NURS 8022 Advanced Pathophysiology Exam 3 Study Guide, Exams of Pathophysiology

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NURS 8022 Advanced Pathophysiology Exam 3 Study Guide Respiratory Structures of pulmonary system – NOT ON STUDY GUIDE  Lobes (3 on right, 2 on left) - segments – lobules  Blood vessels serve the pulmonary system  Chest wall/thoracic cage  Diaphragm: involved in ventilation – dome shaped muscle that separates the thoracic and abdominal cavities  Mediastinum: space between lungs containing heart, great vessels, and esophagus  Conducting airways o Upper airways: warms and humifies air  Nasopharynx and oropharynx o Larynx: connects upper and lower airways o Lower airways  Trachea, bronchi, terminal bronchioles  Carina: ridge where the trachea divides into the right and left bronchi  Hila: where the right and left bronchi enter the lungs, along with blood and lymph vessels  Goblet cells: produce mucus  Cilia: hair-like structures – work with goblet cells to propel foreign material up and enable it to be coughed up  Pleura: serous membrane – adheres firmly to the lungs and folds over itself o Visceral: covering the lungs; Parietal: lining the thoracic cavity o Pleural space: fluid lubricates the pleural surfaces allowing them to slide over each other  Pressure in pleural space: negative (-4 to –10); keeps lungs from collapsing  Inspiration – chest cage pulled outward on lungs creates greater negative pressure Understand basic structure and function of alveoli  Gas exchange airways: acinus - “berry” o Respiratory bronchioles o Alveolar ducts o Alveoli  Primary gas exchange units  Oxygen enters the blood and carbon dioxide is removed  Epithelial cells  Type 1 alveolar cells: provide alveolar structure  Type 2 alveolar cells: surfactant production – prevents lung collapse  Contain alveolar macrophages: ingest foreign material and remove it through lymphatic system Surfactant – its function and where it comes from  Detergent like substance secreted by type 2 alveolar epithelial cells in lungs  Keeps alveoli open and free of fluid and pathogens (collectins)  Decrease surface tension by blocking H20 and H+ binding in alveolar space – prevents collapse – allow airflow in more easily Understand the mechanics of the pulmonary circulation and how it relates to systemic circulation  Pulmonary circulation functions: o Facilitate gas exchange o Deliver nutrients to lung tissue o Acts as a blood reservoir for the left ventricle o Serves as a filtering system that removes clots, air, and other debris from the circulation o Pulmonary system pressure is 18 mmHg compared to systemic circulation of 90 mmHg o Gas exchange airways are served by the pulmonary circulation  Low pressure system, high flow – Supplies venous blood from all parts of the body to the alveolar capillaries where O2 is added and CO is removed; contains 100% of CO o Bronchi and other lung structures are served by systemic circulation – bronchial circulation  High pressure system, low flow – supplies blood to trachea, bronchial tree, bronchioles, and out coats (adventia) of pulmonary arteries and veins; contains 1-3% of CO  Pulmonary circulation o Begins at the pulmonary artery, which receives venous blood from the right side of the heart. The pulmonary artery divides into the left and right branches and forms the capillaries that surround the alveoli. After blood is oxygenated via gas exchange, blood returns to the left side of the heart through the pulmonary veins.  Pulmonary artery and accompanying smaller arteries and arterioles have large diameter; systemic vessels are small o Gives the pulmonary artery tree large compliance - accommodate stroke volume and pressure from RV  Pulmonary capillaries surround the acinus  Alveolocapillary membrane o Formed by shared alveolar and capillary walls o Contains the pulmonary capillaries o Where gas exchange occurs  Mechanics of breathing o Major and accessory muscles – The major muscle of breathing is the diaphragm, which performs 80% of the work of breathing. External intercostals function as accessory muscles to raise the ribs up and out, often during respiratory distress. o Alveolar surface tension –Surfactant plays a major role in alveolar surface tension, pulmonary surfactant functions to decrease alveolar surface tension to increase lung compliance and ease the work of breathing. o Elastic properties of the lung and chest wall – The lung and chest wall have elastic properties that permit expansion during inspiration and return to resting volume during expiration. Elastic recoil is the o Diffusion of carbon dioxide from the cells into systemic capillaries o Perfusion of the pulmonary capillary bed by venous blood o Diffusion of carbon dioxide into the alveoli o Removal of carbon dioxide from the lung by ventilation o Carbon dioxide transport  Amount of CO2 in blood is a significant factor in acid-base balance  Retaining too much CO2 will cause an increase in respiratory rate  3 ways: dissolved in plasma, bicarbonate, carb-amino compounds  Bicarbonate: as CO2 moves into the blood is diffuses intothe RBC’s - carbonic anhydratse combines CO2 and H2O to form carbonic acid – carbonic acid dissocaites into HCO3 and H+ - H+ binds to hgb and the HCO3 moves out of the RBC into the plasma  60% venous CO2 is in bicarbonate form  90% arterial CO2 is in bicarbonate form  Alveolar oxygen o Oxygen absorbed from alveoli to blood – alveolar oxygen determined by rate of absorption into blood and rate of entry of new oxygen o Partial pressure normally 104 mmHg  Alveolar carbon dioxide o Removed from alveoli o Partial pressure normally 40 mmHg; increases directly in proportion to rate of CO2 excretion; decreases in inverse proportion to alveolar ventilation  Principles of gas exchange o Diffusion in response to concentration gradients – pressure proportional to concentration  CO2 20 times as soluble as O2 o Diffusion depends on partial pressure of gas o Haldane Effect: Oxygenation of blood in the lungs displaces carbon dioxide from hemoglobin which increases the removal of carbon dioxide Understand basic concepts of the oxyhemoglobin curve and what it represents  Oxyhemoglobin association and dissociation o Hemoglobin molecules bind with oxygen – oxyhemoglobin  Binds in areas of high partial pressure and released in areas of low partial pressure  Continues to bind until hgb binding sites are saturated  Diffusion across alveolocapillary membrane – partial pressure of oxygen molecules is much greater in alveolar gas than it is in capillaries – promotes rapid diffusion from the alveolus into the capillary  Determinants of arterial oxygenation: rate of oxygen transport to the tissues in blood and rate at which oxygen is used by the tissues o When hemoglobin saturation and desaturation are plotted one graph, the result is a distinctive S-shaped curve known as the oxyhemoglobin dissociation curve  Oxyhemoglobin shift o Shift to the left/up  Hemoglobin's increased affinity for oxygen – promotes association in the lungs and inhibits dissociation in the tissues  Alkalosis (high pH) and hypocapnia and hypothermia o Shift to the right/down  Hemoglobin's decreased affinity for oxygen – increase in the ease with which oxyhemoglobin dissociates and oxygen moves into the cells  Happens when cells need more O2  Acidosis (low pH) and hypercapnia and hyperthermia o Bohr effect: shift in the oxyhemoglobin dissociation curve caused by changes in CO2 and H+ concentration in the blood Understand and be able to identify and define abnormal breathing patterns  Kussmaul respirations (hyperpnea) o Slightly increased ventilatory rate, very large tidal volume, no expiratory pause  Cheyne-Stokes respirations o Alternating periods of deep and shallow breathing; apnea lasting 15-60 seconds, followed by ventilations that increase in volume until a peak is reached, after which ventilation decreases again to apnea o Occurs with decreased brainstem blood flow  Hypoventilation o Alveolar ventilation is inadequate in relationship to the metabolic demands o Leads to respiratory acidosis from hypercapnia (CO2 >44) o Causes: airway obstruction, chest wall restriction, altered neurologic control of breathing  Hyperventilation o Alveolar ventilation exceeds the metabolic demands o Leads to respiratory alkalosis from hypocapnia (CO2 <36) o Causes: anxiety, panic attacks, head injury, severe hypoxemia Know how to identify and define hypercapnia, hypocapnia, hypoxia, and hypoxemia  Hypercapnia o Increased CO2 in the arterial blood (PaCO2>44) o Occurs from decreased drive to breathe or an inadequate ability to respond to ventilatory stimulation/hypoventilation - retain too much CO2 – respiratory acidosis o Ex: drugs, brainstem (medulla) injury, spinal cord injury, NMJ dysfunction, respiratory muscle disfunction (myasthenia gravis), thoracic cage abnormalities, airway obstruction, sleep apnea  Hypocapnia o Decreased CO2 in the arterial blood (PaCO2<36) o Caused by hyperventilation – blowing off too much CO2 – respiratory alkalosis o See hyperventilation above  Hypoxemia o Hypoxemia is decreased PaO2 in blood; hypoxia is decreased O2 in cells/reduced level of tissue oxygenation o Most common cause: ventilation-perfusion abnormalities  Shunting: shunting blood to areas that are better ventilated by using vasoconstriction Understand and define the different types of pleural effusions - abnormalities  Pneumothorax: presence of air or gas in the plural space o Primary: spontaneous; occurs unexpectedly in healthy individuals o Secondary: caused by disease, trauma, injury, or condition o Iatrogenic: caused by medical treatments, especially needle aspiration/biopsies o Open: air pressure in pleural space equals barometric pressure because air that is drawn into the pleural space during inspiration is forced back out during expiration – air is not trapped o Tension: site of pleural rupture acts as a one-way valve, permitting air to enter on inspiration but preventing its escape by closing up during expiration – air is trapped – life threatening o S/Sx: sudden pleural pain, tachypnea, possible mild dyspnea  Tension: severe hypoxemia, tracheal deviation away from affected lung, hypotension  Pleural effusion: presence of fluid in the pleural space o Transexudative: watery and diffuses out of the capillaries o Exudative: less watery and contains high concentrations of WBC’s and plasma proteins o Chylothorax: chyle exudate from stomach contents o Hemothorax: blood exudate o S/Sx: dyspnea, pleural pain  Empyema: infected pleural effusion – pus in the pleural space o S/Sx: cyanosis, fever, tachycardia, cough, pleural pain Understand the differences between restrictive and obstructive respiratory alterations. Know which ones are in which category  Restrictive lung disease o Difficult to get air in o Compliance (ability to expand) of lung is reduced – increases stiffness of the lung and limits expansion  A greater pressure than normal is required to give the same increase in volume o Causes: pulmonary fibrosis, pneumonia, pulmonary edema  Stiff lungs, stiff chest wall, weak muscles  Obstructive lung disease o Difficult to get air out o Airway obstruction causes an increase in resistance  Pressure volume relationship is no different – except when breathing rapidly, greater pressure is needed to overcome the resistance to flow and the volume of each breath gets smaller o Causes: asthma, bronchitis, emphysema  Mechanical obstruction, increased resistance, increased tendency for airway closure  Pulmonary HTN o Mean pulmonary artery pressure above 25 mmHg at rest o Causes: elevated left ventricular pressure, increased blood flow through the pulmonary circulation, obliteration or obstruction of the vascular bed, active constriction of the vascular bed produced by hypoxemia or acidosis o Patho: overproduction of vasoconstrictors (thromboxane) and decreased production of vasodilators (NO and prostacyclin); remodeling of pulmonary artery intima; resistance to pulmonary artery blood flow increasing the pressure in the pulmonary arteries; workload of the right ventricle increases and subsequent right ventricular hypertrophy – may be followed by failure and eventually death o S/Sx: masked by primary pulmonary or CV disease; chest x-ray shows enlarged pulmonary arteries and right heart border – echo shows right ventricular hypertrophy o Cor pulmonale – secondary to PAH – pulmonary HTN creating chronic pressure overload in right ventricle  S/Sx: heart appears normal at rest; decreased cardiac output and chest pain with exercise  Bronchogenic cancers o Most frequent cause of cancer death in the US; most common cause: cigarette smoking o Laryngeal  Risk factors: smoking, heightened with smoking and alcohol consumption, GERD, HPV  S/Sx: progressive hoarseness, dyspnea, cough o NSCLC  85% of all lung cancers  Squamous cell carcinoma: nonproductive cough or hemoptysis  Adenocarcinoma: tumor arising from glands – asymptomatic or pleuritic chest pain and SOB  Large cell carcinoma: chest wall pain, pleural effusion, cough, sputum, hemoptysis, airway obstruction resulting in pneumonia o SCLC – neuroendocrine  10-15% of all lung cancers  Worst prognosis – rapid growth and early metastasis  Strongest correlation with smoking  Arise from neuroendocrine tissue – ectopic hormone secretion – paraneoplastic syndromes  Hyponatremia (ADH); Cushing syndrome (ACTH); hypocalcemia (calcitonin); gynecomastia (gonadotropins); carcinoid syndrome (serotonin) o Lung carcinoid tumor  5% of all lung cancers  Grow slowly and rarely spread  Atelectasis o Collapse of lung tissues  Absorption: gradual absorption of air from obstructed or hypo-ventilated alveoli  Compression: external compression on the lung  Surfactant impairment: decreased production or inactivation of surfactant o S/Sx: dyspnea, cough, fever, leukocytosis (inflammatory process)  Pulmonary edema o Excess water in the lung from disturbances of capillary hydrostatic pressure, capillary oncotic pressure, or capillary permeability – increased capillary hydrostatic pressure leads to fluid leaking into lung o Most common cause: left sided heart failure o Post-obstructive pulmonary edema: negative pressure pulmonary edema  Rare, life-threatening complication that can occur after relief of upper airway obstruction – obstruction causes negative pressure to build and build as breathing attempts occur  S/Sx: dyspnea, orthopnea, hypoxemia, increased WOB, pink frothy sputum  ARDS o Characterized by acute lung inflammation and diffuse alveolocapillary injury – injury to pulmonary capillary endothelium, increased capillary permeability, inflammation, surfactant inactivation, edema, atelectasis o Dyspnea and hypoxemia with poor response to oxygen supplementation – hyperventilation and respiratory alkalosis – decreased tissue perfusion, metabolic acidosis, organ dysfunction – increased WOB, decreased TV, and hypoventilation – hypercapnia, respiratory acidosis, worsening hypoxia – decreased cardiac output, hypotension, death  Pulmonary embolism o Occlusion of a portion of the pulmonary vascular bed by a thrombus, embolus, tissue fragment, lipids, or air bubble o Virchow triad: venous stasis, hypercoagulability, and injuries to the endothelial cells that line the vessels o Results in widespread hypoxic vasoconstriction, decreased surfactant, release of neurohumoral substances, atelectasis of affected lung segments further contributing to hypoxemia, pulmonary edema, pulmonary HTN, shock, and even death o S/Sx: sudden onset of pleuritic chest pain, dyspnea, tachypnea, tachycardia, unexplained anxiety  Pneumothorax – see above Not on study guide: TB, abscess, pneumonia, CF, bronchiectasis, bronchiolitis Cardiac Understand the basics of cardiac muscle contraction  Resting membrane potential is similar to skeletal muscle (-85 to –95mV) - threshold potential is +105  Caused by opening of fast sodium channels and slow sodium channels  Slow sodium channels are sodium-calcium channels – open slower and remain open for longer – allows for influx of large quantity of calcium and sodium ions to the interior of the cardiac muscle fiber – maintains prolonged period of depolarization causing the plateau in the AP – calcium ions enter during plateau phase activating the contractile process  Cardiac muscle has low permeability to potassium after onset of AP (not like skeletal) o Decreases the outflux of potassium; prevents early return of AP to resting value  Sodium/calcium channels close and the membrane permeability for potassium ions increases rapidly  Repolarization occurs quickly as potassium moves outward – returns to RMP  Relaxation: occurs at the end of plateau when influx of calcium ions to the interior of the muscle is cut off o Calcium ions in SR and t-tubules are rapidly pumped back into ECF o Transport in SR is the result of calcium-ATPase pump o Sodium that enters in this exchange then pumped out by Na/K ATPase pump o Contraction ceases until new AP occurs  Refractory period: during this time cardiac muscle cannot be re-excited – lasts 0.35-0.3 seconds in ventricles o Relative refractory period of 0.05 sec – period in which re-excitation is more difficult  Excitation contraction coupling: process by which an AP triggers the cycle of events leading to cross bridge activity and contraction o Requires calcium; calcium-troponin C complex facilitates the contraction process o Cross-bridge cycling: attachment of actin to myosin at the cross bridge – thin and thick filaments slide past each other causing contraction Understand cardiac cycle and what each part represents  Cardiac cycle: one contraction and one relaxation – one heartbeat o Diastole: relaxation – ventricles fill o Systole: contraction – blood leaves the ventricles  Phase 1: atrial systole or ventricular diastole  Phase 2: isovolumetric ventricular systole – the ventricles begin to open the pulmonary and aortic values by pressure building  Phase 3: ventricular ejection - semilunar valves open completely (most blood goes in the first ejection  Phase 4: isovolumetric ventricular relaxation - aortic valve closes  Phase 5: passive ventricular filling – mitral and tricuspid valves Understand EKG basics, waves, and intervals  Smaller chambers and thicker chamber walls equal increased contraction force o In ventricular dilation, the force needed to maintain ventricular pressure lessens available contractile force  Heart rate  Effected by cardiovascular control center (sympatheticand parasympathetic), neural reflexes (sinus arrythmia with inspiration and expiration; baroreceptor reflex; Bainbridge reflex [IV infusions]; and atrial receptors), and hormones and biochemicals (epinephrine, norepinephrine, thyroid hormone, growth hormone)  Myocardial contractility  Stroke volume: volume of blood ejected during systole (ventricular contraction)  Force determined by: stretch/preload, nervous system input (symp v parasymp), adequacy of myocardial oxygen supply  Positive inotropes: increase force of contraction o Norepinephrine (sympathetic), epinephrine (adrenal medulla), thyroid hormone, dopamine  Negative inotropes: decrease force of contraction o Acetylcholine (vagus nerve)  Hypoxia decreased contractility  EF: amounts of blood ejected per heartbeat by the ventricles o SV/end-diastolic volume o Normal is 55% or higher o Indicator of ventricular function  Cardiac index: CI = CO/BSA - normal is 2.5-4 L/min/m2  Decreased CO/CI - anything that causes decreased contractility or decreased blood flow to the heart o MI, shock, bradycardia, decreased SV, negative inotropes, increased vascular resistance, cardiac tamponade, hypovolemia, valvular heart disease, high PEEP  Increased CO/CI - anything that causes increased contractility or increased blood flow to the heart o HTN, decreased vascular resistance, pulmonary edema, increased metabolic state, positive inotropes  Factors that regulate blood flow: degree of cardiac contractility, heart rate, venous return to the heart o Blood volume, patency of venous system, degree of arteriolar dilation, differential pressure, skeletal muscle pump, respiratory pump (inspiration causes increase in negative pressure that draws blood into the heart and increases venous return), velocity, viscosity, vascular compliance (opposite of stiffness – veins are more compliant) o Laminar versus turbulent flow o Poiseuille’s Law  Greater the resistance, the lower the blood flow Know different valves and which type they are  Ensure one way blood flow  AV valves: atrioventricular valves o Tricuspid: between right atrium and right ventricle; three leaflets or cusps o Bicuspid (mitral): between left atrium and left ventricle; two leaflets or cusps  Semilunar valves o Pulmonic semilunar valve: from right ventricle to pulmonary artery o Aortic semilunar valve: from left ventricle to the aorta  During atrial contraction: tricuspid and bicuspid (mitral) valves are open as blood is pushed from the atria to ventricles  During ventricular contraction: aortic and pulmonic valves are open as blood is pushed from ventricles to pulmonary system/systemic circulation Potassium and calcium do what to the heart  Excess K+ decreased contractility o Causes heart to become dilated and flaccid; slows heart rate o Hyperpolarization occurs – cannot initiate AP  Excess Ca++ causes spastic contraction  Low Ca++ causes cardiac dilation o Calcium abnormalities are not as big of a concern – blood levels are more regulated Understand electrical pathway of the heart – basics. Know different nodes and what they do  SA node – internodal pathway – AV node – AV bundles – left and right bundles of Purkinje fibers  Begins in SA node (pacemaker of the heart) o Located in right atrium near entry of SVC o Spontaneously depolarizes from 60-100 BPM o Impulse spreads rapidly from SA node along individual atrial muscle cells to depolarize the right and left atria – causes atrial contraction  AV node (40-60 BPM) o Located in posterior wall of right atrium immediately behind the tricuspid valve o Delays cardiac impulse – allows atria to empty blood into the ventricles before ventricular contraction  AV bundles o Normally one-way conduction through bundles – prevents re-entry of conduction o The only conducting path between the atria and ventricles o Divides into left and right bundles o Transmission time between AV bundles and last of ventricular fibers is the QRS time (0.06 sec)  Purkinje fibers (20-40 BPM) o From AV node through AV bundle into ventricles o Fast conduction – large fibers transmit AP’s quickly – gap junctions enhance velocity  Similar to saltatory conduction Know sympathetic and parasympathetic effects on the heart  Sympathetic - “fight or flight” o Increases electrical conductivity and the strength of the myocardial contraction o Increased sinus node discharge, rate of conduction impulse o NT’s: norepinephrine, epinephrine  Norepinephrine  Vasoconstrictive by interacting with blood vessel alpha 1 receptors  Does not act on beta 2 receptors  Epinephrine  Vascoconstrictor (alpha 1) and vasodilator (beta 2) o Adrenergic receptor function  Alpha or beta adrenergic recptors  Stimulation of both B1 and B2 increases HR (chronotropy) and force of contraction (inotropy)  Beta 1 – normal heart o Activation leads to increases in contractile force and HR o Located on: cardiac pacemaker, myocardium, salivary gland ducts, sweat glands o Norepi and epi o Renin release – aldosterone – vasoconstriction – increase BP  Beta 2 – vascular and non-vascular smooth muscle o Regulatory o Inverse response of cell – stimulation leads to decreased activity or muscle tone o Located on: smooth muscle, GI tract, bladder, skeletal muscle, arteries, bronchial tree, some coronary arteries (increased coronary blood flow) - vasodilation of bronchioles and skeletal muscle tissue o Epi only  Alpha 1 – direct response o Activity or muscle tone is increased o Located on all vascular smooth muscle, GI and urinary sphincters, dilator muscle of the iris, arrestor pili muscles in hair follicles (goosebumps) o Norepinephrine binds with alpha 1 receptors causing smooth muscle contraction and vasoconstriction of the coronary arteries  Parasympathetic - “rest” o Slows conduction of AP’s through the heart and reduces strength of contraction o Parasympathetic (vagal) nerves – release acetylcholine – innervate SA node and AV fibers  Causes hyperpolarization because of increased K+ permeability in response to acetylcholine  Hyperpolarization causes decreased transmission of impulses/excitability – reduces HR o NT’s: acetylcholine  Cholinergic receptors: muscarinic (slows HR, decreases contractility, bronchial constriction) and nicotinic (only involved in muscle contraction, NMJ)  Other types of control – not on study guide o Brain stem vasomotor center  Connects with PNS via vagus nerve to decrease HR o ADH  Acts on kidneys to increase water reabsorption, vasoconstriction – increased BV, BP o Brain stem and hypothalamic notification  Baroreceptors in carotid sinus involved in negative feedback  Ex) carotid massage for tachy – stimulates parasympathetic response  Increased serum osmolality, increased CO2 and H+ o BNP – brain natriuretic peptide  Found in high concentration in cardiac tissues (ventricles) and released with increased ventricular filling pressure and LV dysfunction (increase in stretch) o ANP – atrial natriuretic peptide FALSE (BOTTOM TWO)  S/Sx: o Heart: dysrhythmias, heart failure, embolisms o Aorta: asymptomatic until it ruptures – then becomes painful o Thoracic: dysphagia, dyspnea are caused by pressure o Abdomen: flow to an extremity is impaired causing ischemia o  Complication: o Aortic dissection: tear in intima or aorta into which blood flows furthering the tear o Disrupts flow through arterial branches o Surgical emergency o S/Sx: ripping chest and pack pain, loss of pulses, BP’s different on arms; c-x-ray: wide mediastinum o Connective tissue disease are predisposing factors DVT patho  Clot in a large vein causing obstruction of venous flow leading to increased venous pressure  Risk factors: Virchow's triad – venous stasis, venous endothelial damage, hypercoagulable state  May cause post-thrombotic syndrome – chronic persistent pain, edema, alteration in limb function Atherosclerosis patho  Form of arteriosclerosis – thickening and hardening caused by the accumulation of lipid-laden macrophages in the arterial wall – plaque development o Leading cause of CAD and CV disease  Progression of disease o Endothelium injury – inflammation of endothelium – cytokines released – cellular proliferation – macrophage migration – LDL oxidation (foam cell formation) w/ oxidative stress – fatty streak – fibrous plaque – complicated plaque (ruptured plaque) Raynaud’s patho  Episodic vasospasm (ischemia) in the arteries and arterioles of the fingers  S/Sx: changes in skin color and sensation caused by ischemia  Phenomenon: secondary to other systemic diseases or conditions  Disease: primary vasospastic disorder or unknown origin o Attacks triggered by brief exposure to cold or emotional stress  Tends to affect young women CAD pathogenesis and s/s  Patho o Any vascular disorder that narrows or occludes the coronary arteries o Results in an imbalance between coronary supply of blood and myocardial demand for oxygen and nutrients o Most common cause: atherosclerosis o Non-modifiable risk factors: family hx, advanced age, male gender or women after menopause o Modifiable risk factors: dyslipidemia, HTN (endothelial injury, increased in myocardial demand), cigarette smoking (vasoconstriction and increase in LDL, decrease in HDL), DM and insulin resistance (endothelial damage, thickening of vessel wall), obesity and/or sedentary lifestyle o Non-traditional risk factors:  Markers of inflammation and thrombosis: CRP – released by liver; indirect measure of plaques and any inflammation  Troponin I  Hyperhomocysteinemia: result of genetic lack of enzymes that breaks down homocysteine (amino acid) or folate, b12, or b6 deficiency  Adipokines: group of hormones released from adipose cells – decreased = increased risk  Infection: inflammation of vessels – vascular disease  Air pollution  Coronary artery calcification, carotid wall thickness o Dyslipidemia: indicator of coronary risk  Increased LDL: role in endothelial injury, inflammation, immune response that are important in atherogenesis  Low HDL: responsible for reverse cholesterol transport – return excess cholesterol from tissues to liver  Elevated serum VLDL (triglycerides)  Increased lipoprotein a Angina pathogenesis and s/s  Unstable angina: reversible myocardial ischemia and a harbinger of impending infarction o Transient episodes of thrombotic vessel occlusion and vasoconstriction occur at the site of plaque damage with a return of perfusion before significant myocardial necrosis occurs  Stable angina: predictable chest pain with exertion  Prinzmetal angina (variant): unpredictable chest pain  Silent ischemia: no detectible symptoms; common with DM  Angina pectoris: transient substernal chest discomfort MI pathogenesis and s/s  Prolonged ischemia causes irreversible damage to the heart muscle (myocyte necrosis)  Structural and functional changes: o Myocardial stunning: temporary loss of contractile function that persists for hours to days after perfusion has been restored o Hibernating myocardium: tissue that is persistently ischemic undergoes metabolic adaptation to prolong myocyte survival o Remodeling: process that occurs in the myocardium after an MI; hypertrophy, scarring o Repair: consists of degradation of damaged cells, proliferation of fibroblasts, and synthesis of scar tissue  Mediated by aldosterone, angiotensin II, catecholamines, adenosine  Angiotensin II effects  Systemic: peripheral vasoconstriction and fluid retention  Local: growth factor for vascular smooth muscle cells, myocytes, and cardiac fibroblasts; promotes catecholamine release; causes coronary artery spasms; involved in remodeling  Functional changes o Depends on size and site of infarction o Decreased cardiac contractility with abnormal wall motion o Altered left ventricular compliance o Decreased SV, EF o Increased LVEDP o SA or AV node malfunction o Papillary muscle rupture; septal rupture (systolic murmur); ventricular free wall rupture (tamponade) o Conduction – arrythmias  Two major types: subendocardial and transmural o STEMI – require immediate intervention – full thickness damage o NSTEMI – suggest that additional myocardium is still at risk; partial thickness damage  S/Sx o Sudden severe chest pain, N/V, diaphoresis, dyspnea o Ecg changes Staging of Heart FailureClasses of Heart Failure  LVEF <40% - ventricular remodeling/hypertrophy  Manifestations are the result of pulmonary vascular congestion and inadequate perfusion of the systemic circulation  S/Sx: dyspnea, orthopnea, cough with frothy sputum, fatigue, decreased urine output, edema, paroxysmal nocturnal dyspnea  PE: pulmonary edema (cyanosis, inspiratory crackles, pleural effusions), hypotension or hypertension, S3 gallop (excess fluid slapping), evidence of underlying CAD or HTN o Diastolic heart failure – filling problem  Pulmonary congestion despite normal stroke volume and cardiac output or ejection fraction  LVEF >40%; Heart failure with preserved ejection fraction  Decreased compliance of left ventricle and abnormal diastolic relaxation which leads to increased end diastolic pressure – transmitted to pulmonary circulation – causes pulmonary congestion  Causes: HTN, ischemia, afib, ventricular hypertrophy, aging, DM  S/Sx: non-specific; dyspnea, exercise intolerance, fatigue, weakness  Right heart failure o Seen with pulmonary disease = cor pulmonale o Normally due to left sided heart failure o Back up into the pulmonary system from left sided heart failure leads to eventual right heart failure  Other causes: intrinsic pulmonary disease, pulmonary HTN, COPD, volume overload conditions, infarcted right ventricle, congenital heart disease, PE, heart valve disease o S/Sx: pedal edema, ascites, hepatosplenomegaly, elevated JVP-JVD, sacral edema, nocturia, jaundice, coagulopathy Pediatric congenital heart defects, identify different types, s/s and how they are classified  Heart failure  Acyanotic defects: allow shunting from high-pressure left heart to lower-pressure right heart; CHF sx – untreated leads to pulmonary HTN o Patent ductus arteriosus (PDA)  Vessel located between junction or main and left pulmonary arteries  Failure of ductus arteriosus to close results in persistent patency – allows blood to shunt from aorta to pulmonary artery causing left to right shunt  Results in increased pulmonary blood flow resulting in increased pulmonary venous return to the LA and LV with increased workload on the left side of the heart  S/Sx: dyspnea, fatigue, poor feeding; continuous, machinery-type murmur; risk for bacterial endocarditis o Atrial septal defect (ASD)  Abnormal opening between the atria – blood flows from high pressure left atria to low pressure right atria – leads to right atrial and ventricular enlargement  Major types: ostium primum defect (low in septum); ostium secundum (center – most common); sinus venosus (high in septum)  S/Sx: often asymptomatic; dx by murmur; pulmonary symptoms on exertion at later age o Ventricular septal defect  Abnormal communication between ventricles – shunting from high pressure left ventricle to low pressure right ventricle  Common congenital heart lesion (25-33%); depends on size and degree of PVR  Pulmonary over-circulation accounts for symptoms in large VSD  S/Sx: heart failure, poor weight gain, murmur and systolic thrill  Cyanotic defects: complex with right to left shunting and cyanosis – obstruction causes increased right sided pressure – still moves from high to low o Manifest with hypoxemia and cyanosis  Mild hypoxemia: occasional cyanosis  Severe hypoxemia: feeding intolerance, poor weight gain, tachypnea, dyspnea  Chronic hypoxemia: small for age, cognitive/motor delays, polycythemia, exertional dyspnea, easily fatigued, exercise intolerance, nail bed clubbing o Tetralogy of Fallot  Syndrome represented by four defects:  VSD; overriding aorta straddles the VSD; pulmonary valve stenosis; right ventricle hypertrophy  S/Sx: cyanosis and clubbing, feeding difficulty, squatting  Hypercyanotic spell or “tet spell” that generally occurs with crying and exertion  Obstructive defects: right or left sided outflow tract obstructions that prohibit blood flow out of the heart – results in pressure load on the ventricles o Coarctation of the aorta  Narrowing of the lumen of the aorta that impedes blood flow; almost always found in the juxtaductal position (directly at the insertion of the closed ductus arteriosus in the aortic arch)  Causes condition in which there are higher pressures proximal to the site of stenosis and lower pressures distal  Direction of shunting depends on pressure different between pulmonary artery and aorta and location of the ductus (always moves high to low)  Aorta BP > pulmonary artery BP = left to right shunting – resulting in increased pulmonary venous return to the left side of the heart – hypertrophy of LV – HF  S/Sx:  Newborns with CHF; once ductus closes – rapid deterioration occurs from hypotension, acidosis, shock  Older children: HTN in upper extremities, decreased or absent pulses in lower extremities, cool mottled skin, leg cramps during exercise (LE hypotension; UE hypertension) o Hypoplastic left heart syndrome  Left sided cardiac structures develop abnormally – left ventricle, aorta, and aortic arch are underdeveloped; mitral atresia or stenosis observed  Obstruction to blood flow from the left ventricular outflow tract results in high pressure leading to saturated blood entering the LA and then mixing with desaturated blood in the RA through atrial septal communication  As ductus closes, systemic perfusion is decreased – hypoxemia, acidosis, shock – fatal if un-tx  Mixed defects: desaturated blood and saturated blood mix in the chambers or great arteries of the heart – results in desaturated systemic blood flow and cyanosis – pulmonary congestion occurs because of preferential pulmonary blood flow – leads to HF  Capillary hydrostatic pressure (BP)  Pushes water from the capillary to interstitial space  Capillary (plasma) oncotic pressure (from plasma proteins in capillary)  Pulls water from the interstitial space back into the capillary using osmosis  Interstitial hydrostatic pressure  Pushes water from interstitial space into the capillary  Interstitial oncotic pressure (from plasma proteins in interstitium)  Pulls water from the capillary into the interstitial space using osmosis  Starling's Hypothesis: net filtration is equal to the forces favoring filtration minus the forces opposing filtration  Forces favoring filtration or forces opposing reabsorption:  Capillary hydrostatic pressure (BP) - push  Interstitial oncotic pressure - pull  Forces opposing filtration or forces favoring reabsorption:  Interstitial hydrostatic pressure - push  Capillary (plasma) oncotic pressure – pull  Major forces for filtration and reabsorption are those within the capillary  Capillary hydrostatic pressure (BP) - push - filtration  Capillary (plasma) oncotic pressure - pull - reabsorption  Arterial end of the capillary  Hydrostatic pressure > interstitial oncotic pressure  Water pushes/filters into the interstitial space  Filtration  Venous end of the capillary  Capillary (plasma) oncotic pressure > intersitial hydrostatic pressure  Water is pulled into the circulation/capillary  Reabsorption  Integrity of capillary membrane is essential in capillary filtration of fluid Patho of edema  Edema: accumulation of fluid in the interstitial spaces o Causes:  Increased capillary hydrostatic pressure – ex: venous obstruction  Decreased plasma oncotic pressure – ex: losses or diminished production of albumin  Increased capillary permeability – ex: inflammation and immune response – proteins leak  Lymph obstruction – ex: lymphedema  Sodium retention – increases hydrostatic pressure o Pathophysiology:  Increase in forces favoring fluid filtration from the capillaries or lymphatic channels into the tissues o Manifestations:  Localized: limited to site of trauma or specific organ system  Ex: sprained ankle; cerebral edema, pulmonary edema, ascites, plueral effusion  Generalized  Ex: dependent edema  Associated with weight gain, swelling, tight clothes/shoes, limited ROM, and symptoms associated with underlying pathologic condition  Third-spacing  Fluid movement into space that is not available for metabolic processes or perfusion  Ex: interstitial space, pleural space, pericardial space Role of sodium in fluid balance  Sodium: most abundant ion in ECF – responsible for osmotic balance of ECF – where Na is, water follows o Roles include:  Neuromuscular irritability, acid-base balance, cellular reactions, transport of substances o Normal: 135-145 mEq/L  Hormonal regulation of sodium o Aldosterone, natriuretic peptides, and natriuretic peptides and RASS Hormonal control of fluid; aldosterone, natriuretic peptides, and ADH basic functions  Water balance – also associated with Na balance o Aldosterone: a mineralocorticoid steroid synthesized and secreted from the adrenal cortex and acts on the distal tubule of the kidney  Secreted when blood sodium levels are depressed, potassium levels increase, or renal perfusion is decreased  Leads to:  Sodium and water reabsorption back into circulation  Potassium and hydrogen secretion to be lost in urine o Natriuretic peptides: hormones that include atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)  ANP produced by myocardial atria; BNP produced in myocardial ventricles  Natural antagonist to RAAS  Decreases BP  Increases sodium and water excretion  Released when there is increased atrial pressure (increased volume) d – ex: CHF  Results in:  Decrease in BP – decreases atrial pressure – inhibits release of ANP and BNP  Negative feedback loop o ADH: antidiuretic hormone  Released when there is an increase in plasma osmolality, decrease in blood volume, or decrease in BP  Results in:  Decreased atrial pressure and ultimately the secretion of ADH  Increased water reabsorption – restoration of blood volume  Increases permeability of renal tubules and collecting ducts of kidneys  Increased blood volume returns to heart, increases atrial pressure, and stops release of ADH  Negative feedback loop RAAS basics  Thirst perception  Osmolality receptors (osmoreceptors): in hypothalamus; stimulated from hyperosmolality, dry mouth, plasma-volume depletion  Increases water intake by causing thirst sensation  Baroreceptors (volume receptors): in CV system; stimulated from depleted plasma volume  Causes release of ADH to retain volume  Renin-Angiotensin-Aldosterone System o Sympathetic nerve stimulation and decreased perfusion/blood pressure in the renal vasculature – releases renin in the juxtaglomerular cells of the kidney o Renin stimulates release of angiotensin I (inactive)  Calcium  Severe: muscle weakness, loss of muscle tone, flaccid, paralysis, cardiac arrest; with very severe the cells become unexcitable because they are near or exceeding the RMP o Bones and teeth, blood clotting, hormone secretion, cell receptor function, muscle contractions o Normal: 8.6-10.5 o Regulated by:  PTH:  Increases via kidney reabsorption  Secreted in response to low serum calcium  Vitamin D  Increases calcium absorption from GI tract; enhances renal and bone absorption  Calcitonin  Decreases plasma calcium levels by inhibiting absorption in gut and kidney o Hypocalcemia: <8.5  Causes:  Inadequate intake or absorption; decreases in PTH and vitamin D; blood transfusions  Manifestations:  Increases neuromuscular excitability (partial depolarization)  Muscle spasms, convulsions, tetany  Chvostek (tap facial nerve – twitch) and Trousseau (BP cuff – wrist twitch) signs o Hypercalcemia: >12  Causes:  Hyperparathyroidism – increased PTH; bone mets; excess vitamin D; immobilization; acidosis  Manifestations:  Decreased neuromuscular excitability  Muscle weakness, kidney stones, constipation, heart block  Hypophosphatemia o Causes: intestinal malabsorption and renal excretion, vitamin D deficiency, antacid use, alcohol abuse o Manifestations: diminished release of oxygen, osteomalacia, muscle weakness, bleeding disorders, leukocyte alterations  Hyperphosphatemia o Causes: exogenous or endogenous addition of phosphate to ECF, long term use of phosphate enemas or laxatives, renal failure o High phosphate levels associated with low calcium levels o Manifestations: same as hypocalcemia with possible calcification of soft tissue  Chloride o Extracellular ion; tends to follow sodium; inverse relationship to bicarbonate o Important anion in maintenance of iron balance and in gastric juice  Magnesium: 1.8-2.4 o Intracellular cation; stored in muscle and bones; interacts with calcium; involved in neuro excitability o Hypomagnesemia  Causes: malabsorption, hypocalcemia and hypokalemia  Manifestations: neuromuscular irritability, tetany, convulsions, increased reflexes o Hypermagnesemia  Causes: renal failure  Manifestations: skeletal muscle depression, muscle weakness, hypotension, respiratory depression, bradycardia Understand how to classify and identify different acid/base imbalances – Metabolic/respiratory acidosis/alkalosis  pH: negative logarithm of the H+ concentration o H+ high: low pH – acidic o H+ low: high pH – alkaline o To maintain the body’s normal pH the H+ must be neutralized by the retention of bicarbonate or the excretion of H+  Alterations of hydrogen and bicarbonate concentrations in body fluids are common in disease processes  Regulated by bones, lungs, kidneys  Renal regulation (slow) or pulmonary regulation (fast)  Metabolic acid-base function or respiratory acid-base function o pH < 6.8 or > 7.8 = death  Acidosis: pH less than 7.35 o Systemic increase in H+ or loss of base  Alkalosis: pH greater than 7.45 o Systemic decrease in H+ or excess of base  Respiratory acidosis o Elevation of pCO2 as a result of ventilation depression or alveolar hypoventilation; causes true hypercapnia  Causes: brainstem trauma, over sedation (depression of respiratory center), respiratory muscle paralysis, disorders of the chest wall, disorders of the lung parenchyma  Compensation: not as effective since kidneys are slow to conserve bicarb and eliminate H+  Labs: pH <7.35; CO2>45  Manifestations: headache, restlessness, blurred vision, apprehension, lethargy, muscle twitching, tremors, convulsions, coma  Must be careful with correcting because rapid reduction of PCO2 can cause respiratory alkalosis with seizures and death  Respiratory alkalosis o Depression of pCO2 as a result of hyperventilation; causes hypocapnia  Causes: high altitudes, hypermetabolic states (fever, anemia, thyrotoxicosis), early salicylate intoxication, anxiety or panic disorder, improper use of ventilators  Compensation: kidneys decreases H+ excretion and absorb bicarbonate  Labs: pH >7.45; CO2 <38  Manifestations: dizziness, confusion, paresthesia's, convulsions, coma, signs of hypocalcemia  pH increased – less acid to compete with calcium - calcium binds with free albumin – decreases serum calcium  Metabolic acidosis o Depression of HCO3- from ECF or an increase in noncarbonic acids  Causes: lactic acidosis, renal failure, DKA, starvation  H+ move to intracellular space and K+ moves to extracellular space to maintain ion balance (both +)  Compensation: respiratory hyperventilation – decreasing carbonic acid  Labs: pH <7.35; HCO3- <24  Manifestations: headache, lethargy, kussmaul respirations  Elevated or normal anion gap may help determine cause  Metabolic alkalosis o Elevation of HCO3-; usually as a result of an excessive loss of metabolic acids –  Causes: vomiting, GI suctioning, excessive bicarbonate intake, hyperaldosteronism, diuretics  Compensation: respiratory hypoventilation; kidneys conserve H+ and eliminate bicarbonate  Labs: pH >7.45; HCO3- >26  Manifestations: weakness, muscle cramps, hyperactive reflexes, signs of hypocalcemia  pH increased – less acid to compete with calcium - calcium binds with free albumin – decreases serum calcium  ABG normal values o pH: 7.35-7.45 - based on H+ o PaCO2: 35-45 – partial pressure of carbon dioxide o HCO3- (bicarbonate): 22-26 – calculated value of amt of bicarb in bloodstream o Base excess: -2-+2 – excess indicates amt of excess or insufficient level of bicarb o SaO2: 95-100% - arterial oxygen saturation Basics about buffering systems  Buffer: chemical that can bind excessive H+ (acid) or OH-(base) without a significant change in pH o Located in ICF and ECF o Consist of a buffering pair – weak acid and its conjugate base o Carbonic acid-bicarbonate system  In lung and kidney  Greater the partial pressure of CO2 the more carbonic acid is formed  At pH 7.4 - ratio of bicarbonate to carbonic acid is 20:1 – ratio must be maintained  Lungs can decrease carbonic acid by getting rid of more CO2  Kidneys can reabsorb or regenerate bicarbonate but do not act as fast as the lungs o Protein buffering (intracellular buffers)  Proteins have negative charges – buffer positive H+  Work with hgb o Respiratory and renal buffering  Acidosis: increased ventilation; excrete H+ in urine  Alkalosis: decreased respirations; reabsorption of HCO3- o Cellular ion exchange  Inverse exchanges of K+ for H+ in acidosis and alkalosis Understand compensation  If bicarb decreases, pH decreases – acidosis  Compensation - pH can be returned to normal if carbonic acid also decreases o Respiratory system compensates by increasing or decreasing ventilation  Blowing off or retaining CO2 o Renal system compensates by producing acidic or alkaline urine  Get rid of H+ or bicarb Understand aging effects on fluid and dehydration  Older adults: %TBW decreases as we age o Causes:  Increased adipose tissue  Decreased muscle mass  Sympathetic fibers (autonomic)  Allows bladder to fill  Skeletal motor neurons in pudendal nerve (somatic)  External urethral sphincter – voluntary  Damage can cause incontinence  Micturition – urination GFR, importance, how regulated, what it represents  Glomerular Filtration Rate: filtration of plasma into the Bowman space per unit of time o Normal >60% o Directly related to the perfusion pressure in the glomerular capillaries o If MAP decreases or vascular resistance increases – renal blood flow and GFR decreases  Regulation: o Autoregulation  80-180 mmHg provides constant GFR  BP increases - afferent arterioles constrict to prevent increase in filtration pressure and vice versa  Prevents wide fluctuation in BP being transmitted to glomerular capillaries  Myogenic mechanism (stretch)  Decrease in systemic pressure - glomerular perfusion increases o Stretch on afferent arteriolar smooth muscle decreases – arteriole dilates– more blood delivered to glomerulus  Increase in system pressure – glomerular perfusion decreases o Arteriole smooth muscle contracts – decreases blood flow to glomerulus  Tubuloglomerular feedback (NaCl content)  When sodium filtration increases - GFR decreases o Macula densa cells sense and stimulate afferent arteriolar vasoconstriction  When sodium filtration decreases – GFR increases o Afferent arterioles vasodilate o Neural regulation  Sympathetic nervous system  Vasoconstriction – decreased GFR  Baroreceptor reflex  Vasoconstriction of afferent arterioles with activation of a1-adenoreceptors – decreases perfusion and GFR  Exercise and change of body position  Activate renal sympathetic neurons – causes mild vasoconstriction  Severe hypoxia  Stimulation of chemoreceptors; decreases renal blood flow by sympathetic stimulation o Hormones (RAAS) - review  Increases systemic arterial pressure and increases sodium reabsorption – increase BV/BP/RBF  Renin: enzyme formed and stored in afferent arterioles of JGA  Forms angiotensin I which is activated by ACE to angiotensin II  Angiotensin II o Stimulates secretion of aldosterone by the adrenal cortex o Is a potent vasoconstrictor o Stimulates ADH secretion and thirst sensation RAAS system basics – see above Concentration of urine  Via nephron – filtration, tubular reabsorption, tubular secretion, excretion  Glomerular filtration: o Freely permeable to water and relatively impermeable to large colloids such as plasma proteins  Important permeability factors: size and electrical charge  + more permeable o Net filtration pressure = forces favoring (capillary hydrostatic pressure – push) and forces opposing (capillary oncotic pressure and hydrostatic pressure in Bowman capsule – pull)  Also glomerular hydrostatic pressure, capsular hydrostatic pressure, blood oncotic pressure  Concentration of urine o Begins in proximal tubule  Active reabsorption of majority of sodium o Concentration occurs in the Loop of Henle  Descending loop: water reabsorption, sodium diffuses in  Ascending loop: sodium reabsorbed by active transport, water stays in  Urea secretion in thin segment o Distal tubule  Reabsorption of sodium and water only with ADH, bicarbonate  Secretion of potassium, urea, hydrogen, drugs o Collecting ducts  Reabsorption of water only with ADH  Reabsorption of secretin of sodium, potassium, hydrogen  Final concentration of urine completed  Peds and renal function  Decreased ability to remove excess water and solutes; decreased concentrating ability  Narrow margin for fluid and electrolyte balance  Increased risk for dehydration  Increased risk for drug toxicity Aging and renal function  Decrease in renal blood flow and GFR o Altered sodium and water balance  Number of nephrons decrease due to renal vascular and perfusion changes  Response to acid-base changes is delayed  Increased risk for drug toxicity  Alterations in thirst sensation and water intake leading to dehydration Understand basics of renal hormones - see above How to test for renal function - see above Urinary obstructive disorders  Blockage of urine flow within the urinary tract o Causes:  Anatomic or functional defect  Obstructive uropathy: anatomicchanges in the urinary system caused by obstruction o Severity based on: location, completeness, involvement of one or both upper urinary tracts, duration, nature and/or cause of obstructive lesion o Complications:  Hydroureter: dilation of ureters  Hydronephrosis: dilation of renal pelvis and calyces  Ureterohydronephrosis: dilation of both  Tubulointerstitial fibrosis: deposition of excessive amounts of extracellular matrix  Leads to excess cellular destruction and death of nephrons o Compensatory hypertrophy and hyperfunction  Loss of function of one kidney with obstructive disease leads to an increase in size and increased function of unaffected kidney o Relief of obstruction is usually followed by a physiologic post-obstructive diuresis and may cause fluid and electrolyte imbalance along with dehydration  Alterations in tubular transport and water reabsorption and volume expansion contribute Renal calculi, patho, s/s, most common types, acidity of urine and its effect on calculi formation  AKA: Kidney stones: masses of crystals, protein, or mineral salts form in urinary tract and may cause obstruction  Types – classified by minerals that make up stone o Calcium oxalate and calcium phosphate: 70-80%  Most common o Struvite (magnesium, ammonium, phosphate): 15%  Forms in alkaline urine during infection (Klebsiella, Pseudomonas) o Uric acid: 7%  Excretion of large amounts of uric acid in the urine; ex: gouty arthritis o Staghorn  Large and fill the minor and major calyces; more common in women – r/t recurrent UTI’s o Genetic disorders of amino acid metabolism  Excess urine can cause cystinuria, stone formation in the presence of low urine pH; xanthine  Patho o Supersaturation of one or more salts – higher concentration of salt than volume is able to dissolve o Precipitation of salt from liquid to solid state d/t temp, urine pH* more important o Growth into a stone via crystallization or aggregation o Embedded in matrix o Presence or absence of stone inhibitors o Acidity of urine and its effect on stone formation  Alkaline urinary pH: increases risk of calcium phosphate stone formation  Acidic urine: increases risk of uric acid stone  Potassium citrate, pyrophosphate, magnesium: prevent stone formation  S/Sx  Infection of one or both upper urinary tracts (ureter, renal pelvis, and interstitium) o Acute pyelonephritis: acute infection of the renal pelvis interstitium – *E. Coli, proteus, pseudomonas  Inflammatory process usually focal and irregular – affects pelvis, calyces and medulla  Causes medullary infiltration of SBC’s with renal inflammation, edema, and purulent urine  Affects tubules – glomeruli spared  2 step process: bacteria attach and cause inflammatory response – release of mediators cause increased permeability and WBC’s are able to get into urine  S/Sx:  Acute onset of symptoms with fever, chills, and flank and groin pain; UTI s/sx  Older adults have non-specific symptoms: low grade fever, malaise – need to catch – urosepsis o Chronic pyelonephritis: persistent or recurring episodes of acute that lead to scarring  Risk increases with renal infections and obstructive pathologic conditions – prevents elimination of bacteria – progressive inflammation – alteration of renal pelvis and calyces – destruction of tubules – atrophy, dilation, and diffuse scarring – impaired urine concentrating ability  S/Sx:  Early (mild; HTN, frequency, dysuria, flank pain); Loss of tubular function (inability to conserve sodium, hyperkalemia, metabolic acidosis); progressive (renal failure) Glomerulonephritis, patho, s/s, types  Patho o Formation of immune complexes in circulation – deposit in glomerulus o Antibodies produced against organism that cross-react with glomerular endothelial cells o Activation of complement system – recruitment and activation of immune cells and mediators o Decreased GFR – decreased glomerular perfusion from inflammation, glomerular sclerosis/scarring, thickening of the glomerular basement membrane, increased permeability to proteins and RBC’s  S/Sx: o Hematuria with RBC casts (smoky, brown-tinged urine), proteinuria (3-5g/day w/albumin) - low serum albumin and edema from lack of albumin, severe or progressive glomerular disease – eventual oliguria  Oliguria: output <30 mL/hr or <400 mL/day  Types o Nephrotic sediment  Contains massive amounts of protein and lipids – microscopic or no blood o Nephritic sediment  Blood is present with RBC casts, WBC casts, varying degrees of protein (usually not severe)  Caused by increased permeability of the glomerular filtration membrane due to systemic immune complexes or infection leading to inflammation o Chronic  Progressive course leading to chronic kidney failure  Reduction in nephron mass – compensatory hypertrophy and hyperfiltration – interglomerular HRN (to try to increase GFR in remaining healthy nephrons) - sclerosis and further nephron loss  S/Sx: proteinuria, hypercholesterolemia Nephrotic syndrome, s/s patho  Excretion of 3g or more of protein in urine as a result of glomerular injury  S/Sx: o Foamy urine, hypoalbuminemia (peripheral edema), prone to infection (loss of immunoglobulin), vitamin D deficiency, hyperlipidemia/lipiduria (from liver compensating for lack of protein), hypothyroidism AKI patho  Sudden decline in kidney function with a decrease in GFR and accumulation of nitrogenous waste products in the blood o Uremia: urea in blood – syndrome of renal failure  Elevated BUN and creatinine; fatigue, anorexia, N/V, pruritis, neuro changes, retention of toxic wastes, electrolyte disorders, proinflammatory state  Manifestation of azotemia  Azotemia: increased serum urea levels and frequently increased creatinine levels  Caused by renal insufficiency or renal failure  Measured clinically but no symptoms  Increase in serum creatinine and BUN  Results from extracellular volume depletion, decreased renal blood flow, or toxic/inflammatory injury to the kidney cells  3 categories: prerenal, intrarenal, postrenal Prerenal, intrarenal, postrenal  Prerenal: renal hypoperfusion o *Most common cause of ARF o Occurs rapidly over hours – is reversible o Elevation of BUN and creatinine, GFR declines because of decrease in filtration pressure  Intrarenal: involves the renal parenchymal or interstitial tissue – acute tubular necrosis caused by ischemia o Occurs most often after surgery; also - sepsis, obstetric complications, severe trauma, burns o Injury effects mostly proximal tubules and thick ascending limp of loop of Henle – decreased GFR caused by obstruction of lumens o Post ischemic or nephrotoxic  Post ischemic  Persistent hypotension, hypoperfusion, hypoxemia – produces ischemia, reduced ATP, toxic oxygen free radicals – loss of antioxidant protection – cell swelling, injury, necrosis – inflammatory cytokine release contributes to tubular injury and increases neutrophil adhesion  Nephrotoxic  Produced by numerous antibiotics (-mycin); drugs accumulate in renal cortex and cause renal failure  Postrenal: associated with acute urinary tract obstruction – rare o Bilateral ureteral obstruction, bladder outlet obstruction, prostatic hypertrophy, tumors, neurogenic bladder, urethral obstruction – increase in intraluminal pressure upstream from site of obstruction with gradual fall in GFR o S/Sx:  Pattern of several hours of anuria with flank pain followed by polyuria o Can occur after catheterization of ureter which causes inflammation of the tubular lumen Acute tubular necrosis – patho, s/s, intrarenal - see above CKD, patho, manifestations, system effects  Progressive loss of renal function associated with systemic diseases  Kidney damage – GFR <60 mL/min for 3 months or more, irrespective of cause  S/Sx: do not occur until renal function declines to less than 25% of normal  Patho:  Systemic effects *positive feedback loop o Proteinuria and uremia – due to glomerular hyperfiltration; damages interstitial kidney tissue from inflammation o Creatinine and urea clearance – GFR falls, plasma creatinine increases o Fluid and electrolyte balance  Sodium and potassium excretion initially – retention with advanced disease (oliguria)  Concentration and dilution ability diminish  Metabolic acidosis when GFR 30-40%  Increased phosphate from reduced excretion - decreased renal synthesis of calcium, vit D  Fractures  Proteinuria – decreased serum protein – loss of muscle mass  Hyperinsulinemia and glucose intolerance related to insulin resistance