Respiratory System Past Paper PDF

Exam #3 Study Guide Respiratory 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 cel...

Exam #3 Study Guide Respiratory 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 18mmHg compared to systemic circulation of 90mmHg 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 CO2 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 ○ 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  Gives the pulmonary artery tree large compliance - accommodate stroke volume and pressure from RV ○ Pulmonary capillaries surround the acinus ○ Alveolocapillary membrane  Formed by shared alveolar and capillary walls  Contains pulmonary capillaries  Where gas exchange occurs Mechanics of breathing ○ Major and accessory muscles  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. ○ Alveolar surface tension – surfactant plays a major role in alveolar surface tension  functions to increase lung compliance and ease the work of breathing ○ 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 tendency of the lungs to return to the normal resting state after inspiration.  Compliance is the measure of the lung and chest wall distensibility. Increased compliance indicates the lungs are abnormally easy to inflate and has lost some elastic recoil. A decrease in compliance indicates the lungs are abnormally stiff and difficult to inflate. ○ Airway resistance  Resistance of the respiratory tract to air flow during inspiration and expiration.  Increased with bronchitis, asthma, mucous, edema, or spasm. ○ Work of breathing  Amount of work that must be performed to overcome the elastic and resistive properties of the lung  Determined by lung recoil, chest wall recoil, and surface tension of the alveoli Lymphatics ○ Lymph vessels present in all supportive tissues of the lung ○ Particulate material entering the alveoli is partly removed by the lymph channels ○ Plasma protein leaking from lung capillaries is removed from lung tissue  Helps prevent pulmonary edema and supports the negative pressure in the lungs to help them from collapsing – sucking motion Understand the role of the ANS on the pulmonary system Phrenic nerve (C3-C5) innervates the diaphragm ○ Receives voluntary and involuntary respiratory messages from CNS Respiratory center Located in the brainstem Dorsal respiratory group: sets the basic automatic rhythm ○ Receives impulses from peripheral chemoreceptors in the carotid and aortic bodies ○ Detects the PaCO2 and the amounts of oxygen in the arterial blood Ventral respiratory group: contains inspiratory and expiratory neurons ○ Becomes active when increased ventilatory effort is required Pneumotaxic and apneustic centers: located on the pons Modifiers of the inspiratory depth and rate are established by the medullary centers Brainstem receives feedback ○ Carbon dioxide and hydrogen  Increased blood CO2 or H+ (decreased pH – acidic) stimulate brainstem respiratory centers to increase respiration to allow blowing off CO2 and decrease blood acidity  Increased CO2 and H+ (decreased pH – acidic) stimulate increased firing of aortic and carotid bodies (peripheral chemoreceptors) – relay messages to brainstem via CN9 and CN10 to increase respiration ○ Oxygen  Decreased PaO2 carotid and aortic bodies increase signaling to brainstem ○ Exercise  Motor cortex send direct innervation to stimulate brainstem  Proprioceptive info from contracting skeletal muscle or nerve impulses generated locally for skeletal hypoxia return to brainstem to stimulate respiratory center ○ Hering-Breuer inflation reflex  Stretch receptor in bronchiolar and bronchial tree send inhibitory impulses to brainstem that limit excessive inspiration ○ Central chemoreceptors ○  Reflects PaCO2 Stimulated by H+ (pH) in CSF (low pH/acidosis)  Increases respiratory rate and depth Peripheral chemoreceptors  Located in the aorta and carotid bodies  Stimulated by hypoxia (PaO2)  Responsible for all the increase in ventilation that occurs in response to arterial hypoxemia Understand perfusion and ventilation and how it relates to each other, shunting Ventilation: amount of air getting to the alveoli ○ Minute volume= RR x TV  Normal is 6L/min ○ Alveolar ventilation: how much air is getting to parts where gas exchange takes place  Normal is 4.2L/min  Accounts for dead space (150 mL)  ABG – PaCO2 Perfusion: amount of blood being sent to the lungs ○ Normal V/Q ratio = 4L/min ventilation and 5L/min perfusion ○ 4/5 = 0.8 Perfusion exceeds ventilation in the bases of the lungs because of gravity ○ Lower ratio Low PaO2 and high PaCO2 Ventilation exceeds perfusion in the apices of the lungs ○ Higher ratio High PaO2 and low PaCO2 Changes will change normal ratio ○ Can be physiologically controlled Just by standing up! V/Q mismatch ○ Shunting  Steps taken to normalize the ratio, control perfusion, increase efficiency  Hypoxic (pulmonary artery) vasoconstriction V/Q ratio is low (too little ventilation or too much blood) Causes blood coming into the area to be directed to other parts of the lung Decreases the perfusion of the hypoxic region will raise the V/Q ratio and bring the arterial blood gasses closer to what we expect Most important cause: low alveolar partial pressure of oxygen (PaO2) also caused by acidemia and inflammatory mediators ○ Bronchoconstriction  V/Q ratio is high (too much ventilation or not enough blood)  Causes bronchi to constrict slightly to increase the resistance and decrease the amount of ventilation coming into an area that is not well perfused  Limits the amount of alveolar dead space that occurs and minimizes the ‘wasted work’ How is oxygen and carbon dioxide most commonly found in the body Oxygen delivery Ventilation of the lungs ○ Diffusion of oxygen from the alveoli into the capillary blood ○ Perfusion of systemic capillaries with oxygenated blood ○ Diffusion of oxygen from systemic capillaries into cells Carbon dioxide removal ○ Diffusion of carbon dioxide from the cells into systemic capillaries ○ Perfusion of the pulmonary capillary bed by venous blood ○ Diffusion of carbon dioxide into the alveoli ○ Removal of carbon dioxide from the lung by ventilation 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-aminocompounds  Bicarbonate: as CO2 moves into the blood is diffuses into the RBC’s - carbonic anhydrase combines CO2 and H2O to form carbonic acid – carbonic acid dissociates 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 ○ Oxygen absorbed from alveoli to blood alveolar oxygen  determined by rate of absorption into blood and rate of entry of new oxygen ○ Partial pressure normally 104mmHg Alveolar carbon dioxide ○ Removed from alveoli ○ Partial pressure normally 40mmHg  increases directly in proportion to rate of CO2 excretion decreases in inverse proportion to alveolar ventilation Principles of gas exchange ○ Diffusion in response to concentration gradients pressure proportional to concentration CO2 20 times as soluble as O2 ○ Diffusion depends on partial pressure of gas ○ 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 ○ 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 ○ When hemoglobin saturation and desaturation are plotted on a graph, the result is a distinctive S-shaped curve known as the oxyhemoglobin dissociation curve Oxyhemoglobin shift ○ 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 ○ 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 (lowpH) and hypercapnia and hyperthermia 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) ○ Slightly increased ventilatory rate, very large tidal volume, no expiratory pause Cheyne-Stokes respirations ○ Alternating periods of deep and shallow breathing; apnea lasting 15-60seconds, followed by ventilations that increase in volume until a peak is reached, after which ventilation decreases again to apnea ○ Occurs with decreased brainstem blood flow Hypoventilation ○ Alveolar ventilation is inadequate in relationship to the metabolic demands ○ Leads to respiratory acidosis from hypercapnia (CO2>44) ○ Causes: airway obstruction, chest wall restriction, altered neurologic control of breathing Hyperventilation ○ Alveolar ventilation exceeds the metabolic demands ○ Leads to respiratory alkalosis from hypocapnia (CO244) ○ Occurs from decreased drive to breathe or an inadequate ability to respond to ventilatory stimulation/hypoventilation ○ Retain too much CO2 – respiratory acidosis ○ Ex: drugs, brainstem (medulla) injury, spinal cord injury, NMJ dysfunction, respiratory muscle dysfunction (myasthenia gravis), thoracic cage abnormalities, airway obstruction, sleep apnea Hypocapnia ○ Decreased CO2 in the arterial blood (PaCO210mmHg) during inspiration  Status asthmaticus: not reversed by usual measures Life threatening Ominous signs of impending death: silent chest, PaCO2 >70  ○ ○ ○ Bronchitis ○ Hyper secretion of mucus and chronic productive cough that lasts at least 3 months of the year and for at least 2 consecutive years  Inspired irritants increase mucus production, size and number of mucus glands, and bronchial edema  Thick mucus compromised lungs defenses ○ Hypertrophied bronchial smooth muscle ○ Hypoxemia (V/Q mismatch) and hypercapnia ○ Airways collapse early in expiration– gas trapped in lungs ○ S/Sx: decreased exercise tolerance, wheezing and SOB, copious productive cough, polycythemia from chronic hypoxemia, decreased FEV1, increased infections ○ Acute bronchitis: acute infection or inflammation of airways or bronchi commonly following viral illness  Symptoms similar to pneumonia but no consolidation or chest infiltrates  Nonproductive cough occurs in paroxysms and is aggravated by cold, dry, or dusty air Emphysema ○ Permanent enlargement of the gas-exchange airways accompanied by the destruction of the alveolar walls without obvious fibrosis ○ Loss of elastic recoil ○ Destruction of the alveoli occurs through the breakdown of elastin in the septa as a result of an imbalance between proteases and antiproteases, oxidative stress, and apoptosis of the lung’s structural cells ○ Also produces large air spaces within the lung parenchyma (bullae) and air spaces adjacent to pleurae (blebs) ○ Types:  Centriacinar (centrilobular): septal destruction occurs in the respiratory bronchioles and alveolar ducts; upper lobes Alveolar sac remains intact Tends to occur in smokers with chronic bronchitis  Panacinar (panlobular): involves the entire acinus; damage is more randomly distributed; involves lower lobes  Primary: inherited deficiency of the enzyme a1-antitrypsin  Secondary: caused by cigarette smoke, air pollution, occupational exposures, and childhood respiratory infections ○ S/Sx: dyspnea on exertion, at rest when progressed, little coughing with little sputum, thin, tachypnea, prolonged expiration, use of accessory muscles, pursed lips, increased AP diameter, tripod positioning COPD ○ Airflow limitation that is not fully reversible; ○ usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gasses ○ Chronic bronchitis + emphysema ○ Risk factors: tobacco smoke, occupational dusts and chemicals, indoor and outdoor air pollution, any factor that affects lung growth during gestation and childhood, alpha1 antitrypsin gene mutation Pulmonary HTN ○ Mean pulmonary artery pressure above 25mmHg at rest ○ 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 ○ 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 ○ 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  Corpulmonale– 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 ○ Most frequent cause of cancer death in the US; ○ most common cause: cigarette smoking ○ Laryngeal  Risk factors: smoking, heightened with smoking and alcohol consumption, GERD, HPV  S/Sx: progressive hoarseness, dyspnea, cough ○ 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 ○ 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) ○ Lung carcinoid tumor  5% of all lung cancers  Grow slowly and rarely spread Atelectasis ○ 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 S/Sx: dyspnea, cough, fever, leukocytosis (inflammatory process) Pulmonary edema ○ Excess water in the lung from disturbances of capillary hydrostatic pressure, capillary oncotic pressure, or capillary permeability ○  capillary hydrostatic pressure leads to fluid leaking into lung  Most common cause: left sided heart failure ○ 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 ○ ○ ○ Characterized by acute lung inflammation and diffuse alveolocapillary injury Injury to pulmonary capillary endothelium, increased capillary permeability, inflammation, surfactant inactivation, edema, atelectasis Patho:  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 ○ Occlusion of a portion of the pulmonary vascular bed by a thrombus, embolus, tissue fragment, lipids, or air bubble ○ Virchow triad: venous stasis, hypercoagulability, and injuries to the endothelial cells that line the vessels  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 ○ 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 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 ○ Upper airways: warms and humidifies air  Nasopharynx and oropharynx  Larynx: connects upper and lower airways ○ 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 Visceral: covering the lungs Parietal: lining the thoracic cavity 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 Cardiac Understand the basics of cardiac muscle contraction Resting membrane potential is similar to skeletal muscle (-85to–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) ○ 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 ○ Calcium ions in SR and t-tubules are rapidly pumped back into ECF  Transport in SR is the result of calcium-ATPase pump ○ ○ ○ Sodium that enters in this exchange then pumped out by Na/K ATPase pump 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  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  Requires calcium; calcium-troponin C complex facilitates the contraction process  Cross-bridge cycling: attachment of actin to myosin at the crossbridge – 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 Diastole: relaxation – ventricles fill 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 P wave: atrial depolarization PR interval: time from the onset of atrial activation to the onset of ventricular activation QRS complex: sum all of ventricular depolarization ST interval: ventricular myocardium depolarized QT interval: “electrical systole” of the ventricles ○ Varies inversely with the heart rate; approximates time of ventricular contraction Function of atria and ventricle Atria act as primer pumps 80% of blood flows directly into ventricle from atria before atrial systole Atrial contraction causes an additional 20% If atria fail, the patient is not normally symptomatic unless under stress – ex) exercise Right heart function: pumps blood through pulmonary circulation – low pressure system Left heart function: pumps oxygenated blood through systemic circulation; delivers waste products to the lungs, kidneys, and liver – high pressure system Understand volumes, EF, Cardiac output, preload, and afterload Cardiac output: volume of blood flowing through either the systemic or the pulmonary circuit ○ HR x SV = CO in L/min  Normal at rest is 5 L/min ○ Factors that affect cardiac output: preload, afterload, Frank Starling Law, Laplace’s Law, heart rate, myocardial contractility Preload: “filling pressure” ○ The pressure generated at the end of diastole (ventricular relaxation) ○ Represents fluid returning to the heart ○ Increased preload represents increased myocardial oxygen consumption–heart is working harder  Determined by: amounts of venous return to the ventricle, blood left in the ventricle after systole (end-systolic volume) ○ Right ventricle preload = CVP ○ Left ventricle preload = pulmonary artery occlusion or wedge pressure ○ When preload exceeds physiologic range - further muscle stretching - decreased CO Afterload: “resistance” ○ The resistance to ejection during systole ○ Increased afterload=  work of the heart and oxygen demand  Caused by: vasoconstriction, valvular stenosis,  blood volume  Decreased afterload: heart contracts more rapidly  Increased afterload: slows contractions and  heart workload ○ Right ventricle afterload = PVR (pulmonary vascular resistance) ○ Left ventricle afterload = SVR (systemic vascular resistance) Frank Starling Law: Related to the volume of blood at the end of diastole/preload and stretch placed on the ventricle ○ Myocardial stretch determines the force of myocardial contraction ○ More stretch =  force of contraction ○ Greater stretch during diastole= greater force of contraction= greater amount of blood pumped out ○ Laplace Law: Contractile force within a chamber depends on the radius of the chamber and the thickness of its wall Smaller chambers and thicker chamber walls =  contraction force In ventricular dilation, the force needed to maintain ventricular pressure lessens available contractile force Heart rate ○ Effected by cardiovascular control center (sympathetic and parasympathetic), neural reflexes (sinus arrhythmia 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:  force of contraction  Norepinephrine(sympathetic), epinephrine (adrenal medulla), thyroid hormone, dopamine ○ Negative inotropes:  force of contraction  Acetylcholine (vagus nerve) Hypoxia decreased contractility EF: amounts of blood ejected per heartbeat by the ventricles SV/end- diastolic volume ○ Normal is 55% or higher ○ Indicator of ventricular function Cardiac index: CI = CO/BSA - normal is 2.5-4 L/min/m 2 ○  CO/CI - anything that causes  contractility or decreased blood flow to the heart MI, shock, bradycardia,  SV, negative inotropes,  vascular resistance, cardiac tamponade, hypovolemia, valvular heart disease, high PEEP ○  CO/CI - anything that causes  contractility or  blood flow to the heart HTN,  vascular resistance, pulmonary edema,  metabolic state, positive inotropes ○ Factors that regulate blood flow: degree of cardiac contractility, heart rate, venous return to the heart ○ 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) Laminar vs. turbulent flow ○ 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 ○ Tricuspid: between right atrium and right ventricle; three leaflets or cusps ○ Bicuspid (mitral): between left atrium and left ventricle; two leaflets or cusps Semilunar valves ○ Pulmonic semilunar valve: from right ventricle to pulmonary artery ○ 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 ○ Causes heart to become dilated and flaccid; slows heart rate ○ Hyperpolarization occurs – cannot initiate AP Excess Ca++ causes spastic contraction Low Ca++ causes cardiac dilation ○ Calcium abnormalities are not as big of a concern– blood levels are more regulated Understand the 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) ○ Located in right atrium near entry of SVC ○ Spontaneously depolarizes from 60-100 BPM ○ 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) ○ Located in posterior wall of right atrium immediately behind the tricuspid valve ○ Delays cardiac impulse ○ Allows atria to empty blood into the ventricles before ventricular contraction AV bundles ○ Normally one-way conduction through bundles– prevents re-entry of conduction ○ The only conducting path between the atria and ventricles ○ Divides into left and right bundles ○ Transmission time between AV bundles and last of ventricular fibers is the QRS time (0.06sec) Purkinje fibers (20-40 BPM) ○ From AV node through AV bundle into ventricles ○ 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” ○ Increases electrical conductivity and the strength of the myocardial contraction ○ Increased sinus node discharge, rate of conduction impulse ○ NT’s: norepinephrine, epinephrine  Norepinephrine Vasoconstrictive by interacting with blood vessel alpha 1 receptors Does not act on beta 2 receptors  Epinephrine Vasoconstrictor (alpha 1) and vasodilator (beta 2) ○ Adrenergic receptor function  Alpha or beta adrenergic receptors  Stimulation of both 1 and 2  HR (chronotropy) and force of contraction (inotropy) Beta 1 Normal heart Activation leads to increases in contractile force and HR Located on: cardiac pacemaker, myocardium, salivary gland ducts, sweat glands Norepi and epi Renin release  aldosterone  vasoconstriction   BP  Beta 2 – vascular and non-vascular smooth muscle  Alpha 1 Regulatory Inverse response of cell – stimulation leads to  activity or muscle tone 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  Epionly– direct response Activity or muscle tone is increased  Located on all vascular smooth muscle, GI and urinary sphincters, dilator muscle of the iris, arrector pili muscles in hair follicles (goosebumps)  Norepinephrine binds with alpha1 receptors causing smooth muscle contraction and vasoconstriction of the coronary arteries Parasympathetic - “rest” ○ Slows conduction of AP’s through the heart and reduces strength of contraction ○ 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 ○ NT’s: acetylcholine  Cholinergic receptors: muscarinic (slows HR,  contractility, bronchial constriction) and nicotinic (only involved in muscle contraction, NMJ)  Other types of control – not on study guide ○ Brainstem vasomotor center  Connects with PNS via vagus nerve to decrease HR ○ ADH  Acts on kidneys to increase water reabsorption, vasoconstriction–increased BV, ○ ○ ○ ○ BP Brainstem 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+ 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) ANP– atrial natriuretic peptide  Found in atria and released in response to stretch Both BNP and ANP have diuretic, natriuretic and antihypertensive effects by inhibiting RAAS Understand basic functions of lymphatic system Special vascular system that picks up excess fluid and returns it to the venous circulation Moves lymphocytes and leukocytes between different components of the immune system Comprised of lymph nodes and vessels with a one-way flow valve system Lymphatic fluid: primarily water and small amounts of dissolved proteins, mostly albumin SVCS patho Progressive occlusion of the SVC that leads to venous distention ○ Blocks the return of blood to the heart ○ Caused by lung ca – oncologic emergency S/Sx: ○ Edema and venous distention in the upper extremities and face ○ Fullness feeling in head ○ Headache, visual disturbances, impaired consciousness ○ Skin of face and arms purple and taut Hypertension – different types, pathogenesis, and s/s, including malignant hypertension Disease of the arteries ○ interstitial oncotic pressure, Water pushes/filters into the interstitial space, Filtration Venous end of the capillary: Capillary (plasma) oncotic pressure > interstitial 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 Causes: ○  Capillary Hydrostatic Pressure–ex: venous obstruction ○  Plasma Oncotic Pressure – ex: losses or diminished production of albumin ○  capillary permeability – ex: inflammation and immune response–proteins leak ○ Lymph-obstruction – ex: lymphedema, Sodium retention –  hydrostatic pressure Pathophysiology:  in forces favoring fluid filtration from the capillaries or lymphatic channels into the tissues Manifestations: ○ Localized: limited to site of trauma or specific organ system Ex: sprained ankle; cerebral edema, pulmonary edema, ascites, pleural 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 Roles include: Neuromuscular irritability, acid-base balance, cellular reactions, transport of substances. Normal: 135-145mEq/L Hormonal regulation of sodium: 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 Aldosterone: a mineralocorticoid steroid synthesized and secreted from the adrenal cortex and acts on the distal tubule (and collecting ducts) of the kidney. ○ Secreted when blood sodium levels are , potassium levels , or renal perfusion is . ○ Leads to: Sodium and water reabsorption back into circulation, Potassium and hydrogen secretion to be lost in urine 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,  BP,  sodium and water excretion, released when there is  atrial pressure ( volume) ○ ex: CHF Results in:  in BP –  atrial pressure – inhibits release of ANP and BNP; Negative feedback loop ADH: antidiuretic hormone ○ Released when there is an  in plasma osmolality,  in blood volume, or  in BP. ○ Results in:  atrial pressure and ultimately the secretion of ADH,  water reabsorption – restoration of blood volume,  permeability of renal tubules and collecting ducts of kidneys,  blood volume returns to heart,  atrial pressure, and stops release of ADH. ○ Negative feedback loop Thirst perception ○ Osmolality receptors (osmoreceptors): in hypothalamus; stimulated from hyperosmolality, dry mouth, plasma-volume depletion ○  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 Sympathetic nerve stimulation and  perfusion/blood pressure in the renal vasculature  releases renin from the juxtaglomerular cells of the kidney Renin stimulates release of angiotensin I (inactive) RAAS basics: ○ Converted to angiotensin II (active) by ACE in pulmonary vessels ○ Two major functions of angiotensin II: Stimulates the secretion of aldosterone  Aldosterone stimulates reabsorption of sodium and water to restore fluid balance (ADH) ○ Vasoconstriction:  systemic BP restoring renal perfusion ○ Results in: Restoration of sodium levels, fluid volume, and renal perfusion (Leads to inhibition of the release of renin) ○ Negative feedback loop Hypotonic, isotonic, hypertonic basics - Hyponatremias and what they are associated with Hypotonic solutions: have a lower osmotic pressure than another solution ○ Less solute and more water ○ Cell swells ○ Osmolality 300 Dehydration Hypertonic alterations: ○ Hypernatremia  Water loss or Na gain (water movement from ICF to ECF, dehydration of cell)  Manifestations: Convulsions, pulmonary edema, hypotension, tachycardia ○ Hyperchloremia  Causes: Hypernatremia (Cl follows Na) or bicarbonate deficit; secondary pathologic processes  No specific symptoms ○ Water deficits  Dehydration, pure water deficits (rare), renal free water clearance  Manifestations: Tachycardia, weak pulse, postural hypotension, elevated hct, elevated serum sodium levels, headache, dry skin, dry mucous membranes Isotonic solutions: have same osmotic pressure across membrane ○ Free movement of water across the membrane without changing the concentration of solutes on either side ○ Osmolality between 275-300 Isotonic alterations: ○ Total body water change with proportional electrolyte change– no change in concentration ○ Ex: hemorrhage, severe wound drainage, excess diaphoresis, intestinal losses, decreased fluid intake Isotonic volume depletion = hypovolemia Isotonic volume excess = hypervolemia Understand electrolyte abnormalities Potassium: major intracellular cation ○ Aldosterone, insulin, epinephrine, and alkalosis pull K into the cells ○ Aldosterone deficiency, insulin deficiency, strenuous exercise, and acidosis pull K out of the cells ○ Inverse relationship with H+ ○ Maintained by kidneys via excretion and by how much is absorbed in the stomach from dietary sources as well as aldosterone and insulin secretion, and changes in pH ○ Purpose: Essential for the transmission and conduction of nerve impulses, normal cardiac rhythms, and skeletal and smooth muscle contraction ○ Regulates ICF osmolality and deposits glycogen in liver and skeletal muscle cells ○ Hypokalemia: 5.5  Causes: Increased intake; shift to ECF; decreased excretion; hypoaldosterone state; hypoxia; acidosis (exchange of H+ in to increase pH); insulin deficiency; cell trauma  Manifestations:  Mild: tingling, restlessness, intestinal cramping and diarrhea, peaked T waves on ECG; cells are more excitable  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 Calcium ○ Bones and teeth, blood clotting, hormone secretion, cell receptor function, muscle contractions ○ Normal: 8.6-10.5 ○ 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 ○ Hypocalcemia: 12  Causes: Hyperparathyroidism – increased PTH; bone mets; excess vitamin D; immobilization; acidosis  Manifestations: Decreased neuromuscular excitability Muscle weakness, kidney stones, constipation, heart block Phosphorus ○ Hypophosphatemia  Causes: intestinal malabsorption and renal excretion, vitamin D deficiency, antacid use, alcohol abuse  Manifestations: diminished release of oxygen, osteomalacia, muscle weakness, bleeding disorders, leukocyte alterations ○ Hyperphosphatemia  Causes: exogenous or endogenous addition of phosphate to ECF, long term use of phosphate enemas or laxatives, renal failure  High phosphate levels associated with low calcium levels  Manifestations: same as hypocalcemia with possible calcification of soft tissue Chloride ○ Extracellular ion; tends to follow sodium; inverse relationship to bicarbonate ○ Important anion in maintenance of iron balance and in gastric juice Magnesium: ○ 1.8-2.4 ○ Intracellular cation; stored in muscle and bones; interacts with calcium; involved in neuro-excitability ○ Hypomagnesemia  Causes: malabsorption, hypocalcemia, and hypokalemia  Manifestations: neuromuscular irritability, tetany, convulsions,  reflexes ○ 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 ○ H+ high:low pH – acidic ○ H+low:high pH – alkaline ○ 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 pH 7.8=death ○ Acidosis: pH less than 7.35  Systemic increase in H+ or loss of base ○ Alkalosis: pH greater than 7.45  Systemic decrease in H+ or excess of base Respiratory acidosis ○ 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 & eliminate H+ ○ Labs: pH 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 ○ Depression of pCO2 as a result of hyperventilation; causes hypocapnia ○ Causes: high altitudes, hyper metabolic 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 women; age 50-60 ○ Risk factors: *smoking, obesity, HTN Adenocarcinomas that arise from tubular epithelium in the renal cortex Clear cell or papillary – clear cell have much better prognosis and are the most common Caused by mutation of the von Hippel-Lindau gene located on chromosome 3p S/Sx: ○ ○ ○ ○ Hematuria (microscopic–early) Dull and aching flank pain Palpable flank mass in thinner individual Systemic: present in advanced stage, weight loss, fatigue, tumor fever, anemia (hematuria and lack of EPO), HTN (elevated renin), altered liver fxn tests Early stage is often silent Mets: lung, lymph nodes, liver, bone, thyroid, CNS Bladder tumors Urothelial (transitional cell) carcinoma most common ○ Risk factors: males >60, smoking, exposure to metabolites of dyes, amines, or chemicals; arsenic in water, phenacetin consumption ○ Patho: Oncogenes of ras gene and TP53 mutation of tumor suppressor genes Papillary more common Can develop as secondary cancer by invasion of other cancers from borderline organs ○ S/Sx: Gross painless microscopic hematuria– often recurrent and associated with UTI symptoms ○ May have flank pain with tumor growth and obstruction Cause of death is often mets UTIs, s/s, patho UTI: inflammation of the urinary epithelium after invasion and colonization of pathogens in the urinary tract; retrograde movement of bacteria Classification ○ Complicated (functional or anatomical dysfunction) vs. Uncomplicated Cystitis: bladder inflammation (not UTI) Pyelonephritis: inflammation of upper urinary tract Patho: ○ Protective mechanisms: washed out during urination, acidic and high osmolality of urea, Tamm-Hosfall protein (antimicrobial), bactericidal secretions, ureterovesical junction (closes to prevent reflux), mucus secreting glands in women, length of male urethra men, Lewis blood group more prone ○ Pathogens: E.coli and staphylococcus saprophyticus   Virulence: ability to evade, adherence to uroepithelium, resist host’s defense mechanism Phagocytosis of bacteria in urine maximized at pH of 6.5-7.5 S/Sx ○ Frequency, dysuria, urgency, low back or supra pubic pain Cystitis: inflammation of bladder ○ Acute or chronic ○ Asymptomatic or s/sx of UTI without the presence of bacteria ○ Interstitial cystitis: nonbacterial infectious cystitis Result of autoimmune reaction responsible for inflammatory response that includes mast cell activation, altered epithelial permeability, and increased sensory nerve sensitivity ○ S/Sx:  most common in women 20-30 years old and immunocompromised; bladder fullness, frequency, small urine volume, chronic pelvic pain, negative urine cx Pyelonephritis Infection of one or both upper urinary tracts (ureter, renal pelvis, and interstitium) 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 ○ 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: Formation of immune complexes in circulation ○ Deposit in glomerulus ○ ○ S/Sx: ○ ○ ○ Antibodies produced against organism that cross-react with glomerular endothelial cells Activation of complement system–  Recruitment and activation of immune cells and mediators   GFR–  glomerular perfusion from inflammation, glomerular sclerosis/scarring, thickening of the glomerular basement membrane,  permeability to proteins and RBC’s 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