PROBLEM SET 7. Assigned: April 1, 2004 Due: April 9, 2004

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Harvard-MIT Division of Health Sciences and Technology HST.542J: Quantitative Physiology: Organ Transport Systems Instructors: Roger Mark and Jose Venegas MASSACHUSETTS INSTITUTE OF TECHNOLOGY Departments of Electrical Engineering, Mechanical Engineering, and the Harvard-MIT Division of Health Sciences and Technology 6.022J/2.792J/BEH.371J/HST542J: Quantitative Physiology: Organ Transport Systems PROBLEM SET 7 Assigned: April 1, 2004 Due: April 9, 2004

Problem 1 In this problem, consider the different factors which, in combination, give rise to the pressure differences encountered in the lung during breathing. For this purpose, use a simple model comprised of five generations with the geometry described below. Generation Number of Airways Total Cross-sectional Area (cm 2 ) Length (cm) 1 1 2 10 2 4 3 2 3 16 5 1.5 4 128 10 1.0 5 2000 50 0.5 In the following questions, consider inspiration at a normal breathing rate of 0.5 L/sec. Assume the flow to be steady and the fluid to be ν = 0.15 cm 2 /sec and ρ = 2 10 3 gm/cm 3. (Remember ν = µ/ρ, the kinematic viscosity.) A. Compute the mean flow velocity in each generation assuming a uniform distribution of ventilation. B. Assume the flow to be inviscid and calculate the total pressure difference between the first and fifth generations. This represents the pressure difference necessary to decelerate a fluid particle as it passes through the network. C. Assume, as a first approximation, that the flow in each airway is laminar (check your Reynolds numbers to see if this is reasonable) and fully developed. Calculate the pressure difference acting across the network (first to fifth generation) due to viscous forces alone. This represents the pressure drop necessary to overcome the tendency of wall friction to impede the flow. (Note that the actual pressure drops in the upper airways will tend to be greater than those estimates due to secondary flow and the boundary layer developing after each branch.) D. Recognizing that, in the real case, these two factors act in concert to produce the observed pressure difference, compare your answers in (B) and (C) to see which effect dominates. 2004/211 2 6.022j 2004: Problem Set 7

Problem 2 If a dog is breathing ordinary air, and the left main bronchus is suddenly occluded, the left lung will completely collapse in about 1/2 hour. If the dog had been breathing 100% 0 2 for some tine previously, collapse occurs in about 5 minutes. Discuss the process of collapse and explain the more rapid collapse after breathing pure oxygen. Include as part of your discussion a qualitative description of the total pressure in the left lung as a function of time. You may find the following typical values of arterial and venous partial pressure useful. Breathing Air Breathing 100% O 2 Arterial P O2 = 100, P CO2 = 40 P O2 = 660, P CO2 = 40 Venous P O2 = 40, P CO2 = 46 P O2 = 90, P CO2 = 46 You may assume that as the total volume of gas in the left lung changes, the total gas pressure remains close to atmospheric. 2004/535 6.022j 2004: Problem Set 7 3

Problem 3 On a hot summer day, a dog pants to eliminate heat. During panting, breathing rates of 300 breaths per minute are common and tidal volumes fall to roughly equal to the dog s dead space volume. A. Using the conventional model of pulmonary gas exchange (based an the division of the lung into a single dead space and single alveolar space) compare the following two ventilation states in terms of relative values for P a,o2 and P a,c O2 : Normal Breathing Panting f = 20/min f = 300/min V T = 400ml V T = 167ml V D V A = 150ml = 2000ml assuming that cardiac output, metabolic rate, and inspired gas composition all remain constant. B. What objections might be raised to the use of such a simplistic model for high frequency, low tidal volume breathing? 2004/536 4 6.022j 2004: Problem Set 7

Problem 4 It is thought that airway smooth muscle can shorten by as much as about 30% when exposed to a broncho-constrictive agent such as histamine. In asthmatics, the effect of smooth muscle constriction has been shown to be accentuated by a pathologic thickening of the airway wall. In order to analyze the consequence of these two effects in concert, consider the following simple model of a small airway, shown here in cross-section. In this model, the smooth muscle is assumed to be confined to a band surrounding the inner tissues of the wall (submucosa, mucosa). a L a sm smooth muscle submucosa A. Obtain an expression for the ratio of lumenal radii before and after a 30% reduction in smooth muscle length a L /a L,o (the subscript o indicates a pre-constriction value). Assume that the wall area inside of the smooth muscle A W remains constant and that both the smooth muscle and the internal lumen remain circular in cross-section. B. A typical value for a sm,o /a L,o might be 1.05; for an asthmatic airway, the same ratio might be 1.1 (or higher). Calculate the ratio of a L /a L,o in both cases. Assuming that these airways are located sufficiently peripheral so that the Reynolds number is < 50, by what percentage does the flow resistance of the normal airway change? What happens to the resistance of the asthmatic airway? Consider the implications of inhomogeneity in the degree of smooth muscle constriction or the degree of wall thickening on the distribution of ventilation. 2004/531 6.022j 2004: Problem Set 7 5