RESPIRATORY FAILURE

1. RESPIRATORY FAILURE Miklós Molnár Semmelweis University Institute of Pathophysiology 2005

2. Respiration • Function of the respiratory system is to supply the body with oxygen for aerobic metabolism and to remove its major metabolic waste product-carbon dioxide (0.2-4 L/min). • Does it by 3 Distinct Mechanisms: • Ventilation: Delivery of ambient air to the alveoli • Diffusion: Movement of oxygen and carbon dioxide across the alveolar air sac and capillary wall • Circulation: Method by which oxygen is carried from site of gas exchange to the cells where active metabolism occurs

3. Respiration Is dependent on vital links of various anatomic subcomponents

4. Spinal Cord Central Nervous System Neuromuscular System Lower Airways and Alveoli Thorax and Pleura Cardiovascular System and Blood Upper Airways Seven anatomic subcomponents whose functions are vital to the maintenance of normal respiration. Interruption in the function of any of the links has serious implications for the functioning of the system as a whole. (adapted from Bone RC: Acute Respiratory Failure: Definition and Overview. In Bone R, ed: Pulmonary and Critical Care Medicine. St. Louis: Mosby, 1997).

5. Control of Breathing • Central chemoreceptors • Respiratory center – medulla oblongata • pH (behind the blood-brain barrier) • Peripheral chemoreceptors – carotid bodies (carotis, arch of aorta) • pH/pCO2, pO2 • mechanoreceptors(lung, chest wall) • mechanicalstrech, chemical irritation, • J-receptors • (juxtacapillarlocalization blood volume,interstitial edema)

7. Ventilatory Responses to Physiologic Stimuli • Hypercapnia • Gradual increase of frequency(pCO2=40-70 mmHg, linear-3 l/min/mmHg) • Hypoxia • normal PaO2=90 mmHg no effect, PaO2=50-55 mmHg yes • Metabolic acidosis • activityof the peripheralchemoreceptor ↑ hyperventilation pCO2↓,later in theCNS- 24-48 h. • Metabolic alkalosis • activityof the peripheralchemoreceptor ↓ hypoventilation pCO2↑, later in theCNS- 24-48 h.

8. Abnormality of the Control of Breathing

9. normal tachypnoe Air flow Kussmaul 6 min Time (min) Abnormal Breathing Pattern Apnoe: breathing stops at expiration Apneusia: breathing stops at inspiration

10. Cheyne Stokes Cluster Breathing (Biot Breathing) 1 min Time (min) Abnormal Breathing Pattern

11. Abnormal Breathing Pattern(Ataxic breathing) Voluntary Self-controlled 1 min Time (min)

12. Abnormal Breathing PatternSleep apnea Hypoventillation and an irregular respiratory pattern during sleep with apnea last for 15-20 sec during the REM phase, usually. Types: Central apnea (complete cessation of respiratory efforts - encephalitis, central ischemia) Obstructive apnea (intermittent upper airway obstruction, morbid obesity, redundant pharingeal soft tissue, reduced upper airway size due to enlarged lymphatic tissue) Mixedapnea (Central apnea followed by obstructive one)

13. Types of Apnea Central apnea Airflow Muscle activity Obstructive apnea Airflow Muscle activity Volume Mixed apnea Airflow Muscle activity

14. Anatomy of obstructive sleep apnea. Coronal section of the head and neck showing the segment over which sleep related narrowing can occur (arrows).

15. Pathophysiology An obese young woman with the short, thick neck typically seen in patients with obstructive sleep apnea.

16. Pathophysiology Enlarged uvula resting on the base of the tongue (large arrow), along with hypertrophied tonsils (small arrows). The posterior pharyngeal erythema may be secondary to repeated trauma from snoring or gastroesophageal reflux

17. Pathophysiology Elongated soft palate (arrows). In this patient, an increased anteroposterior dimension caused the soft palate to rest on the base of the tongue in the relaxed position.

18. Clinical Manifestation • Family members or partners complaint that the patient has loud snoring, nocturnal gasping or choking.

19. Pathophysiologic Consequences • Sleep Apnea Syndrome is profoundly associated with hypertension independent of all relevant risk factors. • Arrhythmias from mild to severe. • Motor vehicle accident : Six time increased accident rate compared to the general population.

20. Treatment

22. Oxygen Carbon dioxide Water vapour Nitrogen

23. Someone told me that each equation I included in the book would halve the sales. Stephen Hawking “A Brief History of Time”: 1988.

24. Alveolar O2tension (PAO2=100 mmHg) Capillary blood leaving the alveolus (Pc’O2=100 mmHg) Arterial O2tension (PaO2=90 mmHg) Pulmonary Gas Exchange Ideal Alveolar Gas Equation Calculation of PAO2 (considering ideal alveolus): PAO2= PIO2 – PACO2 x FIO2 + (1-FIO2) R FIO2 : fraction of inspired O2 (0.21 in room air) R: gas exchange ration – metabolic respiratory quotient (CO2 production/O2consumption=0.7-1.0, typical value of about 0.8) PIO2: pO2 of the inspired gas (PIO2= 0.21x(760-47)=150 mmHg) PAO2= PIO2 – PaCO2 x 1.25

25. Representation of the Decrease in Partial Pressure of O2 from Inspired Air

26. Effectiveness of Oxygene Exchange in the Lung(Alveololar-Arterial oxygen difference) • Alveolo-arterial gragient • Idealsituation P(A-a)=0 • Right-to-left shunt (2-4 %), ventilation-perfusion mismatch. P (A–a) = 2.5 + 0.21 x (age in years) • If P(A - a) > 20 mmHg on room air is abnormal usually due to a parenchymal abnormality of the lung

27. SaO2 100 Oxygen Content of Blood (CaO2) • Bound to hemoglobin(major part) • Dissolved in plasma(small amount) CaO2= Hb x 1.39 x + 0.0031 x PaO2 Hb: hemoglobin (g/100ml) 1.39 : oxygen-carrying capacity of Hb (ml O2/g Hb) SaO2:% of Hb that is bound to O2 = (oxygen saturation) 0.0031: solubility coefficient for O2 in plasma (ml O2/100 ml/mmHg) PaO2: partial pressure of O2 in arterial blood

28. Dissociation Curve of Oxyhemoglobin Adaptations Right shift: acidosis fever, 2,3-DPG Left shift: alkalosis cold Clinically important Physiologicly important % of SO2 PO2 (mmHg)

29. Why the O2 content is so important ? Hb=15 g% Hb=15 g% Hb=15 g% 100 ml 100 ml 200 ml PaO2 30 mmHg + PaO2 96 mmHg = PaO2 ? mmHg ??? (30 + 96 )/2 = 63 mmHg ??? !! WRONG !!

30. Right Answer % of SO2 O2content(ml/100 ml blood) PO2 (mmHg) (12.4 + 19.8) / 2 = 16.1 ml O2/ 100 ml  PaO2= 42 mmHg

31. Respiratory Failure Impaired gas exchange: Hypoxia with or without hypercapnia Can be subclassified into acute and chronic presentations

32. Definitions of Respiratory FailureHypoxemia • Acute respiratory failure occurs when: • pulmonary system is no longer able to meet the metabolic demands of the body • Hypoxemic respiratory failure: • PaO2 60 mmHg when breathing room air • Hypercapnic respiratory failure: • PaCO2  50 Hgmm

33. Classification of Respiratory Failure Predominant HypercapnicaHypoxemiab Type Minutes to hours; no compensatory changes Minutes to hours; no compensatory changes Acute Days to months; compensatory changes present pH and HCO3 Days to months; compensatory changes present hemoglobin Chronic a PaCO2 > 50 mmHg b PaO2 < 60 mmHg

34. Respiratory Failure Pump failure Lung failure Nervous System Thoracic cage Resp. muscle Nervous System Thoracic cage Resp. muscle Hypercapnia Hypoxemia Breakdown of respiratory failure into its two major components: Pump failure and lung failure. The end results of pump failure is hypercapnia, and the end result of lung failure is hypoxemia.

35. BRAIN Drug overdose Cerebrovascular accident SPINAL CORD, NEUROMUSCULAR Myastenia Gravis Syndrome Polio Guillian-Barre’ Spinal cord trauma or tumor CHEST WALL Flail Chest Kyphoscoliosis UPPER AIRWAYS Vocal cord paralysis or paradoxicalmotion Tracheal stenosis, laryngospasm LOWER AIRWAYS & LUNGS Asthma Bronchitis Chronic Obstructive Pulmonary Disease Pulmonary Embolism Acute Respiratory Distress Preumonia Alveolar Hemorrhage HEART Congestive Heart Failure Valvular Abnormalities Examples of Disease that Causes Respiratory Failure Pump Failure Lung Failure

36. Pathophysiology of Respiratory Failure Pathophysiologic mechanisms for respiratory failure include: • Diffusion abnormalities: disturbances in gas transfer across the alveolar capillary bed • Ventilation-perfusion imbalance and intrapulmonary shunt: problems with matching pulmonary blood flow and ventilation • Alveolar hypoventilation: decreased alveolar ventilation

37. Diffusion Abnormalities • The process by which O2 and CO2 move passively across the alveolar capillary membrane that depends upon its physical properties (thickness, area, and diffusibility) and solubility of the gas • Problem mainly in chronic, less so in acute respiratory failure

38. Problems with Matching Pulmonary Blood Flow and Ventilation • Ideally each alveolar capillary exchange unit would have perfect matching of ventilation and perfusion to ensure optimum gas exchange across each unit • This does not happen even in normal individuals where V/Q ranges in different lung regions from 0.6 to 3.0, mean overall is 1.0 • In disease states, balance of ventilation and perfusion may be disturbed further: • ventilation-perfusion inequality - imbalances of V/Q • intrapulmonary shunt: mixed venous blood not exposed to the alveolus

41. Problems with Matching Pulmonary Blood Flow and Ventilation • In disease states, balance of ventilation and perfusion may be disturbed further: • ventilation-perfusion inequality - imbalances of V/Q • intrapulmonary shunt: mixed venous blood not exposed to the alveolus

43. Hypoventilation • To prevent the development of respiratory acidosis, the carbon dioxide produced each day (17,000 meq acid) must be exhaled by the lungs at the same rate • The relationship among alveolar ventilation (VA), carbon dioxide production (VCO2) and the partial pressure of carbon dioxide in the blood (PaCO2) is expressed using a modification of the Fick principle of mass balance that quantitates VCO2 as the product of VA and the fractional concentration of CO2 in the alveolar gas

44. Diagnosis of Respiratory Failure • History and Physical Examination • patient symptoms • physical examination • Laboratory Tests

45. Patient Symptoms in Respiratory Failure • Mental function: headache, visual disturbances, confusion, memory loss, hallucinations, loss of consciousness. • Dyspnea (resting vs. exertional). • Cough, sputum production, chest pain.

46. Arterial Blood Gas Analysis • The most important lab test to subclassify respiratory failure • Provides an indication of the duration and severity of respiratory failure • Gives 3 Types of Information: • presence and degree of hypoxemia (PaO2) • presence and degree of hypercapnia (PaCO2) • arterial Acid-Base Status (pH)

47. Hypoxemia • Reduction of partial pressure of oxygen in the blood • Resting PaO2 normally 75-80mmHg, 60mmHg lower limit of safety • Oxygenation failure considered if PaO2 < 50-60mmHg on FiO2 40% or greater • Decreases in PaO2 Occur Secondary To: • intracardiac or intrapulmonary shunting of blood • V/Q mismatch • alveolar hypoventilation • Alveolar gas equation is helpful in sorting out causes of hypoxemia

48. Hypercapnia • Hypercapnia in an increase PaCO2 > 50 mmHg. • PaCO2 = KVO2 * VA • VCO2 (carbon dioxide) is produced by the oxidative metabolism of carbon containing food products. • Any increase in VCO2 or decrease in VA will result in hypercapnia.

49. Respiratory Failure Examples of Lung vs. Pump Failure • Disorders causing respiratory failure can usually be divided into those causing lung failure (impaired oxygenation) vs. pump failure (hypercapnia). • Adult Respiratory Distress Syndrome (ARDS) is an example of lung failure, drug overdose is an example of pump failure.

50. ARDS - Clinical Case • 43 year old respiratory therapists with asthma, develops acute exacerbation and aspirates during endotracheal intubation. Following intubation, progressive severe hypoxemia refractory to 100% O2 develops. • Lab Data • ABG on 100% FiO2, shows PaO2 114, PaCO2 32, pH 7.47 on VT 600cc, RR 18. A-a gradient=56mmHg. • CXR shows diffuse alveolar infiltrates. • Management • mechanical ventilation, AC ventilation, high FiO2 with increasing levels of PEEP to decrease shunting. • Aggressive use of bronchodilators to alleviate bronchospasm. • Diuresis, enteral feeding, DVT and GI bleed prophylaxis.`