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Which one of these variables is most critically regulated: extracellular fluid (ECF) volume or ECF osmolality or ECF pH or effective arterial blood volume?

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Which one of these variables is most critically regulated: extracellular fluid (ECF) volume or ECF osmolality or ECF pH or effective arterial blood volume?

E.S.Prakash, MBBS, MD

Division of Basic Medical Sciences

Mercer University School of Medicine

Macon, GA, USA

E-mail: prakash_es at mercer dot edu

Submitted 17 Nov 2011; revised Mar 13 2012; accepted and published 27 Jul 2012

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The question stated in the title of this article arises because there are several clinical conditions characterized by abnormalities in three or all of these variables. When hypovolemia, occurring as a result of vomiting, is accompanied by metabolic alkalosis, the kidneys avidly reabsorb sodium, chloride and bicarbonate, and urine may become acidic (‘paradoxical aciduria’). [1] This suggests that regulation of ECF volume overrides mechanisms defending changes in ECF pH.

Release of antidiuretic hormone (ADH) is triggered by increases in sodium concentration of ECF as well as decreases in ECF or blood volume. [2-4] Primary adrenocortical insufficiency (Addison’s disease) is characterized by hyponatremia, a decrease in plasma osmolality, and may additionally be characterized by hyperkalemia and metabolic acidosis. [4-7] The cause of hyponatremia in primary adrenocortical insufficiency is mainly a decrease in the content and concentration of sodium and chloride in ECF secondary to deficiency of glucocorticoids and mineralocorticoids.  Since sodium is the dominant osmole in ECF, these individuals must have ECF volume contraction especially in the absence of compensatory or pathologic elevation in secretion and or activity of ADH.  Several reports document elevated plasma arginine vasopressin (AVP) in Addison’s disease [6-9]. However,some investigators have found AVP levels to be normal in this condition [10-11]; symptoms and signs depend on the extent and rapidity of destruction of the adrenal cortex and may not be clinically apparent until about 90% of adrenocortical function is lost. [5]

Individuals with adrenocortical insufficiency have also been shown to have raised plasma renin activity despite replacement therapy with fludrocortisone and cortisone acetate [12]. Plasma renin concentration has been shown to be elevated in those with Addison’s disease receiving glucocorticoids and a placebo, and is reduced in a dose dependent fashion in those treated with fludrocortisone [13].  All of these observations point to a decrease in ECF volume in untreated primary adrenocortical insufficiency.

Leaf and Mamby [14] have described a female patient with Addison’s disease inadequately treated with 5 mg of deoxycorticosterone acetate who responded to an oral water load of 500 ml with a fall in plasma osmolality, a rise in urine osmolality, and a demonstrable rise in antidiuretic activity in the serum.  Clearly, the osmoregulatory mechanisms were not showing the ‘expected’ response to a decrease in plasma osmolality. In contrast, in a euvolemic individual, a water diuresis would be expected.  In the same article [14], these authors report an identical pattern in dogs depleted of 130 meq of extracellular electrolyte and volume by peritoneal dialysis so as to result in hyponatremia. These animals were then given a 300 ml water load by a stomach tube. In contrast to the hypotonic diuretic response to the 300 ml water load in the euvolemic normonatremic dog, the response observed in the hypovolemic hyponatremic dog to the same water load was a 6-7 fold lower urine flow rate, a significantly higher antidiuretic activity in serum, and urine osmolality remained twice as high as plasma osmolality. With all these observations taken together, it appears that under conditions of hypovolemia, maintenance of the amount of salt and thereby the volume of ECF is prioritized over control of osmolality of ECF.

Goldsmith et al. [15] have examined responses to oral water load of 15-20 ml/kg body weight in patients with congestive heart failure and healthy control subjects.  The decrease in urinary osmolality following water load was significantly lower in patients with congestive heart failure compared to healthy subjects, and urine remained concentrated in relation to plasma.  Following water load, plasma AVP levels in patients with congestive heart failure reduced to a much smaller extent than in control subjects.

A decrease in effective arterial blood volume (the volume of blood contained in the systemic arteries) and a decrease in atrial pressure induce release of ADH though osmolality may be normal. [16] Effective arterial blood volume is the volume of arterial blood in the systemic circulation that perfuses tissues.  It is possible that effective arterial blood volume is reduced while ECF volume is elevated. ‘Arterial underfilling’ accompanied by an increase in ECF volume is known to occur in three states: congestive heart failure with edema; cirrhosis complicated by portal hypertension and ascites; and nephrotic syndrome with edema.

There is evidence that release of ADH is regulated in part by arterial baroreceptors and low-pressure baroreceptors. When atrial pressures are raised but effective arterial blood volume and arterial blood pressure are reduced as may happen in low cardiac output heart failure, arterial baroreflex mediated stimulation of ADH release dominates low-pressure baroreceptor mediated suppression of ADH release. [17] The afferent pathways for intravascular volume mediated regulation of ADH release are the neural pathways from the arterial baroreceptors and or low-pressure baroreceptors to the nucleus of the tractus solitarius (NTS) via branches of the glossopharyngeal nerves and the vagi respectively. From the NTS, impulses reach the paraventricular nucleus via the caudal ventrolateral medulla. [3,4]  A decrease in effective arterial blood volume leads to a decrease in renal blood flow, this activates the renin-angiotensin system, [16] and angiotensin II is a stimulator of ADH release. [4]

As for comparing tolerance to deviations in hydrogen ion concentration and osmolality of ECF from normal, I do not know of a clinical situation in which both plasma osmolality and hydrogen ion concentration change in the absence of a significant change in ECF volume. The normal range of hydrogen ion concentration in arterial plasma is 35-45 nM (a variation of 12.5% either way from 40 nM), and the osmolality of normal human plasma ranges from 280 to 296 mOsm/Kg H2O, a variation of 2.5% [3], significantly smaller compared to normal variations in hydrogen ion concentration of arterial plasma.  On this basis, it may be reasonable to infer that osmolality of ECF is more rigorously controlled than the hydrogen ion concentration of ECF.

The arguments presented are summarized in a Table (available in the PDF version of this article).

It seems reasonable to infer that homeostatic mechanisms prioritize defense of ECF volume over control of either osmolality or pH of ECF; also, it is clear that effective arterial blood volume is more critically regulated than ECF volume. Teleologically, under conditions of hypovolemic hyponatremia, conservation of ECF volume by antidiuretic mechanisms or its repletion by water drinking may allow for eventual normalization of ECF osmolality by intake of salt in the diet. [14] The practical importance of this knowledge is the possibility that changes in ECF and or blood volume might underlie seemingly paradoxical changes in either osmolality and or pH of ECF in clinical conditions such as those discussed above.  It is helpful to bear this in mind since blood or ECF volume is rarely if ever measured in clinical practice, and physical signs and symptoms are not very sensitive indicators of mild hypovolemia [18].


Disclosure: the author is the editor and publisher of Medical Physiology Online.


Hyperlinks below were last accessed 26 Jul 2012

[1] Galla JH. Metabolic alkalosis. Journal of the American Society of Nephrology 2000; 369-375  [Full Text]

[2] Weitzman RE, Glatz TH and Fisher DA. The effect of hemorrhage and hypertonic saline upon plasma oxytocin and arginine vasopressin in conscious dogs. Endocrinology 1978; 103; 6: 2154-2160 [Full Text]

[3] Ganong WF. Chapter 14 – Central regulation of visceral function. In: Review of Medical Physiology, Mc Graw Hill, International Edition, 2005, pp. 242-247.

[4] Andreoli TE, Reeves WB and Bichet DG. Endocrine control of water balance. In: Comprehensive Physiology, Online ISBN: 9780470650714, Wiley Online Library, Jan 2011 [Full Text]

[5] Aron DC, Findling JW, Tyrrell JB. Glucocorticoids and adrenal androgens, Chapter 10. In: Greenspan’s Basic and Clinical Endocrinology, Gardner DG and Shoback D (editors), Lange – Mc Graw Hill, 2007.

[6] Laczi F, Janáky T, Iványi T, Julesz J and László FA. Osmoregulation of arginine-8-vasopressin secretion in primary hypothyroidism and in Addison’s disease Acta Endocrinol 1987; 114: 389-395 [Full Text]

[7] Ahmed ABJ, George BC, Gonzalez-Auvert C, Dingman JF. Increased plasma arginine vasopressin in clinical adrenocortical insufficiency and its inhibition by glucosteroids. Journal of Clinical Investigation 1967; 46: 111-123 [Full Text]

[8] Kamoi K, Tamura T, Tanaka K, Ishibashi M, Yamaji T. Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency. Journal of Clinical Endocrinology and Metabolism. 1993; 77: 1584-8. [Full Text]

[9] O’Rahilly S. Secretion of antidiuretic hormone in hyponatraemia: not always “inappropriate”. British Medical Journal 1985; 290: 1803–1804.  [Full Text]

[10] Grenbäck E, Hulting AL, Bucht E, Petersson M. Plasma galanin, vasopressin, and oxytocin in patients with Addison’s disease. Horm Metab Res. 2007; 39: 589-95 [Full Text]

[11] Wittert GA, Livesey JH, Florkowski C, Or HK, Donald RA, Espiner EA. Acutely raised corticotropin levels in Addison’s disease are not associated with increased plasma arginine vasopressin and corticotropin-releasing factor concentrations in peripheral plasma. Journal of Clinical Endocrinology and Metabolism. 1993; 76: 192 196. [Full Text]

[12] Jadoul M, Ferrant A, De Plaen JF, Crabbe J. Mineralocorticoids in the management of adrenocortical insufficiency. Journal of Endocrinologic Investigations 1991; 14: 87-91 [Full Text]

[13] Cohen N, Gilbert R, Wirth A, Casley D and Jerums G. Atrial natriuretic peptide and plasma renin levels in assessment of mineralocorticoid replacement in Addison’s disease. The Journal of Clinical Endocrinology & Metabolism 1996; 81: 1411-1415 [Full Text]

[14] Leaf A and Mamby AR. An antidiuretic mechanism not regulated by extracellular fluid tonicity. Journal of Clinical Investigation 1952; 31: 60-71 [Full Text]

[15] Goldsmith SR, Francis GS, and Cowley AW. Arginine vasopressin and the renal response to water loading in congestive heart failure. American Journal of Cardiology 1986; 58: 295-299 [Full Text]

[16] Schrier R. Decreased effective blood volume in edematous disorders: what does this mean?  Journal of the American Society of Nephrology 2007; 18: 2028-2031 [Full Text]

[17] Shen YT, Cowley AW Jr, and Vatner SF. Relative roles of cardiac and arterial baroreceptors in vasopressin regulation during hemorrhage in conscious dogs. Circulation Research 1991; 68: 1422-1436 [Full Text]

[18] McGee S, Abernethy WB 3rd, Simel DL. The rational clinical examination. Is this patient hypovolemic? Journal of the American Medical Association 1999; 281: 1022-9. [Full Text]


Peer Reviewers:

Balint Kacsoh, MD, PhD, Professor of Histology and Cell Biology, Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA, USA. E-mail: kacsoh_b at mercer dot edu

Warren Thomas, PhD,Biomedical Research Lecturer, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. E-mail: wthomas at rcsi dot ie

Editor: Peer review of this manuscript was supervised by guest editor Madanmohan, MBBS, MD, D.Sc, Department of Physiology, Mahatma Gandhi Medical College and Research Institute, Puducherry, India. E-mail: drmadanmohan999 at rediffmail dot com

The reviewers and the editor disclose no conflict of interests related to this submission.

Please cite this article as: Prakash ES. Which one of these variables is most critically regulated: extracellular fluid (ECF) volume or ECF osmolality or ECF pH or effective arterial blood volume? Medical Physiology Online 2012; published Jul 27 2012. Available from  (page numbers are not for citation purposes)

Prepublication Record: The Prepublication record containing the original version of the manuscript, reviewers comments, editor’s comments, the authors’ response can be accessed at

License: This is an open access article distributed under the terms of the Creative Commons Attribution License  which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited.

Written by Elapulli S. Prakash

July 27, 2012 at 1:51 PM

Posted in Uncategorized

The Cause of Infantile Hypertrophic Pyloric Stenosis: one man’s journey.

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The Cause of Infantile Hypertrophic Pyloric Stenosis: one man’s journey.

Ian M. Rogers FRCS, FRCP, PGCME (Dundee),

Visiting Professor of Surgery, AIMST University Faculty of Medicine,

08100 Bedong, Kedah, Malaysia. E-mail: irogers2000 at hotmail dot com

Submitted Dec 20, 2011; accepted Jan 19 2012; published Feb 25 2012

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It is an adage oft repeated and certainly true. Listen to the patient; he is telling you the diagnosis. So must it be with the cause of infantile hypertrophic pyloric stenosis (IHPS).  The infant is certainly very generous with his clues. The presentation at 3 weeks of age, the 5/1 male predominance, the natural cure with time with temporary medical treatment, the strong familial tendency, the complete disappearance of the tumor after simply dividing the hypertrophied sphincter, the persistence of the tumor in the thriving baby after gastroenterostomy, [1] and the repeated observation of primogeniture all should combine to make the process easy. Many medical and surgical detectives have no doubt pondered the problem and yet the cause remains completely unknown.

In the beginning, in this, the most common cause of neonatal upper GI obstruction, pylorospasm and indeed work hypertrophy was the favored explanation. [2] This theory silently lapsed presumably for want of corroborative data.  37 years ago as a young surgical trainee, I came across the 1941 paper by Miller in which he documented the phenomenon of neonatal hyperacidity. He reported that the immediate post-partum gastric neutrality became quickly hyperacid after a few hours and remained so for several days. Miller proposed the trans-placental passage of a gastric secretagogue as an explanation, 10 years before the discovery of gastrin. [3]

Our attempts to prove gastrin transfer as a cause, while non-confirmatory, showed for the first time that fasting gastrin levels rise from birth to very high levels at 4 days of life. [4] Rising gastrin at a time of rising acidity strongly suggests that gastrin is the cause of the acidity. [5] The entry of acid into the duodenum is well known to be a potent stimulus to pyloric sphincter contraction in adults. The most potent cause of pyloric muscle contraction in dogs is the entry of acid into the duodenum. [6,7] When gastrin 11 is given intravenously to adults, the first consequence is pyloric delay, presumably from pyloric contraction. [8] In adults with hyperacid disease, the early symptom of post-prandial bloating (pyloric delay), is quickly relieved when acid secretion is abolished by timely antacid therapy.  Indeed, selected cases of pyloric stenosis in adults may be successfully managed by antacid therapy. [9]

Milk feeds accumulating behind a closed sphincter would stimulate further gastrin secretion by combining temporary alkalinity with antral distension. [5] Such an acid-producing positive feedback would lead to repeated sphincter contraction, work hypertrophy and IHPS. Pyloric stenosis artificially induced in rats has also been shown to be a potent trophic stimulus to gastric (and parietal cell) hyperplasia with associated hyperacidity. [10, 11]

This early gastrin theory was investigated by measuring fasting gastrin levels in babies with IHPS and matching controls. We established that fasting gastrin levels were statistically no different in the babies with IHPS [12] while basal acid secretion was greatly increased. [13] The hypersecretion of acid in IHPS has been confirmed using histamine stimulated acid studies both before and, most importantly, 1 week after pyloromyotomy. [14]

Soon after these papers were published, the papers of Professor John Dodge came to light. He had been able to produce pyloric stenosis in new-born puppy dogs by giving injections of pentagastrin to their mothers before birth. More than 60% of puppies were affected and 16% were found at post mortem examination to have superficial pyloric ulceration. [15] Even more puppies were affected if pentagastrin was continued after birth. An explicit interpretation was not given but pentagastrin-induced acid secretion in the puppy appears the most likely cause particularly since it is known that gastrin crosses the mammalian placenta. [16]

Personal career considerations then intervened and I rejoined my pilgrimage many years later and revisited the problem anew. The following persistent questions all prompted by the clinical features, still remained unanswered.

  1. What makes some babies develop IHPS when normal babies do not?
  2. Why does IHPS occur more frequently in male babies?
  3. How does self-cure occur with the passage of time?
  4. Why is IHPS more frequent in the first born?
  5. How does pyloromyotomy, and not gastro-enterostomy, cause the tumor to disappear? [1]

The only certain observed abnormality up till this time was hyperacidity. What if an inherited primary hyperacidity, that is acidity at the top of the normal distribution curve, were the primary cause? Indeed, when viewed from the perspective of a primary hyperacidity, the answers suddenly came thick and fast.

For example one need no longer ponder on the relatively normal fasting gastrin levels. Indeed if negative feedback control of gastrin release by hydrochloric acid is functioning at this age and this is by no means certain, gastrin level should be lower in IHPS. Their normality would be consistent with a relatively insensitivity of this feedback mechanism at this age (vide infra).  Any baby in the pyloric age group who persistently vomits and who is alkalotic is invariably found to have IHPS. [17] The obvious implication is that babies with IHPS are hypersecretors of acid.

Adults who have had IHPS have been shown repeatedly to suffer from the adult consequences of hyperacidity such as duodenal ulcer with high volume acid secretion and are subjected more often to peptic ulcer surgery. [18]

Such hyperacid babies would provoke the cycle of sphincter work hypertrophy earlier and more persistently, and progress to a self-sustaining work hypertrophy. The presence of normal fasting gastrins would be expected. Such babies would be genetically selected and the condition would consequently be familial. Normal babies would have insufficient acid to trigger the process. The importance of a functioning sphincter and work hypertrophy, is clearly integral to the cause. Divide the sphincter – the tumour disappears. Bypass it and it remains. Work hypertrophy is also supported by the erythromycin phenomenon; a 7-fold increase in the incidence of IHPS has been reported among newborn infants who received erythromycin in antibiotic doses for post-exposure pertussis prophylaxis. [19]

Erythromycin, a macrolide antibiotic, specifically increases antral motility [20] and contraction of the pyloric bulb [21, 22] by binding to motilin receptors. These receptors not only exist in cholinergic nerves but also are thought to exist directly on smooth muscle. The strongest antral contractions induced by large doses of erythromycin are not blocked by atropine and direct muscle stimulation is likely. [23] Indeed the authors of the pertussis report [19] specifically speculate that that the marked gastric motility leads to (work) hypertrophy of the pylorus.

The gastrointestinal hormone motilin is responsible for the mass emptying movements of the stomach. It is classically secreted from the duodenal mucosa when the duodenum is empty or alkalinized. [24-27] The voltage-tension curves for the antral-pyloric region coupled with the narrow pyloric diameter mean that the interdigestive phase 11 first contractions will regularly encounter a closed pylorus consistent with sieving function of phase 2 contractions. [26]

Further enquiries have shown that duodenal pH does not influence endogenous motilin release if the pH is between 2 and 8.5, [26] a range well within the pH range in IHPS. [12] Nutrients in the duodenal cap strongly suppress the typical pulsed interdigestive motilin release, [27] and there is one report of acid in the duodenum stimulating motilin release  [28]

Hence the empty duodenum in IHPS may provide a means whereby motilin maintains the stimulus for pyloric sphincter contraction. Studies in adults with an active duodenal ulcer (and presumed hyperacidity) have shown that Phase 2 gastric contractions, rhythmic and phase-locked but not expulsive, occur in the interdigestive phase. Phase 3 expulsive contractions which empty the stomach require acid-blocking drugs to alkalinize the antral contents. [25, 29]

Antral contractions in the fed state also increasingly meet with a closed pylorus as the condition develops, a scene well known to those who have felt the contracting tumor in the classical test feed.  It is of further interest to record that plasma levels of motilin rise steeply after birth in normal infants reaching levels greater than those in fasting adults by day 24 and that the post-natal increase in motilin and gastrin require that the infant be fed. [30]

The one report of motilin levels in IHPS records low levels, [31] and further corroborative analyses are clearly required. An analysis of the motilin (MLN) gene has compared normal controls with babies with IHPS and no mutations or differences have been detected. [32] The repeated finding of a tenfold increase in IHPS in babies with esophageal atresia [33] may reflect an early exposure to maternal gastrin-induced acidity which would be undiluted and unbuffered by amniotic fluid. The subsequent delayed postnatal introduction of milk feeds would complete the pathogenetic process.

1. A recent decline in the incidence of IHPS that parallels the decline of sudden infant death syndrome (SIDS) has been observed in Sweden, coinciding with the implementation of the Back to Sleep Campaign. [34] Gastric emptying is likely to be increased in the supine position compared to the prone position since duodenal emptying in the prone position requires nutrients to move against gravity. The reduced incidence of IHPS in babies sleeping on their backs has a physiological basis, and may tip the balance to self-cure with time.

2. The male predominance is also explained. The male / female ratio of 5-6: 1 continues to be reported [35] and parallels gender differences in incidence of duodenal ulcer in adult males, a condition known to depend on hyperacidity. Preterm male babies have been clearly shown to have more acid than matched females [36]. This report published in 1959 remains unchallenged and ethical considerations may prevent further nasogastric studies in normally fed term babies.

3. Important analyses of the relationship between neonatal gastrin and acid secretion in normal babies provide a credible explanation of the phenomenon of self-cure. Sequential studies of fasting and post-prandial gastrin were performed up to 6 weeks of life in normally developing infants. When fasting gastrin level is high at around 60 hours of age, there is no postprandial gastrin response. At around 3 weeks of age, fasting gastrin level is a little lower and a post-prandial gastrin response can be detected. [37]. The authors explain these findings on the basis of a relative insensitivity of the negative feedback relationship between circulating gastrin and gastric acid in the first few weeks of life. By this they mean that it has not matured sufficiently to respond inversely to antral acidity.

Hence, between birth and 3 weeks, the normal baby exhibits some of the biochemical findings of a temporary Zollinger-Ellison syndrome (ZES). [38] Gastrin is being maximally secreted commensurate with development and cannot be further increased by food. This phenomenon is the presumed explanation for peak acidity in normal development at between 10-17 days reported and graphically outlined by Agunod. [39] Hence the baby inheriting hyperacidity is especially liable to trigger IHPS within the first few weeks of life. These infants essentially have a mini ZE syndrome with a hyperacidity unfettered by an adequate negative gastrin feedback.  Left untreated, the condition usually leads to a fatal outcome. Pyloromyotomy will provide a quick long-lasting cure by stopping work hypertrophy and allowing acidity to be naturally expelled by peristalsis.

Temporary medical treatment using atropine and gastric wash-outs will reduce acid secretion and antral distension and will allow time for a natural self-cure when a normal mature feedback is established. The natural widening of the lumen with age combined with gastrin control will allow medical treatment to be safely stopped.

4. The first born child is fed by a first-time mother. Babies that vomit, especially babies with IHPS, are typically hungry and vigorous babies. The inexperienced mother is more likely to continue to feed the baby who vomits and the stomach will be seldom allowed to be empty. Hence the process of feed-promoted acid-induced work hypertrophy would continue. A more experienced mother is likely to give the stomach a rest.  The work of Jacoby is of particular interest in this matter. Although a pediatrician, he treated IHPS both surgically and medically. A similar mortality of 1% in 100 surgical and 100 medically treated babies was reported. Great stress was put on the need for relative under nutrition as part of the well controlled titrated atropine therapy in the medically treated group. [40] The very low reported incidence of IHPS in underdeveloped countries such as Africa and Asia [41] may reflect infrequent overfeeding either from poor maternal nutrition of from a different pattern of infant feeding such as an infrequent desire to feed the vomiting baby.

5. Pyloromyotomy renders the sphincter incompetent and widens the lumen. Hence further contraction and work hypertrophy is impossible and the tumor quickly disappears. Gastroenterostomy, the earliest surgical treatment, only bypasses the obstruction. The pathogenetic processes are only partially abolished. Hence it is easy to understand why the tumor has been shown to be still present 40 years after gastroenterostomy. [1]

Other contemporary lines of enquiry:

Recent genetic analyses set up to explore the possibility of a monogenic association have simply confirmed that heterogeneous genetic inheritance is the norm. [41, 42] The concordance rate in monozygotic twins while greater than that in dizygotes, is still only between 0.25 and 0.44. [43] The basic consensus is that IHPS remains a condition which is multigenic and multifactorial- the likely acceptable pathway for the inheritance of constitutional hyperacidity. [44]

The reported abnormalities within the tumor  of various growth factors as well as deficiencies of nitric oxide synthetase, although theoretically attractive, do not stand up to critical analysis. [45] First, for obvious reasons, adequate control specimens are not possible.  Second, the reported accumulation of growth factors in the tumor tissue is no more than one would expect from a work-hypertrophied sphincter. When a repeatedly contracting muscle or a muscle subjected to an increasing load becomes hypertrophic, it does so through the agency of locally attracted growth factors. [46-48] There is no evidence to support genetically controlled inappropriate accumulation of growth factors as a primary process.

Third, as with the genetic studies, there is no attempt to relate genetic abnormalities to the dynamic clinical features.  The search for a necessary time-sensitive environmental precipitant in pathogenesis has led to speculation about self-limiting infection. Throat swab analysis of the common nasopharyngeal viruses has shown no greater frequency in pyloric babies compared to normal matched controls. [49] Helicobacter pylori (H. pylori), the important gastric pathogen and known stimulant of gastric acid secretion has also been investigated. [50]

H. pylori is known to be present in some babies from 6 months in age. In a 5 year follow-up study of mother and child random amplified polymorphic DNA fingerprinting has revealed that mother to baby transmission does occur. [51]

In another study prompted by an index case suspicion of H. pylori organisms on histology, 16 consecutive babies with IHPS underwent gastric biopsy preoperatively. All the urease tests were negative, 4 cases had chronic gastritis, 6 had a mild gastritis and 5 were normal. No H. pylori were discovered on histology. [52] At the age of pyloric presentation immunological tests for H. pylori are unreliable since maternal transmitted immunity may last up to 6 months.

A further study using stool culture for H. pylori in 39 consecutive babies with IHPS failed to discover a single case. Control babies were also negative. [53]

Curiously the major consequence of H. pylori infection in adults- namely hyperacidity – is not mentioned as a possible link between infection and the development of IHPS in any of the cited papers. In the absence of a known cause the gastritis recorded on biopsy presumably would simply be a consequence of prolonged gastric stasis. There is consequently no evidence at present to support an infectious cause.


So there it is. My journey is almost complete. Constitutional hyperacidity at the right time in development begets pyloric spasm which begets work hypertrophy which begets IHPS. We are almost back where we began so many years ago when Thompson [2] first proposed pylorospasm and work hypertrophy as the cause. This theory is perfectly testable.  Babies with IHPS lose lots of acid when they vomit. The associated alkalosis may cause problems with anesthesia by reducing respiratory drive. An adult similarly affected would be appropriately treated with the currently super-effective acid-blocking drugs with an immediate reduction in fluid, acid and potassium loss. Such a preoperative strategy with babies with IHPS is long overdue. It should not come as a surprise if we find that such temporary treatment promotes a lasting cure.

Acknowledgements: I would like to record my thanks to several fellow travelers who have helped me along the way. Firstly, the late John Grant, FRCS, Consultant & Paediatric Surgeon, and Professor Harold Ellis, Emeritus Professor of Surgery, Westminster Hospital, London, UK.

Conflict of interests: none disclosed.


  1. Dickinson SJ, Brant EE. Congenital pyloric stenosis. Roentgen findings 52 years after gastroenterostomy. Surgery 1967; 62: 1092-94.
  2. Thomson J. Observations on congenital hypertrophy of the pylorus. Edinburgh Medical Journal.1921; 26: 1-20.
  3. Miller RA. Observations on the gastric acidity during the first month of life. Archives of Disease in Childhood 1941; 16: 22-30.
  4. Rogers IM, Davidson DC, Lawrence J, et al. Neonatal secretion of gastrin and glucagon. Archives of Disease in Childhood 1974; 49: 796-801.
  5. Waldum HI, Fossmark R, Bakke I, Martinsen C, Qvigstad G. Hypergastrinaemia in animals and man: causes and consequences. Scandinavian Journal of Gastroenterology 2004; 39:505-509.
  6. Cook AR. Duodenal acidification: Role of the first part of the duodenum in gastric emptying and secretion in dogs. Gastroenterology 1974; 67: 85-92.
  7. Fisher RS, Lipshutz W, Cohen S. The hormonal regulation of the pyloric sphincter function. The Journal of Clinical Investigation 1973; 52:1289-1296.
  8. Hunt JN, Ramsbottom N. Effect of gastrin 11 on gastric emptying and secretion during a test meal. British Medical Journal 1967; 4: 386-390.
  9. Talbot D. Treatment of adult pyloric stenosis: a pharmacological alternative? British Journal of Clinical Practice 1993; 47: 220-221
  10. Crean GP, Hogg DF, Rumsey RD. Hyperplasia of the gastric mucosa produced by duodenal obstruction. Gastroenterology 1969; 56:193-199.
  11. Omura N, Kashiwagi H, Aoki T. Changes in gastric hormones associated with gastric outlet obstruction. An experimental study in rats. Scandinavian Journal of Gastroenterology 1993; 28:59-62.
  12. Rogers IM, Drainer IK, Moore MR and Buchanan KD. Plasma gastrin in congenital hypertrophic pyloric stenosis. A hypothesis disproved? Archives of Disease in Childhood 1975, 50: 467-471.
  13. Rogers IM, Drainer IK, Dougal AJ, Black J and Logan R.  Serum cholecystokinin, basal acid secretion and infantile hypertrophic pyloric stenosis. Archives of Diseases in Childhood 1979; 54: 773-75
  14. Heine W, Grager B, Litzenberger M, Drescher U. Results of Lambling gastric juice analysis in infants with spastic hypertrophic pyloric stenosis. Pädiatrie und Pädologie 1986; 21: 119–125 [Article in German] abstract at
  15. Dodge JA, Karim AA. Induction of pyloric hypertrophy by pentagastrin. Gut 1976; 17: 280-284.
  16. Bruckner WL, Snow H, Fonkalsrud EW. Gastric secretion in the canine foetus following maternal stimulation: experimental studies on placental transfer of insulin, histamine and gastrin. Surgery 1970; 67: 360-363.
  17. Maizels M. Alkalosis in the vomiting of infancy. Archives of Diseases in Childhood 1931; 1: 293-302.
  18. Wanscher B, Jensen HE. Late follow-up studies after operation for congenital pyloric stenosis. Scandinavian Journal of Gastroenterology1971; 6: 597-9.
  19. SanFilippo A. Infantile hypertrophic pyloric stenosis related to the ingestion of erythromycin estolate: A report of five cases. Journal of Pediatric Surgery 1976; 11: 177-180.
  20. Honein MA, Paulozzi LJ, Himelright IM et al.  Infantile pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. Lancet 1999: 354: 2101-2106.
  21. Di Lorenzo C, Flores AF, Tomomamas T, Hyman PE. Effect of erythromycin on antroduodenal motility in children with chronic functional gastrointestinal symptoms.  Digestive Diseases and Sciences 1994; 39:1399-1404
  22. Boiron M, Dorval E, Metman EH et al. Erythromycin elicits opposite effects on antro-bulbar and duodenal motility: analysis in diabetics by cineradiography. Archives of Physiology and Biochemistry 1997;105: 591-595
  23. Coulie B, Tack J, Petters T, Janssens J. Involvement of two different pathways to the motor effects of erythromycin on the gastric antrum in humans. Gut 1998; 43: 395-400.
  24. Brown JC, Johnson CP, Magee DF. Effect of duodenal alkalinisation on gastric motility. Gastroenterology 1966; 50: 333-339.
  25. Kusano M, Sekiguchi T, Nishioki T et al. Gastric acid inhibits antral phase III activity in duodenal ulcer patients. Digestive Diseases and Sciences 1993; 38:824-831.
  26. Itoh Z. Motilin and clinical application. Peptides. 1997; 18:593-608
  27. Mori K, Seino Y, Yanaihara N et al. Role of the duodenum in motilin release. Regulatory Peptides 1981; 1: 271-277.
  28. Mitznegg P, Domschke W, Wunsch E et al. Release of motilin after duodenal acidification. Lancet 1976; 11: 888-889.
  29. Segikuchi T, Kusano M, Nishioki T et al. gastroduodenal motor dysfunction and plasma motilin concentration in patients with duodenal ulcers. In Itoh Z. Ed. Motilin. San Diego: Academic Press. 1990; 226-245.
  30. Lucas A, Adrian TE, Christofides N et al. Plasma motilin, gastrin and enteroglucagon and feeding in the newborn. Archives of Diseases in Childhood. 1980; 55, 673-677.
  31. Christofides ND, Mallet E, Bloom SR. Plasma motilin in infantile hypertrophic pyloric stenosis. Biomedical Research 1982; 3: 571-572
  32. Svenningson A, Lagenstrad K, Omrani MD, Nordenskjold K. Absence of motilin gene mutations in infantile hypertrophic pyloric stenosis. Journal of Pediatric Surgery 2008; 43: 443-446.
  33. Vilarino A, Costa E, Ruiz S. Association of oesophageal atresia and hypertrophy of pyloric stenosis. Cirugua Espanola 1977: 31; 239-241.
  34. Persson S, Ekbom A, Granath F, Nordenskjold A. Parallel incidence of sudden infant death syndrome and infantile hypertrophic pyloric stenosis: a common cause? Pediatrics 2001; 108. E70.
  35. El-Gohary Y, Yeap BH, Hempel G, Gillick J. A nine-year single centre experience with circumumbilical Ramstedt’s pyloromyotomy. European Journal of Pediatric Surgery 2010; 20:387-390.
  36. Ames MD. Gastric acidity in the first 10 days of life of the prematurely born baby. American Journal of Diseases of Children 1959; 2: 1123-1126
  37. Rodgers BM, Dix PM, Talbert JL et al. Fasting and postprandial serum gastrin in normal human neonates. Journal of Pediatric Surgery 1978; 13, 13-16.
  38. Zollinger RM, Ellison EH.  Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Annals of Surgery 142 (4): 709–23.
  39. Agunod M. Correlative study of hydrochloric acid, pepsin and intrinsic factor secretion in newborns and infants. American Journal of Digestive Diseases 1969; 14: 400-13.
  40. Jacoby NM. Pyloric stenosis. Selective medical and surgical treatment. Lancet 1962; 119-121
  41. Joseph TP, Nair RR. Congenital hypertrophic pyloric stenosis. Indian Journal of Surgery 1974; 36: 221-223.
  42. Chung E, Curtis D, Chen G, Marsden PA, Twells R, Xu W, and Gardiner M. Genetic evidence for the neuronal nitric oxide synthetase gene (NOS1) as a susceptibility locus for infantile hypertrophic pyloric stenosis. American Journal of Human Genetics 1996; 58: 363-370.
  43. Everett KV, Chiosa BA, Georgouls C et al. Genome-wide high density SNP-based linkage analysis of infantile hypertrophic pyloric stenosis identifies loci on chromosomes 11q14-q22 and Xq23. American Journal of Human Genetics 2008; 82:756-762
  44. Schechter R, Torfs CP, Bateson TF. The epidemiology of infantile hypertrophic pyloric stenosis. Paediatric and Perinatal Epidemiology 1997; 11: 407-427.
  45. Carter CO. The inheritance of congenital pyloric stenosis. British Medical Bulletin 1961; 17: 251-254
  46. Piotrowska A P, Soali V, Puri P. Distribution of heme oxygenase 2 in nerves and interstitial cells of Cajal in the normal pylorus and in infantile hypertrophic pyloric stenosis. Archives of Pathology and Laboratory Medicine. 2003; 127: 1182-1186.
  47. Fath KA, Alexander RW, Delafontaine P. Abdominal coarctation increases insulin-like growth factor I mRNA levels in rat aorta. Circulation Research 1993; 72: 271-277.
  48. Hannson HA, Jenmache E, Shottner A. IGF-I expression in blood level varies with vascular load. Acta Physiologica Scandinavica 1987; 129: 165-169.
  49. Mcheik JN, Dichamp I, Levard G et al. Infantile hypertrophic pyloric stenosis: Are viruses involved? Journal of Medical Virology 2010; 12: 2087-2091.
  50. Dahshan A, Donovan KG, Halabi IM et al. Helicobacter Pylori and infantile hypertrophic pyloric stenosis. Is there a possible relationship? Journal of Pediatric Gastroenterology and Nutrition 2006; 42: 262-264.
  51. Konno M, Fuji N, Yokota S et al. Five-year follow-up study of mother-to-child transmission of Helicobacter pylori infection detected by a random amplified polymorphic DNA fingerprinting Method.  Journal of Clinical Microbiology 2005; 43: 2246-2250.
  52. Paulozzi LJ. Is Helicobacter pylori a cause of infantile hypertrophic pyloric stenosis? Medical Hypothesis 2000; 55:119-125.
  53. Sherwood W, Choudhry M, Lakhoo K. Infantile hypertrophic pyloric stenosis: an infectious cause. Paediatric Surgery International 2007; 1: 61-63.

Reviewers: The original submitted version was reviewed by Dr Yousuf El-Gohary, MA, BCh, BAO, MRCS, Pediatric Surgical Research Fellow, Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA. E-mail: gohary77 at yahoo dot com; and Dr Russell S. Kirby, PhD, MS, FACE, Department of Community and Family Health College of Public Health, University of South Florida, Tampa, Florida, USA E-mail: rkirby at health dot usf dot edu  The revised version was accepted by editor E.S.Prakash. The reviewers and the editor disclose no conflict of interests related to this submission.

Please cite this article as: Rogers IM. The cause of infantile hypertrophic pyloric stenosis: one man’s journey. Medical Physiology Online 2012; Feb 25 2012, available from

License: This is an open access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited.

Written by Elapulli S. Prakash

February 25, 2012 at 11:45 PM

Posted in Uncategorized

Effectiveness of Blended Instruction utilizing On-Line Lectures and Split Classes in delivering in an Applied Exercise Physiology Course

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Teaching and Learning Medical Physiology

Effectiveness of Blended Instruction utilizing On-Line Lectures and Split Classes in delivering an Applied Exercise Physiology Course

James W. Navalta1, T. Scott Lyons1, Guilherme B. Pereira2, Scott W. Arnett1, Mark A. Schafer1, F. Travis Esslinger1 and Gina L. Sobrero1

1Exercise Science Program, Department of Kinesiology, Recreation, and Sport, Western Kentucky University, Bowling Green, Kentucky, USA; 2Physiological Sciences Department, Exercise Physiology Laboratory, Federal University of São Carlos, São Paulo, Brazil

Correspondence to Dr James W. Navalta, Department of Kinesiology, Recreation, and Sport, Western Kentucky University, 1906 College Hts Blvd #11089, Bowling Green, KY, 42101-1089.  E-mail: james dot navalta at wku dot edu  [replace dot with . and at with @]

Submitted 18 Nov 2011; first decision 25 Dec 2011; revision received 12 Jan 2012; accepted 13 Jan 2012

Download Full Text (with Table & Figure) as PDF


Background: To align with shifting institutional priorities, and to establish more time in the laboratory pursuing scholarly research, numbers of students in classes were doubled but courses were taught less frequently. While having less impact on lecture-based courses, this affected laboratory-based classes to a significant extent from a logistical standpoint. Therefore, the purpose of this investigation was to assess a large blended learning environment course compared to a smaller face-to-face class.

Hypothesis: It was hypothesized that a large blended learning class in Applied Exercise Physiology would be just as effective as a smaller traditional face-to-face course.

Methods: Data was collected from two Applied Exercise Physiology courses, one employing traditional face-to-face instruction, and the other blending on-line lectures with split laboratory experiences. Laboratory write-ups, examinations, and a group project were converted to standard z-scores and compared between classes. Significance was accepted at the P ≤ 0.05 alpha level.

Results: Classes were statistically similar in terms of write-up assignments (P = 0.60), examinations (P = 0.72), and final group projects (P = 0.99).

Conclusions: Despite students not attending roughly half of the face-to-face classes compared to the traditional instructional method, the students in the blended learning environment performed just as well on laboratory write-ups, examinations, and the Applied Exercise Physiology final project. Based on these findings, blended instruction can be an effective mode for disseminating course information in a large laboratory-based class.

Abbreviations used: EXS – Exercise Science; N – number of students

The Exercise Science program in the Kinesiology, Recreation, and Sport Department at Western Kentucky University recently underwent a paradigm shift regarding course loads and teaching equivalencies. Previous to 2009, class sizes were capped at 30 students and courses within the major were taught frequently (usually each semester, and during winter or summer sessions at times). As the university wishes to shift from a regional comprehensive institution to one with a national / international presence, the role of scholarly research has been emphasized. Therefore, to align itself with the direction of the university, and to carve out more time in the laboratory pursuing scholarly research, the Exercise Science faculty opted to teach courses with double the student number (60) but less frequently (only once per year, in a set Fall / Spring rotation).

The Applied Exercise Physiology class is by nature a laboratory-intensive course. Students complete six specific laboratory experiences [1] during the beginning two-thirds of the semester including:

  • anaerobic exercise (Wingate anaerobic cycle test, maximal vertical displacement, maximal horizontal displacement)
  • submaximal aerobic activity (Åstrand cycle test, Forestry step test, aerobic run/walk test)
  • maximal oxygen consumption (Bruce treadmill protocol and open spirometry)
  • lung volume and ventilation (determination of Ventilatory Threshold via modified V-slope, ventilatory equivalent, and excess carbon dioxide methods)
  • range of motion (lower body flexibility via traditional sit-and-reach box, YMCA sit-and-reach test, V-sit sit-and-reach test, and wall sit-and-reach tests)
  • body composition (skinfolds, girth measurements, and Body Mass Index)

Throughout the semester, laboratories are incorporated to teach components of an effective scientific write-up (i.e. Introduction, Methods, Results, and Discussion sections). During the last third of the semester, students complete a mini-study using the laboratory techniques gained through the course, and culminate with a simulated research conference in which their work is presented to their peers in both poster and oral format.

To overcome the logistical complications of having approximately sixty students in the laboratory all trying to complete experiences, this past year we utilized on-line video lectures to relay information such as laboratory protocols, computations, and to demonstrate procedures. Because this instruction was delivered through a web-based format, it allowed us to effectively split the class, where half of the students attended lab on the first day and the remaining students completed the laboratory experience on the second day. Thus, we utilized a “blended learning” model with in-class and on-line components [2]. The purpose of this investigation was to assess a large blended learning environment course with both on-line and in-class components compared to a smaller face-to-face class in which students received all instruction in class and attended laboratory experiences each day.

Methods: Data was collected from two Applied Exercise Physiology courses (EXS 325) taught at Western Kentucky University and approved by the Institutional Review board (IRB 12-130). The first class (N=31 students) was offered during 2009 and the traditional method of face-to-face instruction was provided, with students responsible for attending class each day. This class met twice per week throughout a 14 week semester, for a total of 2240 contact minutes (see Table 1, page 4 in the PDF version). For the laboratory experiences, these students had 560 minutes of hands-on learning (Table 1). The second class (N=58 students) was offered during 2010 utilizing on-line Tegrity lectures for delivering instruction and split laboratory experiences  (i.e. 29 students attended lab on Tuesday, and the remaining 29 students completed the same laboratory experience on Thursday). Tegrity (Mc-Graw-Hill Higher Education, Santa Clara, CA, USA) is a lecture-capture software system that can be integrated into and delivered via the Blackboard course management system (Blackboard Inc., Washington, D.C., USA). Given this, students met face-to-face with the instructor once a week through the 14 week semester for 1360 contact minutes, and had 560 minutes of hands-on learning dedicated to laboratory experiences (refer to Table 1). Students were expected to have watched the on-line video lectures and completed assigned homework available through the Blackboard delivery portal prior to their scheduled laboratory day (i.e. on the day in which they were not in class). Each individual was assigned into a laboratory group (with 5-6 students per group), and six groups attended on their assigned lab day. To further alleviate logistical concerns, two graduate assistants were responsible for the facilitation of three laboratory groups each and assisted students through a rotation of laboratory experiences. For example, a student completing the anaerobic capacity laboratory would collect data for the 40-yard dash, then rotate to the vertical jump, and finish the rotation with the Wingate anaerobic cycle test (while being instructed to utilize downtime between stations to complete power output calculations).

For comparison, similar assessment elements from each class were evaluated. Specifically, four laboratory write-ups (representing an Introduction, Methods, Results, and Discussion), two examinations, and the final group project were included in our data analysis. The actual course content was the same between both semesters, the grading rubrics for assessment were the same each semester, and the same instructor graded the laboratory write-ups, evaluated the group projects, and scored the exams. As points for exams differed between classes, we chose to convert raw scores for each student into a standardized z-score, similar to the investigation on blended learning by Ginns [3]. The z-score was calculated as follows: [the raw student score minus the mean score for the class] divided by the standard deviation. The combination of the four individual write-up z-scores was summed so that a single value represented the variable (i.e. a write-up standard score), the combination of two individual examination z-scores was added to denote the score for exams, and these were both added to the z-score representing the final project to give an overall class standardized score (write-up + exam + final project = overall).

Statistical analysis: Differences between classes in the four areas (write-up, exams, final project, and overall) were determined using independent samples t-tests assuming equal variance. Significance was accepted at the P ≤ 0.05 alpha level.

Results: No differences were observed in any of the areas assessed. Classes were statistically similar in terms of write-up assignments (F = 0.28, P = 0.60), examinations (F = 0.13, P = 0.72), final group projects (F = 0.00, P = 0.99), and an overall combination of these areas (F = 0.25, P = 0.62). Variations in standardized scores of individual students for each area are displayed in Figure 1. (see the PDF)


The purpose of this investigation was to evaluate the impact of a blended learning arrangement utilizing on-line lectures to replace in-class instruction, and splitting class laboratory sessions in a large laboratory-focused course. Our findings show that students performed similarly in terms of laboratory write-ups, examinations, and during the completion of group culminating projects. No differences were observed, despite students not attending roughly half of the face-to-face classes compared to the traditional instructional method. This finding is similar to an investigation performed at Central Florida University, where student success rate increased despite face-to-face meeting time being reduced by 66% [4].

While so-called “blended learning” has generated much research [2, 3, 5-9], the broadness of the term has naturally led to some confusion regarding how this type of instruction is to be carried out. In fact, one author has argued against the term [10], proposing that instructors in higher education already employ a blended style of content instruction. In the context of the current investigation, blended learning included a mixture of on-line lectures focused on instructional content, and face-to-face meetings in which hands-on laboratory experiences were completed. Given that the didactical design of blended classes must be tailored toward the focus of each specific discipline [7], it is difficult to compare results from the scientific literature in this area. Nevertheless, Boyle et al. [5] found that a blended learning arrangement increased the pass rates of computer programming undergraduate (by 15-23%) and graduate students (12%). In the present investigation, while no differences were observed between any of the dependent variables measured (laboratory write-ups, examinations, and group projects), the failure rate for the blended learning class was 3.4%, and 6.5% for the traditional course.

While more investigation is necessary, subjective comments from selected students indicated that use of on-line modules allowed them to proceed through the material at their own pace, as well as the option to view the instruction multiple times if desired. The on-line materials were particularly useful to students reviewing for examinations, and as a resource leading up to the final group project. In addition to the noted benefits to students, utilizing the blended format and split classes offered advantages for this instructor of the class. The primary benefit was that the larger class counted double toward teaching load, thus clearing time to spend in the laboratory and research endeavors. In addition, having the pre-recorded Tegrity lectures allowed the instructor to reduce class teaching preparation time. Based on the preliminary data provided in this study, we propose that web-based only instruction and splitting laboratory time between groups in a blended learning environment can be an equally effective mode for disseminating course information in a large laboratory-based class compared to traditional face-to-face classes with smaller numbers that meet each period.

Acknowledgment: James W. Navalta was primarily responsible for the research design, scientific execution, and report of this study. T. Scott Lyons, Guilherme B. Pereira, Scott W. Arnett, Mark A. Schafer, F. Travis Esslinger, and Gina L. Sobrero assisted in research design, data analysis, and preparation of the manuscript.

James W. Navalta will serve as the guarantor for the manuscript.

Sources of financial support: None

Conflict of interest: None


[1] Beam WC, Adams GM. Exercise Physiology Laboratory Manual. 6th Edition. New York: McGraw-Hill, 2011.

[2] Osguthorpe RT, Graham CR. Blended learning environments: definitions and directions. Q Rev Distance Ed. 2003; 4(3): 227-33.

[3] Ginns P, Ellis R. Quality in blended learning: Exploring the relationships between on-line and face-to-face teaching and learning. Internet and Higher Ed. 2007;10:53-64. [Full text]

[4] Dziuban C, Moskal P. Evaluating distributed learning in metropolitan universities. Metropolitan Universities. 2001;12 (1):41-9. [Full text]

[5] Boyle T, Bradley C, Chalk P, Jones R, Pickard P. Using blended learning to improve student success rates in learning to program. J Ed Media. 2003; 28(2-3): 165-78. [Full text]

[6] Derntl M, Motschnig-Pitrik R. The role of structure, patterns, and people in blended learning. Internet and Higher Ed. 2005;8: 111-30.  [Full text]

[7] Kerres M, Witt CD. A didactical framework for the design of blended learning arrangements. J Ed Media. 2003; 28(2-3): 101-13.

[8] Rovai AP, Jordan HM. Blended learning and sense of community: A comparative analysis with traditional and fully online graduate courses. Int Rev Res in Open and Distance Learning. 2004; 5(2):1-13. [Full text]

[9] So H-J, Brush TA. Student perceptions of collaborative learning, social presence and satisfaction in a blended learning environment: relationships and critical factors. Computers & Ed. 2008; 51(1): 318-36. [Full text]

[10] Oliver M, Trigwell K. Can ‘blended learning’ be redeemed? E-Learning. 2005; 2(1): 17-26. [Full text]

Hyperlinks in this manuscript were last accessed Jan 13, 2012.

Reviewers: The original submitted version was reviewed by Dr Kimberly Henige, Department of Kinesiology, California State University, Northridge, CA, USA e-mail: Kimberly dot Henige at csun dot edu; and Dr K A Narayan, Department of Medical Education, AIMST University Faculty of Medicine, Bedong, Kedah, Malaysia  e-mail: narayan dot ka at gmail dot com.  The revised version was accepted by editor E.S.Prakash.  The reviewers and the editor have no conflict of interests related to this submission.

Prepublication Record: The Prepublication record containing the original version of the manuscript, reviewers comments, editor’s comments, the authors’ response can be accessed at

Please cite this article as: Navalta JW, Lyons TS, Pereira GB, Arnett SW, Schafer MA, Esslinger FT, and Sobrero GL. Effectiveness of blended instruction utilizing on-line lectures and split classes in delivering an applied exercise physiology course. Medical Physiology Online 2012; published Jan 14, 2012 available from

License: This is an open access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited.

Written by Elapulli S. Prakash

January 14, 2012 at 4:12 PM

Posted in Uncategorized

Stephen Hales and the practice of science

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Point of View
Stephen Hales and the practice of science
Simon Brown* and David C Simcock**
*School of Human Life Sciences, University of Tasmania,
Locked Bag 1320, Launceston, Tasmania 7250, Australia and
**Institute of Food, Nutrition and Human Health, Massey University,
Private Bag 11222, Palmerston North, New Zealand
Correspondence to Simon Brown (e-mail):
Simon dot Brown at utas dot edu dot au (replace dot with .)

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Submitted 7 Oct 2011; first decision 15 Oct 2011; revised and accepted 17 Oct 2011; published 19 Oct 2011

It would be regrettable were this year to end without some commemoration of the 250th anniversary of the death of the Reverend Stephen Hales DD, FRS. Clinicians and virtually all biologists rely on some aspect of his research. While most of us work within a relatively narrow range, Hales made significant contributions to plant and animal physiology on which we still depend, while also contributing to chemistry [1], inventing ventilation systems and winnowing machines [2] and an instrument to remove urinary calculi through the urethra [3], and publishing papers on the causes of earthquakes [4] and the control of fires [5]. The very full scientific life of Stephen Hales has much to tell us about the modern practice of science.

Stephen Hales was born in 1677 in Bekesbourne, Kent, and went up to Cambridge in 1696, where he was elected to a Fellowship at Corpus Christi College in 1702. He was appointed to the parish of Teddington, Middlesex, in 1708 and remained there for much of every year until his death in 1761. He had married in about 1719, but his wife died a year later and he never remarried. He was elected to the Royal Society in 1718 and was awarded its Copley Medal in 1739 for his “experiments towards the discovery of medicines for dissolving the stone, and preservatives for keeping meat at sea”. In 1753 he was elected a foreign member of the Académie Royale des Sciences. Hales is buried beneath the tower of his church in Teddington, although a monument in Westminster Abbey was erected in his memory at the instigation of the Princess of Wales to whom he acted as chaplain [6, 7].

The experimental approach for which Hales became especially remarkable started in collaboration with William Stuckeley during his Fellowship. In his subsequent work he kept meticulous records of both the methods employed and the observations as is clear from his published work. However, he did not simply observe and catalogue as was common at the time (for example Linnaeus* was a contemporary), he also made measurements and then used them and his data to perform calculations. This is another feature of biological research that has declined with the dwindling mathematical skills of biologists, although computer-assisted statistical testing proliferates.

Here, we provide a brief survey of four areas of interest to Stephen Hales: plant physiology, the chemistry of air, animal physiology and the ventilation of confined spaces. We then consider the wider significance of his extraordinary body of work.
*Sachs [8: 89] wrote that “[i]t was not Linnaeus’ habit to occupy himself with what we should call an enquiry; whatever escaped the first critical glance he left quietly alone; it did not occur to him to examine into the causes of the phenomena that interested him; he classified them and had done with them … Linnaeus was in fact a dangerous guide for weak minds, for his curious logic, among the worst to be met with in the scholastic writers, was combined with the most brilliant powers of description …”. Using slightly less forthright language, Miall [9: 329-336] argued that Linnaeus contributed significantly to the “…temporary and partial arrest of development …” of a century of biological science. This may prompt some to think of a powerful modern parallel.

Plant physiology
Hales’ first publication was Vegetable Staticks [10], which deals with phenomena involved in plant nutrition, growth, gas exchange and water relations, such as transpiration, root pressure and the absorption and conduction of water. In it, he makes the critical suggestion that light might do more than just heat plants [10: 327]. All of this work has long been highly regarded by plant physiologists, for example Sachs [8: 477] wrote
… Hales may be said to have made his plants themselves speak; by means of cleverly contrived and skilfully managed experiments he compelled them to disclose the forces that were at work in them by effects made apparent to the eye, and thus to show that forces of a very peculiar kind are in constant activity in the quiet and apparently passive organs of vegetation. Penetrated with the spirit of Newton’s age, which notwithstanding its strictly ideological and even theological conception of nature did endeavour to explain all the phenomena of life mechanically by the attraction and repulsion of material particles, Hales was not content with giving a clear idea of the phenomena of vegetation, but sought to trace them back to mechanico-physical laws as then understood.

Many of the techniques Hales’ described in Vegetable Staticks are still useful [11, 12].

The care with which Hales described his methods and the use to which he put his results are apparent from the very first experiment described in Vegetable Staticks [10] in which he investigated the water use of a sunflower. In assessing the loss of water from the leaves (now known as transpiration), he had to estimate the total surface area of the leaves on the plant, which he managed with typical simplicity
… I cut off all the leaves of this plant, and laid them in five several parcels, according to their several sizes, and then measured the surface of a leaf of each parcel, by laying over it a large lattice made with threads, in which the little squares were ¼ of an inch each; by numbering of which I had the surface of the leaves in square inches, which multiplied by the number of the leaves in the corresponding parcels, gave me the area of all the leaves [10: 5-6]

He went on to estimate the length of the root system and to calculate the corresponding surface area. The analysis of root systems remains a considerable technical challenge even given modern technology [13]. Using these values he then compared the flux of water into the plant through the roots with the transpiration from the leaves. The first four chapters systematically develop various aspects of plant water relations, including the uptake of water by the roots, root pressure and fluid movement.

Chapter VII [10: 317-357] deals with the growth of plants and includes the statement that
… [w]e may therefore reasonably conclude, that one great use of leaves is what has been long suspected by many, viz. to perform in some measure the same office for the support of the vegetable life, that the lungs of animals do, for the support of the animal life; Plants very probably drawing thro’ their leaves some part of their nourishment from the air. [10: 325]

Two pages later Hales makes another important speculation
… And may not light also, by freely entering the expanded surfaces of leaves and flowers, contribute much to the ennobling the principles of vegetables; for Sir Isaac Newton, puts it as a very probable query, “Are not gross bodies and light convertible into one another! and may not bodies receive much of their activity from the particles of light, which enter their composition?” [10: 327]

In these two passages Hales captured the essence of the dark and light reactions of photosynthesis [14, 15], in which the absorption of light provides the energy to drive the synthesis of the ATP and NADPH (the light reactions) needed to incorporate CO2 into carbohydrate (the dark reactions).

Chemistry of air
In Chapter V of Vegetable Staticks [10: 148-155], Hales described a series of experiments showing that “… air freely enters plants, not only with the principal fund of nourishment by the roots, but also thro’ the surface of their trunks and leaves…” [10: 153]. While we now distinguish between CO2 and O2, among other atmospheric gases, Hales did not, despite Chapter VI of Vegetable Staticks [10: 155-317] which contains
…[a] specimen of an attempt to analyze the air by a great variety of chimio-statical experiments, which shew in how great a proportion air is wrought into the composition of animal, vegetable, and mineral substances, and withal how readily it resumes its former elastick state, when in the dissolution of those substances it is disengaged from them. [10: 155]

That Hales experiments did not prompt him to develop a theory has been portrayed as a failure by some [16: 28-37] and many critics quote a passage from Vegetable Staticks [10: 315] which ends
… our atmosphere is a Chaos, consisting not only of elastick, but also of unelastick air particles, which in great plenty float in it, as well as the sulphureous, saline, watry and earthy particles, which are no ways capable of being thrown off into a permanently elastick state, like those particles which constitute true permanent air.

It is argued that he did not do any experiments to test the nature of the material he distilled and that he did not realise that air was not an element. However, Lavoisier made the similar criticisms of Hales’ successors and acknowledged his own debt to Hales [17]. Furthermore, John Mickleburgh, Professor of Chemistry at Cambridge from 1718 until 1756, suggested that Isaac Newton’s chemical “… hints and notices have since been reduced by the reverend and ingenious Mr. Stephen Hales into plain facts and rendered even visible to our eyes by an almost infinite variety of experiments” [18].

While Hales’ work on the chemistry of air is often discounted, the pneumatic trough used to collect gases is of lasting value [1]. The trough facilitated the progress in the chemistry of gases due to Cavendish, Priestley and others that stimulated Lavoisier in creation of the new chemistry. Holmyard [19: 159] wrote of the trough
… [s]o simple is the device that, having once seen it in use, we are apt to take it purely as a matter of course and rarely regard it as a supreme achievement of the inventive genius. Perhaps this indifference is only natural, but what an immensity of labour lies behind the trite instruction of the text-book: ‘Collect the gas over water at the pneumatic trough’!

Of course the design of the trough was adjusted subsequently, but Hales facilitated important progress in the chemistry of gases.

Animal physiology
Hales began his work on animal physiology during his collaboration with William Stuckeley at Cambridge. After a break during his early years in Teddington, when he concentrated on plant physiology and chemistry, he resumed animal experiments. The main record of this work is contained in Haemastaticks [20] which comprises experiments on blood pressure and circulation using a variety of species, respiration and urinary calculi.

Hales was the first to measure arterial pressure using techniques reminiscent of those described in Vegetable Staticks [20: xviii]. A series of experiments are graphically described in Haemastaticks [20] and are reproduced in various biographies [6, 21]. In essence, in experiments I and II he inserted a cannula into the crural artery of a horse and to that he attached lengths of glass tubing through which blood flowed to a height of about 9 feet (about 2730 mm) corresponding to roughly 210 mm Hg (≈ 2730 mm blood × 1060 kg m-3 blood/13534 kg m-3 Hg).

The combination of measurement and calculation apparent in Vegetable Staticks is applied in the experiments described in Haemastaticks. For example, in one experiment [20: 20-21] he measured the internal surface area of the left ventricle (A) and the height of the column of blood supported by the contracting ventricle (h) from which he estimated that the total volume of blood (V) involved was V = Ah. Using the density of blood (ρ) he then calculated the mass of blood supported by the ventricle using ρV. His work is filled with quantitative measurements and analysis. While we might not consider that this is especially remarkable, it was rare among biologists at the time [22].

These experiments are disconcerting to us, but they also worried some of Hales’ contemporaries. According to Joseph Spence [23: 293], Regius Professor of Modern History from 1742 to 1768, Alexander Pope said of Hales
… he is a very good man; only I’m sorry he has his hands so much imbrued in blood.
… Indeed he commits most of these barbarities with the thought of being of use to man: but how do we know, that we have a right to kill creatures that we are so little above as dogs, for our curiosity, or even for some use to us?

Certainly, it is difficult to believe that he would obtain ethical approval for such experiments today. In defence of Stephen Hales, Smith [24], citing a manuscript letter from Hales to John Mickleburgh dated 17 May 1733, suggests that Hales was concerned by his own experiments. Some support for this suggestion can be found in the preface and in the introduction to Haemastaticks [20: ix and xvii], where Hales states that the “disagreeableness” of his animal experiments discouraged him from pursuing them, but that the hope of deeper insight eventually spurred him on [20: ix]. Moreover, after the publication of Haemastaticks in 1733 Hales again ceased animal experiments and pursued other interests.

Ventilation of confined spaces
Hales knew that exhaled air becomes unfit for respiration [2: 44] and of the long history of mortality associated with crowding in unventilated spaces [25, 26]. The gaols, workplaces and homes of the 18th century were often unventilated and the prevalence of infection was high. The combination of these two factors often had devastating consequences. The problem was especially significant on board the ships of the period and Hales [2: v-vi] argued that
… sea-farers, that valuable and useful part of mankind, have many hardships and difficulties to contend with, so it is of great importance to obviate as many of them as possible: and as the noxious air in ships has hitherto been one of their greatest grievances, by making sick and destroying multitudes of them; so the finding of a means to prevent this great evil, is of vastly more consequence to navigation, than the discovery of the longitude; as being a means of saving innumerable more lives, than that would do.

His focus on ships may have been political expedience, because the system was soon installed in several prisons [27], but he was not alone in this approach. In 1741, Mårten Triewald FRS, ‘Captain of Mechanicks and Military Architect’ to the king of Sweden, devised a similar system that was used in Swedish ships blockading St. Petersburg that summer in the Russo-Swedish War of 1741-1743. The following April, he reported his work to the Royal Academy of Sciences of Sweden and Frederick I ordered that the ventilators be installed in all in his ships. Triewald also sent one of his engines to France where it was approved by the Académie Royale des Sciences, whereupon Louis XV ordered the ventilators to be installed in all his ships.

While Hales’ ventilation system had been installed in several prisons [27], the process was accelerated by one extraordinary event. After a sitting at the Old Bailey in May 1750, the Lord Mayor of London, a Lord Chief Justice, two judges, an alderman and at least forty other people died [28, 29]. For much of that day, 300 prisoners from Newgate Prison were crowded into a small space adjacent to the courtroom and it was thought that they were the source of gaol fever, later suggested to be typhus [25]. This event prompted the establishment of a committee to investigate how to procure for Newgate Prison “… such a purity of air, as might prevent the rise of those infectious distempers, which not only had been destructive to the prisoners themselves, but dangerous to others …” [30: 42]. A ventilation system was installed in Newgate Prison in April 1752 [31, 32] and within a year Hales [27] had some evidence that it had had some effect. Later he reported on the benefits of installing his ventilation system on board ships [33], as Mårten Triewald had been able to before him [34].

What else can we learn from Hales?
Stephen Hales combined elegantly simple experiments with calculation. While this might seem commonplace today, it was novel among biological scientists of the eighteenth century [22]. This prompted Sir Francis Darwin to write
… though essentially a physiologist, he seems to me to have been a chemist and physicist who turned his knowledge to the study of life, rather than a physiologist who had some chemical knowledge. [35: 67]

Darwin went on to cite Whewell [36: 431], who argued that “why” meant “through what cause” to a physicist, but “to what end” to a physiologist, and suggested that by this test Hales would be a physicist.

Hales himself felt that he had to justify his approach because, in the preface to Haemastaticks, he writes
… In natural philosophy, we cannot depend on any mere speculations of the mind; we can only with mathematicians reason with any tolerable certainty from proper data, such as arise from the united testimony of many good and credible experiments.

… Yet it seems not unreasonable on the other hand tho’ not far to indulge yet to carry our reasonings a little further than the plain evidence of experiments will warrant; since at the utmost boundaries of those things which we clearly know, there is a kind of twilight cast from what we know, on the adjoining border of terra incognita, it seems therefore reasonable in some degree to indulge conjecture there; otherwise we should make very slow advances in future discoveries, either by experiments or reasoning. [20: vi-vii]

It is regrettable that too often modern scientists report measurements, but are reluctant to ‘indulge conjecture’.

The second message apparent from the work of Stephen Hales is that breadth of interest can be an advantage. In each of the four aspects of his work that we have outlined, which does not exhaust the range of his activity, he made significant contributions. Hales was too modest a man to make this point himself, but his extraordinary range of interests reflects an unwillingness to be dissuaded from a path by artificial discipline boundaries.

Even 250 years after his death, Stephen Hales is remarkable. To the modern scientist, often constrained to work on a single problem by convention and career considerations, the scope of his research is almost inconceivable. The elegant simplicity of his experiments is a challenge to us all.

Conflict of interests: none related to this article was declared.


[1] Parascandola J and Ihde AJ. History of the pneumatic trough. Isis. 1969, 60: 351-361;

[2] Hales S. A description of ventilators: whereby great quantities of fresh air may with ease be conveyed into mines, goals, hospitals, work-houses and ships, in exchange for their noxious air. An account also of their great usefulness in many other respects: as in preserving all sorts of grain dry, sweey, and free from being destroyed by weevels, both in grainaries and ships: and in preserving many other sorts of goods. As also in drying corn, malt, hops, gun-powder, etc. and for many other useful purposes. London: W. Innys, R. Manby and T. Woodward; 1743.

[3] Hales S. A proposal to bring small passable stones soon and with ease out of the bladder. Philosophical Transactions of the Royal Society of London. 1744, 43: 502-505;

[4] Hales S. Some considerations on the causes of earthquakes. Philosophical Transactions of the Royal Society of London. 1749, 46: 669-681;

[5] Hales S. A proposal for checking in some degree the progress of fires. Philosophical Transactions of the Royal Society of London. 1748, 45: 277-279;

[6] Burget GE. Stephen Hales (1677-1761). Annals of Medical History. 1925, 7: 109-116.

[7] Clark-Kennedy AE. Stephen Hales, DD, FRS. British Medical Journal. 1977, 2: 1656-1658;

[8] von Sachs J. History of botany (1530-1860). Oxford: Clarendon Press; 1906.

[9] Miall LC. The early naturalists: their lives and work (1530-1789). London: Macmillan and Co., Limited; 1912.

[10] Hales S. Vegetable Staticks: or, an account of some statical experiments on the sap in vegetables: being an essay towards a natural history of vegetation. Also, a specimen of an attempt to analyse the air, by a great variety of chymio-statical experiments. London: W. and J. Innys and T. Woodward; 1727.

[11] White PR. Vegetable staticks: evidence concerning cell secretion, root-pressure, and gas diffusion in the functioning and morphogenesis of excised plant tissue. American Scientist. 1942, 30: 119-136;

[12] Hershey DR. Linking history and hands-on biology. Bioscience. 1991, 41: 628-630;

[13] Himmelbauer ML, Loiskandl W and Kastanek F. Estimating length, average diameter and surface area of roots using two different image analyses systems. Plant and Soil. 2004, 260: 111-120.

[14] Gest H. Sun-beams, cucumbers, and purple bacteria. Photosynthesis Research. 1988, 19: 287-308.

[15] Govindjee and Krogmann D. Discoveries in oxygenic photosynthesis (1727-2003): a perspective. Photosynthesis Research. 2004, 80: 15-57

[16] Ramsay W. The gases of the atmosphere. The history of their discovery. 4th ed. London: Macmillan and Co., Limited; 1915.

[17] Beretta M. Lavoisier as a reader of chemical literature. Revue d’histoire des sciences. 1995, 48: 71-94; Tiny URL

[18] Coleby LJM. John Mickleburgh. Annals of Science. 1952, 8: 165-174;

[19] Holmyard EJ. Makers of chemistry. Oxford: Clarendon Press; 1931.

[20] Hales S. Haemastatique, ou la statique des animaux: experiences hydrauliques faites sur des animaux vivans. Avec un recueil de quelques expériences sur les pierres que l’on trouve dans les reins & dans la vessie; & des recherches sur la nature de ces concrétions irréguliéres. Geneva: Cramer and Fréres Philibert; 1744.

[21] Anonymous. Archaeologica medica. XXXVI. Stephen Hales, a pioneer in modern physiology. British Medical Journal. 1897, 2: 1191;

[22] Roller DHD. Stephen Hales and quantitative mechanism. Bios. 1960, 31: 195-204;

[23] Spence J. Anecdotes, observations, and characters, of books and men. Collected from the conversation of Mr Pope, and other eminent persons of his time. London: W.H. Carpenter; 1820.

[24] Smith IB. The impact of Stephen Hales on medicine. Journal of the Royal Society of Medicine. 1993, 86: 349-352;

[25] Webb FC. History of gaol fever in England. British Medical Journal. 1857, s4-1: 666;

[26] Collins CH and Kennedy DA. Gaol and ship fevers. Perspectives in Public Health. 2009, 129: 163-164;

[27] Hales S. An account of the good effect of ventilators, in Newgate and the Savoy prison. Gentleman’s Magazine. 1753, 23: 70-71;

[28] Pringle J. The Black Sessions at the Old Bailey accounted for. Gentleman’s Magazine. 1753, 23: 21-22;

[29] Pringle J. Observations on the diseases of the army. 4th ed. London: A. Millar, D. Wilson, T. Durham and T. Payne; 1764.

[30] Pringle J. A account of several persons seized with the gaol-fever, working in Newgate; and of the manner, in which the infections was communicated to one intire family. Philosophical Transactions of the Royal Society of London. 1753, 48: 42-55;

[31] Anonymous. A description of the ventilators which were fixed in Newgate; where being work’d by a windmill they draw the foul air out of the several wards; which were made by Mr Stibbs, carpenter in Fore Street London Wall. Gentleman’s Magazine. 1752, 22: 179-182;

[32] Anonymous. A description of the windmill, which is fixed on Newgate to work the ventilators; this mill was made by Mr. Cowper in Penny Fields, Poplar. Gentleman’s Magazine. 1752, 22: 182;

[33] Hales S. An account of the great benefit of ventilators in many instances, in preserving the health and lives of people, in slave and other transport ships. Philosophical Transactions of the Royal Society of London. 1755, 49: 332-339;

[34] Trievald M. Väderväxlings machin – påfunnen och ingifven. Kungliga Vetenskapsakademiens Handlingar. 1744, 5: 251-260;

[35] Darwin F. Stephen Hales 1677-1761. In: Oliver FW, ed. Makers of British botany. Cambridge: Cambridge University Press; 1913:65-83.

[36] Whewell W. History of the inductive sciences from the earliest to the present time. Vol 3. London: John W. Parker; 1847.

Hyperlinks in this manuscript were last accessed 17 Oct 2011.

Reviewers: The original submitted version was reviewed by:
Ken Saladin, Professor of Biology, Georgia College, Milledgeville, GA 31061, USA. E-mail: ksaladin at windstream dot net

Erik Murchie, Division of Plant and Crop Sciences, School of Biosciences, University of Nottingham, UK. E-mail: Erik dot Murchie at nottingham dot ac dot uk

Ramesh K Marya,
Professor of Physiology, Faculty of Medicine, AIMST University, 08100 Bedong, Kedah, Malaysia. E-mail: rkumarmarya at yahoo dot com

The revised version was accepted by editor E.S.Prakash. The reviewers and the editor disclose no conflict of interests related to this submission.

Prepublication Record: The Prepublication record containing the original version of the manuscript, reviewers comments, editor’s comments, the authors’ response can be accessed at

Please cite this article as: Brown S and Simcock DC. Stephen Hales and the practice of science. Medical Physiology Online 2011; published 19 Oct 2011. Available from (page numbers are not for citation purposes)

License: This is an open access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited.

Written by Elapulli S. Prakash

October 18, 2011 at 7:16 PM

Posted in Uncategorized

A simple method for demonstrating some factors affecting erythrocyte sedimentation rate.

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Anumeha Bhagat
Department of Physiology, Government Medical College Hospital, Chandigarh 160031, India. E-mail: dranumeha_bhagat at yahoo dot com

Submitted 19 Aug 2011; first decision 17 Sep 2011; revision submitted and accepted 21 Sep 2011; published 24 Sep 2011.

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Medical students are commonly given a practical demonstration as to how erythrocyte sedimentation rate (ESR) is determined. In our medical college, students are taught the Westergren and Wintrobe methods for determination of ESR. After filling the Westergren and Wintrobe tubes as required with anticoagulated blood they are kept undisturbed for one hour. Between setting the test up and the typical time at which the reading is taken, students are introduced to the concept of ESR. Besides the fact that the method was demonstrated, in the preceding years, the process of teaching students factors affecting ESR involved a theoretical discussion. Some students do have difficulty with some of the underlying concepts. With this in mind, a model that simulates some of the factors that affect ESR was used to demonstrate to our students some of the factors affecting ESR, and this is described below.

The concepts addressed using the model were:

1. Physical forces governing ESR
Red modeling clay available in the laboratory was used to make a model of red blood cells (RBC). We first measured equal portions of clay using an electronic physical balance. The weight of the modeled RBC ranged from 0.037 to 0.039 milligrams. These were then rolled by hand and shaped to simulate RBC (Figure 1). Twenty five to thirty such RBC were prepared a day prior to the actual demonstration. For demonstration we took a measuring cylinder (100 ml), labeled A. The cylinder was filled up to the 100 mark with liquid paraffin and this simulated normal plasma. There are two opposing physical forces i.e. a downward force created due to the downward movement of the RBC and an upward force due to displacement of the fluid around the settling RBCs, which determine the rate of RBC settling. In order to help students understand these forces, we picked up a model RBC using glass stirrers and dropped it very closely on the surface of the liquid paraffin in tube A (Figure 2). Students recorded their observations and also noted the time single RBC took to settle using a stopwatch. Students observed that for a second or two the RBC remained on the surface and then settled to the bottom of the tube at a steady rate. The total time from dropping the RBC to its settling at the bottom of the cylinder was 6 seconds and 63 milliseconds. Since the height of the liquid column was 100 mm the rate of fall of RBC is 15.08 millimeters per second. Since the specific gravity of liquid paraffin (simulating plasma) is less than that of our model of RBC, model RBC stay on the surface for only a second or two and then begin settling down. A downward force is created due to the downward movement of the RBC. The fall of the modeled RBCs causes an upward displacement of the medium, producing an upward current and a retarding force [1]. Normally there is a balance between these two forces and minimal settling occurs.

Figures 1-3 are in the PDF version of this manuscript.

2. Importance of rouleaux formation in determining ESR
Five model RBCs were stuck together with their flat surfaces facing each other so as to simulate a rouleaux (Figure 3). It was then dropped close to the surface of liquid paraffin with the help of a glass stirrer and the total time from dropping the rouleaux to settling was noted to be 1 second 56 milliseconds. This helped us demonstrate that the formation of rouleaux enhances ESR. The reason for this is that due to rouleaux formation, aggregates of large volume but relatively small surface area are produced, accelerating RBC sedimentation [1].

3. Effect of plasma viscosity on ESR
Two additional measuring cylinders (100 ml each) were labeled B and C respectively. Cylinder B filled with glycerin diluted by 50% with water and cylinder C was filled with glycerin diluted by 20% with water. The solution in tube B simulated a decrease in plasma in relation to that in tube C. Rouleaux of an identical number of RBCs were dropped in each of these tubes at the same time and the sedimentation rate was noted in each. The settling time in tube B was 1 second 35 milliseconds and 9 seconds 10 milliseconds in tube C. This demonstrated the fact that reduction of plasma viscosity is one potential mechanism of an increase in ESR.

I wish to share this simulation with readers of the journal as I hope this might help students learn some of the factors affecting ESR more easily. I tried this with my class of 40 students and my overall impression was that they found it helpful.

[1] Lee GR et al [ed.]. Wintrobe’s Clinical Hematology (Volume 1), Lea & Febiger, Philadelphia / London, 1993, pp.16

Funding – none disclosed
Conflict of Interests – none disclosed

Please cite this article as: Bhagat A. A simple method for demonstrating some factors affecting erythrocyte sedimentation rate. Medical Physiology Online 2011; published 24 Sep 2011; available from

License: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited.

Dr Madanmohan Trakroo, Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India; and Dr Anand Bhaskar, Department of Physiology, Christian Medical Vellore, India, reviewed the first version of this manuscript. Dr Madanmohan Trakroo is a member of the Senior Advisory Board of Medical Physiology Online. Their comments for the authors are available in the Prepublication Record. The reviewers reports no conflict of interests related to this review.

The original submission, revised version and responses to reviewers was reviewed and the revised manuscript was accepted by the editor E.S.Prakash. The accepted version was further edited for brevity, clarity and style by the editor and approved by the author. The editor has no conflict of interests related to this submission.

Prepublication Record: The prepublication record containing the original version of the manuscript, reviewers comments, editor’s comments, the authors’ response, can be accessed at

Written by Elapulli S. Prakash

September 24, 2011 at 1:45 PM

Posted in Uncategorized

Reluctance to think: unable or unwilling?

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Point of View
Reluctance to think: unable or unwilling?

Simon Brown
School of Human Life Sciences, University of Tasmania,
Locked Bag 1320, Launceston, Tasmania 7250, Australia
Correspondence to Dr Simon Brown at: Simon dot Brown at utas dot edu dot au

Submitted 2 Jul 2011; first decision 15 Jul 2011; revision received 21 Jul 2011;
accepted and published 21 Jul 2011

PDF of this article

Students have started to tell me that they do not want or need to think about science. Those concerned were undergraduate and graduate students pursuing degrees in various biomedical sciences. The thinking expected was entirely normal for science, involving the synthesis of information, problem analysis, calculation, the solution and analysis of practical problems and question development, for example. I have not solicited expressions of reluctance, but I have attempted to elicit more information from those students volunteering them.

While this explicit reluctance to think is new to me, there are reports of similar observations [1-3]. Of course, we are all reluctant to think sometimes, but the new willingness of students to express it implies a more profound problem. If education is intended in part to train students how to learn and think for themselves [4], the reluctance of students to practise this compromises the value of education. For those students intending to practise medicine, work as scientists, formulate health policy, teach or engage in any of the many other occupations that might suit biomedical scientists, an ability to think effectively and efficiently is essential [5]. Students must be helped to prevent a reluctance to think becoming a habit.

Effective thinking relies on both the ability and the willingness to think [4]. Moreover, the ability to think necessarily implies a recognition of the possibility of error [6], which is relatively uncommon among students. There is a considerable difference between the thought patterns of practising scientists and clinicians and those of students. It takes time for thought and practice to develop the questioning, analysis, pattern matching, deduction and educated guesswork that contribute to thinking [7-9]. This is reinforced by a Xhosa speaking South African student of speech and hearing therapy who wrote “… I fail because I have to learn more than the words of your teaching — I have to give back to you the way you think. This is what you are really testing, this is how you assess my ‘intelligence’. You test to see whether I have learnt to think like you yet” [10]. Even if students are willing to think, they may not be as capable as we might hope because they may not have had enough time to develop the necessary thinking skills.

The reluctance of students to think prompts at least four questions. These relate to the significance of the reluctance, the reasons for refusing, the consequences of refusing and how we might encourage students to be more willing to think better. I consider each of these in turn.

What does the reluctance signify?
The reluctance to think could have at least four different interpretations. First, students may believe that they are not required to think or, if it is expected, that it will be done by someone else, such as the teacher [1, 3]. While this may seem unlikely, such a view must have been fostered in class (although it may not have been ours) and it may be that the explicit expectations of the students are insufficient [11]. Second, the student may not really understand what is expected. This may mean that teacher and student do not communicate or that the student does not have a clear understanding of what thinking might be required. Third, the student might understand or have some idea what is expected, but does not know how to go about it. Finally, the student might simply be overwhelmed by work, assessment, personal issues, the demands of holding down a job while studying, for example. This is very common: most of us have had the experience of a student struggling in class simply through lack of sleep resulting from working into the early hours to earn a living.

Why are students reluctant?
The explanations given to me fell into two broad categories: some just wanted ‘the’ answer, and others claimed to be able to think, but did not want to and did not ‘like’ being pushed to do so. Assuming that a student demanding ‘the’ answer is temporarily unable to think, these explanations correspond to deficiencies in Siegel’s [4] two requirements for effective thinking.

The first explanation implies that the student considers that there is only one correct ‘answer’ that is known to the teacher and that all other responses are wrong. Such a view neglects the possibility that there might be several ways of considering a problem [12], that more than one of these might be helpful and that a consideration of an issue from several perspectives might be what the teacher actually wants to elicit. Moreover, it incorrectly presupposes that a ‘wrong’ answer might not provide an indication as to the nature of a better one or to other questions that might be asked [13: 211]. Of course it may be that no definitive answer is known or it may be that there are several partial ‘answers’, which is the nature of science.

This explanation reflects the dualistic thinking that is common [6]. This sort of thinking is reinforced by the formulaic nature of most journal articles, of which Richard Feynman [14] said at the start of his Nobel Prize lecture “[w]e have a habit in writing articles published in scientific journals to make the work as finished as possible, to cover all the tracks, to not worry about the blind alleys or to describe how you had the wrong idea first, and so on. So there isn’t any place to publish, in a dignified manner, what you actually did in order to get to do the work …”. Experienced scientists appreciate how science actually works, but the impression of omniscience conveyed by so much science communication reinforces the dualistic thinking of students.

The predominance of dualistic thinking prompts one to ask what might have happened to students in their previous education that might explain it. Young children ask many questions and clearly do not believe that there is only one answer [15]. By the time a student enters university those skills are largely lost, so questioning may be educated out of young people [16]. There is some evidence that science teachers tend to misrepresent the nature of science to their students [17] which may contribute to the development of the dualistic thinking that can take many years to reverse [6]. Some forms of assessment may also reinforce dualistic thinking because of the implication that there is only one ‘right’ way of considering any problem [18]. Certainly, some students concentrate on what it is necessary to know in order to pass the examination. Consequently, it may be unreasonable to expect students to think like a scientist [19] because most students can only think dualistically [6]. Of course, an important aim of teaching is to foster the development of the ability to think in a more sophisticated manner.

The second explanation is a lack of a desire to think. This represents a greater problem because it may reflect an underlying intellectual laziness that can become a dangerous habit for a biomedical scientist [5]. Of course, it is demanding to think and we all have moments when it is beyond us or subjects about which we are reluctant to think on occasion. If the unwillingness is due to a lack of interest, exhaustion or being over worked it can be difficult to assist. However, more can be done to help if the lack of a desire to think arises from a fear of failure.

Some consequences of not thinking
It is important to have a body of knowledge on which to rely, but the ability to manipulate the information and consider a problem in various ways is essential. The volume and complexity of technical material that students have to come to terms with is enormous and represents a considerable burden. Despite this, students often attempt to memorise almost everything [19]. If they were willing and able to think well, so that they could identify patterns and work things out from a few important pieces of information, students would be empowered, their burden would be reduced and unnecessary stress alleviated. Gagné [20] distinguishes between concepts and principles. A concept can often be encapsulated in a name, whereas a principle involves combinations of or actions on concepts [20]. For example, the concept ‘three’ enables one to identify a group of three objects and distinguish it from groups of different sizes. However, the higher order principles that 2 + 1 = 3, 5 – 2 = 3 or 6/2 = 3 imply a deeper understanding of ‘threeness’. Obviously, an attempt to memorise every instance involving ‘three’ would be futile and misses the point that the principles are transferrable (to ‘four’, for example).

What can be done to encourage a willingness to think?

Several simple techniques can encourage a willingness to think, but their success depends on the establishment of a supportive environment in the classroom. First, demonstrate the appropriate thinking skills, perhaps by including the reasoning in lectures not just detail, even if this must be at the expense of content. Second, admit your own ignorance, because the first step in learning is to learn to identify an absence of knowledge and because it provides an opportunity to involve students in an exploration of the problem. Third, explicitly require that every student think and provide regular opportunities for each of them to practise. Fourth, encourage students to discuss problems with each other in person rather than just electronically. Fifth, assess thinking, having warned your students that you will do so, and accept that this may require recognition of more than one ‘right’ answer.

Some students are reluctant to think, either because of a lack of ability or unwillingness. Irrespective of the reason, students must be persuaded that the ability to think is at least as important as the body of knowledge on which they usually focus. While we may expect too much of some students, it is necessary to help all of them to develop the necessary skills. Thinking strategies should be demonstrated and practised in class and students should be expected to show that they are able to think at an appropriate level.

Funding – none; Conflict of Interests – none declared.


[1] Friedman AM and Heafner TL. “You think for me, so I don’t have to.” The effect of a technology-enhanced, inquiry learning environment on student learning in 11th-grade United States history. Contemporary Issues in Technology and Teacher Education. 2007, 7: 199-216;

[2] Birkhead T. We’ve bred a generation unable to think. Times Educational Supplement. 6 February 2009, 2009;

[3] Beachboard MR and Beachboard JC. Critical-thinking pedagogy and student perceptions of university contributions to their academic department. Informing Science. 2010, 13: 53-71;

[4] Siegel H. The rationality of science, critical thinking, and science education. Synthese. 1989, 80: 9-41;

[5] Kopelman LM. Philosophy and medical education. Academic Medicine. 1995, 70: 795-805;

[6] Brown S. “On the other side of the barrier is thinking”. Acta Didactica Napocensia. 2009, 2: 1-8;

[7] Inhelder B and Piaget J. The growth of logical thinking from childhood to adolescence. New York: Basic Books, Inc.; 1958.

[8] Vygotsky LS. Thought and language. Cambridge: MIT Press; 1962.

[9] Perry WG, Jr. Forms of intellectual and ethical development in the college years: a scheme. New York: Holt, Rinehart and Winston; 1970.

[10] Mpumlwana N. The monster of professional power. Teaching in Higher Education. 2000, 5: 535-540;

[11] Rowe WG and O’Brian J. The role of Golem, Pygmalion, and Galatea effects on opportunistic behavior in the classroom. Journal of Management Education. 2002, 26: 612-628;

[12] Brown S and Salter S.
Analogy in science and science teaching. Advances in Physiology Education. 2010, 34: 167-169;

[13] Viennot L.
Reasoning in physics. The part of common sense. New York: Kluwer Academic Publishers; 2001.

[14] Feynman RP. The development of the space-time view of quantum electrodynamics. Science. 1966, 153: 699-708;

[15] Stead EA, Jr and Starmer CF. Restoring the joy in learning. Medical Physiology Online. 16 January 2008;

[16] Kuhn D. Children and adults as intuitive scientists. Psychological Review. 1989, 96: 674-689;

[17] Benson GD. The misrepresentation of science by philosophers and teachers of science. Synthese. 1989, 80: 107-119;

[18] Rogers EM. Examinations: powerful agents for good or ill teaching. American Journal of Physics. 1969, 37: 954-962;

[19] Copes L. Can college students reason? Spring Meeting of the Seaway Section, Mathematical Association of America, 1975; Toronto;

[20] Gagné RM. The learning of concepts. School Review. 1965, 73: 187-196;

Hyperlinks in this manuscript were last accessed 21 Jul 2011. Please cite this article as: Brown S. Reluctance to think: unable or unwilling? Medical Physiology Online 2011; available from

Reviewers: The original submitted version was reviewed by Dr Frank Starmer, Duke-NUS Graduate Medical School, Singapore; Dr Balint Kacsoh, Mercer University School of Medicine, USA, and the editor E.S.Prakash. The reviewers and the editor have no conflict of interests related to this submission.

Prepublication Record: The Prepublication record containing the original version of the manuscript, reviewers comments, editor’s comments, the authors’ response can be accessed at

License: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited.

Written by Elapulli S. Prakash

July 22, 2011 at 8:59 PM

Freeing didactic lectures from monotony with a brief mid-lecture presentation on innovations in biomedical technology unrelated to the original lecture

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Point of View

Freeing didactic lectures from monotony with a brief mid-lecture presentation on innovations in biomedical technology unrelated to the original lecture

Rajashekar Rao Barkur*, Ullas Kamath*, and K.G.Mohandas Rao

Departments of Biochemistry*, and Anatomy, Melaka Manipal Medical College (Manipal Campus), International Center for Health Sciences, Manipal, Karnataka 576104, India.

Correspondence to Dr Mohandas Rao at mohandaskg at gmail dot com

Submitted 18 Mar 2010; first decision 13 Apr 2010; first revision received 19 Apr 2010;

Second revision accepted 25 Apr 2010; published 27 Apr 2010

This article does not have an abstract.

Download Full text of the article

Funding – none

Conflict of Interests – none

Please cite this article as: R.R.Barkur, U Kamath and K G Mohandas Rao. Freeing didactic lectures from monotony with a mid-lecture presentation unrelated to the original lecture. Medical Physiology Online 2010; published 27 April 2010 available from

Reviewer: Dr William H Cliff, Niagara University, USA, reviewed the first version of this manuscript. His comments for the authors are available in the Prepublication Record. The reviewer reports no conflict of interests related to this review.

The revised version of the manuscript was reviewed, further revision requested and the second revision accepted by Editor E.S.Prakash. The accepted version was further edited for brevity, clarity and style by the editor and approved by the authors. The editor has no conflict of interests related to this submission.

Prepublication Record: The prepublication record containing the original version of the manuscript, reviewers comments, editor’s comments, the authors’ response, and the revised versions of the manuscript can be accessed at

License: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited.

Written by Elapulli S. Prakash

April 27, 2010 at 1:03 PM

Can we use will power to negate effect of general anesthetics?

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Can we use will power to negate effect of general anesthetics?

Is it possible for an individual to consciously alter or negate the effect of a drug? For example, can an individual use his will power to remain conscious after being administered a general anaesthetic? Can an individual retain motor function using his will even after being administered skeletal muscular relaxants, eg succinyl choline?. Just out of curiosity..

Janarthan Rama Murti
Second Year Medical Student, AIMST University, Malaysia

E-mail: scientist768 at gmail dot com

Written by Elapulli S. Prakash

April 4, 2010 at 11:38 PM

To give or not to give lecture slides to students before I deliver the lecture?

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To give or not to give lecture slides to students before I deliver the lecture?

E.S.Prakash, Department of Physiology, Faculty of Medicine, AIMST University, 08100 Bedong, Kedah, Malaysia.

E-mail: dresprakash at gmail dot com

Download PDF of the Letter

Supplement 1 Slides of an entire lecture [Sample]

Supplement 2 Slides used for providing a Preview of an upcoming lecture [Sample]

Supplement 3 Post-test [Sample]

Submitted 25 Feb 2010; revised, accepted and published 22 Mar 2010

Acknowledgment: The author is the editor and publisher of Medical Physiology Online.

This manuscript was reviewed and accepted for publication as a letter by Dr David J Solomon, Professor of Medicine, Michigan State University, East Lansing, Michigan, USA. E-mail: dsolomon at msu dot edu

Dr Solomon is a member of Senior Advisory Board of Medical Physiology Online.

Please cite this article as: Prakash ES To give or not to give my lecture slides to students before I deliver the lecture? Medical Physiology Online 2010; available from

Prepublication Record: The prepublication record containing the original version of the manuscript, editor’s comments and author’s response can be accessed at

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, is properly cited.

Written by Elapulli S. Prakash

March 21, 2010 at 11:26 PM

Posted in 256080

Announcement: 8th Inter-Medical School Physiology Quiz, 2010

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At the 7th Inter-Medical School Physiology Quiz held on 2 and 3 October 2009 at the University of Malaya [for details, click here], over 30 teams participated including teams from medical schools in Malaysia, Thailand, Japan, China, Singapore, Srilanka, India, Philippines, and Indonesia. The team from National University of Singapore emerged the winner. The team from Chulalongkorn University, Bangkok came second, and the team from Monash University, Malaysia team came third.

Mc Graw Hill Inc., donated a  2 -volume set of ‘Harrison’s Principles of Internal Medicine’ to each member of the  winning team. Oxford-Fajar Malaysia also donated book prizes to the teams that came second and third. All the 30 plus University teams enjoyed another stimulating and memorable physiology quiz and new friends were made across states and nations.

The 8th Inter-Medical School Physiology Quiz (IMSPQ) will be hosted by University of Malaya in Kuala Lumpur, and is tentatively scheduled for the last week of September 2010. There is no registration fee for participants, and organizers will provide free food and accommodation arrangements to all student participants. For further information, kindly contact the programme chairperson Dr Cheng Hwee Ming at hmingcheng at gmail dot com

Contributed by

Dr Cheng Hwee Ming

Department of Physiology

Faculty of Medicine

University of Malaya

Kuala Lumpur, Malaysia

E-mail: hmingcheng at gmail dot com

Written by Elapulli S. Prakash

March 11, 2010 at 3:41 AM

Posted in 256080