SlideShare ist ein Scribd-Unternehmen logo

Pulmonology Review

•Als PPTX, PDF herunterladen•
•
Jess Little
Jess Little

Review

Gesundheit & Medizin
1 von 419
PULMONARY REVIEW
PHYSIOLOGY
Mechanics of Breathing • Pressure difference is the driving force for air flow, Q = ΔP / R • Between breaths, alveolar pressure = atmospheric pressure • Inspiration: Diaphragm contracts → lung volume increases → alveolar pressure decreases → air flows into the lungs until alveolar pressure = atmospheric pressure again • Tidal volume (VT) = volume inspired in one normal breath (500mL) • Volume in lungs after inspiration = FRC + VT • Functional residual capacity: the volume in the lungs at the end-expiratory position • Expiration: diaphragm relaxes → lung volume decreases → alveolar pressure increases → air flows out of the lungs • Forced expiration: contraction of expiratory muscles further increases alveolar pressure to force air out. Intrapleural pressure increases too, but as long as the transmural pressure is still positive, the lungs will not collapse. Expiration will be rapid and forceful. • COPD: Lung elasticity is decreased, so during forced expiration, intrapleural pressures increase to normal values but alveolar pressures are lower because of their increased compliance. The gradient becomes negative & airways collapse.
Lung Volumes and Capacities
Pressure Changes during Breathing
Forced Expiration and COPD In a person with COPD forced expiration may cause the airways to collapse. In COPD, lung compliance increases because of loss of elastic fibers. During forced expiration, intrapleural pressure is raised to the same value as in the normal person. However, because the structures have diminished elastic recoil, alveolar pressure and airway pressure are lower than in a normal person. The large airways collapse because the transmural pressure gradient across them reverses, becoming a negative (collapsing) transmural pressure. Obviously, if the large airways collapse, resistance to airflow increases and expiration is more difficult.
Transmural Pressures • Transmural pressure: • Pressure difference across a structure • Transpulmonary pressure: • Difference between intra-alveolar pressure & intrapleural pressure • Calculated as alveolar pressure minus intrapleural pressure • Transthoracic pressure: • Difference between intrapleural pressure & pressure outside the chest wall (outside the body)
Pulmonary Compliance
Hysteresis • Hysteresis: the phenomenon that the compliance curves for inspiration and expiration are different. • For a given pressure, lung volume is higher during expiration than during inspiration, therefore compliance is greater during expiration. • Inspiration – • Low volume; liquid molecules are closely packed; intermolecular forces are high • Surfactant is released to break the forces (Surfactant = a phospholipid produced by type II alveolar cells that acts as a detergent to reduce surface tension & increase lung compliance) • Lung volume increases faster than surfactant can be added → curve starts off flat & gradually steepens as more surfactant is added. • Expiration – • Starts at high volume; intermolecular forces are low • Surface area decreases faster than surfactant can be removed → increasing density of surfactant per surface area decreases surface tension & increases compliance → curve starts off flat • As expiration proceeds – surfactant is removed at a similar rate as volume decreases, so the compliance curve has a fairly constant slope
Compliance and Elastance • Compliance: Describes distensibility of system. ΔV/ΔP • “How easily an object stretches” • Elastance: inversely correlated with compliance. ΔP/ΔV "Snap back" or elastic recoil force. • “Ability of an object to return to its original position or shape” • Emphysema  increased compliance, decreased elastance • Fibrosis  decreased compliance, increased elastance
Compliance of Lung and Chest Wall
Pneumothorax • Normally, the intrapleural space has a negative pressure • This negative intrapleural pressure is created by two opposing elastic forces pulling on the intrapleural space • When a sharp object punctures the intrapleural space, air is introduced (pneumothorax), and intrapleural pressure suddenly becomes equal to atm pressure; thus, instead of its normal negative value, intrapleural pressure becomes ZERO • Two main consequences of pneumothorax • Without negative intrapleural pressure to hold lung open, lung collapses • Without negative intrapleural pressures to keep the chest wall from expanding, the chest wall springs out
Compliance and Elastance Pathology
Emphysema and Compliance • Emphysema is associated with loss of elastic fibers in the lungs  increased compliance  increased (steeper) slope of the volume-versus- pressure curve  at a given volume, the collapsing (elastic recoil) force is decreased. • At the original value for FRC, chest wall expansion outweighs lung’s collapsing force. In order for the opposing forces to be balanced, volume must be added to the lungs to increase their collapsing force. • Thus, the combined lung and chest-wall system seeks a new higher FRC, where the two opposing forces can be balanced; the new intersection point, where airway pressure is zero, is increased. • A patient with emphysema is said to breathe at higher lung volumes (in recognition of the higher FRC) and will have a barrel-shaped chest.
Fibrosis and Compliance • Fibrosis (decreased lung compliance). Fibrosis, a so-called restrictive disease, is associated with stiffening of lung tissues and decreased compliance. • A decrease in lung compliance is associated with a decreased slope of the volume-versus-pressure curve for the lung. • At the original FRC, the tendency of the lungs to collapse is greater than the tendency of the chest wall to expand, and the opposing forces will no longer be balanced. To reestablish balance, the lung and chest-wall system will seek a new lower FRC; the new intersection point, where airway pressure is zero, is decreased.
FRC • Functional Residual Capacity (FRC) is the volume of air present in the lungs at the end of passive expiration. • At FRC, the elastic recoil forces of the lungs and chest wall are equal but opposite. There is no exertion at this point by any of the respiratory muscles. • FRC is the sum of Expiratory Reserve Volume (ERV) and Residual Volume (RV) and since it includes the residual volume, it cannot be measured by spirometry. • RV can be measured by helium dilution or body pleythysmography.
Air Flow and Resistance The medium-sized bronchi are the sites of highest airway resistance. It would seem that the smallest airways would provide the highest resistance to airflow, based on the inverse fourth power relationship between resistance and radius. However, because of their parallel arrangement, the smallest airways do not have the highest resistance.
Pulmonary vascular resistance is about 1/10 of systemic vascular resistance It has a minimum value at intermediate lung volumes
Blood Gas Pressures
Respiratory Volumes TLC Total Lung capacity 6.0L FRC Functional Residual Capacity 2.4L VC Vital Capacity 4.7L VT Tidal Volume 0.5L FVC Forced Vital Capacity 4.7L VA Alveolar Ventilation N/A FEV1 Volume of FVC in 1 second N/A
Constants
• Anatomic dead space (~ 150 mL) = the volume of the conducting airways (nose/mouth, trachea, bronchi, bronchioles) • Alveolar ventilation = total rate of air movement into and out of the alveoli, expressed in mL/min. (500 mL/breath - 150 mL/breath) x 15 breaths/min = 5250 mL/min
Alveolar Ventilation • VT = tidal volume • RR = respiratory rate • VD = dead space • Total ventilation (aka minute ventilation) = VT x RR • Normal: 500 mL/breath x 15 breaths/min = 7500 mL/min • Alveolar ventilation (VA) = (VT - VD) x RR
Alveolar Ventilation Equation • Fundamental Equation of Physiology: Interdependence of CO2 and Ventilation • Increasing VA decreases PACO2 and PaCO2 and increases pH : ALKALOSIS • Decreasing VA increases PACO2 and PaCO2 and decreases pH : ACIDOSIS
Alveolar Gas Equation • Predicts PAO2 based on alveolar PACO2 • PIO2 = (760-47) mmHg * 0.21 = 150mmHg • PAO2 = 150 – (40mmHg/0.8) = 100mmHg
A-a Gradient • PAO2 – PaO2 • In a normal person, the A-a difference is close to zero (but not zero), because while O2 will equilibrate in the alveoli, there is a small amount of blood (~2%) that bypasses the alveoli (aka the "physiological shunt"), and PaO2 (obtained via a blood sample) is a mixture of all blood, including shunted blood. • To calculate the estimated normal A-a gradient : [Person’s Age/4] + 4 • Three scenarios that result in an increased gradient: • Diffusion defects (e.g. fibrosis, pulmonary edema) • V/Q defects • Right-to-left shunts (cardiac, intrapulmonary) • NOT Hypoventilation and High altitude
Dead Space • Anatomic dead space: Volume of conducting airways • (nose/mouth, trachea, bronchi, bronchioles) • Physiologic dead space: Total volume of the lungs that does not participate in gas exchange = “anatomic dead space” plus any functional dead space in the structures that contain alveoli • Dead space ventilation is usually approximately 2ml/kg (ideal body weight)
If you increase your RR and your VT by 20% respectively, you will see a GREATER increase in alveolar ventilation with an increase in VT BIGGER DEEPER BREATHS WORK
Diffusion of Gases
Diffusion Changes • In emphysema, DL decreases because destruction of alveoli results in a decreased SA for gas exchange. • In fibrosis or pulmonary edema, DL decreases because the diffusion distance (membrane thickness or interstitial volume) increases. • In anemia, DL decreases because the amount of hemoglobin in red blood cells is reduced (recall that DL includes the protein-binding component of O2 exchange). • During exercise, DL increases because additional capillaries are perfused with blood, which increases the SA for gas exchange.
Diffusion Limited vs. Perfusion Limited • Gas exchange across the alveolar/pulmonary capillary barrier is either diffusion-limited or perfusion-limited • CO is a diffusion-limited gas meaning that as long as the partial pressure gradient is maintained, diffusion will continue across the length of the capillary, so it can be used to measure the diffusing capacity. • Partial pressure gradient maintained because CO is bound to hemoglobin in capillary blood so CO does not equilibrate by the end of the capillary • Nitrous oxide (N2O) is a perfusion limited gas so it can be used to measure perfusion capacity
The slower equilibration of O2 at high altitude is exaggerated in a person with fibrosis. Pulmonary capillary blood does not equilibrate by the end of the capillary, resulting in values for PaO2 as low as 30 mm Hg, which will seriously impair O2 delivery to the tissues.
Hypoxemia and Hypercapnia • Hypoxemia: a decrease in arterial Po2 • Causes of hypoxemia: high altitude, hypoventilation, diffusion defect, V/Q defect, right-to-left shunt • Hypercapnia: abnormally elevated levels of CO2 in the blood • Causes of hypercapnia: hypoventilation, lung disease, respiratory acidosis
CO2 moves from alveolar gas to pulmonary capillary blood 20 times faster than O2 due to a 20 times higher CO2 diffusion coefficient
Blood Flow is Highest in Zone 3 of the lung due to pressure. It is 20X higher.
Ventilation Rates are highest in Zone 3 of the lung due to gravity
V/Q • V/Q ratio is the ratio of alveolar ventilation to pulmonary blood flow (ventilation/perfusion ratio, measured in L/min over L/min). • The normal value is 0.8. • If V/Q ratio is normal, then PaO2 will be at its normal value (100 mm Hg), as is PaCO2 (40 mm Hg).
V/Q and Gas Exchange
V/Q Defects
Physiological vs. Pathological Shunt • Physiologic shunt -A small fraction of the pulmonary blood flow (about 2%) bypasses the alveoli • Result is that PaO2 will always be slightly less than PAO2 • Made up of 2 components • Bronchial blood flow, which serves metabolic functions of bronchi • Coronary blood flow that drains directly into the left ventricle via the thebesian veins • Pathologic Shunts- • Right-to-left-Blood can pass from the right to left heart if there is a defect in the wall between the ventricles • Hypoxemia ALWAYS occurs because significant fraction of output is never delivered to the lungs for oxygenation • Hypoxemia CANNOT be corrected by having the person breathe a high O2 gas • Usually only minimal increase in PaCO2 (systemic arterial blood PCO2) • Left-to-right-More common and does not cause hypoxemia • Can be from patent ductus arteriosus or traumatic injury • Elevated PO2 in the right side of the heart
2% of blood bypasses pulmonary circulation in physiological shunt of healthy people
O2 CO2 TRANSPORT
Dissolved O2 is free in solution and accounts for approximately 2% of the total O2 content of blood. The remaining 98% of the total O2 content of blood is reversibly bound to hemoglobin inside the red blood cells.
O2 Content
O2 Delivery • Cardiac Output x O2 Content
Henry’s Law Henry’s law deals with gases dissolved in solution (e.g., in blood). To calculate a gas concentration in the liquid phase, the partial pressure in the gas phase first is converted to the partial pressure in the liquid phase; then, the partial pressure in liquid is converted to the concentration in liquid. ONLY APPLIES TO DISSOLVED (NOT BOUND) GAS
O2 Hemoglobin Dissociation Curve
The percent saturation of heme sites does not increase linearly as PO2 increases. Rather, percent saturation increases steeply (change in affinity) as PO2 increases from zero to approximately 40 mm Hg, and it then levels off between 50 mm Hg and 100 mm Hg.
Unloading • This sigmoidal shape explains the mechanism of oxygen unloading in the capillaries. In regions of low PO2 such as 40 mmHg in mixed venous blood, the affinity between hemoglobin and oxygen is decreased and oxygen dissociates and enters tissues. The opposite is true in regions of high PO2 such as in the alveoli (100 mmHg). • Also related to concentrations of CO2 (Bohr and Haldane Effect)
P50 • A change in the value of P50 is used as an indicator for a change in affinity of hemoglobin for O2. • An increase in P50 reflects a decrease in affinity – RIGHT SHIFT • A decrease in P50 reflects an increase in affinity – LEFT SHIFT
Shifts in O2 Hemoglobin curve • Right Shifts • P50 is higher: DECREASED AFFINITY • Increased PCO2 (Bohr Effect) • Decreased pH • Increased Temperature • Increased 2,3,-DPG • Left Shifts • P50 is lower: INCREASED AFFINITY • Decreased PCO2 • Increased pH • Decreased Temperature • Decreased 2,3-DPG
2,3-DPG • 2,3-DPG is a byproduct of glycolysis in red blood cells. • 2,3-DPG binds to the b chains of deoxyhemoglobin and reduces their affinity for O2. • This decrease in affinity causes the O2-hemoglobin dissociation curve to shift to the right and facilitates unloading of O2 in the tissues. • 2,3-DPG production increases under hypoxic conditions. For example, living at high altitude causes hypoxemia, which stimulates the production of 2,3-DPG in red blood cells. • In turn, increased levels of 2,3-DPG facilitate the delivery of O2 to the tissues as an adaptive mechanism.
The Effect of CO • Decreases O2 bound to hemoglobin and also causes a left shift of the O2-hemoglobin dissociation curve • Decreases O2 content of hemoglobin AND decreases unloading in the tissues • BAD.
The Effect of Anemia
CO2 Transport • Dissolved CO2 (5%), straight up in the blood • Carbaminohemoglobin (3%), bound to hemoglobin, albumin or other proteins • HCO3- (>90%), chemically modified by carbonic anhydrase • Exact percentages vary, but the vast majority is in HCO- 3
Chloride Shift and CO2 Transport • Carbonic Anhydrase in RBCs catalyzes the combination of COand 2 HO to form HCO223 • HCOdissociates into H+ and HCO- 23 3 • H+ remains in the RBC and HCO3 - is filtered into plasma in exchange for Cl- • H+ is buffered in RBCs by deoxyhemoglobin
Haldane vs. Bohr Effect
PFTS
Spirogram
Important Values • VT = 500mL • IRV = 3000 mL • ERV = 1200mL • RV = 1200mL • VC = 4700 mL • FRC = 1200mL • TLC = 5900mL • Dead Space = 150mL
4 Volumes, 4 Capacities • 4 Volumes • Tidal volume • Inspiratory reserve volume • Expiratory reserve volume • Residual volume • Four Capacities: • Inspiratory Capacity  IRV + TV • Functional residual capacity  ERV + RV • Vital Capacity  TV + IRV + ERV • Total Lung Capacity  IRV +TV + ERV + RV
Residual Volume cannot be measured by Spirometry
Flow Volume Curve
Diffusion, DLCO • DLCO : lung diffusing capacity • DL can be measured using carbon monoxide. • The test involves breathing in air with low concentrations of CO, and the rate of disappearance of CO from the gas mixture is proportional to the DL. • In certain pathological processes the DL changes predictably. • Emphysema, the DL goes down because destruction of alveoli decrease surface area for gas exchange. • Pulmonary fibrosis or edema, DL decreases because the diffusion distance increases. • Exercise, the DL increases because more capillaries are perfused with blood, thus increasing the surface area for exchange. • Anemia, the DL decreases because the amount of hemoglobin in RBCs decreases.
3 Categories of Lung Disease • Obstructive • Restrictive • Interstitial • Primary neurologic • Primary muscular • Primary skeletal • Vascular
Localizing Disease • Airway • Asthma • COPD (chronic bronchitis & emphysema) • Interstitium and Alveoli • ILD • Emphysema • Alveolar Filling (WBC, RBC, Water, Protein) • Blood Vessels • PE • PAH • Pulm Ven HTN • Neuromuscular and Chest Wall • Pleural disease • Neurologic deficiency • Muscular weakness
Algorithm FEV1/FVC Low Obstructed Reversible Yes: Asthma No: COPD DLCO Low: Emphysema Normal: Bronchitis Normal FVC/ TLC Low: Restrictive DLCO Low: ILD Normal: Neuromuscular Normal DLCO Low: Vascular Normal: Normal
Normal Values • FEV1/FVC: 80 to 120% of predicted for most PFTs • Exceptions - FEV1/FVC: > 70% • Use actual value not % predicted • Change with bronchodilator • > 12% in FEV1 or FVC and 200 cc’s • TLC: 80 to 120% of predicted for most PFTs • TLC : Low (Restricted), High (Hyper-inflated) • DLCO : < 80% is considered abnormal
ACUTE RESPIRATORY FAILURE
Types of ARF • Typical (normal) ABG values: >60 mmHg for PaO2 and <50 mmHg for PaCO2 • There are two types of acute respiratory failures: in both types there will be decreased PaO2 (<60 mmHg). Thus in order to distinguish between the two types, we evaluate the PaCO2. • 1. Acute Hypoxemic Respiratory Failure: PaCO2 ≤ 40 mmHg • Hypoxemia without hypercapnia • Inability to properly take up oxygen • There is insufficient oxygen in the blood but near normal CO2 • 2. Acute Hypercapnic Respiratory Failure: PaCO2 > 40 mmHg • Hypoxemia with hypercapnia • Inability to eliminate carbon dioxide • There is too much carbon dioxide in the blood
A-a Gradient • In a patient w/ hypoxemia and PaCO2 ≤ 40 mmHg: • Increased A-a gradient → intrapulmonary issue • Normal A-a gradient → extrapulmonary issue • An increase in the A-a gradient suggests an inability to extract enough oxygen (e.g., defects in diffusion, V/Q mismatch, or right-to-left shunting). • If the patient is hypoxic and has a normal A-a gradient, it suggests the problem is not in extracting O2 from the blood pointing to other etiologies like being at a higher elevation.
Hypoxemic Respiratory Failure with Increased A-a Gradient • 1. Pulmonary embolism • 2. Atelectasis • 3. Pneumonia • 4. Interstitial lung disease • 5. Infection • 6. ARDS
Hypoxemic Respiratory Failure with Normal A-a Gradient • High Altitude • Decreased FIO2 (asphyxia, drowning) • Airway Obstruction • Foreign body • Laryngeal spasm • Obesity and external compression of larynx • Obstructive sleep apnea • Obstruction of airway apparatus – kinking / obstruction of endotracheal tube • Asthma • Tumor
Hypercapnic Respiratory Failure • Depression of the neurologic system • Narcotics • Overdose • Coma • Disease of the chest wall or neuromuscular apparatus • Myesthenia Gravis • Guillian Barre Syndrome • COPD or other lung diseases
Clinical Signs and Sx • Breathing rate • Tidal volumes • Labored respiration/Paradoxical breathing • Asynchronous ventilatory patterns • Prolonged inspiratory phase: Stridor and upper airway obstruction • Prolonged expiratory phase: Asthma/COPD • Patient posture (cannot lay flat) • Ability to converse • Tachycardia with increased work of breathing • Patient tell you they are exhausted • Pulse ox <90% • PaO2 < 60 mmHg • PaCO2 > 50 mmHg
Clinical Utility of Venous Blood Gas • Venous blood gas is sometimes used when arterial blood cannot be obtained due to diminished pulses or patient movement. • Venous blood gas gives a picture of how critical the patient is. If the venous O2 is really low, then the body is extracting the majority of O2 from blood and the patient is very critical. Normal mixed venous O2 saturation is 65-70%. • Central venous blood is preferred over peripheral venous blood because of their better correlation to arterial blood gases. • Central venous pH is usually 0.03-0.05 pH units lower than arterial pH. PCO2 is usually 4 to 5 mmHg higher than arterial PCO2. • Peripheral venous pH is usually 0.02-0.04pH units lower than arterial pH. The venous PCO2 is about 3-5mmHg higher than arterial PCO2.
Identify the patient who may require intubation and mechanical ventilation. • Patients with severe dyspnea • Respiratory rate 35bpm • Unable to gasp more than 3 words • Very abnormal breathing pattern • Tachycardia/arrhythmias • Hyper/hypotension • Sweating • Abnormal arterial blood gases-60/50 club • Arterial PCO2 has risen to cause • Lowered pH (below 7.25-7.30) • Impaired mental status • PO2 over 60 mmHg cannot be achieved with inspired O2 concentration less than 40% - 60%
NEURAL CONTROL OF BREATHING
Lung Volume and Airway Patency • 2 types of striated muscles regulate the flow of air in and out of lungs: • Pump and Airway muscles • Pump muscles: Define volume of chest cavity: motor neurons in the spinal cord • Inspiratory: diaphragm and external intercostals • Expiratory: internal intercostals and abdominal (passive process at rest) • Airway muscles: regulate the flow of air through the airway: motor neurons located in the lower brainstem • Two aspects of ventilatory control: • (1) degree of inspiratory drive or central inspiratory activity • (2) the timing mechanism (which controls the termination of inspiration). • Determining factors act in concert to set the respiratory rate and tidal volume and thus the minute ventilation and specific pattern of breathing.”
3 Phases of Breathing • Inspiration: The diaphragm is recruited in an incremental fashion during inspiration: Innervated by phrenic nerve • Passive Expiration (E1): Air is forced out of the lungs due to the recoil of the elastic fibers in the lungs. • During this phase the phrenic nerve is still active but at lower level than it was in inspiration. • The expiratory branch of the recurrent laryngeal nerve activates the laryngeal constrictors, which oppose lung recoil. • The activity of these two nerves produces a smoother expiratory flow and results in better gas exchange in the lungs. • Active expiration (E2): only occurs if chemoreceptors are stimulated by hypoxia or hypercapnia or during exercise. • Expiratory muscles activity is essential to speed up breathing frequency. Inspiratory duration is virtually invariant in a healthy individual. The breathing rate increases almost entirely via shortening of expiratory phase. L • Lumbar nerve innervates muscles of phase 2
Rhythm vs. Pattern Generation • Pattern: the orderly recruitment of pump and airway muscles during the respiratory cycle: • pontomedullary network of neurons • pattern generator is regulated by • cortex (volitional control) • limbic system (emotions) • state of vigilance (sleep vs awake) • blood gases (chemoreception) • feedbacks from lung and chest sensory afferents • Rhythm: generates the respiratory rate • PreBotzinger complex: controls timing of inspiration
Neural Breathing Centers • Ventral respiratory column refers to a bilateral stretch of reticular formation that contains rhythm generating and pattern-generating respiratory neurons • The preBötzinger Complex is a small segment of the VRC where the eupneic breathing rhythm is generated. • Located in the ventrolateral medulla • Pneumotaxic center in dorsal pons • The nucleus solitary tract (NTS) receives sensory afferents including afferents from the lungs and carotid bodies. • The region is also sometimes called dorsal respiratory group and, in some species, contains phrenic premotor neurons. • Inspiratory motoneurons including phrenic motor neurons receive most of their input from the brainstem
Mechanoreceptors vs. Chemoreceptors • Central Chemoreceptors: detect PCO2 and acid • Hypoxia in the CNS suppresses breathing • Peripheral Chemoreceptors (the carotid and aortic) detect artery hypoxia and arterial PCO2 • Respond more quickly to a change in arterial PCO2 than central chemoreceptors • Irritant receptors: (rapidly adapting) chemosensitive C fibers • Respond to cold, airflow, pollutants, irritants and inflammation • Mechanoreceptors (slowly adapting) • Lung inflation stretches the terminal endings of mechanosensitive sensory afferents located in the trachea and bronchi. • Activation of these afferents is sustained when the stretch is maintained • Initiate Hering Breuer reflex (see LO6) • Mechanoreceptors (rapidly adapting) • Encode rate of change of tension
Chemoreceptors • Peripheral chemoreceptors are located in the carotid bodies and in the aortic body, located between the pulmonary artery and aortic arch. • Detect CO2 and O2 • REACT FASTER THAN CENTRAL CHEMORECEPTORS • Central respiratory chemoreceptors reside at the ventral surface of the medulla oblongata. • Detect only CO2 • Retrotrapezoid nucleus • Fissura pontomedullaris • Inferior olive • Precerebellar structure. • CNS Hypoxia depresses breathing
MOA Peripheral Chemoreception • Hypoxia depolarizes type I cells (glomus cells) by turning off potassium conductances. • The depolarization causes Ca to enter and produces the exocytosis of transmitters (most important: ACh, ATP). • ACh and ATP depolarize the peripheral end of sensory afferents. • Carotid body afferents project to the nucleus solitary tract via the glossopharyngeal nerve where the information is relayed to the central pattern generator to cause an increase in breathing rate and amplitude.
MOA Central Chemoreception • RTN neurons (bright green) are glutamatergic. They innervate only the regions involved in respiratory rhythm and pattern generation • RTN neurons are activated by acidification • A mutation of transcription factor Phox2b in man prevents the development of RTN neurons. The result is Congenital Central Hypoventilation Syndrome (Ondine’s curse), a disease in which breathing is no longer stimulated by CO2 and breathing stops during sleep (breathing while awake is Ok although PCO2 is less tigthly regulated). • These patients are ventilator-dependant throughout their life.
Hering Breur Reflex • Reflex triggered to prevent overinflation of the lung mediated by slowly adapting mechanoreceptors. • Initiated by lung inflation, which stretches the terminal endings of slowly adapting mechanosensitive sensory afferents located in the trachea and bronchi  influx of sodium  depolarization and action potential generation • The axons travel in thoracic branches of the vagus nerve, and the cell bodies are found in the nodose ganglion. • Via the NTS, the information is relayed to the pons and the ventral respiratory column, resulting in decreased activity of inspiratory motoneurons, which helps terminate inspiration. • They are termed “slowly adapting” because their activation is sustained when the stretch is maintained. • This reflex is weaker in the adult and stronger in the neonate and is of minor medical importance.
Rapid Mechanoreceptors • Respond only briefly to a stretch. They encode the rate of change of the tension as opposed to its absolute level. Rapidly adapting mechanoreceptors also exist in the lung but they are not involved in the H-B reflex.
Chemosensitive C Fiber Afferents • Present throughout the trachea and bronchi and can produce a variety of skeletomotor and autonomic reflexes. • Exposure to pollutants and irritants triggers activation of both rapidly adapting receptors and C-fiber afferents, which then mediate mucus production, glottal closure and apnea, bronchoconstriction, and cough. • Glottis closure prevents further inhalation of particulate matter, irritants or toxins, and cough is a powerful expiratory effort against a closed glottis.
Sighs • Sighs are periodic unusually large inspirations. • Their frequency is increased by (1) being awake as opposed to sleep, and (2) by hypoxia, probably by stimulation of the carotid bodies. • Most likely serve to prevent atelectasis
Automaticity and Voluntary Control • In general, the process of breathing is a normal rhythmic activity that occurs without conscious effort. It is controlled by the central respiratory generator located in the medulla, which sends signals to the respiratory muscles. Input from the pons to the generator is necessary for a normal, coordinated breathing pattern. • The cerebral cortex exerts a conscious or voluntary control over ventilation. This cortical override of automatic control can be seen with either voluntary breath holding or hyperventilation.
CO2 is the variable most tightly regulated by breathing
Waking vs. Sleeping Drives • Breathing automaticity is maintained by several classes of mechanisms. The chemical drive is the excitatory influence of chemoreceptors (both central and peripheral) on the central respiratory pattern generator (CPG). • When one is awake, the CPG also receives excitatory inputs from “waking drives” including neural feedback that gauges the metabolic activity of skeletal muscles and the reticular activating system. • When one is asleep (non-REM sleep), however, the waking drive is greatly reduced or absent, and the chemical drive becomes the dominant influence. • Clinical significance: During sleep, breathing is more shallow, less stable (more prone to stop → apnea), and depends highly on the chemoreceptor drive.
CNS hypercapnia will produce sleep disturbance and promote awakening, like in sleep apnea. The increases in CO2 leads to a sudden urge and stimulation to breathe. CNS hypoxia has a depressant effect
Morphine and Breathing • Morphine depresses the brainstem respiratory pattern generator (including the central chemoreflex). The resulting slow and shallow breathing causes hypoxia and hypercarbia. • Carotid body stimulation by hypoxia/CO2 maintains a modicum of breathing but only up to a point. • If morphine exceeds a certain brain concentration, its direct CNS depressant effect combined with the depressant effects of brain hypoxia cannot be overcome by carotid body stimulation and breathing stops, leading to cardiovascular collapse and death.
SIDS • Rare but responsible for a significant % of early infant deaths • Potential causes and contributing factors • Defect in arousal elicited by hypercapnia or hypoxia. • Overactive / abnormal airway protective reflexes (cough, laryngeal reflexes). • Developmental problems (abnormality of lower brainstem serotonergic neurons, possibly) • Environmental factors (air pollution, tobacco smoke, nicotine). • Treatment: • Preventative (eliminate presumed contributing factors). • Supine sleeping position (most effective; reduction of mortality estimated at > 50% in the US). • Alarm to detect loss of breathing
SIDS Mechanism • During prone sleeping re-breathing exhaled air can increase CO2 and decrease O2 levels • Initiates the arousal response that begins with sigh. • Successful arousal results in head lifting and repositioning • If arousal fails, a more severe hypoxic state is reached and eupneic breathing will transition to gasping • This transition is mediated by respiratory network reconfiguration of the preBötC. • Should an infant fail to both arouse and autoresuscitate, the irreversible hypoxic insult leads to asphyxiation and the occurrence of SIDS
Hypercapnia • When is hypercapnia really bad for you? • Acutely, when PaCO2 is greater than 8.0 to 9.3 kPa (60 to 70 mmHg) • Patients with chronic hypercapnia may not develop symptoms until the PaCO2 rises acutely to greater than 90 mmHg because they have a compensatory increase in the plasma bicarbonate concentration; • As a result, a larger elevation in PaCO2 is required to produce the same reduction in pH.
O2 and COPD Patients • Oxygen given to COPD patients may cause secondary hypercapnia • 1. Ventilation perfusion mismatching (MOST IMPORTANT): • Your lungs have a finite supply of blood flow. In COPD, you have alveoli that are well ventilated, and alveoli that are poorly ventilated. Under normal conditions, there is proper matching between perfusion and ventilation. Less oxygen in certain alveoli → less blood flow to those alveoli. This frees blood flow to the well ventilated ones so you can effectively remove CO2. If pure O2 is given, the trickle of pure O2 is sufficient to cause perfusion of poorly ventilated alveoli, reducing blood flow to well ventilated ones. Less blood flow to well ventilated alveoli → less CO2 removal and hypercapnia • 2. The affinity of CO2 for hemoglobin decreases (Haldane effect). • -The Haldane effect refers to the rightward displacement of the CO2-hemoglobin dissociation curve in the presence of increased oxygen saturation • 3. Minute ventilation decreases because the hypoxic activation of the carotid chemoreceptors is removed (very small impact on hypercapnia)
Altitude Effects • Short term: • If PO2 < 60mmHg, hypoxemia is severe enough to stimulate peripheral chemoreceptors (carotid and aortic bodies) → increased ventilation • Increased ventilation means that extra CO2 will be expired and arterial PCO2 will decrease causing a respiratory alkalosis (pH increase) • pH increase will inhibit central and peripheral chemoreceptors and offset the increase in ventilation rate • Long term: • 1) Body increases production of 2,3 DPG to shift heme dissociation curve to the right and unload more O2 into tissues • 2) Within several days, HCO3- excretion increases (renal compensation for respiratory alkalosis). This takes away the chemoreceptor inhibition, allowing for a higher ventilation rate
Diving Reflex • Exposure of the face, nostrils and upper airway to water triggers diving reflex. • Triggered by activation of facial and ethmoid nerve sensory afferents. • First component: Airway protection. • Breathing is instantaneously stopped. • Second component: O2 saving strategy. • Reduced O2 consumption is caused by sympathetically mediated vasoconstriction in muscles and GI. • Parasympathetically-mediated bradycardia. Cardiac O2 consumption and cardiac output are reduced • Brain perfusion is maintained at a normal level
Shallow Water Black Out • Forced and prolonged hyperventilation before a dive is practiced to stay under water longer. This is done under the mistaken assumption that hyperventilation increases stores of blood PO2. • This is not the case since Hb is saturated with O2 even with normal ventilation. What hyperventilation does is to lower PaCO2 (respiratory alkalosis) which allows the diver to stay submerged a little longer because it delays the urge to breathe which is largely driven by CO2 accumulation. • The practice of excessive hyperventilation before a dive is dangerous because a prolonged dive may cause sufficient CNS hypoxia to produce loss of consciousness and drowning.
Exercise and Breathing • During exercise, ventilation first arises in a stepwise fashion and then exponentially before leveling out. When exercise is stopped, there is an initial stepwise fall followed by a steady decline back to baseline ventilation. • Central command (top down control of breathing during exercise) and reflexes from muscles and joint mechanoreceptors cause the initial rise in ventilation at the onset and the rapid fall at the end of dynamic exercise • Humoral factors and reflexes from metabotropic receptors probably accounts for the delayed increase in ventilation at the onset of exercise and the slow recovery at the end of dynamic exercise
Exercise and Blood Gas Values • During light to moderate exercise, the lungs are able to compensate for muscles using more oxygen and producing more carbon dioxide. Thus, the arterial gases should not change unless the exercise becomes severe.
SLEEP APNEA
Prevalence of Sleep Apnea • 20% in patients over 60 years old! • 9% in Women • 24% in Men • Prevalence increases with age until midlife but is constant after age 60ish.
Types of Apnea • Apnea: • >10 second cessation of breathing, especially during sleep • Hypopnea: • Abnormally slow or shallow breathing • Reduction of airflow by 30% or more with 4% drop in SaO2 OR • Reduction of airflow by 50% or more with 3% drop in SaO2 + arousal • according to class, also lasts at least 10 seconds • Respiratory-event related arousal: • Arousals from sleep that do not meet the definition of apnea or hypopnea, but DO disturb sleep. • Obstructive sleep apnea: • Disruption of airflow while asleep due to narrowed, blocked, or floppy airway. • Central sleep apnea: • Absent respiratory effort. Breathing stops and starts due to lack of proper neuromuscular function. • Mixed sleep apnea: • Apnea due to a combination of Central Sleep Apnea and Obstructive Sleep Apnea • Typically begins as central (without ventilatory effort) and presents with airway obstruction when ventilatory effort resumes (OSA)
Apnea-hypopnea index (AHI): • Number of apneic and hypopneic episodes per hour • Normal <5 • Mild 5-15 • Moderate 15-30 • Severe >30
Pathogenesis of Sleep Apnea • Upper airway size naturally decreases during sleep due to decreased neural stimulation of the upper airway dilator muscles. This itself does not cause apnea. OSA occurs in individuals with naturally smaller airways and increased airway collapsibility. • Upper airway size: smaller in OSA • Craniofacial disorders • Enlarged tonsils and adenoids: major risk factor in children between ages 3-5 • Increased tongue size (Down’s Syndrome patients) • Increased Airway Collapsibility • In obesity, soft tissues of neck can push down and constrict airway. • OSA is more common in patients with nasal obstruction (mouth breathing leads to negative pressure that collapses the pharynx)
Risk Factors • Obesity • Single most important risk factor for OSA in middle-age adults” • Enlarged tonsils, Enlarged Adenoids • Surgery in children, not adults • Enlarged Tongue (as seen in Down’s Syndrome) • Craniofacial/ Airway abnormalities • Mallampati Classification 3 or 4 • Neck size >17 inches • For women: Post-menopause • Age • Prevalence of OSA increases with age until age 60 • Endocrine changes: • Hypothyroidism => thick and beefy tongue • Acromegaly
Clinical Presentation OS • Snoring (majority of pts - 50% of pts partners report sleeping in a separate bedroom) • Apneic episodes • Unrefreshing or restless sleep • Excessive daytime somnolence or fatigue • Drowsiness while driving • Decreased libido • Declines in cognition • Weight gain
Clinical Presentation OS in Children • Overweight • Craniofacial Abnormalities • Large tonsils • Nightmares • Daytime somnolence • Daytime mouth breathing • Use Polysomnography to confirm • First line treatment: tonsillectomy, adenoidectomy
Differential Diagnosis • Restless Leg Syndrome • Narcolepsy • Delayed sleep-phase syndrome • Insufficient Sleep Syndrome • Sleepiness due to meds
Diagnosis • The “gold standard” for the diagnosis of OSA is full overnight polysomnography, performed in an attended laboratory setting. This includes monitoring of sleep with electroencephalography (EEG), chin and anterior tibialis electromyography (EMG), monitoring of breathing with oronasal airflow and snoring, thoracic and abdominal effort and pulse oximetry, electrocardiography (ECG), and body position. • Scoring of sleep stages and arousals from sleep is performed from the EEG and EMG data. • Apneas and hypopneas are scored according to the combination of oronasal airflow data, thoracoabdominal effort, and oxyhemoglobin saturation • Unattended sleep studies can be used in patients with very severe disease. NOT RECOMMENDED IN CENTRAL APNEA.
Obstructive vs. Central Apneas Obstructive Central
Sequelae of OS • Pathophysiologic mechanisms • 1. Apneic events lead to sleep fragmentation - disturbs sleep and patient stuck in lighter stages of sleep • OSA can lead to sexual dysfunction • Increased risk of depression • Significantly increased risk for motor vehicle accidents (2x more) • 2. Deoxygenation/reoxygenation causes oxidative stress similar to ischemia/reperfusion events  increase in proinflammatory molecules • Refractory Hypertension • Arrhythmias • Cardiovascular Events • Stroke • Atherosclerosis • Insulin resistance • INCREASED MORTALITY
Treatment of OS • CPAP • Delivers constant pressurized air during both inspiration and expiration • Bilevel positive airway pressure (BPAP) • Delivers high fixed level of pressure during inspiration and lower fixed pressure during expiration • Easier to tolerate for severe patients • Weight loss • Positional therapy • Oral appliance therapy • Patients with mild - moderate OSA • Those who are unable or unwilling to use PAP • Surgical Treatment • Optimal for children • Unpredictable and less effective in adults
Causes of Central Apnea • Hypocapnic: • Alteration of CO2 apnea threshold during sleep • Periodic breathing at high altitude • Cheynes Stokes • Instability of Respiratory Control System • Hypercapnic • Neuromuscular Diseases • Sleep-Related Hypoventilation • Brain stem lesions (syringomyelia specifically mentioned) • Spinal cord disorders • Stroke • Muscle disorders (muscular dystrophy)
Cheyne Stokes Breathing Cycles of 60-120 seconds Waxing and waning pattern w/ lack of rib cage or abdomen movement
Causes of Cheyne-Stokes Apneas • Systolic heart failure • Stroke • Encephalopathies
Some things to know from quiz… • A. • The airway in obesity is decreased in size primarily in the lateral dimension. • B. • The upper airway has properties of a Starling resistor and demonstrates a critical pressure at which the airway collapses. In normal individuals, this is a negative pressure, but in those with many obstructive apneas, this pressure is positive • C. • Following sleep onset, the neural input to the upper airway dilator muscles decreases significantly, much more so than to the phrenic nerves. • D. • Individuals with obstructive sleep apnea develop what has been called the pharyngeal myopathy of OSA. It is hypothesized that vibrations from snoring initiate an inflammatory response within the muscles.
Obesity Hypoventilation Syndrome • BMI > 30 • Awake alveolar hypoventilation • Sleep-disordered breathing • Daytime hypoxemia • Dyspnea on exertion • Serum Bicarbonate Level > 27 mEq/L (elevated bicarb) • indicates increased paCO2 • Diagnosis with ABGs
Treatment of Obesity Hypoventilation • CPAP • 50% of patients need CPAP + Supplemental Oxygen • Non-invasive ventilation BPAP + Backup Rate • For use if CPAP + Oxygen is ineffective • Weight Loss • Bariatric surgery in some patients, but patients with obesity hypoventilation syndrome are not recommended for bariatric surgery.
ASTHMA
Cytokines and TH2 Response • IL-4, IL-5, IL-9, IL-13 • Lymphocytes of TH2 phenotype (CD4+) are thought to be a prominent component of the inflammatory response in asthma. • IL-5 has a chemoattractant effect for eosinophils, stimulates growth, stimulates activation, and stimulates eosinophilic degranulation. • IL-4 is inflammatory by activating B lymphocytes, enhancing synthesis of IgE, and promoting TH2 differentiation. • IL-13 also induces IgE synthesis, as well as mediating many various effects of cells involved with the inflammation of asthma. • IL-9 promotes growth of TH2 cells, B cells and Mast cells, IgE production and production of cytokines by smooth muscle cells
IL-4 and IgE • IL-4 promotes release of IgE antibodies from B cells
3 Functions of IL-4 • 1. B cell activation • 2. IgE synthesis • 3. Differentiation of Th2 cells
IL-4 vs. IL-13 • Similarity: Both play a role in making Th2 cells. IL-4 induces the differentiation while IL-13 induces the production of Th2 cells. Both make lung endothelium produce VCAM, making it “sticky” for eosinophils. Both induce IgE production • Differences: IL-13 has broader effects on epithelium and smooth muscle cells
IL-5 • IL-5 is the only known eosinophil hematopoietin aka it causes production of eosinophils from bone marrow stem cells • IL-5 is an important survival factor for eosinophils • IL-5 is chemotactic for mature eosinophils and a priming factor for enhanced functional activities
Clinical Asthma and Allergen Removal • Removal from environment improves but does not eliminate asthma • Studies show improvement in lung function, quality of life, allergic mediator release, and rescue medication use • However, bronchial hyperreactivity (“twitchy” airways) and airway inflammation persist FOREVER
Innate vs. Adaptive Immunity in Asthma • If asthma were a disease of the adaptive immune system, then therapies targeting adaptive immune responses would be curative: • Anti-IgE • Anti-Thelper/Thelper cytokines • Immunotherapy • Allergen/antigen avoidance • With an authentic allergic, T cell-mediated disease (i.e. seasonal allergic rhinitis), exposure actually correlates with symptoms, and the disease resolves in the absence of exposure • New Theory: • Epigenetic programming of epithelial cells promotes release of cytokines IL-25, IL- 33 and TSLP even in absence of T cells driving eosinophilia and day-to-day symptoms • Adaptive immune responses via T/B cell responses primarily drive exacerbations and are well treated by targeted immune therapies
Remodeling-prone Asthma • Airway remodeling likely results from chronic inflammation and the associated production and release of mediators like growth factors • Remodeling  epithelial damage, airway fibrosis (collagen), and smooth muscle hyperplasia • Increase in SMCs  hyperresponsiveness of the airway to stimuli  Persistent airflow obstruction • Overdistention of the lungs and airway occlusion by thick mucous plugs • Histology: • Edema and cellular infiltrates within the bronchial wall • “Fragile” appearance of the epithelium and detachment of epithelial cells • Hypertrophy and hyperplasia of the smooth muscle layer • Increased deposition of collagen (basement membrane thickening) = fibrosis. • Hypertrophy of mucous glands
Steroid Resistance • Inhaled corticosteroids are the recommended standard medication for persistent asthma • Start at low dose in mild disease and move to higher doses • Most of the clinical efficacy of ICS’s is obtained at lower doses • Steroid-resistant asthma is defined by the failure to improve FEV1 by 15% after treatment with high oral corticosteroid doses for 2 weeks • Characterized by persistent eosinophilia despite a high dose of inhaled corticosteroid • Largely a T lymphocyte problem (continued production of cytokines IL4, IL5, and IL13) despite corticosteroid presence. • Steroid resistance does NOT affect the side effect profile (i.e. osteoporosis, metabolic syndrome, HBP, DM, obesity, myopathy, glaucoma/cataracts, etc.) • Corticosteroids are ineffective in resistant asthma, • DON’T prescribe them
Eosinophilic vs. Non-eosinophilicAsthma • Eosinophilic asthma = steroid sensitive (except in steroid-resistant) • Non-eosinophilic asthma = steroid resistant • May exacerbate symptoms by inhibiting apoptosis of PMNs
Omalizumab • Allergen-exacerbated asthma is diagnosed by: • 1) evidence of a specific IgE (via skin prick or IgE immunoassay) • 2) evidence of allergen-exacerbation of symptoms (allergic rhinitis, asthma) • Omalizumab binds free IgE in the serum at the same site that the high-affinity IgE receptor (on mast cells) binds. Thus, IgE cannot bind to its receptor on mast cells. Eventually, the number of IgE receptors on mast cells decreases over time. • Omalizumab seems to significantly improve the number of asthma exacerbations, but it does NOT eliminate asthma • It has a minimal influence on lung function, symptoms, or severity • This is likely because allergens exacerbate asthma but have little to do with day-to-day asthma symptoms or severity
Aspirin Sensitive Asthma • Some people have asthma exacerbation after taking ASA or NSAIDs b/c the inhibition of COX results in a shifting of arachidonic acid pathways toward the production of bronchoconstrictor leukotrienes. • AERD is characterized by pathognomonic elevation of LTC4 synthase expression with profoundly increased, constitutive, and aspirin-induced leukotriene production. It also has a pathognomonic elevation of leukotriene receptor expression. • Leukotriene Modifiers significantly improve sx in these patients • Leukotriene receptor antagonists (Montelukast, Zafirlukast) improve lung function, decrease bronchodilator use, reduce symptoms, and improve quality of life • Zileuton - may be effective in reducing upper airway symptoms (loss of smell, rhinorrhea, congestion)
ASTHMA MANAGEMENT
Asthma Predictive Index
Exacerbating Factors • Viral Infections • Most common cause of asthma symptoms in the 0-4 age group. • Allergies • GERD • Chronic sinusitis • Obstructive sleep apnea • Allergic bronchopulmonary aspergillosis
PHARMACOLOGY
Beta Agonists • MOA: • Stimulation of B2 receptors in SMCs activates Gs adenylyl cyclase  increased cAMP  increased conductance of Ca++-sensitive K+ channels  Hyperpolarization • Airway smooth muscle relaxation and bronchodilation • cAMP also inhibits histamine release from mast cells and TNF release from monocytes • Clinical Use: Primary therapy for Asthma and COPD • Short acting: albuterol, levalbuterol • Long acting: Salemterol, Fomoterol • Side Effects • Tachyarrhythmia • Tremulousness (trembling) • Muscle cramps • Nervousness • Hypokalemia
Anticholinergics • MOA: • Competitive inhibition of ACh at muscarinic receptors relaxes bronchial constriction normally caused by parasympathetic (ACh) stimulation of M3 receptors • Parasympathetic stimulation of M1 and M3 receptors causes mucus secretion as well, so anticholinergics decrease mucus secretion • Clinical Use: First line for COPD also used in asthma • Short acting: Ipratropium • Long acting: Tiotropium • Side Effects • Constipation • Xerostomia (dry mouth) • Pharyngitis • Urinary retention • Sinusitis • Upper respiratory infection
Methylxanthines • Theophylline (1,3 dimethylxanthine) • rarely used today • MOA: • Nonselective PDE inhibitor (increases cAMP) and an adenosine receptor antagonist → relaxes smooth muscle through blocking adenosine receptors on mast cells • Also inhibits synthesis and secretion of inflammatory mediators from numerous cell types, including mast cells and basophils • Clinical Use: Rare, Acute and chronic asthma • Side Effects: • NARROW THERAPEUTIC WINDOW • Nausea & vomiting • tremors • irritability • restlessness • tachyarrhythmias (Afib)
Corticosteroids • MOA: Suppression of inflammatory responses by interference with multiple signal transduction and gene expression pathways. • Decrease cytokine formation • Decrease PAF production • Inhibit cysteinyl leukotrienes • Clinical Use: • FIRST LINE THERAPY (inhaled not systemic) • Risk of adverse effects increases with dose • Side Effects: • HPA Suppresion • Hypertension • Immunosuppression • Osteoporosis • Myopathy • Cataracts • Growth arrest • Fat redistribution
Leukotriene Modifiers • MOA: • LTD4 receptor antagonists (zafirlukast, montelukast) • Reversible inhibitor of cysteinyl leukotriene-1 receptor • 5-lipoxygenase inhibitors (zileuton) • Prevents conversion of arachidonic acid to leukotriene A4 • LB4 is also decreased • Clinical Use: • Preventative treatment of asthma, especially AERD • Anti-leukotriene agents can be effective as monotherapy in the treatment of mild to moderate persistent asthma. • Not as effective as ICGCs. • Side Effects • Abnormal LFTs • Headache • Eosinophilic Vasculitis.
Omalizumab • MOA: • DNA-derived humanized monoclonal Ab • At recommended doses, omalizumab reduces free IgE by more than 95%, thereby limiting the amount of IgE bound to Fc R1-bearing cells • Also decreases amount of FcRI receptor expressed on these cells • Clinical Use • Allergic Asthma • Chronic Idiopathic Urticaria • Side Effects: • Thrombocytopenia, • Anaphylaxis, • Dermatologic • Costly
PDE Inhibitors • PDE4 Inhibitor: increases intracellular cAMP and reduces neutrophil and eosinophil infiltration • PDE4 is a major enzyme that hydrolyzes and inactivates cAMP • Romflumilast • Clinical Use: Prevention of COPD Exacerbations • Side Effects: • Diarrhea, nausea • Headache • Decreased appetite • Weight loss • Suicidal thoughts
Mucolytics • 1) Hypertonic Agents • Ex: Inhaled hypertonic saline or mannitol • MOA: Hypertonic agents draw water into the airway to lower mucus viscosity. • Side Effects: Can cause bronchospasm  therefore used following a bronchodilator • General: cheap with good results (disadvantage: time consuming) • 2) N-acetyl cysteine (NAC): CF and Bronchiectasis • MOA: Lowers mucus viscosity by cleaving disulfide bonds via its free sulfhydryl group. • Side Effects: bronchospasms (use 15 min. after bronchodilator), smells, expensive • 3) Inhaled DNAse: CF • MOA: Breaks down purulent sputum by cleaving DNA strands. • Side Effects: laryngitis, pharyngitis, chest pain, conjunctivitis, dyspnea, expensive, change in voice • 4) Ivacaftor: CF • MOA: CFTR protein potentiator for G551D mutation of CF. Decreases [Cl-] in sweat. • Side Effects: Increased LFTs, rash, abdominal pain, HA, nausea, dizziness, nasal congestion, nasopharyngitis, upper resp infxn.
Therapy for Pulmonary Hypertension
Prostanoids • MOA: • Prostacyclin stimulates adenylate cyclase to convert ATP to cAMP  decrease in intracellular Ca SMC relaxation • Prostacyclin also inhibit platelet aggregation • Clinical Use: • Pulmonary Hypertension • Side Effects: • Hypotension • Flushing • Jaw pain • Headache • Nausea/vomiting, • Hypersplenism, • Line infection
Guaifenesin • MOA: Irritant of vagal receptors in the gastrum activating parasympathetic reflexes which result in secretion of a less viscous mucous. • Clinical Use: Expectorant used to help with clearing of phlegm in setting of acute respiratory infections • Does not suppress cough reflex • Use Dextromethorphan • Side Effects: • Minimal Side Effects
COMMON COLD
Seasonal Patterns of Viruses • Rhinovirus • Sharp increase in September • Parainfluenza • October/November peak • Coronavirus/RSV • Winter months • Influenza • Mid to late winter • Adenovirus • Year round
Frequency of Infection • 1 to 5 year olds (preschool children): 8+ colds per year • 6 to 12 year olds (school children): 5 to 6+ colds per year • Adolescents: 4 to 5 colds per year • Adults: 2 to 3 colds per year
Modes of Transmission • 3 Modes • “Hand contact: Self-inoculation of one’s own conjunctivae or nasal mucosa after touching a person or object contaminated with cold virus -most efficient transmission • MOST COMMON • Inhalation of small particle droplets that become airborne from coughing (droplet transmission) -more so with influenza • Deposition of large particle droplets that are expelled during sneezing and land on nasal or conjunctival mucosa
Pathogenesis • Deposition on nasal mucosa • Mucociliary transport to nasopharynx • Virus enters epithelial cell after receptor binding • Replication begins within 8 to 10 hrs of inoculation • Influx of PMN’s in nasal submucosa and epithelium • Increase albumin and inflammatory mediators in nasal secretions • Nasal mucosa remains intact • Symptoms begin in 1 to 2 days
Natural History • Day 1 to 2: Sore or scratchy throat, congestion • Day 2 to 3: Nasal obstruction, sneeze and rhinorrhea • Day 4 to 5: Cough • Day 7: Resolved • May last up to 2 weeks in 25% of adults
Differential Diagnosis • Common cold • Allergic or seasonal rhinitis • Bacterial pharyngitis • Sinusitis • Influenza • Pertussis • Nasal foreign body
Allergic Rhinitis Itchy, watery eyes, nasal congestion, sneezing, scratchy throat, fever uncommon “Allergic Shiners” Bacterial Pharyngitis Prominent sore throat, Absent nasal congestion/cough, fever common, purulent exudate, swollen tonsils, erythema of pharynx Sinusitis Presents after a cold begins to improve, facial or tooth pain, purulent nasal/post-nasal drainage, don’t respond to decongestants, fever, malaise Influenza Abrupt onset, fever, myalgias, headache, malaise, nasal congestion, cough, sore throat Pertussis Catarrhal phase: 1 week, low-grade fever, rhinorrhea, malaise, sneeze, mild cough Paroxysmal phase: 1-6 weeks, bursts of rapid coughs, gasp, whoop, apnea, emesis Nasal Foreign Body Nasal congestion, purulent nasal discharge(usually uniteral), sneeze, halitosis, young child
Children < 6 ◦ Fever ◦ Nasal congestion ◦ Rhinorrhea Clear to green ◦ Sneeze ◦ Cough ◦ Irritability ◦ Swollen glands ◦ 7 to 14 days Older children and adults ◦ Nasal congestion ◦ Rhinorrhea Clear to green ◦ Sore, scratchy throat ◦ Malaise ◦ Sinus fullness ◦ Hoarseness ◦ Sneeze, cough ◦ 5 to 7 days Symptoms and Signs
Prophylaxis • Frequent handwashing with non-antibacterial soap and water • Hand sanitizers may be less effective • Virucidal tissues may decrease secondary transmission of respiratory infection within the household or other close-contact settings • Physical barriers: gloves, masks, gowns, etc. Likely beneficial Maybe beneficial Unclear benefit No benefit Zinc Probiotics Gargling Vitamin C Ginseng Vitamin D Exercise Echinacea Garlic
Symptomatic Treatment for Adults • Nasal symptoms • Single dose of nasal decongestant in adults • Antihistamine/decongestant combinations • Newer non-sedating antihistamines not effective • Guaifenesin • Cough • Dextromethorphan • Inhaled ipratropium bromide • Fever, achiness • Acetaminophen • NSAID’s • ANTIBIOTICS ARE NOT EFFECTIVE
Symptomatic Treatment for Children • Very few effective treatments!!!
Complications • Secondary effects of localized inflammation - Bacterial superinfection • Inflammatory response in susceptible host- Asthma • More extensive viral infection in susceptible host • Viral-induced wheezing: • Bronchiolitis • Pneumonia : rhinovirus and RSV may cause severe lower respiratory tract infection in infants and children • Bacterial acute otitis media : may complicate 30% to 50% of URIs in young children • Paranasal sinus abnormalities • Bacterial sinusitis : may complicate 8% to 10% of URIs in children • Pre-orbital cellulitis • Orbital cellulitis • Orbital abscess
ALLERGIC RHINITIS AND SINUSITIS
List three functions of the sinuses. • Insulate brain • Crumple zone to protect brain from injury • Decrease weight of skull
Sinusitis • Inflammation of mucous membranes lining paranasal sinuses • In adults sinusitis most often occurs in maxillary sinus, whereas in children it is most common in ethmoid sinus
You are born with 4 sinuses
Anatomic landmarks of the nasal cavity and paranasal sinuses.
Key clinical features of Migraine • Unilateral throbbing pain • Phonophobia / photophobia • Nausea / Vomiting • Lasting hours to days (but probably less than a week) • Triggers can include: allergies (histamine release), sinusitis, sinonasal contact points • Can trigger vasomotor symptoms including: rhinorrhea/nasal congestion, ocular tearing • Migraine triggers the maxillary branch of the trigeminal nerve, and the nerve winds up also triggering ocular tearing, rhinorrhea, symptoms of nasal congestion. =
Allergic vs. Nonallergic Rhinitis • Rhinitis: irritation and inflammation of mucous membrane in nose • Rhinorrhea: nasal cavity is filled with a significant amount of mucus • Allergic Rhinitis • Paroxysmal sneezing with seasonal variation • Pruritus • Anterior/Clear rhinorrhea • Allergic conjunctivitis • Positive Family history • + skin allergy test • Non-allergic Rhinitis • Less sneezing • No pruritis • Posterior drainage
Pathognomonic Signs of Allergic Rhinitis • Allergic shiners; periocular edema • Dennie’s Morgan’s lines – wrinkles from long term edena • Supratip nasal creases • Large bluish turbinate – venous blood due to congestion
Treatment for Allergic Rhinitis • First Line: Nasal Corticosteroids • Environmental Control • Saline Irrigation • Antihistamines • Reduce production of clear secretions • Reduces pruritus and sneezing • Clinically much less effective than nasal steroids • Decongestants • Ephedrine, Phenylephrine, Dextromorphan • Vasoconstriction by alpha-agonists (epinephrine, NE) will decrease the blood flow and therefore decrease inflammation and mucus formation at the site of application. • Leukotriene modifiers • Montelukast/Zafirlukast • Zileuton • Nasal cromolyn • Allergen immunotherapy
Immunotherapy in Allergic Rhinitis • Clinical Indications: • Poor response to pharmacotherapy/allergen avoidance • Unacceptable adverse effects of medications • Desire to avoid long-term pharmacotherapy and reduce costs • Possible prevention of asthma in children • 85-90% of patients who receive high-dose maintenance IT report significant efficacy: • reduced symptoms • reduction in medication requirements • IT must be administered in a setting where prompt recognition and treatment of anaphylaxis is assured
Acute Infectious Rhinosinusitis • Symptoms: • Purulent nasal discharge • Nasal obstruction • Facial pain/pressure/fullness • Almost always viral • Acute Bacterial Rhinosinusitis (ABRS) vs. Viral Acute Rhinosinusitis (Viral ARS) • 0.5-2.0% of VRS progresses to ABRS • Diagnosis based on duration and/or pattern • More likely to be ABRS if symptomatic for >10 days or if the symptoms improve, then worsen
Antibiotic Therapy • Antibiotics ONLY indicated in ABRS, ineffective for VRS • First line therapy: Amoxicillin/Clavulanic Acid • PCN allergy: • Adults: Doxycyclin • Children: Respiratory quinolone or Clindamycin + 3rd gen Cephalosporin • NO ROLE for macrolides
Treatment for Viral Sinusitis • Supportive • Saline Irrigations (no evidence) • Topical vs. Systemic decongestants • Oxymetazoline (Afrin) • Phenylephrine (Neosynephrine, Sudafed PE) • Pseudoephedrine (Sudafed) • Pain control • Systemic steroids – no evidence • Topical steroids – weak evidence
Rhinitis/Sinusitis and Asthma • Sinonasal pathology is the most common co-morbidity among patients with asthma • In patients with asthma, inflammation in the nose and sinuses share features of disease in the lung • Allergic rhinitis is a risk factor for asthma • Childhood allergic rhinitis significantly associated with the presence of asthma • Asthmatics with sinusitis are more likely to have nasal polyps complicating their sinus disease than non-asthmatics, and asthmatics are more likely to have persistent disease over years that requires multiple surgeries
Chronic Rhinosinusitis w/ or w/out Polyps • Diagnosis: • 1. Twelve weeks or longer of two or more of the following: • Mucopurulent drainage • Nasal obstruction → congestion • Facial pressure-fullness • Decreased sense of smell • 2. AND documentation of inflammation by one or more of the following findings: • Purulent mucus OR edema in the middle meatus or ethmoid region • Polyps in nasal cavity OR middle meatus • Radiographic imaging showing inflammation of the paranasal sinuses
Nasal polyps are often associated with Cystic Fibrosis
Rhinosinusitis with Nasal Polyposis • The characteristic presentation of CRS with NP is gradually worsening nasal congestion/obstruction, sinus fullness and pressure, fatigue, posterior nasal drainage, and hyposmia or anosmia. • In contrast, fever and severe facial pain are uncommon. • On physical examination, large polyps are often visible with anterior rhinoscopy, while smaller polyps require nasal endoscopy or imaging. Nasal polyps lack sensation.
Eosinophilic Sinusitis • More likely to have polyps and/or asthma • 32% of asthmatics have polyps • 20% of patients with polyps have asthma • Less likely to have pain • Th2-mediated process • Mucous is laden with eosinophils, leukotrienes, IL-4 and IL-5 • Treatment: Corticosteroids • Saline Irrigations • Leukotriene or IgE Inhibitors
Sinus Surgery • Rhinosinusitis Sinus Surgery = Functional Endoscopic Sinus Surgery • Reserved for medical failures • Improves quality of life in 72-76% of patients • Average improvement of 16-22% • Sinus Surgery Improves Asthma • Reduces symptoms, lowers steroid dose & frequency of steroid use • Improves lung function • Decreases bronchial hyperreactivity • NOT SUPERIOR TO MEDICAL THERAPY
Nasal Polyps can develop from Rhinitis, Cystic Fibrosis and Aspirin Intolerant Asthma
OTOLARYNGOLOGY PATHOLOGY
Differential Diagnosis of Hoarseness  Infectious  Acute laryngitis: common cold, URI (virus) or voice strain  Neoplastic  Squamous cell carcinoma  Idiopathic  Papilloma  Iatrogenic  Injury to recurrent laryngeal nerve (e.g. thyroid surgery)  Functional  Laryngeal polyp/nodule (Singer’s nodule)  Smoking  GERD  LPRD (laryngopharyngeal reflux)  Parkinson’s or stroke  Allergies  Thyroid problems
Define stridor and evaluate the child who presents with stridor. • High pitched inspiratory and expiratory sound that serves as a sign of fixed upper airway obstruction • Epiglottitis: H. Influenzae • Croup: Parainfluenza
Pleomorphic Adenoma • Most common salivary gland neoplasm • Clinical features • Wide age distribution • Most common in 4th decade • Female > male • Most common location: parotid gland • Gross features • Overall well-circumscribed • Often with small protrusions into adjacent normal tissue; may lead to local recurrences • Microscopic features • Biphasic: Admixture of epithelial and stromal elements • Epithelium: Glands or cords of small cuboidal cells • Stroma: Fibromyxoid +/- cartilaginous differentiation • Prognosis • Vast majority are benign, Recurrence rate is highly dependent on adequacy of original resection • Malignant transformation: Occurs in ~5% of cases
Warthrin Tumor • Clinical features • Wide age distribution • Most common in 6th and 7th decades • Male >> female • Most common location: parotid gland • Bilateral in 10% of cases • Gross features • Well-delineated, lobulated mass • May be cystic or multicystic • Microscopic features • Epithelium: • Oncocytic - large, eosinophilic, granular cells • Lymphoid tissue: • May form lymphoid follicles • Prognois: Benign
Mucoepidermoid Carcinoma • Clinical features • Most common in 5th decade • Most common malignant salivary gland tumor in children • Female > male • Low-grade and high-grade types • Gross features • Low-grade: Well-circumscribed mass with cystic areas • High-grade: Solid, infiltrative pattern of growth • Microscopic features • Three distinct cell types: • Squamous • Mucin-producing • Intermediate • Low-grade: well-differentiated • High-grade: poorly-differentiated • Prognosis • Highly dependent on grade • Low-grade: 5 yr survival of 98% • High-grade: 5 yr survival of 56%
Adenoid Cystic Carcinoma • Clinical features • Most common malignant tumor of minor salivary glands • Wide age distribution: 20 - 80 yo • Median age = 50 yo • Gross features • Solid infiltrative pattern of growth • Can invade nerves and move to brain • Microscopic features • Small, cuboidal, cytologically bland cells • Arranged in cribriform patterns • Some of the lumen-like spaces contain distinctive eosinophilic materia • Prognosis: Poor, highly malignant, perineural invasion
Laryngeal Polyp • Distinctive non-inflammatory reactive change • Etiology: Injury - “misuse” of voice • S/sx: Hoarseness • Gross: Polypoid mass on vocal cords • Microscopic: Varies with stage of evolution of lesion • Prognosis: benign
Juvenile Laryngeal Papillomatosis • Age: presents in children / adolescents • Etiology: human papilloma virus (HPV) • Gross: • Multiple papillary growths on vocal cords • May spread throughout larynx • Microscopic features • Papillary growths of well-differentiated squamous epithelium • Prognosis • Repeated recurrences • Usually benign • Vary rarely development of squamous cell carcinoma
Squamous Cell Carcinoma • Clinical Features • > 90% of laryngeal carcinomas are SCC • Age - 5th decade or older • Male > > > female • Risk factors: • Cigarette smoking • Heavy alcohol consumption • Gross features • Mass protruding into airway, may be ulcerated • Typically 1 - 4 cm • Microscopic features • Cytologically malignant squamous epithelium • Prognosis • Glottic tumors • Arise from true vocal cords • Tend to remain localized • Transglottic tumors • Tumor crosses laryngeal ventricle • High rate of lymph node metastases
COPD AND BRONCHIETETASIS
Emphysema • Pathophysiology: • Abnormal enlargement of air spaces distal to terminal bronchioles • Destruction of alveolar walls resulting from elastase-antielastase imbalance • Centriacinar (respiratory bronchioles) in upper lobes vs panacinar (alveolar ducts; associated with alpha-1 antitrypsin deficiency) in lower lobes • Collapse of airways due to loss of alveolar compliance • Gross Morphology: • Hyperinflated lungs, Air trapping, Dilated alveoili • Bullae on surface of lungs (panacinar) • Smoking  upper lobe (Centriacinar) • Hyperinflated lungs, flattened diaphragms, increased retrosternal clear space on CXR Microscopic: • Inflammation, fibrosis and carbonaceous pigment common in adjacent alveolar and bronchial walls
Barrel Chest Prolonged expiration with pursed lips, forces walls open to allow expiration
Chronic Bronchitis • Pathophysiology: • Enlargement of the bronchial mucous glands and expansion of goblet cell population. Hypersecretion of mucus  mucous plugs. • Gross Morphology: • Visible bronchi • Principal sites of increased air resistance in COPD are the small distal airways • Hyperinflated lungs, flattened diaphragms, increased retrosternal clear space on CXR • Microscopic: • Brown-pigmented macrophages with sparse neutrophil and lymphocytes in walls of terminal bronchioles • Fibrosis, goblet cell and squamous cell metaplasia of epithelium, smooth muscle enlargement, scattered regions of mucous plugging • Seromucinous gland hyperplasia
Chronic Bronchitis is diagnosed clinically: Chronic productive cough lasting 3 months over at least 2 years
Asthma • Pathophysiology • Bronchial asthma is a chronic relapsing inflammatory disease with hyper-reactive airways, leading to episodic, reversible bronchoconstriction owing to increased responsiveness of the tracheobroncheal tree to various stimuli. • Gross Morphology • Lungs are greatly distended with air and show patchy atelectasis with occlusion of airways by thick mucus plugs. • Microscopic • Sub-basement membrane fibrosis • Edema and inflammatory infiltrate in bronchial walls with eosinophils. • Hypertrophy of bronchial wall musculature and submucosal glands. • Whorls of shed epithelium forming mucous plugs (Curschmann’s spirals) • Collection of crystaloid made up of debris of eosinophil membranes (Charcot- Leyden crystals)
Asthma is most often associated with allergic stimuli: Type 1 HSR IL4 (IgE), 5 (Eos) , and 10 (TH2) Also IL-13 and IL-9
Bronchiectasis • Abnormal permanent dilatation of the bronchi and bronchioles. • Caused by repeated cycles of airway infection/inflammation • Distal airways become thickened • Mucosal surfaces develop edema and suppuration • Neovascularization of the adjacent bronchial arterioles occurs. • Hemoptysis, Sputum • Bronchiectasis shares many clinical features with chronic obstructive pulmonary disease (COPD) • Inflamed and easily collapsible airways • Obstruction to airflow • Frequent office visits and hospitalizations. • Dx: Chronic daily cough with viscid sputum production and presence of bronchial wall thickening and luminal dilatation on HRCT.
Bronchiectasis • Presentation • Cough • Purulent sputum production • Hemoptysis • Recurrent infection • Bronchial hyper-reactivity • Obstructive lung disease
Localizing Bronchiectasis • Upper Lobe • Cystic Fibrosis • Lower Lobe • Aspiration Syndromes • Right Middle Lobe and Lingula • Nontuberculous Mycobacterial Infection • Central • Allergic Bronchopulmonary Aspergillosis
Treatment of Bronchiectasis • 1. Antibiotics • 2. Bronchopulmonary drainage • 3. Bronchodilators • Chest Physical Therapy • Inhaled DNA-ase for CF patients
Presence of P. Aeroginosa portends a worse prognosis in bronchiectasis
Pink Puffers and Blue Bloaters • Pink Puffers - associated with severe emphysema • Cachexia, unrelenting dyspnea, severe lung hyperinflation, normal (or near normal) ABG at rest because the body compensates by hyperventilating (hence the puffer). Low cardiac output  muscle wasting and weight loss. The pink can be from a number of things, one of which is using neck and chest muscles to breathe. • Blue Bloaters - associated with chronic bronchitis • Stout body habitus, chronic cough and sputum, dyspnea, severe hypoxia and hypercapnia (leading to polycythemia and signs of right-sided heart failure)
COPD vs. Asthma • Factors that favor COPD over Asthma • Older age • current/past smoker • Hx acute bronchitis • chronic cough, sputum production or wheezing • Factors that favor Asthma over COPD • Young age • No smoking history • Atopy • Variability of Sx over time • Reversible obstruction
Natural Progression of COPD • Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow obstruction and an abnormal inflammatory response in the lungs • Innate and adaptive immune responses to long term exposure to noxious particles and gases, particularly cigarette smoke. • This amplified response may result in mucous hypersecretion (chronic bronchitis), tissue destruction (emphysema), and disruption of normal repair and defence mechanisms causing small airway inflammation and fibrosis (bronchiolitis). • 1. Inflammation • 2. Imbalance of Proteases and Antiproteases • 3. Oxidative Stress
COPD Diagnosis Airflow limitation measured by FEV1 % Predicted All patients with FEV1/FVC reduced to < 0.70 GOLD 1 Mild >80% GOLD 2 Moderate 50 – 80% GOLD 3 Severe 30 – 50% GOLD 4 Very Severe <30%
COPD Classification Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC A Low Risk Less Symptoms GOLD 1-2 FEV1 > 50% ≤ 1 < 10 0-1 B Low Risk More Symptoms GOLD 1-2 FEV1 > 50% ≤ 1 ≥ 10 ≥ 2 C High Risk Less Symptoms GOLD 3-4 FEV1 < 50% ≥ 2 <10 0-1 D High Risk More Symptoms GOLD 3-4 FEV1 < 50% ≥ 2 ≥ 10 ≥ 2
Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC A Low Risk Less Symptoms GOLD 1-2 FEV1 > 50% ≤ 1 < 10 0-1 Patient Category 1st Choice Tx 2nd Choice Tx 3rd Choice Tx A SAMA PRN or SABA PRN LAMA or LABA or SAMA+SABA PDE inh (Theophylline) Category A Therapy
Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC B Low Risk More Symptoms GOLD 1-2 FEV1 > 50% ≤ 1 ≥ 10 ≥ 2 Patient Category 1st Choice Tx 2nd Choice Tx 3rd Choice Tx B LAMA or LABA LAMA+LABA SABA and/or SAMA Theophylline Category B Therapy
Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC C High Risk Less Symptoms GOLD 3-4 FEV1 < 50% ≥ 2 <10 0-1 Patient Category 1st Choice Tx 2nd Choice Tx 3rd Choice Tx C ICS and LAMA or LABA LAMA+LABA or LAMA+PDE4I or LABA+PDE4I SABA and/or SAMA Theophylline Category C Therapy
Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC D High Risk More Symptoms GOLD 3-4 FEV1 < 50% ≥ 2 ≥ 10 ≥ 2 Patient Category 1st Choice Tx 2nd Choice Tx 3rd Choice Tx D ICS and LAMA and/or LABA ICS+LAMA+LABA or ICS+LAMA+PDE4I or ICS+LABA+PDE4I Mucolytics SABA and/or SAMA Theophylline Category D Therapy
First Line: Tiotropium + SABA prn Steroids for exacerbations (Advair)
Pharmacotherapy
Alpha 1 Antitrypsin Deficiency • α1-antitrypsin is a protease inhibitor and protects lung tissue against neutrophil elastase and other proteases. • Encoded by the gene PI • M: Normal wild type • Z: Most common mutant leading to deficiency • ZZ homozygous: Severe Disease • Symptoms • Lung • COPD: Panacinar emphysema • Possible bronchiectasis or asthma • Suspected from uncontrolled destruction by neutrophil elastase in the lung • Liver • Childhood liver disease • Adulthood cirrhosis of liver & hepatocellular carcinoma • Suspected from abnormal deposition of dysfunctional AAT protein • Skin • Necrotizing panniculitis, vasculitis, urticaia, angioedema
Alpha 1 Antitrypsin Diagnosis • Emphysema in a young age (< 45 yo) • Emphysema in non-smokers • Basilar distribution of emphysema • Concurrent liver or skin disease • Serum levels of AAT: below 50 mg/dL • Genotyping to look for S or Z alleles
PFTS Disease PFT Pattern Asthma Obstructive and Reversible Chronic Bronchitis Obstructive, Irreversible, Normal DLCO Emphysema Obstructive, Irreversible, Low DLCO Bronchiectasis Obstructive Cystic Fibrosis Obstructive, FEV1 correlates with outcomes
Cystic Fibrosis • Autosomal Recessive defect in CFTR chloride channel • CFTR dysfunction reduces chloride secretion from the epithelialial cells into the airway lumen  sodium absorption into the cell is markedly increased  thinning of the airway surface’s liquid lining layer  impaired mucociliary clearance. • Chronic infection  PMN-dominated inflammatory response. • Neutrophil products (proteolytic enzymes and oxidants) mediate the subsequent pathologic changes: bronchiectasis, bronchiolectasis, bronchial stenosis, and fibrosis. • Mucous plugging of airways • 1. Production of thick, tenacious secretions from exocrine glands • 2. Elevated concentrations of sodium, chloride, and potassium in sweat
Cystic Fibrosis • Clinical Presentation • Pancreatic insufficiency • Recurrent episodes of tracheobronchial infection • Bronchiectasis • Intestinal obstruction • Sterility in males • Diagnosis: • (1) Identification of mutations known to cause cystic fibrosis in both CFTR genes • (2) Characteristic abnormalities in measurements of nasal mucosal electrical potential difference • (3) Abnormal sweat electrolytes
CF Work Up • Cystic fibrosis causes obstructive lung disease, initially with decreased flows at low lung volumes. • Forced expiratory volume in 1 second (FEV1) is the best correlate of outcome and starts to differ markedly from normal during adolescence. • The rate of decline in FEV1 often predicts the clinical course. • Early in the disease, the chest radiograph demonstrates hyperinflation and peribronchial thickening. Computed tomography can demonstrate bronchiectasis early in the course of the disease. • Airway infection, which is the key clinical manifestation, can be detected by sputum culture or bronchoalveolar lavage.
INTERSTITIAL LUNG DISEASE
Overview • Patients have dyspnea, tachypnea, end-inspiratory crackles, and eventual cyanosis, without wheezing or other evidence of airway obstruction. • The classic functional abnormalities are reductions in diffusion capacity, lung volume, and lung compliance. • Chest radiographs show bilateral lesions that take the form of small nodules, irregular lines, or ground-glass shadows, all corresponding to areas of interstitial fibrosis. • Eventually, secondary pulmonary hypertension and right-sided heart failure associated with cor pulmonale may result. • Although the entities can often be distinguished in the early stages, the advanced forms are hard to differentiate because all result in scarring and gross destruction of the lung, often referred to as end-stage lung or honeycomb lung.
Causes • Idiopathic • Idiopathic interstitial pneumonias • Granulomatous • Sarcoidosis • Occupational and environmental : Pneumoconioses • Coal worker pneumoconiosis (CWP) • Silicosis • Asbestosis • Berylliosis • Drug induced • Amiodarone • Bleomycin and busulfan • Cyclophosphamide • Methotrexate and methysergide • Nitrosourea and nitrofurantoin • Connective tissue disease • Systemic sclerosis • SLE • RA • Collagen vascular disease
Idiopathic Interstitial Pneumonias • Idiopathic pulmonary fibrosis • Non-specific interstitial pneumonia • Respiratory bronchiolitis-associated interstitial lung disease • Desquamative interstitial pneumonia • Cryptogenic organizing pneumonia • Acute interstitial pneumonia • Lymphoid interstitial pneumonia
Clinical Features • History: • Subacute or chronic • Chronic • pulmonary hypertension • right sided heart failure (cor pulmonale). • Symptoms: • Progressive dyspnea • Cough • Late inspiratory crackles • Respiratory alkalosis • No wheezing • Signs: • Restrictive PFTs (reduced FEV1 and FVC with normal ratio, decreased TLC) • Reduced DLCO. • Variable inflammation and fibrosis of the interstitial, alveolar, and vascular compartments of the lungs. • Decreased PaO2
IPF Clinical Course • IPF begins insidiously with gradually increasing dyspnea on exertion and dry cough. • Most patients are 55 to 75 years old at presentation. • Hypoxemia, cyanosis, and clubbing occur late in the course. • Usually there is a gradual deterioration in pulmonary status despite medical treatment with immunosuppressive drugs such as steroids, cyclophosphamide, or azathioprine. • The median survival is about 3 years after diagnosis. • Lung transplantation is the only definitive therapy.
IPF: Gross and Microscopic Morphology • Gross Morphology • Cobblestoned Pleura as a result of the retraction of scars along the interlobular septa. • Fibrosis occurs preferentially in the lower lobes, the subpleural regions, and along the interlobular septa. • Spacial/Temporal Heterogeneity • Microscopic • 1) Patchy interstitial fibrosis • 2) Fibroblastic foci • 3) Honeycomb fibrosis • The dense fibrosis causes the destruction of alveolar architecture and formation of cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epithelium • Early: exuberant fibroblastic proliferation • Late: areas become more collagenous and less cellular.
UIP NSIP Spacial/temporal heterogeneity Spacial/temporal homogeneity
In order to diagnose ILD, you need to use a combination of history, clinical findings, histologic findings, and/or radiographic findings. You cannot rely on one modality alone
PFTs • Reduced FEV1 • Reduced FVC • Normal FEV1/FVC ratio • Decreased TLC • Reduced DLCO • PFTs At Rest: Diagnosis • PFTs With Exercise • Monitor the effectiveness of treatments • Monitor the course of the disease • The reductions in lung volumes become more pronounced with disease progression. • 3 reasons to do physiologic testing • 1) Clues to diagnostic category • 2) Assess the severity of impairment • 3) Assess change objectively
2 criteria for diagnosis of IPF: 1) Exclude other known causes of ILD (ex: sarcoidosis, pneumoconiosis, etc) 2) Diagnose UIP either by HRCT or surgical lung biopsy
HRCT • Interlobular septal thickening and reticulation • Symmetrical, lower lobe, subpleural • Macroscopic honeycombing • Symmetrical, lower lobe, subpleural • Traction bronchiectasis • Bilateral infiltrative lesions in the form of small nodules, irregular lines, or ground-glass shadows
HRCT Interlobular septal thickening Reticulation Honeycombing Traction bronchiectasis
Mosaic Attenuation: Air Trapping Expiratory Normal
Bronchoscopy and Surgical Lung Biopsy • Bronchoscopy is diagnostic for sarcoidosis in >90% of cases • Perform bronchoscopy if: • Hemoptysis and radiographic ILD findings are present • Acute onset of ILD • Subacute or chronic presentation of ILD if sarcoidosis, hypersensitivity pneumonitis, pulmonary Langerhans histiocytosis, or infection are suspected • Bronchoscopy is less helpful in patients with radiographic findings that suggest IPF • No established role in assessment of progression or response to therapy • Obtain a lung biopsy in patients with atypical or progressive symptoms and signs: • Age less than 50 years • Fever • Weight loss • Hemoptysis • Signs of vasculitis • Atypical radiographic features • Unexplained extrapulmonary manifestations • Rapid clinical deterioration, or sudden change in radiographic appearance
Treatment • General Lung Disease • Stop smoking • Supplemental oxygen if needed • Immunization against S. pneumoniae and flu • Pulmonary rehabilitation • Consider lung transplantation • Enrollment in clinical trials • End-of-life planning • Specific to ILD • No specific therapy works for IPF • Quality of data for effectiveness of therapy is poor • Immunosuppressive therapy may be effective in some but not others • Immunosuppressive therapy side-effects are common and dangerous • Duration and intensity of appropriate treatment differs markedly
Anatomy: Pulmonary Interstitium • Definition: Collection of support tissues within the lung that includes the alveolar epithelium + pulmonary capillary endothelium + basement membrane + perivascular and perilymphatic tissue • Divided into 3 zones- • Axial (surrounding bronchovascular tree) • Parenchymal (surrounding pulmonary parenchyma) • Peripheral (adjacent to the pleura)
Anatomy: Secondary Pulmonary Lobule • Smallest unit of lung structure marginated by connective tissue septa: fundamental unit of lung structure • Irregularly polyhedral, variable size (1-2.5 cm) • Contains: • Small bronchiole • Pulmonary artery branch • 12 or fewer acini usually • Marginated by interlobular septa • Contain pulmonary veins and lymphatics • Septa allow for visualization
Autoimmune Diseases such as SLE, Rheumatoid Arthritis, Scleroderma, and Dermatomyositis-Polymyositis can cause ILD, but have a much better prognosis and can be treated with immunosuppresive therapy.
Hypersensitivity Pneumonitis • Spectrum of immunologically mediated, predominantly interstitial, lung disorders caused by intense, often prolonged exposure to inhaled organic antigens • In contrast to Asthma, involves pathologic changes of ALVEOLAR WALLS • A common and potentially treatable cause of ILD • Farmer’s lung (thermophilic actinomyces), Bird-fancier’s lung, Indoor mold • Histology: • Centered on bronchioles • (1) Interstitial pneumonitis, consisting primarily of lymphocytes, plasma cells, and macrophages (NOT EOSINOPHILS) • (2) Noncaseating granulomas in 2/3 of patients • (3) Interstitial fibrosis with fibroblastic foci, honeycombing, and obliterative bronchiolitis (late stages). • Centrilobular nodules on HRCT
HP Clinical Course • Acute attacks, which follow inhalation of antigenic dust in sensitized patients, consist of recurring episodes of fever, dyspnea, cough, and leukocytosis. • Micronodular interstitial infiltrates may appear in the chest radiograph • Pulmonary function tests show an acute restrictive disorder. • Symptoms usually appear 4 to 6 hours after exposure and may last for 12 hours to several days. They recur with reexposure. • If exposure is continuous and protracted, a chronic form of the disease supervenes, leading to progressive respiratory failure, dyspnea, and cyanosis and a decrease in total lung capacity and compliance.
Chronic Inflammatory Infiltrate centered on small airways: bronchiolitis Lymphocytic Bronchiolitis Noncaseating Granuloma
IPF vs. Hypersensitivity Pneumonitis • Timing • IPF: Gradual onset, chronic non productive cough • HP: Subacute, Symptoms within hours of exposure • Prognosis • IPF: Survival is less than 3 years • HP: Good prognosis if diagnosed in subacute phase • Treatment • IPF: Only lung transplant • HP: Immunosuppression and antigen avoidance
Sarcoidosis • Systemic disease characterized by non-caseating granulomas in multiple organs/systems • African American Females, non-smokers, 20-39 • Diagnosis of exclusion: NEVER A SURE THING • Gross Morphology: • Symmetric hilar and mediastinal lymphadenopathy +/- lung infiltrates • Histology • Well-formed nonnecrotizing granulomas composed of aggregates of tightly clustered epithelioid macrophages, often with giant cells. • Granulomas  fibrosis and hyalinization • Stellate inclusions (‘asteroid bodies’) often seen within giant cells of granulomas • Diagnosis w/ bronchoscopy in 90% of cases
Granulomas
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review
Pulmonology Review

Empfohlen

Respiratory physiology by Dr RamKrishna
Respiratory physiology by Dr RamKrishnaRespiratory physiology by Dr RamKrishna
Respiratory physiology by Dr RamKrishnaram krishna
 
pulmonary function test
pulmonary function testpulmonary function test
pulmonary function testmohamed abuelnaga
 
Pneumology - Ventilation physiology-and-work-of-breathing
Pneumology - Ventilation physiology-and-work-of-breathingPneumology - Ventilation physiology-and-work-of-breathing
Pneumology - Ventilation physiology-and-work-of-breathingAmmedicine Medicine
 
Body plethesmography
Body plethesmographyBody plethesmography
Body plethesmographyAnusha Jahagirdar
 
Respiratory physiology
Respiratory physiologyRespiratory physiology
Respiratory physiologyPratik Tantia
 
Resperattory system
Resperattory systemResperattory system
Resperattory systemRichard Alave
 
Pulmonary function tests: A brief Insight- By RxVichuZ! :)
Pulmonary function tests: A brief Insight- By RxVichuZ! :)Pulmonary function tests: A brief Insight- By RxVichuZ! :)
Pulmonary function tests: A brief Insight- By RxVichuZ! :)RxVichuZ
 
pulmonary function test
pulmonary function test pulmonary function test
pulmonary function test imsurgeon
 

Empfohlen

Respiratory physiology by Dr RamKrishna
Respiratory physiology by Dr RamKrishnaRespiratory physiology by Dr RamKrishna
Respiratory physiology by Dr RamKrishnaram krishna
 
pulmonary function test
pulmonary function testpulmonary function test
pulmonary function testmohamed abuelnaga
 
Pneumology - Ventilation physiology-and-work-of-breathing
Pneumology - Ventilation physiology-and-work-of-breathingPneumology - Ventilation physiology-and-work-of-breathing
Pneumology - Ventilation physiology-and-work-of-breathingAmmedicine Medicine
 
Body plethesmography
Body plethesmographyBody plethesmography
Body plethesmographyAnusha Jahagirdar
 
Respiratory physiology
Respiratory physiologyRespiratory physiology
Respiratory physiologyPratik Tantia
 
Resperattory system
Resperattory systemResperattory system
Resperattory systemRichard Alave
 
Pulmonary function tests: A brief Insight- By RxVichuZ! :)
Pulmonary function tests: A brief Insight- By RxVichuZ! :)Pulmonary function tests: A brief Insight- By RxVichuZ! :)
Pulmonary function tests: A brief Insight- By RxVichuZ! :)RxVichuZ
 
pulmonary function test
pulmonary function test pulmonary function test
pulmonary function test imsurgeon
 
Pulmonary function test
Pulmonary function testPulmonary function test
Pulmonary function testraghu srikanti
 
Compliance and resistance
Compliance and resistanceCompliance and resistance
Compliance and resistancehamna rafaqat
 
Physiology of respiratory system
Physiology of respiratory systemPhysiology of respiratory system
Physiology of respiratory systemSelva Kumar
 
Asthma biomarkers: FENO
Asthma biomarkers: FENOAsthma biomarkers: FENO
Asthma biomarkers: FENOChulalongkorn Allergy and Clinical Immunology Research Group
 
Introduction to Pulmonary function test
Introduction to Pulmonary function testIntroduction to Pulmonary function test
Introduction to Pulmonary function testPrince Maurya
 
Breathing mechanics
Breathing mechanicsBreathing mechanics
Breathing mechanicsgaganbrar18
 
Control of Ventilation /Lung Physiology by Nahid Sherbini
Control of Ventilation /Lung Physiology by Nahid SherbiniControl of Ventilation /Lung Physiology by Nahid Sherbini
Control of Ventilation /Lung Physiology by Nahid SherbiniNahid Sherbini
 
Pulmonary Function Test ppt
Pulmonary Function Test pptPulmonary Function Test ppt
Pulmonary Function Test pptIfra Khan
 
Compliance of the lungs and chest wall
Compliance of the lungs and chest wallCompliance of the lungs and chest wall
Compliance of the lungs and chest wallRyan Mutitima
 
Lung mechanics
Lung mechanicsLung mechanics
Lung mechanicsmauryaramgopal
 
Lesson 2 ventilation and gas exchange
Lesson 2 ventilation and gas exchange Lesson 2 ventilation and gas exchange
Lesson 2 ventilation and gas exchange Ferhad Shakir
 
Heliox therapy .pptx
Heliox therapy .pptxHeliox therapy .pptx
Heliox therapy .pptxssuser8b3d27
 
Lung volumes and capacities
Lung volumes and capacitiesLung volumes and capacities
Lung volumes and capacitiesMieynn Ramsed
 
Body plethysmography - Basics
Body plethysmography - BasicsBody plethysmography - Basics
Body plethysmography - BasicsAtheenaPandian Enterprises
 
Control of breathing
Control of breathingControl of breathing
Control of breathingAnindya Jana
 
Respiratory physiology
Respiratory physiologyRespiratory physiology
Respiratory physiologyPravin Prasad
 
Mechanical Ventilation
Mechanical VentilationMechanical Ventilation
Mechanical VentilationShalini Garg
 
5) gas exchange and diffusion
5) gas exchange and diffusion5) gas exchange and diffusion
5) gas exchange and diffusionAyub Abdi
 
Bronchial Thermoplasty
Bronchial ThermoplastyBronchial Thermoplasty
Bronchial Thermoplastycschoolmaster
 
Lung volume reduction surgery ( LVRS )
Lung volume reduction surgery ( LVRS ) Lung volume reduction surgery ( LVRS )
Lung volume reduction surgery ( LVRS ) Mashail Alrayes
 
Airchanges hvac
Airchanges hvacAirchanges hvac
Airchanges hvacShaikh Ahmed
 
Understanding ABGs and spirometry
Understanding ABGs and spirometryUnderstanding ABGs and spirometry
Understanding ABGs and spirometryShivashankar S
 

Weitere ähnliche Inhalte

Was ist angesagt?

Pulmonary function test
Pulmonary function testPulmonary function test
Pulmonary function testraghu srikanti
 
Compliance and resistance
Compliance and resistanceCompliance and resistance
Compliance and resistancehamna rafaqat
 
Physiology of respiratory system
Physiology of respiratory systemPhysiology of respiratory system
Physiology of respiratory systemSelva Kumar
 
Introduction to Pulmonary function test
Introduction to Pulmonary function testIntroduction to Pulmonary function test
Introduction to Pulmonary function testPrince Maurya
 
Breathing mechanics
Breathing mechanicsBreathing mechanics
Breathing mechanicsgaganbrar18
 
Control of Ventilation /Lung Physiology by Nahid Sherbini
Control of Ventilation /Lung Physiology by Nahid SherbiniControl of Ventilation /Lung Physiology by Nahid Sherbini
Control of Ventilation /Lung Physiology by Nahid SherbiniNahid Sherbini
 
Pulmonary Function Test ppt
Pulmonary Function Test pptPulmonary Function Test ppt
Pulmonary Function Test pptIfra Khan
 
Compliance of the lungs and chest wall
Compliance of the lungs and chest wallCompliance of the lungs and chest wall
Compliance of the lungs and chest wallRyan Mutitima
 
Lesson 2 ventilation and gas exchange
Lesson 2 ventilation and gas exchange Lesson 2 ventilation and gas exchange
Lesson 2 ventilation and gas exchange Ferhad Shakir
 
Heliox therapy .pptx
Heliox therapy .pptxHeliox therapy .pptx
Heliox therapy .pptxssuser8b3d27
 
Lung volumes and capacities
Lung volumes and capacitiesLung volumes and capacities
Lung volumes and capacitiesMieynn Ramsed
 
Control of breathing
Control of breathingControl of breathing
Control of breathingAnindya Jana
 
Respiratory physiology
Respiratory physiologyRespiratory physiology
Respiratory physiologyPravin Prasad
 
Mechanical Ventilation
Mechanical VentilationMechanical Ventilation
Mechanical VentilationShalini Garg
 
5) gas exchange and diffusion
5) gas exchange and diffusion5) gas exchange and diffusion
5) gas exchange and diffusionAyub Abdi
 
Bronchial Thermoplasty
Bronchial ThermoplastyBronchial Thermoplasty
Bronchial Thermoplastycschoolmaster
 
Lung volume reduction surgery ( LVRS )
Lung volume reduction surgery ( LVRS ) Lung volume reduction surgery ( LVRS )
Lung volume reduction surgery ( LVRS ) Mashail Alrayes
 

Was ist angesagt? (20)

Pulmonary function test
Pulmonary function testPulmonary function test
Pulmonary function test
 
Compliance and resistance
Compliance and resistanceCompliance and resistance
Compliance and resistance
 
Physiology of respiratory system
Physiology of respiratory systemPhysiology of respiratory system
Physiology of respiratory system
 
Asthma biomarkers: FENO
Asthma biomarkers: FENOAsthma biomarkers: FENO
Asthma biomarkers: FENO
 
Introduction to Pulmonary function test
Introduction to Pulmonary function testIntroduction to Pulmonary function test
Introduction to Pulmonary function test
 
Breathing mechanics
Breathing mechanicsBreathing mechanics
Breathing mechanics
 
Control of Ventilation /Lung Physiology by Nahid Sherbini
Control of Ventilation /Lung Physiology by Nahid SherbiniControl of Ventilation /Lung Physiology by Nahid Sherbini
Control of Ventilation /Lung Physiology by Nahid Sherbini
 
Pulmonary Function Test ppt
Pulmonary Function Test pptPulmonary Function Test ppt
Pulmonary Function Test ppt
 
Compliance of the lungs and chest wall
Compliance of the lungs and chest wallCompliance of the lungs and chest wall
Compliance of the lungs and chest wall
 
Lung mechanics
Lung mechanicsLung mechanics
Lung mechanics
 
Lesson 2 ventilation and gas exchange
Lesson 2 ventilation and gas exchange Lesson 2 ventilation and gas exchange
Lesson 2 ventilation and gas exchange
 
Heliox therapy .pptx
Heliox therapy .pptxHeliox therapy .pptx
Heliox therapy .pptx
 
Lung volumes and capacities
Lung volumes and capacitiesLung volumes and capacities
Lung volumes and capacities
 
Body plethysmography - Basics
Body plethysmography - BasicsBody plethysmography - Basics
Body plethysmography - Basics
 
Control of breathing
Control of breathingControl of breathing
Control of breathing
 
Respiratory physiology
Respiratory physiologyRespiratory physiology
Respiratory physiology
 
Mechanical Ventilation
Mechanical VentilationMechanical Ventilation
Mechanical Ventilation
 
5) gas exchange and diffusion
5) gas exchange and diffusion5) gas exchange and diffusion
5) gas exchange and diffusion
 
Bronchial Thermoplasty
Bronchial ThermoplastyBronchial Thermoplasty
Bronchial Thermoplasty
 
Lung volume reduction surgery ( LVRS )
Lung volume reduction surgery ( LVRS ) Lung volume reduction surgery ( LVRS )
Lung volume reduction surgery ( LVRS )
 

Andere mochten auch

Understanding ABGs and spirometry
Understanding ABGs and spirometryUnderstanding ABGs and spirometry
Understanding ABGs and spirometryShivashankar S
 
Testomonial 1 after_new_cv
Testomonial 1 after_new_cvTestomonial 1 after_new_cv
Testomonial 1 after_new_cvShaikh Ahmed
 
Upper and lower respiratory disease usmle
Upper and lower respiratory disease usmleUpper and lower respiratory disease usmle
Upper and lower respiratory disease usmleZhi Tian Chen
 
11.17.08(a): Alveolar Ventilation
11.17.08(a): Alveolar Ventilation11.17.08(a): Alveolar Ventilation
11.17.08(a): Alveolar VentilationOpen.Michigan
 
Ethanol as a transportation fuel
Ethanol as a transportation fuelEthanol as a transportation fuel
Ethanol as a transportation fuelArpita Saxena
 
Abg By Faruk Cfh
Abg By Faruk CfhAbg By Faruk Cfh
Abg By Faruk Cfhguest3f4099
 
09.12.08(b): An Introduction to Blood Gas Analysis
09.12.08(b): An Introduction to Blood Gas Analysis 09.12.08(b): An Introduction to Blood Gas Analysis
09.12.08(b): An Introduction to Blood Gas Analysis Open.Michigan
 
Prognostic Role Of Aa Do2 In Acute Pulmonary Embolism
Prognostic Role Of Aa Do2 In Acute Pulmonary EmbolismPrognostic Role Of Aa Do2 In Acute Pulmonary Embolism
Prognostic Role Of Aa Do2 In Acute Pulmonary EmbolismDang Thanh Tuan
 
Branding abg gallery
Branding abg galleryBranding abg gallery
Branding abg gallerySophia Ahn
 
ABG Seminar for PNA Cebu
ABG Seminar for PNA CebuABG Seminar for PNA Cebu
ABG Seminar for PNA Cebuinks76
 
Blood gases interpretation elkhatib
Blood gases interpretation elkhatibBlood gases interpretation elkhatib
Blood gases interpretation elkhatibMohamed El-Khatib
 
Abg And Acid Base Status
Abg And Acid Base StatusAbg And Acid Base Status
Abg And Acid Base StatusDang Thanh Tuan
 
Arterial blood gas analysis in clinical practice (2)
Arterial blood gas analysis in clinical practice (2)Arterial blood gas analysis in clinical practice (2)
Arterial blood gas analysis in clinical practice (2)Mohit Aggarwal
 
Arterial Blood Gases (3)
Arterial Blood Gases (3)Arterial Blood Gases (3)
Arterial Blood Gases (3)Dang Thanh Tuan
 
Tutorial 2 abg summary
Tutorial 2 abg summaryTutorial 2 abg summary
Tutorial 2 abg summaryVivianOh96
 

Andere mochten auch (20)

Airchanges hvac
Airchanges hvacAirchanges hvac
Airchanges hvac
 
Understanding ABGs and spirometry
Understanding ABGs and spirometryUnderstanding ABGs and spirometry
Understanding ABGs and spirometry
 
Testomonial 1 after_new_cv
Testomonial 1 after_new_cvTestomonial 1 after_new_cv
Testomonial 1 after_new_cv
 
Circulatory system ara
Circulatory system araCirculatory system ara
Circulatory system ara
 
Upper and lower respiratory disease usmle
Upper and lower respiratory disease usmleUpper and lower respiratory disease usmle
Upper and lower respiratory disease usmle
 
11.17.08(a): Alveolar Ventilation
11.17.08(a): Alveolar Ventilation11.17.08(a): Alveolar Ventilation
11.17.08(a): Alveolar Ventilation
 
Ethanol as a transportation fuel
Ethanol as a transportation fuelEthanol as a transportation fuel
Ethanol as a transportation fuel
 
ABG A World Of Opportunities
ABG A World Of OpportunitiesABG A World Of Opportunities
ABG A World Of Opportunities
 
Abg By Faruk Cfh
Abg By Faruk CfhAbg By Faruk Cfh
Abg By Faruk Cfh
 
09.12.08(b): An Introduction to Blood Gas Analysis
09.12.08(b): An Introduction to Blood Gas Analysis 09.12.08(b): An Introduction to Blood Gas Analysis
09.12.08(b): An Introduction to Blood Gas Analysis
 
Prognostic Role Of Aa Do2 In Acute Pulmonary Embolism
Prognostic Role Of Aa Do2 In Acute Pulmonary EmbolismPrognostic Role Of Aa Do2 In Acute Pulmonary Embolism
Prognostic Role Of Aa Do2 In Acute Pulmonary Embolism
 
Branding abg gallery
Branding abg galleryBranding abg gallery
Branding abg gallery
 
ABG Seminar for PNA Cebu
ABG Seminar for PNA CebuABG Seminar for PNA Cebu
ABG Seminar for PNA Cebu
 
Blood gases interpretation elkhatib
Blood gases interpretation elkhatibBlood gases interpretation elkhatib
Blood gases interpretation elkhatib
 
Abg And Acid Base Status
Abg And Acid Base StatusAbg And Acid Base Status
Abg And Acid Base Status
 
ABG slidshare
ABG slidshareABG slidshare
ABG slidshare
 
Arterial blood gas analysis in clinical practice (2)
Arterial blood gas analysis in clinical practice (2)Arterial blood gas analysis in clinical practice (2)
Arterial blood gas analysis in clinical practice (2)
 
Arterial Blood Gases (3)
Arterial Blood Gases (3)Arterial Blood Gases (3)
Arterial Blood Gases (3)
 
增加血氧含量減肥項目
增加血氧含量減肥項目增加血氧含量減肥項目
增加血氧含量減肥項目
 
Tutorial 2 abg summary
Tutorial 2 abg summaryTutorial 2 abg summary
Tutorial 2 abg summary
 

Ähnlich wie Pulmonology Review

ZONES OF LUNG AND VENTILATION PERFUSION.pptx
ZONES OF LUNG AND VENTILATION PERFUSION.pptxZONES OF LUNG AND VENTILATION PERFUSION.pptx
ZONES OF LUNG AND VENTILATION PERFUSION.pptxganeshrhitnalli
 
Compliance Resistance & Work Of Breathing
Compliance Resistance & Work Of Breathing Compliance Resistance & Work Of Breathing
Compliance Resistance & Work Of Breathing Zareer Tafadar
 
VENTILATION AND PERFUSION FOR NURSING ANATOMY
VENTILATION AND PERFUSION FOR NURSING ANATOMYVENTILATION AND PERFUSION FOR NURSING ANATOMY
VENTILATION AND PERFUSION FOR NURSING ANATOMYSongoma John
 
The respiratory system
The respiratory systemThe respiratory system
The respiratory systemEman Abdallah
 
Ventilator settings & clinical application jaskaran singh
Ventilator settings & clinical application jaskaran singhVentilator settings & clinical application jaskaran singh
Ventilator settings & clinical application jaskaran singhJaskaran Singh Rahi
 
respiratory physiology for anesthesia.pptx
respiratory physiology for anesthesia.pptxrespiratory physiology for anesthesia.pptx
respiratory physiology for anesthesia.pptxAbdullah Saad
 
Anatomy and physiology of the respiratory system
Anatomy and physiology of the respiratory systemAnatomy and physiology of the respiratory system
Anatomy and physiology of the respiratory systemDr Shibu Chacko MBE
 
DOC-20231211-WA0001..pdf
DOC-20231211-WA0001..pdfDOC-20231211-WA0001..pdf
DOC-20231211-WA0001..pdfsmrsah9
 
ManagingChestDrainage-2د/ رشيد الشرفي الصدر.pptx
ManagingChestDrainage-2د/ رشيد الشرفي الصدر.pptxManagingChestDrainage-2د/ رشيد الشرفي الصدر.pptx
ManagingChestDrainage-2د/ رشيد الشرفي الصدر.pptxRasheedSadek
 
Physio chapter 13 lungs
Physio chapter 13 lungsPhysio chapter 13 lungs
Physio chapter 13 lungsdaanesh88
 
Pulmonary physiology in health part i
Pulmonary physiology in health part iPulmonary physiology in health part i
Pulmonary physiology in health part iSamiaa Sadek
 

Ähnlich wie Pulmonology Review (20)

ZONES OF LUNG AND VENTILATION PERFUSION.pptx
ZONES OF LUNG AND VENTILATION PERFUSION.pptxZONES OF LUNG AND VENTILATION PERFUSION.pptx
ZONES OF LUNG AND VENTILATION PERFUSION.pptx
 
Mechanics of breathing
Mechanics of breathingMechanics of breathing
Mechanics of breathing
 
Compliance Resistance & Work Of Breathing
Compliance Resistance & Work Of Breathing Compliance Resistance & Work Of Breathing
Compliance Resistance & Work Of Breathing
 
VENTILATION AND PERFUSION FOR NURSING ANATOMY
VENTILATION AND PERFUSION FOR NURSING ANATOMYVENTILATION AND PERFUSION FOR NURSING ANATOMY
VENTILATION AND PERFUSION FOR NURSING ANATOMY
 
The respiratory system
The respiratory systemThe respiratory system
The respiratory system
 
Ventilator settings & clinical application jaskaran singh
Ventilator settings & clinical application jaskaran singhVentilator settings & clinical application jaskaran singh
Ventilator settings & clinical application jaskaran singh
 
Physiology of respiration
Physiology of respirationPhysiology of respiration
Physiology of respiration
 
respiratory physiology for anesthesia.pptx
respiratory physiology for anesthesia.pptxrespiratory physiology for anesthesia.pptx
respiratory physiology for anesthesia.pptx
 
Respiration by dr. mudassar
Respiration by dr. mudassarRespiration by dr. mudassar
Respiration by dr. mudassar
 
Respiratory..ppt
Respiratory..pptRespiratory..ppt
Respiratory..ppt
 
Anatomy and physiology of the respiratory system
Anatomy and physiology of the respiratory systemAnatomy and physiology of the respiratory system
Anatomy and physiology of the respiratory system
 
Respiratory physiology 2
Respiratory physiology 2Respiratory physiology 2
Respiratory physiology 2
 
DOC-20231211-WA0001..pdf
DOC-20231211-WA0001..pdfDOC-20231211-WA0001..pdf
DOC-20231211-WA0001..pdf
 
ManagingChestDrainage-2د/ رشيد الشرفي الصدر.pptx
ManagingChestDrainage-2د/ رشيد الشرفي الصدر.pptxManagingChestDrainage-2د/ رشيد الشرفي الصدر.pptx
ManagingChestDrainage-2د/ رشيد الشرفي الصدر.pptx
 
PUA respiration
PUA respiration PUA respiration
PUA respiration
 
Oxygenation Status
Oxygenation StatusOxygenation Status
Oxygenation Status
 
Physio chapter 13 lungs
Physio chapter 13 lungsPhysio chapter 13 lungs
Physio chapter 13 lungs
 
Ventilators
Ventilators Ventilators
Ventilators
 
Ventilation final
Ventilation finalVentilation final
Ventilation final
 
Pulmonary physiology in health part i
Pulmonary physiology in health part iPulmonary physiology in health part i
Pulmonary physiology in health part i
 

Mehr von Jess Little

Pulmonology Radiology
Pulmonology RadiologyPulmonology Radiology
Pulmonology RadiologyJess Little
 
Pulmonology Histology
Pulmonology HistologyPulmonology Histology
Pulmonology HistologyJess Little
 
Mind Brain and Behavior
Mind Brain and BehaviorMind Brain and Behavior
Mind Brain and BehaviorJess Little
 
MBB Localizing Lesions
MBB Localizing LesionsMBB Localizing Lesions
MBB Localizing LesionsJess Little
 
GI anatomy review
GI anatomy reviewGI anatomy review
GI anatomy reviewJess Little
 
Cardiovascular Review
Cardiovascular ReviewCardiovascular Review
Cardiovascular ReviewJess Little
 
Cardiovascular Histology
Cardiovascular HistologyCardiovascular Histology
Cardiovascular HistologyJess Little
 
Cardiovascular Drugs
Cardiovascular DrugsCardiovascular Drugs
Cardiovascular DrugsJess Little
 
Cardiovascular Anatomy
Cardiovascular AnatomyCardiovascular Anatomy
Cardiovascular AnatomyJess Little
 
Endorepro review
Endorepro reviewEndorepro review
Endorepro reviewJess Little
 
Endo Repro Anatomy and Histology
Endo Repro Anatomy and HistologyEndo Repro Anatomy and Histology
Endo Repro Anatomy and HistologyJess Little
 

Mehr von Jess Little (17)

Renal Histology
Renal HistologyRenal Histology
Renal Histology
 
Renal Review
Renal ReviewRenal Review
Renal Review
 
Pulmonology Radiology
Pulmonology RadiologyPulmonology Radiology
Pulmonology Radiology
 
Pulmonology Histology
Pulmonology HistologyPulmonology Histology
Pulmonology Histology
 
Mind Brain and Behavior
Mind Brain and BehaviorMind Brain and Behavior
Mind Brain and Behavior
 
MBB Review
MBB ReviewMBB Review
MBB Review
 
MBB Localizing Lesions
MBB Localizing LesionsMBB Localizing Lesions
MBB Localizing Lesions
 
MBB Anatomy
MBB AnatomyMBB Anatomy
MBB Anatomy
 
Mbb 2 b
Mbb 2 bMbb 2 b
Mbb 2 b
 
GI anatomy review
GI anatomy reviewGI anatomy review
GI anatomy review
 
GI Review
GI ReviewGI Review
GI Review
 
Cardiovascular Review
Cardiovascular ReviewCardiovascular Review
Cardiovascular Review
 
Cardiovascular Histology
Cardiovascular HistologyCardiovascular Histology
Cardiovascular Histology
 
Cardiovascular Drugs
Cardiovascular DrugsCardiovascular Drugs
Cardiovascular Drugs
 
Cardiovascular Anatomy
Cardiovascular AnatomyCardiovascular Anatomy
Cardiovascular Anatomy
 
Endorepro review
Endorepro reviewEndorepro review
Endorepro review
 
Endo Repro Anatomy and Histology
Endo Repro Anatomy and HistologyEndo Repro Anatomy and Histology
Endo Repro Anatomy and Histology
 

Kürzlich hochgeladen

VIP Call Girls Mumbai Arpita 9910780858 Independent Escort Service Mumbai
VIP Call Girls Mumbai Arpita 9910780858 Independent Escort Service MumbaiVIP Call Girls Mumbai Arpita 9910780858 Independent Escort Service Mumbai
VIP Call Girls Mumbai Arpita 9910780858 Independent Escort Service Mumbaisonalikaur4
 
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Availablenarwatsonia7
 
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment BookingCall Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment Bookingnarwatsonia7
 
Hematology and Immunology - Leukocytes Functions
Hematology and Immunology - Leukocytes FunctionsHematology and Immunology - Leukocytes Functions
Hematology and Immunology - Leukocytes FunctionsMedicoseAcademics
 
97111 47426 Call Girls In Delhi MUNIRKAA
97111 47426 Call Girls In Delhi MUNIRKAA97111 47426 Call Girls In Delhi MUNIRKAA
97111 47426 Call Girls In Delhi MUNIRKAAjennyeacort
 
Book Call Girls in Kasavanahalli - 7001305949 with real photos and phone numbers
Book Call Girls in Kasavanahalli - 7001305949 with real photos and phone numbersBook Call Girls in Kasavanahalli - 7001305949 with real photos and phone numbers
Book Call Girls in Kasavanahalli - 7001305949 with real photos and phone numbersnarwatsonia7
 
Call Girls Hosur Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hosur Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Hosur Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hosur Just Call 7001305949 Top Class Call Girl Service Availablenarwatsonia7
 
Glomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptxGlomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptxDr.Nusrat Tariq
 
Call Girl Service Bidadi - For 7001305949 Cheap & Best with original Photos
Call Girl Service Bidadi - For 7001305949 Cheap & Best with original PhotosCall Girl Service Bidadi - For 7001305949 Cheap & Best with original Photos
Call Girl Service Bidadi - For 7001305949 Cheap & Best with original Photosnarwatsonia7
 
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service ChennaiCall Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service ChennaiNehru place Escorts
 
Mumbai Call Girls Service 9910780858 Real Russian Girls Looking Models
Mumbai Call Girls Service 9910780858 Real Russian Girls Looking ModelsMumbai Call Girls Service 9910780858 Real Russian Girls Looking Models
Mumbai Call Girls Service 9910780858 Real Russian Girls Looking Modelssonalikaur4
 
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service MumbaiLow Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbaisonalikaur4
 
Call Girls Viman Nagar 7001305949 All Area Service COD available Any Time
Call Girls Viman Nagar 7001305949 All Area Service COD available Any TimeCall Girls Viman Nagar 7001305949 All Area Service COD available Any Time
Call Girls Viman Nagar 7001305949 All Area Service COD available Any Timevijaych2041
 
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort ServiceCollege Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort ServiceNehru place Escorts
 
Hemostasis Physiology and Clinical correlations by Dr Faiza.pdf
Hemostasis Physiology and Clinical correlations by Dr Faiza.pdfHemostasis Physiology and Clinical correlations by Dr Faiza.pdf
Hemostasis Physiology and Clinical correlations by Dr Faiza.pdfMedicoseAcademics
 
See the 2,456 pharmacies on the National E-Pharmacy Platform
See the 2,456 pharmacies on the National E-Pharmacy PlatformSee the 2,456 pharmacies on the National E-Pharmacy Platform
See the 2,456 pharmacies on the National E-Pharmacy PlatformKweku Zurek
 
Call Girls Frazer Town Just Call 7001305949 Top Class Call Girl Service Avail...
Call Girls Frazer Town Just Call 7001305949 Top Class Call Girl Service Avail...Call Girls Frazer Town Just Call 7001305949 Top Class Call Girl Service Avail...
Call Girls Frazer Town Just Call 7001305949 Top Class Call Girl Service Avail...narwatsonia7
 
Housewife Call Girls Bangalore - Call 7001305949 Rs-3500 with A/C Room Cash o...
Housewife Call Girls Bangalore - Call 7001305949 Rs-3500 with A/C Room Cash o...Housewife Call Girls Bangalore - Call 7001305949 Rs-3500 with A/C Room Cash o...
Housewife Call Girls Bangalore - Call 7001305949 Rs-3500 with A/C Room Cash o...narwatsonia7
 
Call Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service Availablenarwatsonia7
 
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Availablenarwatsonia7
 

Kürzlich hochgeladen (20)

VIP Call Girls Mumbai Arpita 9910780858 Independent Escort Service Mumbai
VIP Call Girls Mumbai Arpita 9910780858 Independent Escort Service MumbaiVIP Call Girls Mumbai Arpita 9910780858 Independent Escort Service Mumbai
VIP Call Girls Mumbai Arpita 9910780858 Independent Escort Service Mumbai
 
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hsr Layout Just Call 7001305949 Top Class Call Girl Service Available
 
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment BookingCall Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
Call Girl Koramangala | 7001305949 At Low Cost Cash Payment Booking
 
Hematology and Immunology - Leukocytes Functions
Hematology and Immunology - Leukocytes FunctionsHematology and Immunology - Leukocytes Functions
Hematology and Immunology - Leukocytes Functions
 
97111 47426 Call Girls In Delhi MUNIRKAA
97111 47426 Call Girls In Delhi MUNIRKAA97111 47426 Call Girls In Delhi MUNIRKAA
97111 47426 Call Girls In Delhi MUNIRKAA
 
Book Call Girls in Kasavanahalli - 7001305949 with real photos and phone numbers
Book Call Girls in Kasavanahalli - 7001305949 with real photos and phone numbersBook Call Girls in Kasavanahalli - 7001305949 with real photos and phone numbers
Book Call Girls in Kasavanahalli - 7001305949 with real photos and phone numbers
 
Call Girls Hosur Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hosur Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Hosur Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Hosur Just Call 7001305949 Top Class Call Girl Service Available
 
Glomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptxGlomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptx
 
Call Girl Service Bidadi - For 7001305949 Cheap & Best with original Photos
Call Girl Service Bidadi - For 7001305949 Cheap & Best with original PhotosCall Girl Service Bidadi - For 7001305949 Cheap & Best with original Photos
Call Girl Service Bidadi - For 7001305949 Cheap & Best with original Photos
 
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service ChennaiCall Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
Call Girls Service Chennai Jiya 7001305949 Independent Escort Service Chennai
 
Mumbai Call Girls Service 9910780858 Real Russian Girls Looking Models
Mumbai Call Girls Service 9910780858 Real Russian Girls Looking ModelsMumbai Call Girls Service 9910780858 Real Russian Girls Looking Models
Mumbai Call Girls Service 9910780858 Real Russian Girls Looking Models
 
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service MumbaiLow Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
Low Rate Call Girls Mumbai Suman 9910780858 Independent Escort Service Mumbai
 
Call Girls Viman Nagar 7001305949 All Area Service COD available Any Time
Call Girls Viman Nagar 7001305949 All Area Service COD available Any TimeCall Girls Viman Nagar 7001305949 All Area Service COD available Any Time
Call Girls Viman Nagar 7001305949 All Area Service COD available Any Time
 
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort ServiceCollege Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
College Call Girls Vyasarpadi Whatsapp 7001305949 Independent Escort Service
 
Hemostasis Physiology and Clinical correlations by Dr Faiza.pdf
Hemostasis Physiology and Clinical correlations by Dr Faiza.pdfHemostasis Physiology and Clinical correlations by Dr Faiza.pdf
Hemostasis Physiology and Clinical correlations by Dr Faiza.pdf
 
See the 2,456 pharmacies on the National E-Pharmacy Platform
See the 2,456 pharmacies on the National E-Pharmacy PlatformSee the 2,456 pharmacies on the National E-Pharmacy Platform
See the 2,456 pharmacies on the National E-Pharmacy Platform
 
Call Girls Frazer Town Just Call 7001305949 Top Class Call Girl Service Avail...
Call Girls Frazer Town Just Call 7001305949 Top Class Call Girl Service Avail...Call Girls Frazer Town Just Call 7001305949 Top Class Call Girl Service Avail...
Call Girls Frazer Town Just Call 7001305949 Top Class Call Girl Service Avail...
 
Housewife Call Girls Bangalore - Call 7001305949 Rs-3500 with A/C Room Cash o...
Housewife Call Girls Bangalore - Call 7001305949 Rs-3500 with A/C Room Cash o...Housewife Call Girls Bangalore - Call 7001305949 Rs-3500 with A/C Room Cash o...
Housewife Call Girls Bangalore - Call 7001305949 Rs-3500 with A/C Room Cash o...
 
Call Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Jayanagar Just Call 7001305949 Top Class Call Girl Service Available
 
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service AvailableCall Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
Call Girls Whitefield Just Call 7001305949 Top Class Call Girl Service Available
 

Pulmonology Review

  • 3. Mechanics of Breathing • Pressure difference is the driving force for air flow, Q = ΔP / R • Between breaths, alveolar pressure = atmospheric pressure • Inspiration: Diaphragm contracts → lung volume increases → alveolar pressure decreases → air flows into the lungs until alveolar pressure = atmospheric pressure again • Tidal volume (VT) = volume inspired in one normal breath (500mL) • Volume in lungs after inspiration = FRC + VT • Functional residual capacity: the volume in the lungs at the end-expiratory position • Expiration: diaphragm relaxes → lung volume decreases → alveolar pressure increases → air flows out of the lungs • Forced expiration: contraction of expiratory muscles further increases alveolar pressure to force air out. Intrapleural pressure increases too, but as long as the transmural pressure is still positive, the lungs will not collapse. Expiration will be rapid and forceful. • COPD: Lung elasticity is decreased, so during forced expiration, intrapleural pressures increase to normal values but alveolar pressures are lower because of their increased compliance. The gradient becomes negative & airways collapse.
  • 4. Lung Volumes and Capacities
  • 6.
  • 7. Forced Expiration and COPD In a person with COPD forced expiration may cause the airways to collapse. In COPD, lung compliance increases because of loss of elastic fibers. During forced expiration, intrapleural pressure is raised to the same value as in the normal person. However, because the structures have diminished elastic recoil, alveolar pressure and airway pressure are lower than in a normal person. The large airways collapse because the transmural pressure gradient across them reverses, becoming a negative (collapsing) transmural pressure. Obviously, if the large airways collapse, resistance to airflow increases and expiration is more difficult.
  • 8. Transmural Pressures • Transmural pressure: • Pressure difference across a structure • Transpulmonary pressure: • Difference between intra-alveolar pressure & intrapleural pressure • Calculated as alveolar pressure minus intrapleural pressure • Transthoracic pressure: • Difference between intrapleural pressure & pressure outside the chest wall (outside the body)
  • 10. Hysteresis • Hysteresis: the phenomenon that the compliance curves for inspiration and expiration are different. • For a given pressure, lung volume is higher during expiration than during inspiration, therefore compliance is greater during expiration. • Inspiration – • Low volume; liquid molecules are closely packed; intermolecular forces are high • Surfactant is released to break the forces (Surfactant = a phospholipid produced by type II alveolar cells that acts as a detergent to reduce surface tension & increase lung compliance) • Lung volume increases faster than surfactant can be added → curve starts off flat & gradually steepens as more surfactant is added. • Expiration – • Starts at high volume; intermolecular forces are low • Surface area decreases faster than surfactant can be removed → increasing density of surfactant per surface area decreases surface tension & increases compliance → curve starts off flat • As expiration proceeds – surfactant is removed at a similar rate as volume decreases, so the compliance curve has a fairly constant slope
  • 11. Compliance and Elastance • Compliance: Describes distensibility of system. ΔV/ΔP • “How easily an object stretches” • Elastance: inversely correlated with compliance. ΔP/ΔV "Snap back" or elastic recoil force. • “Ability of an object to return to its original position or shape” • Emphysema  increased compliance, decreased elastance • Fibrosis  decreased compliance, increased elastance
  • 12. Compliance of Lung and Chest Wall
  • 13. Pneumothorax • Normally, the intrapleural space has a negative pressure • This negative intrapleural pressure is created by two opposing elastic forces pulling on the intrapleural space • When a sharp object punctures the intrapleural space, air is introduced (pneumothorax), and intrapleural pressure suddenly becomes equal to atm pressure; thus, instead of its normal negative value, intrapleural pressure becomes ZERO • Two main consequences of pneumothorax • Without negative intrapleural pressure to hold lung open, lung collapses • Without negative intrapleural pressures to keep the chest wall from expanding, the chest wall springs out
  • 15. Emphysema and Compliance • Emphysema is associated with loss of elastic fibers in the lungs  increased compliance  increased (steeper) slope of the volume-versus- pressure curve  at a given volume, the collapsing (elastic recoil) force is decreased. • At the original value for FRC, chest wall expansion outweighs lung’s collapsing force. In order for the opposing forces to be balanced, volume must be added to the lungs to increase their collapsing force. • Thus, the combined lung and chest-wall system seeks a new higher FRC, where the two opposing forces can be balanced; the new intersection point, where airway pressure is zero, is increased. • A patient with emphysema is said to breathe at higher lung volumes (in recognition of the higher FRC) and will have a barrel-shaped chest.
  • 16. Fibrosis and Compliance • Fibrosis (decreased lung compliance). Fibrosis, a so-called restrictive disease, is associated with stiffening of lung tissues and decreased compliance. • A decrease in lung compliance is associated with a decreased slope of the volume-versus-pressure curve for the lung. • At the original FRC, the tendency of the lungs to collapse is greater than the tendency of the chest wall to expand, and the opposing forces will no longer be balanced. To reestablish balance, the lung and chest-wall system will seek a new lower FRC; the new intersection point, where airway pressure is zero, is decreased.
  • 17. FRC • Functional Residual Capacity (FRC) is the volume of air present in the lungs at the end of passive expiration. • At FRC, the elastic recoil forces of the lungs and chest wall are equal but opposite. There is no exertion at this point by any of the respiratory muscles. • FRC is the sum of Expiratory Reserve Volume (ERV) and Residual Volume (RV) and since it includes the residual volume, it cannot be measured by spirometry. • RV can be measured by helium dilution or body pleythysmography.
  • 18. Air Flow and Resistance The medium-sized bronchi are the sites of highest airway resistance. It would seem that the smallest airways would provide the highest resistance to airflow, based on the inverse fourth power relationship between resistance and radius. However, because of their parallel arrangement, the smallest airways do not have the highest resistance.
  • 19. Pulmonary vascular resistance is about 1/10 of systemic vascular resistance It has a minimum value at intermediate lung volumes
  • 21. Respiratory Volumes TLC Total Lung capacity 6.0L FRC Functional Residual Capacity 2.4L VC Vital Capacity 4.7L VT Tidal Volume 0.5L FVC Forced Vital Capacity 4.7L VA Alveolar Ventilation N/A FEV1 Volume of FVC in 1 second N/A
  • 23. • Anatomic dead space (~ 150 mL) = the volume of the conducting airways (nose/mouth, trachea, bronchi, bronchioles) • Alveolar ventilation = total rate of air movement into and out of the alveoli, expressed in mL/min. (500 mL/breath - 150 mL/breath) x 15 breaths/min = 5250 mL/min
  • 24. Alveolar Ventilation • VT = tidal volume • RR = respiratory rate • VD = dead space • Total ventilation (aka minute ventilation) = VT x RR • Normal: 500 mL/breath x 15 breaths/min = 7500 mL/min • Alveolar ventilation (VA) = (VT - VD) x RR
  • 25. Alveolar Ventilation Equation • Fundamental Equation of Physiology: Interdependence of CO2 and Ventilation • Increasing VA decreases PACO2 and PaCO2 and increases pH : ALKALOSIS • Decreasing VA increases PACO2 and PaCO2 and decreases pH : ACIDOSIS
  • 26. Alveolar Gas Equation • Predicts PAO2 based on alveolar PACO2 • PIO2 = (760-47) mmHg * 0.21 = 150mmHg • PAO2 = 150 – (40mmHg/0.8) = 100mmHg
  • 27.
  • 28. A-a Gradient • PAO2 – PaO2 • In a normal person, the A-a difference is close to zero (but not zero), because while O2 will equilibrate in the alveoli, there is a small amount of blood (~2%) that bypasses the alveoli (aka the "physiological shunt"), and PaO2 (obtained via a blood sample) is a mixture of all blood, including shunted blood. • To calculate the estimated normal A-a gradient : [Person’s Age/4] + 4 • Three scenarios that result in an increased gradient: • Diffusion defects (e.g. fibrosis, pulmonary edema) • V/Q defects • Right-to-left shunts (cardiac, intrapulmonary) • NOT Hypoventilation and High altitude
  • 29. Dead Space • Anatomic dead space: Volume of conducting airways • (nose/mouth, trachea, bronchi, bronchioles) • Physiologic dead space: Total volume of the lungs that does not participate in gas exchange = “anatomic dead space” plus any functional dead space in the structures that contain alveoli • Dead space ventilation is usually approximately 2ml/kg (ideal body weight)
  • 30. If you increase your RR and your VT by 20% respectively, you will see a GREATER increase in alveolar ventilation with an increase in VT BIGGER DEEPER BREATHS WORK
  • 32. Diffusion Changes • In emphysema, DL decreases because destruction of alveoli results in a decreased SA for gas exchange. • In fibrosis or pulmonary edema, DL decreases because the diffusion distance (membrane thickness or interstitial volume) increases. • In anemia, DL decreases because the amount of hemoglobin in red blood cells is reduced (recall that DL includes the protein-binding component of O2 exchange). • During exercise, DL increases because additional capillaries are perfused with blood, which increases the SA for gas exchange.
  • 33. Diffusion Limited vs. Perfusion Limited • Gas exchange across the alveolar/pulmonary capillary barrier is either diffusion-limited or perfusion-limited • CO is a diffusion-limited gas meaning that as long as the partial pressure gradient is maintained, diffusion will continue across the length of the capillary, so it can be used to measure the diffusing capacity. • Partial pressure gradient maintained because CO is bound to hemoglobin in capillary blood so CO does not equilibrate by the end of the capillary • Nitrous oxide (N2O) is a perfusion limited gas so it can be used to measure perfusion capacity
  • 34. The slower equilibration of O2 at high altitude is exaggerated in a person with fibrosis. Pulmonary capillary blood does not equilibrate by the end of the capillary, resulting in values for PaO2 as low as 30 mm Hg, which will seriously impair O2 delivery to the tissues.
  • 35. Hypoxemia and Hypercapnia • Hypoxemia: a decrease in arterial Po2 • Causes of hypoxemia: high altitude, hypoventilation, diffusion defect, V/Q defect, right-to-left shunt • Hypercapnia: abnormally elevated levels of CO2 in the blood • Causes of hypercapnia: hypoventilation, lung disease, respiratory acidosis
  • 36. CO2 moves from alveolar gas to pulmonary capillary blood 20 times faster than O2 due to a 20 times higher CO2 diffusion coefficient
  • 37.
  • 38. Blood Flow is Highest in Zone 3 of the lung due to pressure. It is 20X higher.
  • 39. Ventilation Rates are highest in Zone 3 of the lung due to gravity
  • 40. V/Q • V/Q ratio is the ratio of alveolar ventilation to pulmonary blood flow (ventilation/perfusion ratio, measured in L/min over L/min). • The normal value is 0.8. • If V/Q ratio is normal, then PaO2 will be at its normal value (100 mm Hg), as is PaCO2 (40 mm Hg).
  • 41. V/Q and Gas Exchange
  • 43. Physiological vs. Pathological Shunt • Physiologic shunt -A small fraction of the pulmonary blood flow (about 2%) bypasses the alveoli • Result is that PaO2 will always be slightly less than PAO2 • Made up of 2 components • Bronchial blood flow, which serves metabolic functions of bronchi • Coronary blood flow that drains directly into the left ventricle via the thebesian veins • Pathologic Shunts- • Right-to-left-Blood can pass from the right to left heart if there is a defect in the wall between the ventricles • Hypoxemia ALWAYS occurs because significant fraction of output is never delivered to the lungs for oxygenation • Hypoxemia CANNOT be corrected by having the person breathe a high O2 gas • Usually only minimal increase in PaCO2 (systemic arterial blood PCO2) • Left-to-right-More common and does not cause hypoxemia • Can be from patent ductus arteriosus or traumatic injury • Elevated PO2 in the right side of the heart
  • 44. 2% of blood bypasses pulmonary circulation in physiological shunt of healthy people
  • 46. Dissolved O2 is free in solution and accounts for approximately 2% of the total O2 content of blood. The remaining 98% of the total O2 content of blood is reversibly bound to hemoglobin inside the red blood cells.
  • 48. O2 Delivery • Cardiac Output x O2 Content
  • 49. Henry’s Law Henry’s law deals with gases dissolved in solution (e.g., in blood). To calculate a gas concentration in the liquid phase, the partial pressure in the gas phase first is converted to the partial pressure in the liquid phase; then, the partial pressure in liquid is converted to the concentration in liquid. ONLY APPLIES TO DISSOLVED (NOT BOUND) GAS
  • 51. The percent saturation of heme sites does not increase linearly as PO2 increases. Rather, percent saturation increases steeply (change in affinity) as PO2 increases from zero to approximately 40 mm Hg, and it then levels off between 50 mm Hg and 100 mm Hg.
  • 52. Unloading • This sigmoidal shape explains the mechanism of oxygen unloading in the capillaries. In regions of low PO2 such as 40 mmHg in mixed venous blood, the affinity between hemoglobin and oxygen is decreased and oxygen dissociates and enters tissues. The opposite is true in regions of high PO2 such as in the alveoli (100 mmHg). • Also related to concentrations of CO2 (Bohr and Haldane Effect)
  • 53. P50 • A change in the value of P50 is used as an indicator for a change in affinity of hemoglobin for O2. • An increase in P50 reflects a decrease in affinity – RIGHT SHIFT • A decrease in P50 reflects an increase in affinity – LEFT SHIFT
  • 54. Shifts in O2 Hemoglobin curve • Right Shifts • P50 is higher: DECREASED AFFINITY • Increased PCO2 (Bohr Effect) • Decreased pH • Increased Temperature • Increased 2,3,-DPG • Left Shifts • P50 is lower: INCREASED AFFINITY • Decreased PCO2 • Increased pH • Decreased Temperature • Decreased 2,3-DPG
  • 55. 2,3-DPG • 2,3-DPG is a byproduct of glycolysis in red blood cells. • 2,3-DPG binds to the b chains of deoxyhemoglobin and reduces their affinity for O2. • This decrease in affinity causes the O2-hemoglobin dissociation curve to shift to the right and facilitates unloading of O2 in the tissues. • 2,3-DPG production increases under hypoxic conditions. For example, living at high altitude causes hypoxemia, which stimulates the production of 2,3-DPG in red blood cells. • In turn, increased levels of 2,3-DPG facilitate the delivery of O2 to the tissues as an adaptive mechanism.
  • 56. The Effect of CO • Decreases O2 bound to hemoglobin and also causes a left shift of the O2-hemoglobin dissociation curve • Decreases O2 content of hemoglobin AND decreases unloading in the tissues • BAD.
  • 57. The Effect of Anemia
  • 58. CO2 Transport • Dissolved CO2 (5%), straight up in the blood • Carbaminohemoglobin (3%), bound to hemoglobin, albumin or other proteins • HCO3- (>90%), chemically modified by carbonic anhydrase • Exact percentages vary, but the vast majority is in HCO- 3
  • 59. Chloride Shift and CO2 Transport • Carbonic Anhydrase in RBCs catalyzes the combination of COand 2 HO to form HCO223 • HCOdissociates into H+ and HCO- 23 3 • H+ remains in the RBC and HCO3 - is filtered into plasma in exchange for Cl- • H+ is buffered in RBCs by deoxyhemoglobin
  • 61. PFTS
  • 63. Important Values • VT = 500mL • IRV = 3000 mL • ERV = 1200mL • RV = 1200mL • VC = 4700 mL • FRC = 1200mL • TLC = 5900mL • Dead Space = 150mL
  • 64. 4 Volumes, 4 Capacities • 4 Volumes • Tidal volume • Inspiratory reserve volume • Expiratory reserve volume • Residual volume • Four Capacities: • Inspiratory Capacity  IRV + TV • Functional residual capacity  ERV + RV • Vital Capacity  TV + IRV + ERV • Total Lung Capacity  IRV +TV + ERV + RV
  • 65. Residual Volume cannot be measured by Spirometry
  • 67.
  • 68. Diffusion, DLCO • DLCO : lung diffusing capacity • DL can be measured using carbon monoxide. • The test involves breathing in air with low concentrations of CO, and the rate of disappearance of CO from the gas mixture is proportional to the DL. • In certain pathological processes the DL changes predictably. • Emphysema, the DL goes down because destruction of alveoli decrease surface area for gas exchange. • Pulmonary fibrosis or edema, DL decreases because the diffusion distance increases. • Exercise, the DL increases because more capillaries are perfused with blood, thus increasing the surface area for exchange. • Anemia, the DL decreases because the amount of hemoglobin in RBCs decreases.
  • 69. 3 Categories of Lung Disease • Obstructive • Restrictive • Interstitial • Primary neurologic • Primary muscular • Primary skeletal • Vascular
  • 70. Localizing Disease • Airway • Asthma • COPD (chronic bronchitis & emphysema) • Interstitium and Alveoli • ILD • Emphysema • Alveolar Filling (WBC, RBC, Water, Protein) • Blood Vessels • PE • PAH • Pulm Ven HTN • Neuromuscular and Chest Wall • Pleural disease • Neurologic deficiency • Muscular weakness
  • 71. Algorithm FEV1/FVC Low Obstructed Reversible Yes: Asthma No: COPD DLCO Low: Emphysema Normal: Bronchitis Normal FVC/ TLC Low: Restrictive DLCO Low: ILD Normal: Neuromuscular Normal DLCO Low: Vascular Normal: Normal
  • 72. Normal Values • FEV1/FVC: 80 to 120% of predicted for most PFTs • Exceptions - FEV1/FVC: > 70% • Use actual value not % predicted • Change with bronchodilator • > 12% in FEV1 or FVC and 200 cc’s • TLC: 80 to 120% of predicted for most PFTs • TLC : Low (Restricted), High (Hyper-inflated) • DLCO : < 80% is considered abnormal
  • 74.
  • 75. Types of ARF • Typical (normal) ABG values: >60 mmHg for PaO2 and <50 mmHg for PaCO2 • There are two types of acute respiratory failures: in both types there will be decreased PaO2 (<60 mmHg). Thus in order to distinguish between the two types, we evaluate the PaCO2. • 1. Acute Hypoxemic Respiratory Failure: PaCO2 ≤ 40 mmHg • Hypoxemia without hypercapnia • Inability to properly take up oxygen • There is insufficient oxygen in the blood but near normal CO2 • 2. Acute Hypercapnic Respiratory Failure: PaCO2 > 40 mmHg • Hypoxemia with hypercapnia • Inability to eliminate carbon dioxide • There is too much carbon dioxide in the blood
  • 76. A-a Gradient • In a patient w/ hypoxemia and PaCO2 ≤ 40 mmHg: • Increased A-a gradient → intrapulmonary issue • Normal A-a gradient → extrapulmonary issue • An increase in the A-a gradient suggests an inability to extract enough oxygen (e.g., defects in diffusion, V/Q mismatch, or right-to-left shunting). • If the patient is hypoxic and has a normal A-a gradient, it suggests the problem is not in extracting O2 from the blood pointing to other etiologies like being at a higher elevation.
  • 77. Hypoxemic Respiratory Failure with Increased A-a Gradient • 1. Pulmonary embolism • 2. Atelectasis • 3. Pneumonia • 4. Interstitial lung disease • 5. Infection • 6. ARDS
  • 78. Hypoxemic Respiratory Failure with Normal A-a Gradient • High Altitude • Decreased FIO2 (asphyxia, drowning) • Airway Obstruction • Foreign body • Laryngeal spasm • Obesity and external compression of larynx • Obstructive sleep apnea • Obstruction of airway apparatus – kinking / obstruction of endotracheal tube • Asthma • Tumor
  • 79. Hypercapnic Respiratory Failure • Depression of the neurologic system • Narcotics • Overdose • Coma • Disease of the chest wall or neuromuscular apparatus • Myesthenia Gravis • Guillian Barre Syndrome • COPD or other lung diseases
  • 80. Clinical Signs and Sx • Breathing rate • Tidal volumes • Labored respiration/Paradoxical breathing • Asynchronous ventilatory patterns • Prolonged inspiratory phase: Stridor and upper airway obstruction • Prolonged expiratory phase: Asthma/COPD • Patient posture (cannot lay flat) • Ability to converse • Tachycardia with increased work of breathing • Patient tell you they are exhausted • Pulse ox <90% • PaO2 < 60 mmHg • PaCO2 > 50 mmHg
  • 81. Clinical Utility of Venous Blood Gas • Venous blood gas is sometimes used when arterial blood cannot be obtained due to diminished pulses or patient movement. • Venous blood gas gives a picture of how critical the patient is. If the venous O2 is really low, then the body is extracting the majority of O2 from blood and the patient is very critical. Normal mixed venous O2 saturation is 65-70%. • Central venous blood is preferred over peripheral venous blood because of their better correlation to arterial blood gases. • Central venous pH is usually 0.03-0.05 pH units lower than arterial pH. PCO2 is usually 4 to 5 mmHg higher than arterial PCO2. • Peripheral venous pH is usually 0.02-0.04pH units lower than arterial pH. The venous PCO2 is about 3-5mmHg higher than arterial PCO2.
  • 82. Identify the patient who may require intubation and mechanical ventilation. • Patients with severe dyspnea • Respiratory rate 35bpm • Unable to gasp more than 3 words • Very abnormal breathing pattern • Tachycardia/arrhythmias • Hyper/hypotension • Sweating • Abnormal arterial blood gases-60/50 club • Arterial PCO2 has risen to cause • Lowered pH (below 7.25-7.30) • Impaired mental status • PO2 over 60 mmHg cannot be achieved with inspired O2 concentration less than 40% - 60%
  • 83. NEURAL CONTROL OF BREATHING
  • 84. Lung Volume and Airway Patency • 2 types of striated muscles regulate the flow of air in and out of lungs: • Pump and Airway muscles • Pump muscles: Define volume of chest cavity: motor neurons in the spinal cord • Inspiratory: diaphragm and external intercostals • Expiratory: internal intercostals and abdominal (passive process at rest) • Airway muscles: regulate the flow of air through the airway: motor neurons located in the lower brainstem • Two aspects of ventilatory control: • (1) degree of inspiratory drive or central inspiratory activity • (2) the timing mechanism (which controls the termination of inspiration). • Determining factors act in concert to set the respiratory rate and tidal volume and thus the minute ventilation and specific pattern of breathing.”
  • 85. 3 Phases of Breathing • Inspiration: The diaphragm is recruited in an incremental fashion during inspiration: Innervated by phrenic nerve • Passive Expiration (E1): Air is forced out of the lungs due to the recoil of the elastic fibers in the lungs. • During this phase the phrenic nerve is still active but at lower level than it was in inspiration. • The expiratory branch of the recurrent laryngeal nerve activates the laryngeal constrictors, which oppose lung recoil. • The activity of these two nerves produces a smoother expiratory flow and results in better gas exchange in the lungs. • Active expiration (E2): only occurs if chemoreceptors are stimulated by hypoxia or hypercapnia or during exercise. • Expiratory muscles activity is essential to speed up breathing frequency. Inspiratory duration is virtually invariant in a healthy individual. The breathing rate increases almost entirely via shortening of expiratory phase. L • Lumbar nerve innervates muscles of phase 2
  • 86. Rhythm vs. Pattern Generation • Pattern: the orderly recruitment of pump and airway muscles during the respiratory cycle: • pontomedullary network of neurons • pattern generator is regulated by • cortex (volitional control) • limbic system (emotions) • state of vigilance (sleep vs awake) • blood gases (chemoreception) • feedbacks from lung and chest sensory afferents • Rhythm: generates the respiratory rate • PreBotzinger complex: controls timing of inspiration
  • 87. Neural Breathing Centers • Ventral respiratory column refers to a bilateral stretch of reticular formation that contains rhythm generating and pattern-generating respiratory neurons • The preBötzinger Complex is a small segment of the VRC where the eupneic breathing rhythm is generated. • Located in the ventrolateral medulla • Pneumotaxic center in dorsal pons • The nucleus solitary tract (NTS) receives sensory afferents including afferents from the lungs and carotid bodies. • The region is also sometimes called dorsal respiratory group and, in some species, contains phrenic premotor neurons. • Inspiratory motoneurons including phrenic motor neurons receive most of their input from the brainstem
  • 88. Mechanoreceptors vs. Chemoreceptors • Central Chemoreceptors: detect PCO2 and acid • Hypoxia in the CNS suppresses breathing • Peripheral Chemoreceptors (the carotid and aortic) detect artery hypoxia and arterial PCO2 • Respond more quickly to a change in arterial PCO2 than central chemoreceptors • Irritant receptors: (rapidly adapting) chemosensitive C fibers • Respond to cold, airflow, pollutants, irritants and inflammation • Mechanoreceptors (slowly adapting) • Lung inflation stretches the terminal endings of mechanosensitive sensory afferents located in the trachea and bronchi. • Activation of these afferents is sustained when the stretch is maintained • Initiate Hering Breuer reflex (see LO6) • Mechanoreceptors (rapidly adapting) • Encode rate of change of tension
  • 89. Chemoreceptors • Peripheral chemoreceptors are located in the carotid bodies and in the aortic body, located between the pulmonary artery and aortic arch. • Detect CO2 and O2 • REACT FASTER THAN CENTRAL CHEMORECEPTORS • Central respiratory chemoreceptors reside at the ventral surface of the medulla oblongata. • Detect only CO2 • Retrotrapezoid nucleus • Fissura pontomedullaris • Inferior olive • Precerebellar structure. • CNS Hypoxia depresses breathing
  • 90. MOA Peripheral Chemoreception • Hypoxia depolarizes type I cells (glomus cells) by turning off potassium conductances. • The depolarization causes Ca to enter and produces the exocytosis of transmitters (most important: ACh, ATP). • ACh and ATP depolarize the peripheral end of sensory afferents. • Carotid body afferents project to the nucleus solitary tract via the glossopharyngeal nerve where the information is relayed to the central pattern generator to cause an increase in breathing rate and amplitude.
  • 91. MOA Central Chemoreception • RTN neurons (bright green) are glutamatergic. They innervate only the regions involved in respiratory rhythm and pattern generation • RTN neurons are activated by acidification • A mutation of transcription factor Phox2b in man prevents the development of RTN neurons. The result is Congenital Central Hypoventilation Syndrome (Ondine’s curse), a disease in which breathing is no longer stimulated by CO2 and breathing stops during sleep (breathing while awake is Ok although PCO2 is less tigthly regulated). • These patients are ventilator-dependant throughout their life.
  • 92. Hering Breur Reflex • Reflex triggered to prevent overinflation of the lung mediated by slowly adapting mechanoreceptors. • Initiated by lung inflation, which stretches the terminal endings of slowly adapting mechanosensitive sensory afferents located in the trachea and bronchi  influx of sodium  depolarization and action potential generation • The axons travel in thoracic branches of the vagus nerve, and the cell bodies are found in the nodose ganglion. • Via the NTS, the information is relayed to the pons and the ventral respiratory column, resulting in decreased activity of inspiratory motoneurons, which helps terminate inspiration. • They are termed “slowly adapting” because their activation is sustained when the stretch is maintained. • This reflex is weaker in the adult and stronger in the neonate and is of minor medical importance.
  • 93. Rapid Mechanoreceptors • Respond only briefly to a stretch. They encode the rate of change of the tension as opposed to its absolute level. Rapidly adapting mechanoreceptors also exist in the lung but they are not involved in the H-B reflex.
  • 94. Chemosensitive C Fiber Afferents • Present throughout the trachea and bronchi and can produce a variety of skeletomotor and autonomic reflexes. • Exposure to pollutants and irritants triggers activation of both rapidly adapting receptors and C-fiber afferents, which then mediate mucus production, glottal closure and apnea, bronchoconstriction, and cough. • Glottis closure prevents further inhalation of particulate matter, irritants or toxins, and cough is a powerful expiratory effort against a closed glottis.
  • 95. Sighs • Sighs are periodic unusually large inspirations. • Their frequency is increased by (1) being awake as opposed to sleep, and (2) by hypoxia, probably by stimulation of the carotid bodies. • Most likely serve to prevent atelectasis
  • 96. Automaticity and Voluntary Control • In general, the process of breathing is a normal rhythmic activity that occurs without conscious effort. It is controlled by the central respiratory generator located in the medulla, which sends signals to the respiratory muscles. Input from the pons to the generator is necessary for a normal, coordinated breathing pattern. • The cerebral cortex exerts a conscious or voluntary control over ventilation. This cortical override of automatic control can be seen with either voluntary breath holding or hyperventilation.
  • 97. CO2 is the variable most tightly regulated by breathing
  • 98. Waking vs. Sleeping Drives • Breathing automaticity is maintained by several classes of mechanisms. The chemical drive is the excitatory influence of chemoreceptors (both central and peripheral) on the central respiratory pattern generator (CPG). • When one is awake, the CPG also receives excitatory inputs from “waking drives” including neural feedback that gauges the metabolic activity of skeletal muscles and the reticular activating system. • When one is asleep (non-REM sleep), however, the waking drive is greatly reduced or absent, and the chemical drive becomes the dominant influence. • Clinical significance: During sleep, breathing is more shallow, less stable (more prone to stop → apnea), and depends highly on the chemoreceptor drive.
  • 99. CNS hypercapnia will produce sleep disturbance and promote awakening, like in sleep apnea. The increases in CO2 leads to a sudden urge and stimulation to breathe. CNS hypoxia has a depressant effect
  • 100. Morphine and Breathing • Morphine depresses the brainstem respiratory pattern generator (including the central chemoreflex). The resulting slow and shallow breathing causes hypoxia and hypercarbia. • Carotid body stimulation by hypoxia/CO2 maintains a modicum of breathing but only up to a point. • If morphine exceeds a certain brain concentration, its direct CNS depressant effect combined with the depressant effects of brain hypoxia cannot be overcome by carotid body stimulation and breathing stops, leading to cardiovascular collapse and death.
  • 101. SIDS • Rare but responsible for a significant % of early infant deaths • Potential causes and contributing factors • Defect in arousal elicited by hypercapnia or hypoxia. • Overactive / abnormal airway protective reflexes (cough, laryngeal reflexes). • Developmental problems (abnormality of lower brainstem serotonergic neurons, possibly) • Environmental factors (air pollution, tobacco smoke, nicotine). • Treatment: • Preventative (eliminate presumed contributing factors). • Supine sleeping position (most effective; reduction of mortality estimated at > 50% in the US). • Alarm to detect loss of breathing
  • 102. SIDS Mechanism • During prone sleeping re-breathing exhaled air can increase CO2 and decrease O2 levels • Initiates the arousal response that begins with sigh. • Successful arousal results in head lifting and repositioning • If arousal fails, a more severe hypoxic state is reached and eupneic breathing will transition to gasping • This transition is mediated by respiratory network reconfiguration of the preBötC. • Should an infant fail to both arouse and autoresuscitate, the irreversible hypoxic insult leads to asphyxiation and the occurrence of SIDS
  • 103. Hypercapnia • When is hypercapnia really bad for you? • Acutely, when PaCO2 is greater than 8.0 to 9.3 kPa (60 to 70 mmHg) • Patients with chronic hypercapnia may not develop symptoms until the PaCO2 rises acutely to greater than 90 mmHg because they have a compensatory increase in the plasma bicarbonate concentration; • As a result, a larger elevation in PaCO2 is required to produce the same reduction in pH.
  • 104. O2 and COPD Patients • Oxygen given to COPD patients may cause secondary hypercapnia • 1. Ventilation perfusion mismatching (MOST IMPORTANT): • Your lungs have a finite supply of blood flow. In COPD, you have alveoli that are well ventilated, and alveoli that are poorly ventilated. Under normal conditions, there is proper matching between perfusion and ventilation. Less oxygen in certain alveoli → less blood flow to those alveoli. This frees blood flow to the well ventilated ones so you can effectively remove CO2. If pure O2 is given, the trickle of pure O2 is sufficient to cause perfusion of poorly ventilated alveoli, reducing blood flow to well ventilated ones. Less blood flow to well ventilated alveoli → less CO2 removal and hypercapnia • 2. The affinity of CO2 for hemoglobin decreases (Haldane effect). • -The Haldane effect refers to the rightward displacement of the CO2-hemoglobin dissociation curve in the presence of increased oxygen saturation • 3. Minute ventilation decreases because the hypoxic activation of the carotid chemoreceptors is removed (very small impact on hypercapnia)
  • 105. Altitude Effects • Short term: • If PO2 < 60mmHg, hypoxemia is severe enough to stimulate peripheral chemoreceptors (carotid and aortic bodies) → increased ventilation • Increased ventilation means that extra CO2 will be expired and arterial PCO2 will decrease causing a respiratory alkalosis (pH increase) • pH increase will inhibit central and peripheral chemoreceptors and offset the increase in ventilation rate • Long term: • 1) Body increases production of 2,3 DPG to shift heme dissociation curve to the right and unload more O2 into tissues • 2) Within several days, HCO3- excretion increases (renal compensation for respiratory alkalosis). This takes away the chemoreceptor inhibition, allowing for a higher ventilation rate
  • 106. Diving Reflex • Exposure of the face, nostrils and upper airway to water triggers diving reflex. • Triggered by activation of facial and ethmoid nerve sensory afferents. • First component: Airway protection. • Breathing is instantaneously stopped. • Second component: O2 saving strategy. • Reduced O2 consumption is caused by sympathetically mediated vasoconstriction in muscles and GI. • Parasympathetically-mediated bradycardia. Cardiac O2 consumption and cardiac output are reduced • Brain perfusion is maintained at a normal level
  • 107. Shallow Water Black Out • Forced and prolonged hyperventilation before a dive is practiced to stay under water longer. This is done under the mistaken assumption that hyperventilation increases stores of blood PO2. • This is not the case since Hb is saturated with O2 even with normal ventilation. What hyperventilation does is to lower PaCO2 (respiratory alkalosis) which allows the diver to stay submerged a little longer because it delays the urge to breathe which is largely driven by CO2 accumulation. • The practice of excessive hyperventilation before a dive is dangerous because a prolonged dive may cause sufficient CNS hypoxia to produce loss of consciousness and drowning.
  • 108. Exercise and Breathing • During exercise, ventilation first arises in a stepwise fashion and then exponentially before leveling out. When exercise is stopped, there is an initial stepwise fall followed by a steady decline back to baseline ventilation. • Central command (top down control of breathing during exercise) and reflexes from muscles and joint mechanoreceptors cause the initial rise in ventilation at the onset and the rapid fall at the end of dynamic exercise • Humoral factors and reflexes from metabotropic receptors probably accounts for the delayed increase in ventilation at the onset of exercise and the slow recovery at the end of dynamic exercise
  • 109. Exercise and Blood Gas Values • During light to moderate exercise, the lungs are able to compensate for muscles using more oxygen and producing more carbon dioxide. Thus, the arterial gases should not change unless the exercise becomes severe.
  • 111. Prevalence of Sleep Apnea • 20% in patients over 60 years old! • 9% in Women • 24% in Men • Prevalence increases with age until midlife but is constant after age 60ish.
  • 112. Types of Apnea • Apnea: • >10 second cessation of breathing, especially during sleep • Hypopnea: • Abnormally slow or shallow breathing • Reduction of airflow by 30% or more with 4% drop in SaO2 OR • Reduction of airflow by 50% or more with 3% drop in SaO2 + arousal • according to class, also lasts at least 10 seconds • Respiratory-event related arousal: • Arousals from sleep that do not meet the definition of apnea or hypopnea, but DO disturb sleep. • Obstructive sleep apnea: • Disruption of airflow while asleep due to narrowed, blocked, or floppy airway. • Central sleep apnea: • Absent respiratory effort. Breathing stops and starts due to lack of proper neuromuscular function. • Mixed sleep apnea: • Apnea due to a combination of Central Sleep Apnea and Obstructive Sleep Apnea • Typically begins as central (without ventilatory effort) and presents with airway obstruction when ventilatory effort resumes (OSA)
  • 113. Apnea-hypopnea index (AHI): • Number of apneic and hypopneic episodes per hour • Normal <5 • Mild 5-15 • Moderate 15-30 • Severe >30
  • 114. Pathogenesis of Sleep Apnea • Upper airway size naturally decreases during sleep due to decreased neural stimulation of the upper airway dilator muscles. This itself does not cause apnea. OSA occurs in individuals with naturally smaller airways and increased airway collapsibility. • Upper airway size: smaller in OSA • Craniofacial disorders • Enlarged tonsils and adenoids: major risk factor in children between ages 3-5 • Increased tongue size (Down’s Syndrome patients) • Increased Airway Collapsibility • In obesity, soft tissues of neck can push down and constrict airway. • OSA is more common in patients with nasal obstruction (mouth breathing leads to negative pressure that collapses the pharynx)
  • 115. Risk Factors • Obesity • Single most important risk factor for OSA in middle-age adults” • Enlarged tonsils, Enlarged Adenoids • Surgery in children, not adults • Enlarged Tongue (as seen in Down’s Syndrome) • Craniofacial/ Airway abnormalities • Mallampati Classification 3 or 4 • Neck size >17 inches • For women: Post-menopause • Age • Prevalence of OSA increases with age until age 60 • Endocrine changes: • Hypothyroidism => thick and beefy tongue • Acromegaly
  • 116. Clinical Presentation OS • Snoring (majority of pts - 50% of pts partners report sleeping in a separate bedroom) • Apneic episodes • Unrefreshing or restless sleep • Excessive daytime somnolence or fatigue • Drowsiness while driving • Decreased libido • Declines in cognition • Weight gain
  • 117. Clinical Presentation OS in Children • Overweight • Craniofacial Abnormalities • Large tonsils • Nightmares • Daytime somnolence • Daytime mouth breathing • Use Polysomnography to confirm • First line treatment: tonsillectomy, adenoidectomy
  • 118. Differential Diagnosis • Restless Leg Syndrome • Narcolepsy • Delayed sleep-phase syndrome • Insufficient Sleep Syndrome • Sleepiness due to meds
  • 119. Diagnosis • The “gold standard” for the diagnosis of OSA is full overnight polysomnography, performed in an attended laboratory setting. This includes monitoring of sleep with electroencephalography (EEG), chin and anterior tibialis electromyography (EMG), monitoring of breathing with oronasal airflow and snoring, thoracic and abdominal effort and pulse oximetry, electrocardiography (ECG), and body position. • Scoring of sleep stages and arousals from sleep is performed from the EEG and EMG data. • Apneas and hypopneas are scored according to the combination of oronasal airflow data, thoracoabdominal effort, and oxyhemoglobin saturation • Unattended sleep studies can be used in patients with very severe disease. NOT RECOMMENDED IN CENTRAL APNEA.
  • 120. Obstructive vs. Central Apneas Obstructive Central
  • 121. Sequelae of OS • Pathophysiologic mechanisms • 1. Apneic events lead to sleep fragmentation - disturbs sleep and patient stuck in lighter stages of sleep • OSA can lead to sexual dysfunction • Increased risk of depression • Significantly increased risk for motor vehicle accidents (2x more) • 2. Deoxygenation/reoxygenation causes oxidative stress similar to ischemia/reperfusion events  increase in proinflammatory molecules • Refractory Hypertension • Arrhythmias • Cardiovascular Events • Stroke • Atherosclerosis • Insulin resistance • INCREASED MORTALITY
  • 122. Treatment of OS • CPAP • Delivers constant pressurized air during both inspiration and expiration • Bilevel positive airway pressure (BPAP) • Delivers high fixed level of pressure during inspiration and lower fixed pressure during expiration • Easier to tolerate for severe patients • Weight loss • Positional therapy • Oral appliance therapy • Patients with mild - moderate OSA • Those who are unable or unwilling to use PAP • Surgical Treatment • Optimal for children • Unpredictable and less effective in adults
  • 123. Causes of Central Apnea • Hypocapnic: • Alteration of CO2 apnea threshold during sleep • Periodic breathing at high altitude • Cheynes Stokes • Instability of Respiratory Control System • Hypercapnic • Neuromuscular Diseases • Sleep-Related Hypoventilation • Brain stem lesions (syringomyelia specifically mentioned) • Spinal cord disorders • Stroke • Muscle disorders (muscular dystrophy)
  • 124. Cheyne Stokes Breathing Cycles of 60-120 seconds Waxing and waning pattern w/ lack of rib cage or abdomen movement
  • 125. Causes of Cheyne-Stokes Apneas • Systolic heart failure • Stroke • Encephalopathies
  • 126. Some things to know from quiz… • A. • The airway in obesity is decreased in size primarily in the lateral dimension. • B. • The upper airway has properties of a Starling resistor and demonstrates a critical pressure at which the airway collapses. In normal individuals, this is a negative pressure, but in those with many obstructive apneas, this pressure is positive • C. • Following sleep onset, the neural input to the upper airway dilator muscles decreases significantly, much more so than to the phrenic nerves. • D. • Individuals with obstructive sleep apnea develop what has been called the pharyngeal myopathy of OSA. It is hypothesized that vibrations from snoring initiate an inflammatory response within the muscles.
  • 127. Obesity Hypoventilation Syndrome • BMI > 30 • Awake alveolar hypoventilation • Sleep-disordered breathing • Daytime hypoxemia • Dyspnea on exertion • Serum Bicarbonate Level > 27 mEq/L (elevated bicarb) • indicates increased paCO2 • Diagnosis with ABGs
  • 128. Treatment of Obesity Hypoventilation • CPAP • 50% of patients need CPAP + Supplemental Oxygen • Non-invasive ventilation BPAP + Backup Rate • For use if CPAP + Oxygen is ineffective • Weight Loss • Bariatric surgery in some patients, but patients with obesity hypoventilation syndrome are not recommended for bariatric surgery.
  • 129. ASTHMA
  • 130. Cytokines and TH2 Response • IL-4, IL-5, IL-9, IL-13 • Lymphocytes of TH2 phenotype (CD4+) are thought to be a prominent component of the inflammatory response in asthma. • IL-5 has a chemoattractant effect for eosinophils, stimulates growth, stimulates activation, and stimulates eosinophilic degranulation. • IL-4 is inflammatory by activating B lymphocytes, enhancing synthesis of IgE, and promoting TH2 differentiation. • IL-13 also induces IgE synthesis, as well as mediating many various effects of cells involved with the inflammation of asthma. • IL-9 promotes growth of TH2 cells, B cells and Mast cells, IgE production and production of cytokines by smooth muscle cells
  • 131. IL-4 and IgE • IL-4 promotes release of IgE antibodies from B cells
  • 132. 3 Functions of IL-4 • 1. B cell activation • 2. IgE synthesis • 3. Differentiation of Th2 cells
  • 133. IL-4 vs. IL-13 • Similarity: Both play a role in making Th2 cells. IL-4 induces the differentiation while IL-13 induces the production of Th2 cells. Both make lung endothelium produce VCAM, making it “sticky” for eosinophils. Both induce IgE production • Differences: IL-13 has broader effects on epithelium and smooth muscle cells
  • 134. IL-5 • IL-5 is the only known eosinophil hematopoietin aka it causes production of eosinophils from bone marrow stem cells • IL-5 is an important survival factor for eosinophils • IL-5 is chemotactic for mature eosinophils and a priming factor for enhanced functional activities
  • 135. Clinical Asthma and Allergen Removal • Removal from environment improves but does not eliminate asthma • Studies show improvement in lung function, quality of life, allergic mediator release, and rescue medication use • However, bronchial hyperreactivity (“twitchy” airways) and airway inflammation persist FOREVER
  • 136. Innate vs. Adaptive Immunity in Asthma • If asthma were a disease of the adaptive immune system, then therapies targeting adaptive immune responses would be curative: • Anti-IgE • Anti-Thelper/Thelper cytokines • Immunotherapy • Allergen/antigen avoidance • With an authentic allergic, T cell-mediated disease (i.e. seasonal allergic rhinitis), exposure actually correlates with symptoms, and the disease resolves in the absence of exposure • New Theory: • Epigenetic programming of epithelial cells promotes release of cytokines IL-25, IL- 33 and TSLP even in absence of T cells driving eosinophilia and day-to-day symptoms • Adaptive immune responses via T/B cell responses primarily drive exacerbations and are well treated by targeted immune therapies
  • 137. Remodeling-prone Asthma • Airway remodeling likely results from chronic inflammation and the associated production and release of mediators like growth factors • Remodeling  epithelial damage, airway fibrosis (collagen), and smooth muscle hyperplasia • Increase in SMCs  hyperresponsiveness of the airway to stimuli  Persistent airflow obstruction • Overdistention of the lungs and airway occlusion by thick mucous plugs • Histology: • Edema and cellular infiltrates within the bronchial wall • “Fragile” appearance of the epithelium and detachment of epithelial cells • Hypertrophy and hyperplasia of the smooth muscle layer • Increased deposition of collagen (basement membrane thickening) = fibrosis. • Hypertrophy of mucous glands
  • 138. Steroid Resistance • Inhaled corticosteroids are the recommended standard medication for persistent asthma • Start at low dose in mild disease and move to higher doses • Most of the clinical efficacy of ICS’s is obtained at lower doses • Steroid-resistant asthma is defined by the failure to improve FEV1 by 15% after treatment with high oral corticosteroid doses for 2 weeks • Characterized by persistent eosinophilia despite a high dose of inhaled corticosteroid • Largely a T lymphocyte problem (continued production of cytokines IL4, IL5, and IL13) despite corticosteroid presence. • Steroid resistance does NOT affect the side effect profile (i.e. osteoporosis, metabolic syndrome, HBP, DM, obesity, myopathy, glaucoma/cataracts, etc.) • Corticosteroids are ineffective in resistant asthma, • DON’T prescribe them
  • 139. Eosinophilic vs. Non-eosinophilicAsthma • Eosinophilic asthma = steroid sensitive (except in steroid-resistant) • Non-eosinophilic asthma = steroid resistant • May exacerbate symptoms by inhibiting apoptosis of PMNs
  • 140. Omalizumab • Allergen-exacerbated asthma is diagnosed by: • 1) evidence of a specific IgE (via skin prick or IgE immunoassay) • 2) evidence of allergen-exacerbation of symptoms (allergic rhinitis, asthma) • Omalizumab binds free IgE in the serum at the same site that the high-affinity IgE receptor (on mast cells) binds. Thus, IgE cannot bind to its receptor on mast cells. Eventually, the number of IgE receptors on mast cells decreases over time. • Omalizumab seems to significantly improve the number of asthma exacerbations, but it does NOT eliminate asthma • It has a minimal influence on lung function, symptoms, or severity • This is likely because allergens exacerbate asthma but have little to do with day-to-day asthma symptoms or severity
  • 141. Aspirin Sensitive Asthma • Some people have asthma exacerbation after taking ASA or NSAIDs b/c the inhibition of COX results in a shifting of arachidonic acid pathways toward the production of bronchoconstrictor leukotrienes. • AERD is characterized by pathognomonic elevation of LTC4 synthase expression with profoundly increased, constitutive, and aspirin-induced leukotriene production. It also has a pathognomonic elevation of leukotriene receptor expression. • Leukotriene Modifiers significantly improve sx in these patients • Leukotriene receptor antagonists (Montelukast, Zafirlukast) improve lung function, decrease bronchodilator use, reduce symptoms, and improve quality of life • Zileuton - may be effective in reducing upper airway symptoms (loss of smell, rhinorrhea, congestion)
  • 144.
  • 145.
  • 146.
  • 147.
  • 148. Exacerbating Factors • Viral Infections • Most common cause of asthma symptoms in the 0-4 age group. • Allergies • GERD • Chronic sinusitis • Obstructive sleep apnea • Allergic bronchopulmonary aspergillosis
  • 150. Beta Agonists • MOA: • Stimulation of B2 receptors in SMCs activates Gs adenylyl cyclase  increased cAMP  increased conductance of Ca++-sensitive K+ channels  Hyperpolarization • Airway smooth muscle relaxation and bronchodilation • cAMP also inhibits histamine release from mast cells and TNF release from monocytes • Clinical Use: Primary therapy for Asthma and COPD • Short acting: albuterol, levalbuterol • Long acting: Salemterol, Fomoterol • Side Effects • Tachyarrhythmia • Tremulousness (trembling) • Muscle cramps • Nervousness • Hypokalemia
  • 151. Anticholinergics • MOA: • Competitive inhibition of ACh at muscarinic receptors relaxes bronchial constriction normally caused by parasympathetic (ACh) stimulation of M3 receptors • Parasympathetic stimulation of M1 and M3 receptors causes mucus secretion as well, so anticholinergics decrease mucus secretion • Clinical Use: First line for COPD also used in asthma • Short acting: Ipratropium • Long acting: Tiotropium • Side Effects • Constipation • Xerostomia (dry mouth) • Pharyngitis • Urinary retention • Sinusitis • Upper respiratory infection
  • 152. Methylxanthines • Theophylline (1,3 dimethylxanthine) • rarely used today • MOA: • Nonselective PDE inhibitor (increases cAMP) and an adenosine receptor antagonist → relaxes smooth muscle through blocking adenosine receptors on mast cells • Also inhibits synthesis and secretion of inflammatory mediators from numerous cell types, including mast cells and basophils • Clinical Use: Rare, Acute and chronic asthma • Side Effects: • NARROW THERAPEUTIC WINDOW • Nausea & vomiting • tremors • irritability • restlessness • tachyarrhythmias (Afib)
  • 153. Corticosteroids • MOA: Suppression of inflammatory responses by interference with multiple signal transduction and gene expression pathways. • Decrease cytokine formation • Decrease PAF production • Inhibit cysteinyl leukotrienes • Clinical Use: • FIRST LINE THERAPY (inhaled not systemic) • Risk of adverse effects increases with dose • Side Effects: • HPA Suppresion • Hypertension • Immunosuppression • Osteoporosis • Myopathy • Cataracts • Growth arrest • Fat redistribution
  • 154. Leukotriene Modifiers • MOA: • LTD4 receptor antagonists (zafirlukast, montelukast) • Reversible inhibitor of cysteinyl leukotriene-1 receptor • 5-lipoxygenase inhibitors (zileuton) • Prevents conversion of arachidonic acid to leukotriene A4 • LB4 is also decreased • Clinical Use: • Preventative treatment of asthma, especially AERD • Anti-leukotriene agents can be effective as monotherapy in the treatment of mild to moderate persistent asthma. • Not as effective as ICGCs. • Side Effects • Abnormal LFTs • Headache • Eosinophilic Vasculitis.
  • 155. Omalizumab • MOA: • DNA-derived humanized monoclonal Ab • At recommended doses, omalizumab reduces free IgE by more than 95%, thereby limiting the amount of IgE bound to Fc R1-bearing cells • Also decreases amount of FcRI receptor expressed on these cells • Clinical Use • Allergic Asthma • Chronic Idiopathic Urticaria • Side Effects: • Thrombocytopenia, • Anaphylaxis, • Dermatologic • Costly
  • 156. PDE Inhibitors • PDE4 Inhibitor: increases intracellular cAMP and reduces neutrophil and eosinophil infiltration • PDE4 is a major enzyme that hydrolyzes and inactivates cAMP • Romflumilast • Clinical Use: Prevention of COPD Exacerbations • Side Effects: • Diarrhea, nausea • Headache • Decreased appetite • Weight loss • Suicidal thoughts
  • 157. Mucolytics • 1) Hypertonic Agents • Ex: Inhaled hypertonic saline or mannitol • MOA: Hypertonic agents draw water into the airway to lower mucus viscosity. • Side Effects: Can cause bronchospasm  therefore used following a bronchodilator • General: cheap with good results (disadvantage: time consuming) • 2) N-acetyl cysteine (NAC): CF and Bronchiectasis • MOA: Lowers mucus viscosity by cleaving disulfide bonds via its free sulfhydryl group. • Side Effects: bronchospasms (use 15 min. after bronchodilator), smells, expensive • 3) Inhaled DNAse: CF • MOA: Breaks down purulent sputum by cleaving DNA strands. • Side Effects: laryngitis, pharyngitis, chest pain, conjunctivitis, dyspnea, expensive, change in voice • 4) Ivacaftor: CF • MOA: CFTR protein potentiator for G551D mutation of CF. Decreases [Cl-] in sweat. • Side Effects: Increased LFTs, rash, abdominal pain, HA, nausea, dizziness, nasal congestion, nasopharyngitis, upper resp infxn.
  • 158. Therapy for Pulmonary Hypertension
  • 159. Prostanoids • MOA: • Prostacyclin stimulates adenylate cyclase to convert ATP to cAMP  decrease in intracellular Ca SMC relaxation • Prostacyclin also inhibit platelet aggregation • Clinical Use: • Pulmonary Hypertension • Side Effects: • Hypotension • Flushing • Jaw pain • Headache • Nausea/vomiting, • Hypersplenism, • Line infection
  • 160. Guaifenesin • MOA: Irritant of vagal receptors in the gastrum activating parasympathetic reflexes which result in secretion of a less viscous mucous. • Clinical Use: Expectorant used to help with clearing of phlegm in setting of acute respiratory infections • Does not suppress cough reflex • Use Dextromethorphan • Side Effects: • Minimal Side Effects
  • 162. Seasonal Patterns of Viruses • Rhinovirus • Sharp increase in September • Parainfluenza • October/November peak • Coronavirus/RSV • Winter months • Influenza • Mid to late winter • Adenovirus • Year round
  • 163. Frequency of Infection • 1 to 5 year olds (preschool children): 8+ colds per year • 6 to 12 year olds (school children): 5 to 6+ colds per year • Adolescents: 4 to 5 colds per year • Adults: 2 to 3 colds per year
  • 164. Modes of Transmission • 3 Modes • “Hand contact: Self-inoculation of one’s own conjunctivae or nasal mucosa after touching a person or object contaminated with cold virus -most efficient transmission • MOST COMMON • Inhalation of small particle droplets that become airborne from coughing (droplet transmission) -more so with influenza • Deposition of large particle droplets that are expelled during sneezing and land on nasal or conjunctival mucosa
  • 165. Pathogenesis • Deposition on nasal mucosa • Mucociliary transport to nasopharynx • Virus enters epithelial cell after receptor binding • Replication begins within 8 to 10 hrs of inoculation • Influx of PMN’s in nasal submucosa and epithelium • Increase albumin and inflammatory mediators in nasal secretions • Nasal mucosa remains intact • Symptoms begin in 1 to 2 days
  • 166. Natural History • Day 1 to 2: Sore or scratchy throat, congestion • Day 2 to 3: Nasal obstruction, sneeze and rhinorrhea • Day 4 to 5: Cough • Day 7: Resolved • May last up to 2 weeks in 25% of adults
  • 167. Differential Diagnosis • Common cold • Allergic or seasonal rhinitis • Bacterial pharyngitis • Sinusitis • Influenza • Pertussis • Nasal foreign body
  • 168. Allergic Rhinitis Itchy, watery eyes, nasal congestion, sneezing, scratchy throat, fever uncommon “Allergic Shiners” Bacterial Pharyngitis Prominent sore throat, Absent nasal congestion/cough, fever common, purulent exudate, swollen tonsils, erythema of pharynx Sinusitis Presents after a cold begins to improve, facial or tooth pain, purulent nasal/post-nasal drainage, don’t respond to decongestants, fever, malaise Influenza Abrupt onset, fever, myalgias, headache, malaise, nasal congestion, cough, sore throat Pertussis Catarrhal phase: 1 week, low-grade fever, rhinorrhea, malaise, sneeze, mild cough Paroxysmal phase: 1-6 weeks, bursts of rapid coughs, gasp, whoop, apnea, emesis Nasal Foreign Body Nasal congestion, purulent nasal discharge(usually uniteral), sneeze, halitosis, young child
  • 169. Children < 6 ◦ Fever ◦ Nasal congestion ◦ Rhinorrhea Clear to green ◦ Sneeze ◦ Cough ◦ Irritability ◦ Swollen glands ◦ 7 to 14 days Older children and adults ◦ Nasal congestion ◦ Rhinorrhea Clear to green ◦ Sore, scratchy throat ◦ Malaise ◦ Sinus fullness ◦ Hoarseness ◦ Sneeze, cough ◦ 5 to 7 days Symptoms and Signs
  • 170. Prophylaxis • Frequent handwashing with non-antibacterial soap and water • Hand sanitizers may be less effective • Virucidal tissues may decrease secondary transmission of respiratory infection within the household or other close-contact settings • Physical barriers: gloves, masks, gowns, etc. Likely beneficial Maybe beneficial Unclear benefit No benefit Zinc Probiotics Gargling Vitamin C Ginseng Vitamin D Exercise Echinacea Garlic
  • 171. Symptomatic Treatment for Adults • Nasal symptoms • Single dose of nasal decongestant in adults • Antihistamine/decongestant combinations • Newer non-sedating antihistamines not effective • Guaifenesin • Cough • Dextromethorphan • Inhaled ipratropium bromide • Fever, achiness • Acetaminophen • NSAID’s • ANTIBIOTICS ARE NOT EFFECTIVE
  • 172. Symptomatic Treatment for Children • Very few effective treatments!!!
  • 173. Complications • Secondary effects of localized inflammation - Bacterial superinfection • Inflammatory response in susceptible host- Asthma • More extensive viral infection in susceptible host • Viral-induced wheezing: • Bronchiolitis • Pneumonia : rhinovirus and RSV may cause severe lower respiratory tract infection in infants and children • Bacterial acute otitis media : may complicate 30% to 50% of URIs in young children • Paranasal sinus abnormalities • Bacterial sinusitis : may complicate 8% to 10% of URIs in children • Pre-orbital cellulitis • Orbital cellulitis • Orbital abscess
  • 174. ALLERGIC RHINITIS AND SINUSITIS
  • 175. List three functions of the sinuses. • Insulate brain • Crumple zone to protect brain from injury • Decrease weight of skull
  • 176. Sinusitis • Inflammation of mucous membranes lining paranasal sinuses • In adults sinusitis most often occurs in maxillary sinus, whereas in children it is most common in ethmoid sinus
  • 177. You are born with 4 sinuses
  • 178. Anatomic landmarks of the nasal cavity and paranasal sinuses.
  • 179. Key clinical features of Migraine • Unilateral throbbing pain • Phonophobia / photophobia • Nausea / Vomiting • Lasting hours to days (but probably less than a week) • Triggers can include: allergies (histamine release), sinusitis, sinonasal contact points • Can trigger vasomotor symptoms including: rhinorrhea/nasal congestion, ocular tearing • Migraine triggers the maxillary branch of the trigeminal nerve, and the nerve winds up also triggering ocular tearing, rhinorrhea, symptoms of nasal congestion. =
  • 180. Allergic vs. Nonallergic Rhinitis • Rhinitis: irritation and inflammation of mucous membrane in nose • Rhinorrhea: nasal cavity is filled with a significant amount of mucus • Allergic Rhinitis • Paroxysmal sneezing with seasonal variation • Pruritus • Anterior/Clear rhinorrhea • Allergic conjunctivitis • Positive Family history • + skin allergy test • Non-allergic Rhinitis • Less sneezing • No pruritis • Posterior drainage
  • 181. Pathognomonic Signs of Allergic Rhinitis • Allergic shiners; periocular edema • Dennie’s Morgan’s lines – wrinkles from long term edena • Supratip nasal creases • Large bluish turbinate – venous blood due to congestion
  • 182. Treatment for Allergic Rhinitis • First Line: Nasal Corticosteroids • Environmental Control • Saline Irrigation • Antihistamines • Reduce production of clear secretions • Reduces pruritus and sneezing • Clinically much less effective than nasal steroids • Decongestants • Ephedrine, Phenylephrine, Dextromorphan • Vasoconstriction by alpha-agonists (epinephrine, NE) will decrease the blood flow and therefore decrease inflammation and mucus formation at the site of application. • Leukotriene modifiers • Montelukast/Zafirlukast • Zileuton • Nasal cromolyn • Allergen immunotherapy
  • 183. Immunotherapy in Allergic Rhinitis • Clinical Indications: • Poor response to pharmacotherapy/allergen avoidance • Unacceptable adverse effects of medications • Desire to avoid long-term pharmacotherapy and reduce costs • Possible prevention of asthma in children • 85-90% of patients who receive high-dose maintenance IT report significant efficacy: • reduced symptoms • reduction in medication requirements • IT must be administered in a setting where prompt recognition and treatment of anaphylaxis is assured
  • 184. Acute Infectious Rhinosinusitis • Symptoms: • Purulent nasal discharge • Nasal obstruction • Facial pain/pressure/fullness • Almost always viral • Acute Bacterial Rhinosinusitis (ABRS) vs. Viral Acute Rhinosinusitis (Viral ARS) • 0.5-2.0% of VRS progresses to ABRS • Diagnosis based on duration and/or pattern • More likely to be ABRS if symptomatic for >10 days or if the symptoms improve, then worsen
  • 185. Antibiotic Therapy • Antibiotics ONLY indicated in ABRS, ineffective for VRS • First line therapy: Amoxicillin/Clavulanic Acid • PCN allergy: • Adults: Doxycyclin • Children: Respiratory quinolone or Clindamycin + 3rd gen Cephalosporin • NO ROLE for macrolides
  • 186. Treatment for Viral Sinusitis • Supportive • Saline Irrigations (no evidence) • Topical vs. Systemic decongestants • Oxymetazoline (Afrin) • Phenylephrine (Neosynephrine, Sudafed PE) • Pseudoephedrine (Sudafed) • Pain control • Systemic steroids – no evidence • Topical steroids – weak evidence
  • 187. Rhinitis/Sinusitis and Asthma • Sinonasal pathology is the most common co-morbidity among patients with asthma • In patients with asthma, inflammation in the nose and sinuses share features of disease in the lung • Allergic rhinitis is a risk factor for asthma • Childhood allergic rhinitis significantly associated with the presence of asthma • Asthmatics with sinusitis are more likely to have nasal polyps complicating their sinus disease than non-asthmatics, and asthmatics are more likely to have persistent disease over years that requires multiple surgeries
  • 188. Chronic Rhinosinusitis w/ or w/out Polyps • Diagnosis: • 1. Twelve weeks or longer of two or more of the following: • Mucopurulent drainage • Nasal obstruction → congestion • Facial pressure-fullness • Decreased sense of smell • 2. AND documentation of inflammation by one or more of the following findings: • Purulent mucus OR edema in the middle meatus or ethmoid region • Polyps in nasal cavity OR middle meatus • Radiographic imaging showing inflammation of the paranasal sinuses
  • 189. Nasal polyps are often associated with Cystic Fibrosis
  • 190. Rhinosinusitis with Nasal Polyposis • The characteristic presentation of CRS with NP is gradually worsening nasal congestion/obstruction, sinus fullness and pressure, fatigue, posterior nasal drainage, and hyposmia or anosmia. • In contrast, fever and severe facial pain are uncommon. • On physical examination, large polyps are often visible with anterior rhinoscopy, while smaller polyps require nasal endoscopy or imaging. Nasal polyps lack sensation.
  • 191. Eosinophilic Sinusitis • More likely to have polyps and/or asthma • 32% of asthmatics have polyps • 20% of patients with polyps have asthma • Less likely to have pain • Th2-mediated process • Mucous is laden with eosinophils, leukotrienes, IL-4 and IL-5 • Treatment: Corticosteroids • Saline Irrigations • Leukotriene or IgE Inhibitors
  • 192. Sinus Surgery • Rhinosinusitis Sinus Surgery = Functional Endoscopic Sinus Surgery • Reserved for medical failures • Improves quality of life in 72-76% of patients • Average improvement of 16-22% • Sinus Surgery Improves Asthma • Reduces symptoms, lowers steroid dose & frequency of steroid use • Improves lung function • Decreases bronchial hyperreactivity • NOT SUPERIOR TO MEDICAL THERAPY
  • 193. Nasal Polyps can develop from Rhinitis, Cystic Fibrosis and Aspirin Intolerant Asthma
  • 195. Differential Diagnosis of Hoarseness  Infectious  Acute laryngitis: common cold, URI (virus) or voice strain  Neoplastic  Squamous cell carcinoma  Idiopathic  Papilloma  Iatrogenic  Injury to recurrent laryngeal nerve (e.g. thyroid surgery)  Functional  Laryngeal polyp/nodule (Singer’s nodule)  Smoking  GERD  LPRD (laryngopharyngeal reflux)  Parkinson’s or stroke  Allergies  Thyroid problems
  • 196. Define stridor and evaluate the child who presents with stridor. • High pitched inspiratory and expiratory sound that serves as a sign of fixed upper airway obstruction • Epiglottitis: H. Influenzae • Croup: Parainfluenza
  • 197. Pleomorphic Adenoma • Most common salivary gland neoplasm • Clinical features • Wide age distribution • Most common in 4th decade • Female > male • Most common location: parotid gland • Gross features • Overall well-circumscribed • Often with small protrusions into adjacent normal tissue; may lead to local recurrences • Microscopic features • Biphasic: Admixture of epithelial and stromal elements • Epithelium: Glands or cords of small cuboidal cells • Stroma: Fibromyxoid +/- cartilaginous differentiation • Prognosis • Vast majority are benign, Recurrence rate is highly dependent on adequacy of original resection • Malignant transformation: Occurs in ~5% of cases
  • 198. Warthrin Tumor • Clinical features • Wide age distribution • Most common in 6th and 7th decades • Male >> female • Most common location: parotid gland • Bilateral in 10% of cases • Gross features • Well-delineated, lobulated mass • May be cystic or multicystic • Microscopic features • Epithelium: • Oncocytic - large, eosinophilic, granular cells • Lymphoid tissue: • May form lymphoid follicles • Prognois: Benign
  • 199. Mucoepidermoid Carcinoma • Clinical features • Most common in 5th decade • Most common malignant salivary gland tumor in children • Female > male • Low-grade and high-grade types • Gross features • Low-grade: Well-circumscribed mass with cystic areas • High-grade: Solid, infiltrative pattern of growth • Microscopic features • Three distinct cell types: • Squamous • Mucin-producing • Intermediate • Low-grade: well-differentiated • High-grade: poorly-differentiated • Prognosis • Highly dependent on grade • Low-grade: 5 yr survival of 98% • High-grade: 5 yr survival of 56%
  • 200. Adenoid Cystic Carcinoma • Clinical features • Most common malignant tumor of minor salivary glands • Wide age distribution: 20 - 80 yo • Median age = 50 yo • Gross features • Solid infiltrative pattern of growth • Can invade nerves and move to brain • Microscopic features • Small, cuboidal, cytologically bland cells • Arranged in cribriform patterns • Some of the lumen-like spaces contain distinctive eosinophilic materia • Prognosis: Poor, highly malignant, perineural invasion
  • 201. Laryngeal Polyp • Distinctive non-inflammatory reactive change • Etiology: Injury - “misuse” of voice • S/sx: Hoarseness • Gross: Polypoid mass on vocal cords • Microscopic: Varies with stage of evolution of lesion • Prognosis: benign
  • 202. Juvenile Laryngeal Papillomatosis • Age: presents in children / adolescents • Etiology: human papilloma virus (HPV) • Gross: • Multiple papillary growths on vocal cords • May spread throughout larynx • Microscopic features • Papillary growths of well-differentiated squamous epithelium • Prognosis • Repeated recurrences • Usually benign • Vary rarely development of squamous cell carcinoma
  • 203. Squamous Cell Carcinoma • Clinical Features • > 90% of laryngeal carcinomas are SCC • Age - 5th decade or older • Male > > > female • Risk factors: • Cigarette smoking • Heavy alcohol consumption • Gross features • Mass protruding into airway, may be ulcerated • Typically 1 - 4 cm • Microscopic features • Cytologically malignant squamous epithelium • Prognosis • Glottic tumors • Arise from true vocal cords • Tend to remain localized • Transglottic tumors • Tumor crosses laryngeal ventricle • High rate of lymph node metastases
  • 205. Emphysema • Pathophysiology: • Abnormal enlargement of air spaces distal to terminal bronchioles • Destruction of alveolar walls resulting from elastase-antielastase imbalance • Centriacinar (respiratory bronchioles) in upper lobes vs panacinar (alveolar ducts; associated with alpha-1 antitrypsin deficiency) in lower lobes • Collapse of airways due to loss of alveolar compliance • Gross Morphology: • Hyperinflated lungs, Air trapping, Dilated alveoili • Bullae on surface of lungs (panacinar) • Smoking  upper lobe (Centriacinar) • Hyperinflated lungs, flattened diaphragms, increased retrosternal clear space on CXR Microscopic: • Inflammation, fibrosis and carbonaceous pigment common in adjacent alveolar and bronchial walls
  • 206.
  • 207. Barrel Chest Prolonged expiration with pursed lips, forces walls open to allow expiration
  • 208. Chronic Bronchitis • Pathophysiology: • Enlargement of the bronchial mucous glands and expansion of goblet cell population. Hypersecretion of mucus  mucous plugs. • Gross Morphology: • Visible bronchi • Principal sites of increased air resistance in COPD are the small distal airways • Hyperinflated lungs, flattened diaphragms, increased retrosternal clear space on CXR • Microscopic: • Brown-pigmented macrophages with sparse neutrophil and lymphocytes in walls of terminal bronchioles • Fibrosis, goblet cell and squamous cell metaplasia of epithelium, smooth muscle enlargement, scattered regions of mucous plugging • Seromucinous gland hyperplasia
  • 209.
  • 210. Chronic Bronchitis is diagnosed clinically: Chronic productive cough lasting 3 months over at least 2 years
  • 211. Asthma • Pathophysiology • Bronchial asthma is a chronic relapsing inflammatory disease with hyper-reactive airways, leading to episodic, reversible bronchoconstriction owing to increased responsiveness of the tracheobroncheal tree to various stimuli. • Gross Morphology • Lungs are greatly distended with air and show patchy atelectasis with occlusion of airways by thick mucus plugs. • Microscopic • Sub-basement membrane fibrosis • Edema and inflammatory infiltrate in bronchial walls with eosinophils. • Hypertrophy of bronchial wall musculature and submucosal glands. • Whorls of shed epithelium forming mucous plugs (Curschmann’s spirals) • Collection of crystaloid made up of debris of eosinophil membranes (Charcot- Leyden crystals)
  • 212. Asthma is most often associated with allergic stimuli: Type 1 HSR IL4 (IgE), 5 (Eos) , and 10 (TH2) Also IL-13 and IL-9
  • 213. Bronchiectasis • Abnormal permanent dilatation of the bronchi and bronchioles. • Caused by repeated cycles of airway infection/inflammation • Distal airways become thickened • Mucosal surfaces develop edema and suppuration • Neovascularization of the adjacent bronchial arterioles occurs. • Hemoptysis, Sputum • Bronchiectasis shares many clinical features with chronic obstructive pulmonary disease (COPD) • Inflamed and easily collapsible airways • Obstruction to airflow • Frequent office visits and hospitalizations. • Dx: Chronic daily cough with viscid sputum production and presence of bronchial wall thickening and luminal dilatation on HRCT.
  • 214. Bronchiectasis • Presentation • Cough • Purulent sputum production • Hemoptysis • Recurrent infection • Bronchial hyper-reactivity • Obstructive lung disease
  • 215.
  • 216. Localizing Bronchiectasis • Upper Lobe • Cystic Fibrosis • Lower Lobe • Aspiration Syndromes • Right Middle Lobe and Lingula • Nontuberculous Mycobacterial Infection • Central • Allergic Bronchopulmonary Aspergillosis
  • 217. Treatment of Bronchiectasis • 1. Antibiotics • 2. Bronchopulmonary drainage • 3. Bronchodilators • Chest Physical Therapy • Inhaled DNA-ase for CF patients
  • 218. Presence of P. Aeroginosa portends a worse prognosis in bronchiectasis
  • 219. Pink Puffers and Blue Bloaters • Pink Puffers - associated with severe emphysema • Cachexia, unrelenting dyspnea, severe lung hyperinflation, normal (or near normal) ABG at rest because the body compensates by hyperventilating (hence the puffer). Low cardiac output  muscle wasting and weight loss. The pink can be from a number of things, one of which is using neck and chest muscles to breathe. • Blue Bloaters - associated with chronic bronchitis • Stout body habitus, chronic cough and sputum, dyspnea, severe hypoxia and hypercapnia (leading to polycythemia and signs of right-sided heart failure)
  • 220.
  • 221. COPD vs. Asthma • Factors that favor COPD over Asthma • Older age • current/past smoker • Hx acute bronchitis • chronic cough, sputum production or wheezing • Factors that favor Asthma over COPD • Young age • No smoking history • Atopy • Variability of Sx over time • Reversible obstruction
  • 222. Natural Progression of COPD • Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow obstruction and an abnormal inflammatory response in the lungs • Innate and adaptive immune responses to long term exposure to noxious particles and gases, particularly cigarette smoke. • This amplified response may result in mucous hypersecretion (chronic bronchitis), tissue destruction (emphysema), and disruption of normal repair and defence mechanisms causing small airway inflammation and fibrosis (bronchiolitis). • 1. Inflammation • 2. Imbalance of Proteases and Antiproteases • 3. Oxidative Stress
  • 223. COPD Diagnosis Airflow limitation measured by FEV1 % Predicted All patients with FEV1/FVC reduced to < 0.70 GOLD 1 Mild >80% GOLD 2 Moderate 50 – 80% GOLD 3 Severe 30 – 50% GOLD 4 Very Severe <30%
  • 224. COPD Classification Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC A Low Risk Less Symptoms GOLD 1-2 FEV1 > 50% ≤ 1 < 10 0-1 B Low Risk More Symptoms GOLD 1-2 FEV1 > 50% ≤ 1 ≥ 10 ≥ 2 C High Risk Less Symptoms GOLD 3-4 FEV1 < 50% ≥ 2 <10 0-1 D High Risk More Symptoms GOLD 3-4 FEV1 < 50% ≥ 2 ≥ 10 ≥ 2
  • 225. Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC A Low Risk Less Symptoms GOLD 1-2 FEV1 > 50% ≤ 1 < 10 0-1 Patient Category 1st Choice Tx 2nd Choice Tx 3rd Choice Tx A SAMA PRN or SABA PRN LAMA or LABA or SAMA+SABA PDE inh (Theophylline) Category A Therapy
  • 226. Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC B Low Risk More Symptoms GOLD 1-2 FEV1 > 50% ≤ 1 ≥ 10 ≥ 2 Patient Category 1st Choice Tx 2nd Choice Tx 3rd Choice Tx B LAMA or LABA LAMA+LABA SABA and/or SAMA Theophylline Category B Therapy
  • 227. Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC C High Risk Less Symptoms GOLD 3-4 FEV1 < 50% ≥ 2 <10 0-1 Patient Category 1st Choice Tx 2nd Choice Tx 3rd Choice Tx C ICS and LAMA or LABA LAMA+LABA or LAMA+PDE4I or LABA+PDE4I SABA and/or SAMA Theophylline Category C Therapy
  • 228. Patient Category Characteristics GOLD FEV1 Frequency Exacerbation CAT MMRC D High Risk More Symptoms GOLD 3-4 FEV1 < 50% ≥ 2 ≥ 10 ≥ 2 Patient Category 1st Choice Tx 2nd Choice Tx 3rd Choice Tx D ICS and LAMA and/or LABA ICS+LAMA+LABA or ICS+LAMA+PDE4I or ICS+LABA+PDE4I Mucolytics SABA and/or SAMA Theophylline Category D Therapy
  • 229. First Line: Tiotropium + SABA prn Steroids for exacerbations (Advair)
  • 231. Alpha 1 Antitrypsin Deficiency • α1-antitrypsin is a protease inhibitor and protects lung tissue against neutrophil elastase and other proteases. • Encoded by the gene PI • M: Normal wild type • Z: Most common mutant leading to deficiency • ZZ homozygous: Severe Disease • Symptoms • Lung • COPD: Panacinar emphysema • Possible bronchiectasis or asthma • Suspected from uncontrolled destruction by neutrophil elastase in the lung • Liver • Childhood liver disease • Adulthood cirrhosis of liver & hepatocellular carcinoma • Suspected from abnormal deposition of dysfunctional AAT protein • Skin • Necrotizing panniculitis, vasculitis, urticaia, angioedema
  • 232. Alpha 1 Antitrypsin Diagnosis • Emphysema in a young age (< 45 yo) • Emphysema in non-smokers • Basilar distribution of emphysema • Concurrent liver or skin disease • Serum levels of AAT: below 50 mg/dL • Genotyping to look for S or Z alleles
  • 233. PFTS Disease PFT Pattern Asthma Obstructive and Reversible Chronic Bronchitis Obstructive, Irreversible, Normal DLCO Emphysema Obstructive, Irreversible, Low DLCO Bronchiectasis Obstructive Cystic Fibrosis Obstructive, FEV1 correlates with outcomes
  • 234. Cystic Fibrosis • Autosomal Recessive defect in CFTR chloride channel • CFTR dysfunction reduces chloride secretion from the epithelialial cells into the airway lumen  sodium absorption into the cell is markedly increased  thinning of the airway surface’s liquid lining layer  impaired mucociliary clearance. • Chronic infection  PMN-dominated inflammatory response. • Neutrophil products (proteolytic enzymes and oxidants) mediate the subsequent pathologic changes: bronchiectasis, bronchiolectasis, bronchial stenosis, and fibrosis. • Mucous plugging of airways • 1. Production of thick, tenacious secretions from exocrine glands • 2. Elevated concentrations of sodium, chloride, and potassium in sweat
  • 235. Cystic Fibrosis • Clinical Presentation • Pancreatic insufficiency • Recurrent episodes of tracheobronchial infection • Bronchiectasis • Intestinal obstruction • Sterility in males • Diagnosis: • (1) Identification of mutations known to cause cystic fibrosis in both CFTR genes • (2) Characteristic abnormalities in measurements of nasal mucosal electrical potential difference • (3) Abnormal sweat electrolytes
  • 236. CF Work Up • Cystic fibrosis causes obstructive lung disease, initially with decreased flows at low lung volumes. • Forced expiratory volume in 1 second (FEV1) is the best correlate of outcome and starts to differ markedly from normal during adolescence. • The rate of decline in FEV1 often predicts the clinical course. • Early in the disease, the chest radiograph demonstrates hyperinflation and peribronchial thickening. Computed tomography can demonstrate bronchiectasis early in the course of the disease. • Airway infection, which is the key clinical manifestation, can be detected by sputum culture or bronchoalveolar lavage.
  • 238. Overview • Patients have dyspnea, tachypnea, end-inspiratory crackles, and eventual cyanosis, without wheezing or other evidence of airway obstruction. • The classic functional abnormalities are reductions in diffusion capacity, lung volume, and lung compliance. • Chest radiographs show bilateral lesions that take the form of small nodules, irregular lines, or ground-glass shadows, all corresponding to areas of interstitial fibrosis. • Eventually, secondary pulmonary hypertension and right-sided heart failure associated with cor pulmonale may result. • Although the entities can often be distinguished in the early stages, the advanced forms are hard to differentiate because all result in scarring and gross destruction of the lung, often referred to as end-stage lung or honeycomb lung.
  • 239. Causes • Idiopathic • Idiopathic interstitial pneumonias • Granulomatous • Sarcoidosis • Occupational and environmental : Pneumoconioses • Coal worker pneumoconiosis (CWP) • Silicosis • Asbestosis • Berylliosis • Drug induced • Amiodarone • Bleomycin and busulfan • Cyclophosphamide • Methotrexate and methysergide • Nitrosourea and nitrofurantoin • Connective tissue disease • Systemic sclerosis • SLE • RA • Collagen vascular disease
  • 240. Idiopathic Interstitial Pneumonias • Idiopathic pulmonary fibrosis • Non-specific interstitial pneumonia • Respiratory bronchiolitis-associated interstitial lung disease • Desquamative interstitial pneumonia • Cryptogenic organizing pneumonia • Acute interstitial pneumonia • Lymphoid interstitial pneumonia
  • 241. Clinical Features • History: • Subacute or chronic • Chronic • pulmonary hypertension • right sided heart failure (cor pulmonale). • Symptoms: • Progressive dyspnea • Cough • Late inspiratory crackles • Respiratory alkalosis • No wheezing • Signs: • Restrictive PFTs (reduced FEV1 and FVC with normal ratio, decreased TLC) • Reduced DLCO. • Variable inflammation and fibrosis of the interstitial, alveolar, and vascular compartments of the lungs. • Decreased PaO2
  • 242. IPF Clinical Course • IPF begins insidiously with gradually increasing dyspnea on exertion and dry cough. • Most patients are 55 to 75 years old at presentation. • Hypoxemia, cyanosis, and clubbing occur late in the course. • Usually there is a gradual deterioration in pulmonary status despite medical treatment with immunosuppressive drugs such as steroids, cyclophosphamide, or azathioprine. • The median survival is about 3 years after diagnosis. • Lung transplantation is the only definitive therapy.
  • 243. IPF: Gross and Microscopic Morphology • Gross Morphology • Cobblestoned Pleura as a result of the retraction of scars along the interlobular septa. • Fibrosis occurs preferentially in the lower lobes, the subpleural regions, and along the interlobular septa. • Spacial/Temporal Heterogeneity • Microscopic • 1) Patchy interstitial fibrosis • 2) Fibroblastic foci • 3) Honeycomb fibrosis • The dense fibrosis causes the destruction of alveolar architecture and formation of cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epithelium • Early: exuberant fibroblastic proliferation • Late: areas become more collagenous and less cellular.
  • 244.
  • 245.
  • 246. UIP NSIP Spacial/temporal heterogeneity Spacial/temporal homogeneity
  • 247. In order to diagnose ILD, you need to use a combination of history, clinical findings, histologic findings, and/or radiographic findings. You cannot rely on one modality alone
  • 248. PFTs • Reduced FEV1 • Reduced FVC • Normal FEV1/FVC ratio • Decreased TLC • Reduced DLCO • PFTs At Rest: Diagnosis • PFTs With Exercise • Monitor the effectiveness of treatments • Monitor the course of the disease • The reductions in lung volumes become more pronounced with disease progression. • 3 reasons to do physiologic testing • 1) Clues to diagnostic category • 2) Assess the severity of impairment • 3) Assess change objectively
  • 249. 2 criteria for diagnosis of IPF: 1) Exclude other known causes of ILD (ex: sarcoidosis, pneumoconiosis, etc) 2) Diagnose UIP either by HRCT or surgical lung biopsy
  • 250. HRCT • Interlobular septal thickening and reticulation • Symmetrical, lower lobe, subpleural • Macroscopic honeycombing • Symmetrical, lower lobe, subpleural • Traction bronchiectasis • Bilateral infiltrative lesions in the form of small nodules, irregular lines, or ground-glass shadows
  • 251. HRCT Interlobular septal thickening Reticulation Honeycombing Traction bronchiectasis
  • 252. Mosaic Attenuation: Air Trapping Expiratory Normal
  • 253. Bronchoscopy and Surgical Lung Biopsy • Bronchoscopy is diagnostic for sarcoidosis in >90% of cases • Perform bronchoscopy if: • Hemoptysis and radiographic ILD findings are present • Acute onset of ILD • Subacute or chronic presentation of ILD if sarcoidosis, hypersensitivity pneumonitis, pulmonary Langerhans histiocytosis, or infection are suspected • Bronchoscopy is less helpful in patients with radiographic findings that suggest IPF • No established role in assessment of progression or response to therapy • Obtain a lung biopsy in patients with atypical or progressive symptoms and signs: • Age less than 50 years • Fever • Weight loss • Hemoptysis • Signs of vasculitis • Atypical radiographic features • Unexplained extrapulmonary manifestations • Rapid clinical deterioration, or sudden change in radiographic appearance
  • 254. Treatment • General Lung Disease • Stop smoking • Supplemental oxygen if needed • Immunization against S. pneumoniae and flu • Pulmonary rehabilitation • Consider lung transplantation • Enrollment in clinical trials • End-of-life planning • Specific to ILD • No specific therapy works for IPF • Quality of data for effectiveness of therapy is poor • Immunosuppressive therapy may be effective in some but not others • Immunosuppressive therapy side-effects are common and dangerous • Duration and intensity of appropriate treatment differs markedly
  • 255. Anatomy: Pulmonary Interstitium • Definition: Collection of support tissues within the lung that includes the alveolar epithelium + pulmonary capillary endothelium + basement membrane + perivascular and perilymphatic tissue • Divided into 3 zones- • Axial (surrounding bronchovascular tree) • Parenchymal (surrounding pulmonary parenchyma) • Peripheral (adjacent to the pleura)
  • 256.
  • 257. Anatomy: Secondary Pulmonary Lobule • Smallest unit of lung structure marginated by connective tissue septa: fundamental unit of lung structure • Irregularly polyhedral, variable size (1-2.5 cm) • Contains: • Small bronchiole • Pulmonary artery branch • 12 or fewer acini usually • Marginated by interlobular septa • Contain pulmonary veins and lymphatics • Septa allow for visualization
  • 258.
  • 259. Autoimmune Diseases such as SLE, Rheumatoid Arthritis, Scleroderma, and Dermatomyositis-Polymyositis can cause ILD, but have a much better prognosis and can be treated with immunosuppresive therapy.
  • 260. Hypersensitivity Pneumonitis • Spectrum of immunologically mediated, predominantly interstitial, lung disorders caused by intense, often prolonged exposure to inhaled organic antigens • In contrast to Asthma, involves pathologic changes of ALVEOLAR WALLS • A common and potentially treatable cause of ILD • Farmer’s lung (thermophilic actinomyces), Bird-fancier’s lung, Indoor mold • Histology: • Centered on bronchioles • (1) Interstitial pneumonitis, consisting primarily of lymphocytes, plasma cells, and macrophages (NOT EOSINOPHILS) • (2) Noncaseating granulomas in 2/3 of patients • (3) Interstitial fibrosis with fibroblastic foci, honeycombing, and obliterative bronchiolitis (late stages). • Centrilobular nodules on HRCT
  • 261. HP Clinical Course • Acute attacks, which follow inhalation of antigenic dust in sensitized patients, consist of recurring episodes of fever, dyspnea, cough, and leukocytosis. • Micronodular interstitial infiltrates may appear in the chest radiograph • Pulmonary function tests show an acute restrictive disorder. • Symptoms usually appear 4 to 6 hours after exposure and may last for 12 hours to several days. They recur with reexposure. • If exposure is continuous and protracted, a chronic form of the disease supervenes, leading to progressive respiratory failure, dyspnea, and cyanosis and a decrease in total lung capacity and compliance.
  • 262. Chronic Inflammatory Infiltrate centered on small airways: bronchiolitis Lymphocytic Bronchiolitis Noncaseating Granuloma
  • 263.
  • 264. IPF vs. Hypersensitivity Pneumonitis • Timing • IPF: Gradual onset, chronic non productive cough • HP: Subacute, Symptoms within hours of exposure • Prognosis • IPF: Survival is less than 3 years • HP: Good prognosis if diagnosed in subacute phase • Treatment • IPF: Only lung transplant • HP: Immunosuppression and antigen avoidance
  • 265. Sarcoidosis • Systemic disease characterized by non-caseating granulomas in multiple organs/systems • African American Females, non-smokers, 20-39 • Diagnosis of exclusion: NEVER A SURE THING • Gross Morphology: • Symmetric hilar and mediastinal lymphadenopathy +/- lung infiltrates • Histology • Well-formed nonnecrotizing granulomas composed of aggregates of tightly clustered epithelioid macrophages, often with giant cells. • Granulomas  fibrosis and hyalinization • Stellate inclusions (‘asteroid bodies’) often seen within giant cells of granulomas • Diagnosis w/ bronchoscopy in 90% of cases
  • 266.

Hinweis der Redaktion

  1. What are the differences? Why are they there?