LECTURE- 4 RESPIRATORY PHYSIOLOGY COMPETENCY BASED CURRICULUM (2023-24) -.pptx

Respiratory physiology, MBBS 1st year

1. EBES DOCUMENT COMPETENCY BASED RESPIRATORY PHYSIOLOGY Dr J M Harsoda PROF AND HEAD DEPARTMEN OF PHYSIOLOGYSBKSMI AND RC SUMANDEEP VIDYAPEETH

2. COMPETENCY CODE : PY6.2 ( contd …) ALVEOLAR SURFACE TENSION (PULMONARY SURFACTANT) .

3. ALVEOLAR SURFACE TENSION (PULMONARY SURFACTANT) SITE OF FORMATION OF PULMONARY SURFACTANT COMPOSITION OF PULMONARY SURFACTANT MECHANISM OF ACTION PHYSIOLOGICAL FUNCTIONS :- ( 1) REDUCING SURFACE TENSION OF LUNG ALVEOLI. (2) ALVEOLAR STABILIZATION. (3) REDUCING PULMONARY CAPILLARY FILTRATION. CLINICAL SIGNIFICANCE:- (1) RESPIRATORY DISTRESS SYNDROME (RDS) OF NEW BORN (2) ADULT RESPIRATORY DISTRESS SYNDROME (ARDS).

4. Site of formation of pulmonary surfactant Pulmonary surfactant is a complex substance that lines the alveolar surface and markedly decreases surface tension. It is stored in lamellar bodies. Pulmonary surfactant is formed by type – II alveolar cells, which are cuboidal cells located in the corners of the alveoli. Joseph Boyle III (1984) NMS physiology 3 rd Ed.

5. Type – II alveolar cell

6. COMPOSITION OF PULMONARY SURFACTANT Surfactant i s a complex mixture of several phospholipids, proteins, and ions. The most important components are the phospholipid dipalmitoylphosphatidylcholine [DPPC], apoproteins , and calcium ions. PROTIENS:- Four unique protiens have been identified in surfactant:SP -A, SP-B, SP-C and SP-D Guyton and Hall (2006) Text book of medical physiology 11 th Ed. Joseph Boyle III (1984) NMS physiology 3 rd Ed.

7. MECHANISM OF ACTON OF PULMONARY SURFACTANT Phospholipids , dipalmitoylphosphatidylcholine [DPPC] , are strong surface active agents,especially when they are compressed in the surface of an air – fluid interface reduces the surface tension. In quantitative terms, the surface tension of different water fluids is approximately the following: pure water, 72 dynes/cm; normal fluids lining the alveoli but without surfactant, 50 dynes/cm; normal fluids lining the alveoli and with normal amounts of surfactant included, between 5 and 30 dynes/cm. Joseph Boyle III (1984) NMS physiology 3 rd Ed. Guyton and Hall (2006) Text book of medical physiology 11 th Ed.

8. FUNCTIONS OF PULMONARY SURFACTANT 1 Reducing surface tension is the primary function of pulmonary surfactant:- Adsorption of surface active molecules at the alveolar-air interface reduces surface tension. The low surface tension also facilitates the reopening of the collapsed air ways and alveoli 2 Alveolar stabilization by increasing alveolar radius:- The increased radius reduces the transmural pressure required to maintain the alveolar inflation ( per the law of the Young –Laplace). Joseph Boyle III (1984) NMS physiology 3 rd Ed.

9. FUNCTIONS OF PULMONARY SURFACTANT 3 Reducing pulmonary capillary filtration:- Normal surfactant , by lowering surface tension, reduces the retraction forces the lungs. The decreased elastance makes the pulmonary interstitial pressure, reducing pulmonary capillary filtration. Thus, normal surfactant helps to prevent pulmonary edema and haemorrhage . Michael B Wang , Johan Bullock and Joseph Boyle III (1984) NMS physiology 3 rd Ed.

10. CLINICAL SIGNIFICANCE OF PULMONARY SURFACTANT 1 RESPIRATORY DISTRESS SYNDROME (RDS) OF NEW BORN Normal surfactant is formed by the Type-II alveolar cells only after the seventh month of gestation. Infants born prematurely have immature lungs that produce inadequate or abnormal surfactant thus, increase surface tension of lungs that leads to impaired gas exchange, atelectasis , pulmonary edema and haemorrhage within the lungs leading to a high mortality rate. THERAPY:- Includes the application of Positive End Expiratory pressure (PEEP) is use of a ventilator to maintain alveolar pressure above zero at the end of expiration Administration of exogenous surfactant .( Endotracheally ) Michael B Wang , Johan Bullock and Joseph Boyle III (1984) NMS physiology 3 rd Ed.

11. 2 ADULT RESPIRATORY DISTRESS SYNDROME (ARDS) Adult respiratory distress syndrome can be caused by shock, systemic infection or trauma and normobaric (pulmonary) o 2 toxicity that leads to impaired gas exchange, atelectasis , pulmonary edema and haemorrhage within the lungs . THERAPY:- Clinical trials are now underway using exogenous surfactant in an attempt to improve of ARDS. Joseph Boyle III (1984) NMS physiology 3 rd Ed.

12. EBES LEARNING RESPIRATORY DISTRESS SYNDROME

13. EFFECT OF EXERCISE TRAINING IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) REFERENCES INTERVENTION SUBJECT OUT COME RESULT 1 Antonio Patessio et al (1992). Ventilatory and metabolic changes as result of exercise training in COPD patient. CHEST, Vol. 101:5( suppliment ):274s. High level Evidence Patients with COPD feel better & are able to sustain a given level of activity longer after a program of exercise. Identical tests were performed after an 8 week program of cycle ergometer training either for 45 min/day at high work rate or for a proportional longer time at low work rate 19 patients with COPD were selected and performed an incremental test as well as 2 square wave tests at a high & low work rate. Metabolic changes (blood lactate level) and ventilatory changes pulmonary ventilation (VE) The major finding of this study are patients with COPD who experience lactic acidosis during exercise can achieve physiologic training responses from program of endurance training & that training work engendering high level of blood lactate level. After 8 week program of cycle ergometer training the low work rate training group had significantly less lactate & VE decrease (p<0.01) Further in the first group there was increase in exercise tolerance averaging 71% in the high constant work test. There was good correlat . (r=0.73, P<0.005).

14. RESPIRATORY DISTRESS SYNDROME REFERENCES INTERVENTION SUBJECT OUT COME RESULT 1 Contd …. systemic effect (hypotension, reduced systemic vascular resistance, or unexplained metabolic acidosis). Forty-seven patients developed ARDS , and the remaining 160 patients were used as a comparison control group. Our findings indicate that sepsis syndrome , rather than respiratory failure , is the leading cause of death in patients with ARDS The majority of late deaths were related to sepsis syndrome . Of the 22 patients with ARDS who died after 3 days, 16 (73%) met our criteria for sepsis syndrome . There was a sixfold increase in sepsis syndrome after ARDS compared with that in the control group (p less than 0.001).

15. RESPIRATORY DISTRESS SYNDROME REFERENCES INTERVENTION SUBJECT OUT COME RESULT 2 Marcelo Britto Passos Amato, M.D et al (1998) Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome. N Engl J Med 1998; 338:347-354 . High level Evidence In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with After 28 days, 11 of 29 patients (38 percent) in the protective-ventilation group had died, as compared with 17 of 24 (71 percent) in the conventional-ventilation group (P<0.001). The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group

16. RESPIRATORY DISTRESS SYNDROME REFERENCES INTERVENTION SUBJECT OUT COME RESULT 2 Contd …. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge The difference in survival to hospital discharge was not significant; 13 of 29 patients (45 percent) in the protective-ventilation group died in the hospital, as compared with 17 of 24 in the conventional-ventilation group (71 percent, P = 0.37).

17. RESPIRATORY DISTRESS SYNDROME REFERENCES INTERVENTION SUBJECT OUT COME RESULT 3 Brower RG , et al ( 2004). Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. The New England Journal of Medicine [2004, 351(4):327-336]. High level Evidence Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome ( ARDS ) receive positive end-expiratory pressure ( PEEP ) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and. We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end- inspiratory Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower- PEEP group and 13.2+/-3.5 cm of water in the higher- PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent).

18. RESPIRATORY DISTRESS SYNDROME REFERENCES INTERVENTION SUBJECT OUT COME RESULT 3 Contd …. reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistentionand reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention . predetermined combinations of PEEP and fraction of inspired oxygen. plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used. From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower- PEEP group and 13.8+/-10.6 days in the higher- PEEP group (P=0.50).

19. CONCLUSION When sepsis syndrome preceded the ARDS , the abdomen was the predominant source, but when sepsis syndrome occurred after the onset of ARDS there was usually a pulmonary source. Our findings indicate that sepsis syndrome , rather than respiratory failure , is the leading cause of death in patients with ARDS As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge

20. CONCLUSION These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end- inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used.

21. REFERENCES 1 Montgomery AB , et al (1985) Causes of mortality in patients with the adult respiratory distress syndrome The American Review of Respiratory Disease , [1985, 132(3):485-489]. 2 Marcelo Britto Passos Amato, M.D et al (1998) Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome. N Engl J Med 1998; 338:347-354. 3 Brower RG ,et al ( 2004). Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. The New England Journal of Medicine [2004, 351(4):327-336]. 4 K.G. Hickling et al (1990). Low mortality associated with low volume pressure lmited ventilation permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med, 16: 372-377.

22. “Work” of Breathing We have already pointed out that during normal quiet breathing, all respiratory muscle contraction occurs during inspiration; expiration is almost entirely a passive process caused by elastic recoil ( retractive force) of the lungs and chest cage. Thus, under resting conditions, the respiratory muscles normally perform “work” to cause inspiration but not to cause expiration. Energy Required for Respiration:- During normal quiet respiration, only 3 to 5 per cent of the total energy expended by the body is required for pulmonary ventilation. Guyton and Hall (2006) Text book of medical physiology 11 th Ed.

23. WORK OF INSPIRATION The work of inspiration can be divided into three fractions: - (1) That required to expand the lungs against the lung and chest elastic forces, called compliance work or elastic work; (2) That required to overcome the viscosity of the lung and chest wall structures, called tissue resistance work. (3) That required to overcome airway resistance to movement of air into the lungs, called airway resistance work. Guyton and Hall (2006) Text book of medical physiology 11 th Ed.

24. MCQ TEST AFTER END OF LECTURE 1 Normal respiratory frequency in adult: A 14-60/min B 25-35/min C 12-18/min D 20-25/min 2 The total energy expended by the body is required for pulmonary ventilation : A Only 20 to 25 per cent B Only 10 to 12 per cent C Only 3 to 5 per cent D Only 30 to 50 per cent

25. 3 Surfactant is required for: A To cause alveolar collapse B To prevent alveolar collapse C To provide alveolar pressure D To cause atelectasis 4 It is a strong surface active agent of surfactant: A Cholesterol B DPPC ( Dipalmityl phosphotidyl choline ) C Lecithin D Sphyngomyelin

26. 5 Pulmonary surfactant is formed by : A Alveolar macrophages B Type – II alveolar cells C Globlet cells D Type – I alveolar cells

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