIN sensi139izes pain recep139ors eg Dysmenorrhea Meds Inhibi r pros raglandin syn rhesis o ASA Aspirin o NSAIDS Ibuprofen Mo rrin Advil Naproxen Aleve Bradykinin Pro rein Thai circula139es in blood in an inac139ive form Ac rion 0 Powerful vasodila139or 0 Vascular permeabili ry o Smoofh muscle cons139ric139ion o Induces PAIN PAF Pla139ele r Syn rhesized by almosf all inflammafory cells Ac riva ring Ac rion Fac139or o Pla139ele r aggrega rion o Enhances func rion of neu rrophils and monocy res o Pofenf eosinophil chemoaffrac ran r Complemenf Sysfem Primary media ror of bofh nonspecific and specific immune response Group of pro reins normally presen139 in circula rion as inac139ive precursors Ac rion o Produces inflamma rion o Promo res phagocy rosis and cell lysis Acfivafed by o Viruses bac139eria and immune complexes Cy rokines Syn rhesized by primarily by T Helper Cells and Macrophages Func rion o CellTocellcommunica139ion o Acfivafes B and Tcells o S rimula res prolifera rion of CD8 and NKC o Enhances macrophage ac139ivi139y Four Types of Cy rokines o In reruleukins IL 1 18 Acfivafes T lymphocy res Promo res grow rh and differen ria rion of BCells I Syn rhesis of ofher cy rokines Induces sys139emic fever 0 In rerferons a amp l3 Exer rs an riviral ac139ivi139y Produced by hos139 cell invaded by virus Profecfs uninfec red cells from viral invasion and has big rime side effecfs Generally used for HepC chronic 0 Tumor Necrosis Fac139or TNF Produces inflamma rion amp fever Acfivafes phagocy rosis Kills Through apop rosis o Colony Sfimula ring Fac139or CSF 39 Promo res grow rh and ma139ura139ion of neu rrophils eosinophils macrophages ACUTE INFLAMMATORY EXUDATE I ExudaTe composed of fluids and plasma proTeins ThaT leak ouT of blood vessel which combines wiTh neuTrophils and cellular debris from phagocyTes I Four Types of exudaTes I Fluid ThaT occurs as resulT of infecTion oozing of infecTed wound Serous I Thin waTery exudaTe wiTh low proTein counT I Example Skin BlisTer GeniTal Herpes PurulenT I ConTains pus consisTs of neuTrophiIs bacTeria and fluid I InfecTion by pyogenic bacTeria such as sTaphylococci is characTerisTic of This kind of exudaTe I Example Abscess localized collecTion of pus enclosed by surrounding Tissue Hemorrhagic I Injury rupTures blood vessel I ExudaTe looks bloody Fibrinous I Commonly seen in serous caviTies I Forms a Thick sTringy exudaTe I Has high proTein conTenT and increased fibrinogen Example Bowel Adhesions fibrinous pericardiTis CHRONIC INFLAMMATION I Prolonged inflammaTion I LasTs gt 2 weeks weeks monThs years I Caused by O PersisTenT acuTe inflammaTion ThaT is resisTanT To phagocyTosis and oTher inflammaTory mechanisms I Examples 0 Foreign bodies silica asbesTos surgical suTure splinTers dirT O LowVirulence PaThogens Tubercle Bacillus TB Treponema Pallidum Syphilis o AuToimmune reacTion rheumaToid arThriTis I Major cells ThaT are involved Macrophages and LymphocyTes o ProliferaTion of fibroblasTs insTead of exudaTes increases risk of scarring amp deformiTy TISSUE REPAIR AND HEALING Two forms of Tissue Repair 0 RegeneraTion o Fibrous Tissue Repair RegeneraTion Injured Tissue replaced wiTh cells of similar Type and funcTion LiTTle or no evidence of injury LimiTed To Tissue wiTh cells ThaT are able To undergo miTosis Tissue regeneraTion dependenT on Tissue Type labile skin cells sTable hepaTic cells osTeocyTes amp permanenT cardiac cells Fibrous Tissue Repair Occurs wiTh severe injury Damaged Tissue replaced wiTh connecTive Tissue ConnecTive Tissue replacemenT involves The formaTion of granulaTion Tissue amp scar Tissue GranulaTion Tissue Serves as The foundaTion for scar Tissue developmenT IT is pink SofT moisT and granular Bleeds easily ConTains fibroblasTs synThesize and secreTe collagen Collagen involved in The developmenT of fibrous scar Tissue OOO FacTors ThaT AffecT Wound HealTh Age elderly heal more slowly Than young MalnuTriTion Decreased blood flow and oxygen delivery ischemic Tissue heals poorly Impaired inflammaTory and immune response HIV Cancer DiabeTes sTress increased corTisol from adrenal corTex Those Taking immunosuppressanT drugs sTeroids suppress inflammaTory response Wound separaTion Wound infecTion 12 ALTERED IMMUNITY Allergic amp Hypersensitivity Disorders amp HIVAIDS ALLERGIC OR HYPERSENSITIVITY DISORDERS I Refers to excessive or inappropriate activation of the immune system I Four Types 0 Type I IgE Mediate Hypersensitivity 0 Type II AntibodyMediated Cytotoxic Hypersensitivit I II and III all have Ab involvement 0 Type III Immune Complex Mediated Hypersensitivity 0 Type IV Cell Mediated Delayed Hypersensitivity Disorders NO Ab involvement Type I IgE Mediated Hypersensitivity I Antibody IgE I Antigen Allergen Pollens dust mites mold animal dander drugs food insect bites etc I Mast Cells 0 Located in skin amp mucosa 0 Contains granules of inflammatory mediators eg histamine I Stage I Initial Encounter o IgE Antibody attaches to mast cell 0 Mast cell becomes quotsensitizedquot I Stage II Subsequent Exposure 0 Allergen binds to IgE antibody on quotsensitizedquot mast cell 0 Triggers release of histamine amp other inflammatory mediators Vasodilation Vascular permeability Bronchoconstriction I Type 1 IgE Mediated Disorders 0 Systemic Reaction Anaphylactic Reaction 0 Local Reaction atopic genetic predisposition Allergic Rhinitis hay fever Atopic Dermatitis Food Allergies Bronchial Asthma 13 SysTemic ReacTion ANAPHYLACTIC REACTION o Triggered by Drugs InsecT biTessTings Foods Life ThreaTening CharacTerized by widespread vasodilaTion Occurs in persons who have previously been sensiTized May be accompanied by UrTicaria and wiTh or wo Angioedema 39 UrTicaria Hives 39 Angioedema Involves deeper skin layers presenTs wiTh swelling of sofT Tissue of head and neck including eyes lips Tongue and palaTe 0 Signs amp SympToms of Anaphylaxis Skin flushes and becomes warm hives9 iTching ThroaT ThroaT amp Tongue swell 9 airway obsTrucTion RespiraTory ChesT Tigthess wheezing SOB CV HypoTension profound quot39 39 9 circulaTory failure Tachycardia Local ReacTion ALLERGIC RHINITIS 0 Seasonal Pollens or Perennial DusT miTes animal dander molds cockroaches 0 Signs and SympToms FaTigue Malaise Red iTchy eyes Nasal congesTion Runny nose Sneezing ITchy ears palaTe FOOD ALLERGIES 0 Milk Eggs FishShellfish WheaT Soybeans NuTs peanuTs walnuTs pecans almonds cashews o NuTs 9 mosT responsible for anaphylacTic reacTion 14 Type II AnTibody MediaTed HypersensiTiviTy CyToToxic HypersensiTiviTy I AnTibodies IgG or IgM I TargeT Cell surface anTigens RBC I AcTivaTes complemenT cascade ResulTs in phagocyTosis and cell lysis I Clinical Examples 0 IncompaTible Blood Transfusion ABO incompaTibiliTy o EryThroblasTosis FeTalis Rh facTor39 r quot quot39Ty IncompaTible Blood I RecipienT39s anTibodies bind To donor RBC surface anTigen Transfusion I AcTivaTes complemenT sysTem I PhagocyTosis and cell lysis of donor RBC EryThroblasTosis I Mom Rh negaTive feTalis I Baby Rh posiTive I FirsT pregnancy mom sensiTized To anTigens on baby39s RBC I 2quot pregnancy mom39s anTibodies cross placenTa and desTroy feTal RBC39s I Tx Rhogam Type III Immune Complex HypersensiTiviTy I Form immune complexes ClusTers of inTerlocking anTigen and anTibodies I AcTivaTes complemenT sysTem I ComplemenT aTTracTs inflammaTory cells ThaT release Tissue damaging producTs eg lysosomal enzymes I Immune complexes formed in circulaTion produce damage when They are deposiTed in 0 Skin Vessels VasculiTis o Glomeruli GlomerulonephriTis o JoinTs RheumaToid ArThriTis I Clinical Examples 0 SysTemic ReacTion Serum Sickness 0 Local ReacTion ArThrus ReacTion Serum Sickness I Triggered by Drugs esp PCN Foods InsecT venom I AnTigen anTibody complexes deposiTed in blood vessel joinTs amp kidney I Signs SympToms OnseT is 610 days afTer sTarTing anTibioTic o Fever Edema of face neck and joinTs Enlarged lymph nodes and Rash ArThrus I Triggered by Drugs vaccines ReacTion I Localized Tissue necrosis caused by immune complexes Type IV CellMediaTed Disorder I Also called delayed hypersensiTiviTy disorder Takes abouT 23 days To develop I Clinical Examples TB skin TesT Allergic ConTacT DermaTiTis O O 0 Poison IvyOak LaTex Allergy can be Type I or Type IV Nickel jewelry TransplanT RejecTion TB Skin I Used To screen for TB Use PPD Purified ProTein DerivaTive TesT I InjecT PPD inTo forearm inTradermal injecTion amp read iT 4872 hrs laTer I PPD Redness and induraTion aT siTe of injecTion o Occurs in person who has been previously exposed To TB and has sensiTized T Cells 0 Takes 24 weeks afTer TB exposure To produce sensiTized T lymphocyTes Poison I T cells inTeracT wiTh anTigen planT sap planT resin IvyOak I BlisTers erupT in 1224 hours afTer exposure I Rash occurs only where skin comes in conTacT wiTh planT sap I Need more Than 1 exposure To produce sensiTized T lymphocyTes I BlisTer fluid DOES NOT conTain The allergic planT sap LaTex I Allergic reacTion resulTs from laTex proTein coming inTo conTacT wiTh skin mucous membranes Allergy or inTernal organs gloves I Persons aT high risk for sensiTizaTion include o FrequenT exposure To laTex gloves 39 Person who has had many surgeries 39 Kids wiTh spina bifida undergo frequenT examinaTions 39 HealTh care workers May cause a Type I or Type IV mediaTed response Type 1 IgE MediaTed HypersensiTiviTy 0 Less common buT more serious 0 ITchy waTery eyes asThma urTicaria or ANAPHYLAXIS Type IV Cell MediaTed Response 0 More common less serious 0 ConTacT dermaTiTis vesicular rash 0 Develops 4872 hours afTer conTacT wiTh laTex 16 HIV AIDS I HIV Human Immunodeficiency Virus I AIDS Acquired Immunodeficiency Syndrome I HIV primarily infecTs T Helper Cells and Macrophages boTh have CD4 recepTors normal counT is 500 1500 AIDS CD4 counT lt200 Transmission SEXUAL TRANSMISSION I Vaginal InTercourse 0 Virus can be TransmiTTed in eiTher direcTion 0 However men are 2 3x more likely To TransmiT To women Than visa versa Semen conTains more HIV Than vaginal fluid Women exposed To larger qu of infecTious fluid ejaculaTe EjaculaTe reTained in vagina longer period of Time I Anal InTercourse 0 Anal mucosa is fragile Tears easily 0 MosT efficienT means of Transmission Oral Sex 0 Less risky Than vaginal and anal sex 0 HIV can enTer body Thru lining in The mouTh CONTACT WITH INFECTED BLOOD OR BLOOD PRODUCTS I NEEDLE STICK INJURIES 0 Risk is lt 1 99 of needle sTick injuries DO NOT lead To infecTion HBV risk 30 PrevenTion universal precauTions Wear gown gloves proTecTive eye shield Never recap needle Wash hand immediaTely NEEDLE SHARING 0 IV Drug Users IVDU sharing needlessyringes o AThleTes sharing needles To injecT sTeroids TRANSFUSION WITH INFECTED BLOOD 0 Risk is lt 1 0 Blood donaTions screened for HIV sTarTed in 1985 TISSUE TRANSPLANTS 0 Risk is low in US Tissue is TesTed OOO Transmission PERINATAL TRANSMISSION I Approximafely 2030 of infan rs born To HIV infec red moms become infec red I Transmission ra139e decreases if mom r eceives an riviral meds I May be Transmi 39ed Three ways U rero I Accoun rs for 30 of cases I Occurs Thru mafernalplaceni al circula rion Labor amp I Accoun rs for 70 of cases Delivery I Infan r direc139ly exposed To ma139ernal blood amp vaginal secre rions Breasi39 Milk I Accoun rs for lt 1 Phases of HIV PRIMARY INFECTION o Refers To period of Time when HIV firs r en139ers body I Onse r of 55 24 weeks af rer infeci ed o Durafion Las139s a few days To Two weeks 0 Offen misdiagnosed wi139h influenza or mono I Signs amp Sympfoms o Fever fa rigue o Sore Throa r o Headache o Myalgia o Nausea Vomi139ing Diarrhea o Diarrhea o Nigh r swea rs Phases of HIV LATENCY PHASE I No signs or symp roms I Median dura rion 10 years I Virus ac139ively mul riplying and killing CD4 cells Phases of HIV EARLY SIGNS amp SYMPTOMS Signs amp Sympi39oms of immune deficiency bu139 no serious enough To be defined as AIDS Signs amp Symp roms o Fever Fa rigue Candidiasis oral vaginal Seborrheic dermafi ris Cervical Dysplasia Enlarged Lymph Nodes 2 loca139ions x 3 mon rhs Viral Load T CD4 Coun r l 0000 AIDS Develop lifeThrea rening oppor139unis139ic infecfions amp malignancies Examples Complefe s is in rexfbook CD4 coun139 lt 200 cells microli139er of blood HIV Window Period Terminology 0 Time affer infec139ion bu139 before seroconversion 0 HIV an139ibody Tesf NEGATIVE Seroconversion o Poin r a139 which infec red person converfs from a NEGATIVE TO A POSITIVE An ribody Tes r o Mos Take 3 mon rhs To seroconver139 o A few may Take up To 6 mon rhs To seroconver139 HIV Screening I ELISA TEST Tes rs 0 HIV An ribody Tes r o Ini rial Tesf 0 Less expensive 0 If confirm wi139h a Wes139ern Blo r o Ge r resul rs in 2 weeks Wes139ern Blo r Tes r o More expensive 0 More sensi139ive OraSure 0 HIV An ribody Tes r o Moufh Swab 0 Mail specimen To lab for Tes ring Takes 2 weeks To ge139 resul rs o Accura re bu139 no as accura139e as blood Tesfs OraQuick Advance 0 HIV An ribody Tes r 0 Finger s rick or mou rh swab Tesf o Resul rs in 2030 minu res 0 Very accura139e Home Access HIV1 Tes r 0 FDA approved 0 Fing r prick 19 NU 231 Pathophysiology Kidney Disorders Topical Outline 1 2 0 9 89 er Kidney Structure amp Function Review Chapter 23 Lab Tests a Urinalysis UA b Serum Creatinine c Blood Urea Nitrogen BUN Acute Renal Failure Chronic Renal Failure Cystitis bladder infection Pyelonephritis kidney infection Kidney Stones Glomerular Disorders E Nephritic Syndrome U Nephrotic Syndrome c Chronic Glomerulonephritis d Glomerular Lesions Associated with Systemic Disease Bladder Cancer LAB TESTS OF R INAL FUNCTION Urinalysis UA Random Urine Sample best is first pee of the day Midstream Clean Catch Urine Specimen Dipstick Characteristics Normal Value Color 0 Yellow to amber Turbidity cloudiness 0 Clear to My hazy Speci c Gravity measure of o 10101025 hydration higher the number the more dthdrated Vou are pH 0 4580 avg 60 Glucose 0 Negative Ketones 0 Negative Blood 0 Negative Protein protein in urine is one of the 0 first signs of kidney dz Negative to Trace amount Leukocyte Esterase 0 Negative WBC Nitrite o Negative Bacteria Serum Creatinine Normal Values 06 12 mg 0 Small female 06 0 Normal Adult Male 10 o Muscular Adult Male 12 Measures ability of kidneys to clear creatinine from blood Creatinine is a catabolic product of creatine which is used in skeletal muscle contraction Very sensitive indicator of renal function 0 Produced at constant rate depending on muscle mass 0 Not affected by diet or uid intake BUN Blood Urea Nitrogen Normal Value 8 20 mgdl Measures ability of kidneys to excrete urea nitrogen Urea is formed in the liver as a byproduct of protein metabolism Eliminated entirely by the kidneys Less sensitive indicator of renal function BUN in uences by 0 Protein intake 0 Hydration status 0 GI Bleed Blood broken down by intestinal bacteria ARF ACUTE RENAL FAILURE o Abrupt or rapid decline in renal ltration function due to kidney damage Results in the accumulate nitrogenous wastes o Urea Nitrogen o Creatinine o Uric Acid 0 Usually transient lasts for few days 01 weeks OR may develop into chronic renal failure CRF o ARF M01tality Rates 50 have remained the same for past 50 years Mostly affects elderly O ARF CLASSIFICATION Categorized according to similar pathology Category Pathology Causes Prerenal Decreased blood ow to Hypovolemia Hemorrhage GI Losses kidneys i Cardiac Output Heart Failure MI 39 HYPOPeTfUSiOU initiates cell Systemic Vasodilation Anaphylactic or lulury Septic Shock Arteriolar Vasoconstriction o NSAIDs 0 Radio Contrast Dye POStrenal Obstruction of urine Kidney Stones elimination from kidneys Ureteral Stricmres Bladder Tumor Prostate Enlargement Intrafenal Structural damage to kidney Acute Renal Disease IntrinSic o Glomeruli 0 Acute Glomerulonephritis 0 Rental Tubules o Pyelonephritis 0 Intersmial Tissue Acute Tubular Necrosis most common cause of intrarenal ARF o Prolonged Ischemia o Nephrotoxic Substances Antibiotics GentamycinTobramycin Kanamycin Cancer Drugs Cisplatin Radio Contrast Dye Heavy Metals Lead Mercury ATN ACUTE TUBULAR NECROSIS Has well defined s aguence of events Initiation From time of onset of precipitating event to tubular injury Phase Decrease in GFR Increases BUN amp Serum Creatinine Duration Lasts hours or days Maintenance Severe reduction in GFR Phase BUN and Serum Creatinine continue to rise Decrease in urine output Fluid Retention Edema HTN Hyperkalemia Duration 12 weeks Recovery Gradual improvement in kidney function Phase UO starts to increase if Oliguria was present Duration May take several months Types of ATN Patients Oliguric Urine volume lt 400 ml24 hours Usually have worse prognosis Formerly most pts were oliguric but with improved uid replacement drugs etc greater are nonmic N0n01iguric Urine volume gt 400 ml24 hours Abnormalities in blood chemistries Serum Creatinine BUN are usually milder and cause fewer complications CRF CHRONIC RENAL FAILURE Progressive and ir Occurs over period Etiology reversible destruction of kidney of months to years Diabetes Mellitus 30 Hypertension 30 Glomerulonephritis 21 Urologic Disease 0 Kidney Stones 0 Pyelonephritis Pathophysiology Each kidney contains gt 1 million nephrons Damaged nephrons are replaced with scar tissue Kidneys have the ability to adapt o Remaining nephrons compensate for nephrons that have been lost 0 Undergo functional hypertrophy each increasing its function as a means of compensating for those that have been lost Thus symptoms do not occur until disease far advanced O CLASSIFICATION SYSTEM NATIONAL KIDNEY FOUNDATION Stage Description GFR mlmin ml of ltrate formed each min Normal Normal kidney function N0 proteinuria gt 90 mlmin Stage 1 Normal GFR Protein in urine gt 90 mlmin Stage 2 Mild decrease in GFR 6089 mlmin Stage 3 Moderate decrease in GFR 3059 mlmin Stage 4 Severe decrease in GFR 1529 mlmin Usually NO symptoms until Stage 4 because the remaining nenhrons have taken over for the damaged ones Stage 5 Very severe decrease in GFR lt 15 mlmin ESRD End State Renal Disease N0 survival TERMINOLOGY AZOtemia o Accumulation of nitrogenous waste products 0 Urea Nitrogen Creatinine Uric Acid 0 May be asymptomatic Uremia o Urine in the blood 0 Accumulation of nitrogenous waste products 0 Symptomatic 0 Usually End Stage Renal Failure SIGNS amp SYMPTOMS OF END sTAGE RENAL DISEASE F amp E T Potassium o 90 of K eliminated thru kidneys Imbalance o Damaged kidney unable to excrete K hyperkalemia T Sodium amp o Kidneys lose their ability to regulate Na amp H20 Water T vascular volume Edema HTN Pulmonary Congestion l CaICium o Kidneys unable to synthesize active form of Vitamin D Calcitriol Decreased GI absorption of Ca Phosphate o Reciprocal rs between Ca amp PO4 o Decreased renal excretion of PO4 AcidBase Metabolic 0 pH lt 735 Imbalance Acidosis o HCO3 lt 21 mEqL o Retain nitrogenous wastes amp metabolic acids Skin Nails Yellowishbrown hue to skin 2nd to urinary pigment retention nothing to do with jaundice and bilirubin Pale Skin Anemia Bruises easily i platelet function Dry Scaly amp Itchy Pruritis Nails Terry s Nails thin brittle with dark band Uremic Frost advanced Stages Diffuse deposits of tiny white crystals on skin due to high urea concentration


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