Man, Machine, and Homeostasis

Physiologist Claude Bernard lived in a time when very little was known about the mechanisms underlying physiologic findings, and he had ample access to clues garnered from observing machines. Let's consider homeostasis (a concept championed by Bernard), an example for which an engineered machine shed light on a fundamental principle of physiology. Homeostasis is simply the tendency of the body to maintain important physiologic variables (eg, heart rate, blood pressure, PACO2) at constant, preset values. An example is a simplified mechanical governor that could be used to regulate the rotational speed of a steam engine shaft. ‘Autoregulate’ might be a more apt word because the governor performs without external help or guidance, provided it is designed and built properly. It doesn't take much imagination to see an analogy between the mechanical governor and the autonomic nervous system. Both maintain specific variables at a constant set point through a process of feedback loops.

Diffusion Limitation—Montana Style

The pathway of oxygen through the body consists of the diffusion of oxygen across the alveolar-capillary membrane and then the peripheral tissue membranes, followed by the convective transport of oxygen in the blood. Any transport process will have its choke points and limitations. In the case of oxygen, the constraints can take 1 of 2 forms, perfusion limitation or diffusion limitation.

The Two Doctors Fick

We often confuse the ‘Fick principle’ with ‘Fick's law of diffusion.’ They are not the same. Ironically, Fick borrowed heavily from already known physical laws when he first described both his law of diffusion and his principle. Borrowing from Ohm's law of electricity, Fick applied concepts of diffusion and transfer across a resistance to formulate a law of diffusion that could be applied to gas or solute transfer across a membrane. Whether we are talking about transfer across the alveolar-capillary membrane or across a dialysis membrane, the concept is the same. The concept is similar to electricity—you have a transfer rate, resistance, and a gradient. Now let's consider the Fick principle. On the basis of another physical law he understood that, in the steady state, the difference between the amount of oxygen going into a tissue bed minus that leaving the tissue bed must be equal to the oxygen consumed. With a little reworking, this became the Fick principle: Cardiac output = O2 consumption / (arterial O2 - venous O2).

Oxygen and the Gradients of Life

Physiologically, what is the difference between a patient undergoing deep hypothermic circulatory arrest and another patient who has died and cooled to the same temperature? The answer resides inside the cells. During hypothermic arrest, physiologic functions of whole-organ systems are temporarily arrested, but the cells are still busy. Cellular metabolism is also slowed, but it's not completely stopped. One difference between the hypothermic-arrest patient and the dead patient is that the former has live cells and the latter has dead cells. And furthermore, one of the differences between live cells and dead cells is that live cells maintain certain important gradients across their membranes. Another difference is that dead cells have no metabolism. We often refer to cellular metabolism as ‘respiration,’ and we measure it by calculating how much oxygen is being used. This brings us to oxygen. Why do we define cellular metabolism in terms of oxygen consumption?

Starling’s Riddle of the Broken Heart

In 1897, Ernest Starling lectured on heart failure by inducing cardiac tamponade in an anesthetized dog. When the tamponade began to have an effect, the arterial pressure began to fall, but the venous pressures began to rise. In other words, heart failure didn't just decrease one type of pressure, it simultaneously increased another type of pressure. By the end of the experiment, all pressures had converged to the same value. The heart, like any pump, doesn't just raise fluid pressure on one side, it simultaneously lowers fluid pressure on the opposite side. The heart has a peculiar architecture that prefers a slightly filled resting state. Any smaller volume actually requires active contraction—it passively springs open during a part of diastole, suctioning blood into itself. Why then does heart failure cause capillary edema? We understand that the pressure in large veins will rise with heart failure, but capillary pressure is on the left side of the intersection of the curve and the Pms line. As such, capillary pressure should decrease with heart failure, and the tendency toward edema similarly should decrease.

Pressure and Flow—Chickens and Eggs

We tend to assume that when 2 things are associated with each other, one must be causing the other. Nothing could be further from the truth, though. Because we're used to seeing the independent variable (‘cause’) plotted on the x-axis and the dependent variable (‘effect’) on the y-axis, this equation and graph suggest that the pressure gradient causes the paddle wheel flow rate. That, of course, is nonsense. This type of specious thinking is intended to warn you away from assuming that relationships necessarily imply causality. As you've learned already, pressure is not the same thing as energy, and pressure by itself cannot perform work or generate flow. However, flow generated by pressure-volume work (either by the heart or a mechanical pump) certainly can create pressure gradients. In this sort of chicken (flow) or egg (pressure) question, if the only energy-containing term is flow, then I'll say that the chicken came first.

Pushmi-Pullyu and the Right Atrium

What does right atrial pressure (PRA) do to cardiac output (CO)? On the one hand, we've been taught that PRA represents preload for the right ventricle. That is, the higher the PRA, the greater the right ventricular output (and, therefore, CO). This is simply an application of Starling's law to the right side of the heart. On the other hand, we've been taught that PRA represents the downstream impedance to venous return (VR) from the periphery. That is, the higher the PRA, the lower the VR, and therefore, the lower the CO. The point of intersection between the 2 curves defines a unique blood flow rate, which is both CO and VR at the same time.

In the Loop—Left Ventricular Pressures

We've already looked at 2 types of pressure that affect physiology (atmospheric and hydrostatic pressure). Now let's consider the third: vascular pressures that result from mechanical events in the cardiovascular system. As you already know, cardiac output can be defined as the product of heart rate times stroke volume. Heart rate is self-explanatory. Stroke volume is determined by 3 factors—preload, afterload, and inotropy—and these determinants are in turn dependent on how the left ventricle handles pressure. In a pressure-volume loop, ‘afterload’ is represented by the pressure at the end of isovolumic contraction—just when the aortic valve opens (because the ventricular pressure is now higher than aortic root pressure). These loops not only are straightforward but are easier to construct just by thinking them through, rather than by memorization.

Pressure and Its Measurement

In physiologic terms, we are exposed to 3 main sources of pressure: 1) the weight of the atmosphere; 2) hydrostatic forces exerted by the weight of body fluids; and 3) mechanical pressure generated by the heart or other muscles that contract around those fluids. Because cardiopulmonary physiology deals so much with pressure measurements, let's start by defining what pressure really is. Simply put, pressure is force divided by area. It's also important to understand what pressure is not. For example, pressure is not energy. Only when pressure is coupled to a volume change (ie, movement or pressure-volume work) is it a component of energy. This is more than just a semantic point. Although we're fond of saying that fluids move from high to low pressure, that isn't always true. The reason why highlights a fundamental difference between pressure and energy. Pressure is surprisingly difficult to measure. Often, when we think we are measuring pressure, we are actually measuring stretch or movement.

A Breath of Fresh Air—Ventilation

The sine qua non of ventilation is arterial carbon dioxide. If you want to know about ventilation, just check the PaCO2. If it is low or normal, ventilation is fine, regardless of any other parameter, including respiratory rate, tidal volume, or dead space ratio. However, if PaCO2 is high, then alveolar ventilation (VA) is impaired (relative to the carbon dioxide load being presented to the lungs). In a conventional breathing circuit, dead space ends at the Y-shaped junction of the inspiratory and expiratory arms of the circuit and the endotracheal tube. On the machine side of that junction, the inspiratory and expiratory limbs see only fresh inspired or expired gas, respectively, but not both. You should know 2 other things about ventilation. One is the Bohr equation, which estimates the ratio of dead space to tidal volume. The anatomic dead space is estimated as the expired volume that coincides with half maximal nitrogen content. The second thing is the effect of gravity on the distribution of ventilation within the lung.