PubMed Health⌕ Search

Biomedical subjects

J A Wessels

Publications and source records attributed to J A Wessels.

7 recordsLinked to original sources

Integral rein control in physiology II: a general model.

We generalize the principle of integral rein control to include other systems which partition in such a way that the equilibrium values of some variables are not dependent on the equations governing those variables. Instead, they are determined by the dynamics of other, "regulator" variables. We improve our earlier model for the control of glucose by insulin and glucagon by relaxing the condition necessary for it to operate. The two hormones do not have to be inhibited in the same way; they need only respond to the same combination of their concentrations. We also present a model for the control of ionized calcium by PTH and calcitonin and suggest that the role of chromogranin A may be to stabilize an otherwise unstable system.

Blood Glucose↗

The chromogranins and the counter-regulatory hormones: do they make homeostatic sense?

1. The chromogranins are ubiquitous proteins which are co-stored and co-secreted with many peptide hormones. All appear to be powerful inhibitors of endocrine secretions. This poses a problem. 2. When endocrine glands are involved in the efferent limbs of homeostatic loops, they are message transmitters. The self-inhibition caused by the co-secretion of a chromogranin will, on the face of it, erase the message. 3. Pairs of counter-regulatory homeostatic hormones also present a problem. 4. If both members of the pair have clearly defined set points, as suggested by their 'time integral' (or 'growth with time') responsiveness to deviations from set point, then, if the two set points are not exactly the same, one or other member will always register an error, leading, eventually, to an overwhelmingly large and unnecessary response. 5. Our model eliminates both paradoxes, and emphasizes the importance of counter-regulation and the co-secretion of chromogranins in 'zero steady-state error' (ZSSE) homeostasis. 6. If hormone A is secreted into the blood in progressively increasing amounts when [Q], the plasma concentration of substance Q, is low, and in decreasing amounts when [Q] is high; and hormone B responds in the opposite manner, then there will be a [Q], designated [Q]p, at which the secretory rate increase, or decrease, of the two hormones is exactly the same. 7. If, in addition, the secretion of both hormones is stimulated by low plasma chromogranin levels, [Cg], but inhibited by high [Cg] then there will be a different [Q]p for every chromogranin concentration in the blood. 8. At one of these points (at a unique [Q] and [Cg]) the concentration of neither hormone will increase or decrease. This is the equilibrium point to which, according to our model, the system always returns regardless of disturbances within physiological limits. 9. This is robust ZSSE control.

Animals↗

Assessment of a peak flow whistle in nonasthmatic children.

We tested the agreement of peak expiratory flow (PEF) measurements between an electronic spirometer and a peak flow whistle (Whistle Watch, HarMed, Capetown, South Africa). One hundred and three healthy children between ages 6-13 years and with no previous experience in lung function tests participated in the study. Sequential PEF-readings were obtained from the spirometer and the peak flow whistle; all children had an equal number of attempts using both devices. In the case of the spirometer, the highest PEF reading of three acceptable and reproducible efforts was noted as the best PEF (PEF(SPIRO)). Whistle Watch readings were taken as the highest value when the child could activate the whistle. Despite a strong correlation (r = 0.91; R2 = 83%) between the readings of the spirometer and Whistle Watch, there was a lack of agreement between the two devices. For any individual subject, the 95% probability interval ranged between +30.4 to -47 L.min(-1); 64% of the children obtained higher PEF-values on Whistle Watch, compared to the spirometer. These findings suggest that the whistle sound of the peak flow whistle was a significant incentive, which resulted in greater maximal expiratory efforts.

Child↗

A computer simulation of free-range exercise in the laboratory.

We present a technique for simulating dynamic field (free-range) exercise, using a novel computer-controlled cycle ergometer. This modified cycle ergometer takes into account the effect of friction and aerodynamic drag forces on a 70-kg cyclist in a racing position. It also affords the ability to select different gear ratios. We have used this technique to simulate a known competition cycle route in Cape Town, South Africa. In an attempt to analyze the input stimulus, in this case the generated power output of each cyclist, eight subjects cycled for 40 min at a self-selected, comfortable pace on the first part of the simulated route. Our results indicate that this exercise input excites the musculocardiorespiratory system over a wide range of power outputs, both in terms of amplitude and frequency. This stimulus profile thereby complies with the fundamental requirement for nonlinear (physiological) systems analysis and identification. Through a computer simulation, we have devised a laboratory exercise protocol that not only is physiologically real but also overcomes the artificiality of most traditional laboratory exercise protocols.

Computer Simulation↗

Integral rein control in physiology.

We propose that blood glucose is regulated by a principle which we call integral rein control, in which under most conditions both glucagon and insulin are produced and control is achieved by altering the balance between the two. Like other integral control systems, the mechanism achieves zero steady-state error, which explains how the blood glucose level can remain very nearly constant over a wide range of input and demand. In addition, the use of two hormones makes the system stable against relatively large perturbations in either direction. An important feature of the model is that the set point is not fixed by an external reference but arises out of the dynamics, in particular out of the relation between the rates of production of the two hormones. The model therefore predicts that the consequence of an inability to produce insulin will be not just that the control will be less effective but that the set point will be shifted. This allows us to explain why patients with untreated Type I diabetes mellitus have high blood glucose levels even under conditions of low glucose input, and why it is difficult to maintain the normal level of 5 mmol/1 in patients who are being treated with insulin. It also explains why Type II diabetes is easier to treat.

Blood Glucose↗

A simple method for the continuous noninvasive estimate of cardiac output using the Maxima breathing system. A pilot study.

The Maxima is a new breathing system which makes it possible to monitor cardiac output (Q) noninvasively and to follow trends continuously. When used as a rebreathing system in controlled ventilation, the Maxima selectively eliminates alveolar gas and no fresh gas (VF) is eliminated. Without the need for a mixing chamber, eliminated CO2 (FeCO2) may be measured directly. With steady state conditions, and assuming a respiratory quotient of 1, carbon dioxide production (VCO2) = VF x FeCO2. The indirect Fick principle applied to CO2 exchange (Q = VCO2/ venous-to-arterial CO2 content difference (CaCO2-CvCO2) may be modified to Q = VF x FeCO2/(CaCO2-CvCO2). If VF in the breathing system is adjusted so that FeCO2 is equal to CaCO2-CvCO2, then Q = VF. It was found that, in the presence of a normal haemoglobin (13.3 g.dl-1), Q = VF when VF was adjusted to achieve an FeCO2 value of approximately 4.1%. Cardiac output estimates were compared with those obtained using a thermodilution technique in five patients undergoing coronary artery bypass grafting and in four patients with septicaemia in the ICU. Cardiac outputs were estimated from 1. VCO2 measurements and then 2. VCO2 and haemoglobin (Hb). The result of 28 measurements on nine patients with methods 1. and 2. respectively yielded a correlation with thermodilution measurements: coefficient r = 0.91 and 0.94 with a bias of -10.5% and -0.05% and an accuracy of 14% and 9%.

Capnography↗

Glucose homeostasis with infinite gain: further lessons from the Daisyworld parable?

A major unresolved physiological problem is how the rate of hepatic glucose production is increased to match the increased rate of glucose utilization during exercise without a change in arterial blood glucose level. A homeostat with such capabilities is said to have infinite gain. Daisyworld is an imaginary planet orbiting a variable star. The only life is black and white daisies. Black daisies retain heat, slightly warming the planet; white daisies cool it. When the two types of daisies grow best at slightly different temperatures, variations in solar luminosity (over a wide range) cause the ratio of white:black daisies to vary in a manner that keeps the planetary temperature constant. This model therefore achieves infinite gain by having two opposing but interdependent controllers. Here we suggest that the pancreatic islet alpha- and beta-cells might act as black and white daisies. For the analogy to apply, glucagon and insulin must not only have opposing effects on the blood sugar concentration, but the secretion of the one has, at some quantum level, to be at the expense of the other. Electrical coupling between heterocellular groups of alpha- and beta-cells within the pancreatic islets suggests that this might indeed be the case. alpha-Cell activity must, furthermore, promote secretory activity in other alpha-cells; similarly with beta-cells. This is probably mediated via pancreastatin and gamma-amino butyric acid (GABA) which are paracrinically co-secreted with glucagon and insulin, respectively. alpha-Cell activity spreads (at the expense of beta-cell activity) when the blood glucose level is below set point, while beta-cell activity progressively replaces alpha-cell activity above set point. At set point changes in the ratio of alpha:beta-cell activity are inhibited.

Chromogranin A↗