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Response to article by E Harper

Madanmohan, Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India; e-mail: drmadanmohan123 at rediffmail dot com

Referring to the recent review by E Harper in MPO [1], it may be fruitful to compare the effects of physiotherapy, slow pranayams and fast pranayams in multiple sclerosis. I guess that slow pranayams will be more valuable and they are easier to perform. The effect may be apparent in 3 weeks.

Conflict of interests: none

Reference:


Harper E. Premature skeletal muscle fatigue in multiple sclerosis and its implications for exercise therapy. Medical Physiology Online [Serial Online] article 7; volume 1: 2008. Available from http://www.medicalphysiologyonline.org

Reply to Pavithran's question: Which is more important in the genesis of tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis?

E.S.Prakash, Editor, Medical Physiology Online, e-mail: medicalphysiologyonline@gmail.com

I refer to Pavithran's question [1]: Which is more important in the genesis of tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis?

The study by Mullin et al [2] specifically investigated the effects of directly lowering CSF calcium levels without altering serum ionized calcium or pH on neuromuscular responses. In these experiments, the authors note that the tetanic phenomena in the animals could have been caused by calcium levels in the CSF as low as 0.1 mM (normally CSF [Ca] is 1.2 mM). They also observed that exposing the lower spinal cord to a calcium poor solution did not produce a noticeable change in muscular tension indicating that the low concentration of calcium in brain interstitial fluid bathing cell bodies of neurons (and not plasma ionized calcium) was the cause for the increased neuromuscular excitability in these experiments. I do not know of clinical states in which CSF calcium levels would reduce to this extent without changes in serum calcium.

Edmonson and colleagues [3] compared the effects of rapid intravenous infusion of ethylene glycol tetraacetate (EGTA) alone versus hypocapnic alkalosis in thyroparathyroidectomized animals and the interaction between hypocalcemia and alkalosis on the "onset of tetany". Their data indicate that hypocapnic alkalosis reducing arterial PCO2 to between 10-20 mmHg alone is associated with tetany even if it is not accompanied by a significant lowering of ionized calcium in serum. However, in the presence of significant hypocalcemia (serum ionized calcium between 0.5 and 0.9 mM) induced by rapid infusion of EGTA, tetanic symptoms are evident at a slightly higher PCO2 (20-30 mmHg). There is a clear time lag of the order of hours for equilibration of calcium ions across the blood brain barrier. In contrast, changes in minute ventilation produce changes in CSF pH instantly. The authors also note that ventilation with a gas containing 5% CO2 was a more rapid and effective means of terminating tetany produced by EGTA and thyroparathyroidectomy than administration of calcium. Thus, this study by Edmonson et al [3] provides clear evidence of an interaction between serum hypocalcemia and respiratory alkalosis in the genesis of tetany and that CSF pH is a key modulator of neuronal excitability.

Conflict of interests: none

Note: This submission was not peer reviewed.

References:

[1] Pavithran P. Which is more important in the genesis of tetanus and tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis? Medical Physiology Online [serial online] article 3.7, volume 1, 2008, available from http://medicalphysiologyonline.blogspot.com

[2] Mullin FJ, Hastings AB, and Lees WM. Neuromuscular responses to variations in calcium and potassium concentrations in the cerebrospinal fluid. Am J Physiol 1938; 121: 719-727

[3] Edmondson JW, Brashear RE, Li TK. Tetany: quantitative interrelationships between calcium and alkalosis. Am J Physiol 1975; 228: 1082-1086

Reply to Dineash Kumar's Question: When ECF volume is measured, is transcellular fluid volume also measured?

Reply to Dineash Kumar: When ECF volume is measured, is transcellular fluid volume also measured?

E.S.Prakash, Editor, Medical Physiology Online, e-mail: medicalphysiologyonline@gmail.com

To quote C.J.Lote [1], "the markers used to measure extracellular fluid volume do not penetrate into transcellular fluids, or do so extremely slowly. Consequently, transcellular fluid volume is not measured when ECF volume is measured".

In a study [2] in which sodium selenate containing a radioactive isotope of selenium was used as a marker for measuring ECF volume, the marker was detected in cerebrospinal fluid and vitreous of the eye between 3-12 hr after infusion but later disappeared.

Thus, a single tracer is not available to measure the total volume of all transcellular fluids. Transcellular fluid volume is thus measured only when total body water is estimated.

References:

[1] Lote CJ. Principles of Renal Physiology, Springer, 2000.

[2] Albert SN, Albert CA, Hirsch EF et al. Selenate as a substitute for sulfate in the measurement of extracellular fluid volume. Journal of Nuclear Medicine 1966; 7: 290-303 [Free full text]

Conflict of interests: none

Note: This submission was not peer reviewed.

Reply to Ravivarma Rao Panirselvam: Is 5% dextrose an effective osmole?

Reply to Ravivarma Rao Panirselvam: Is 5% dextrose an effective osmole?

E.S.Prakash, Editor, Medical Physiology Online, e-mail: medicalphysiologyonline@gmail.com

A 5% dextrose solution in water has roughly the same osmolality (280 mOsm/Kg H20) as that of normal human plasma. When small amounts of 5% dextrose solution are administered intravenously to an individual whose plasma osmolality is within normal limits, initially, there is little change in plasma osmolality; however, dextrose is taken up by cells and metabolized. Thus, the steady state effect is that of adding water which dilutes plasma [1]. Thus, some water would enter cells. This is why a 5% dextrose solution is used for replenishing intracellular fluid volume. In this instance, water flux across the cell membrane is not due to the restriction of dextrose on one side of the cell membrane – in other words, dextrose does not work as an effective osmole.

However in a diabetic with profound hyperglycemia (example, plasma glucose 400 mg/dL), the entry of glucose into cells is limited by the deficiency of insulin. In this instance, glucose in ECF would function as an effective osmole and bring about water shifts into the ECF resulting in intracellular dehydration.

The principle here is that glucose would function as an effective osmole if glucose transport into cells is a rate limiting step [2].

References:

[1] Ganong WF. Review of Medical Physiology, Mc Graw Hill, International edition, 2005.

[2] Davids MR. Lin SH, Edoute Y et al. Hyponatremia and hypoglycemia during laparoscopic surgery. Quarterly Journal of Medicine 2002; 95: 321 – 330.

Conflict of interests: none

This submission was not peer reviewed.

Stress is indeed bad for your heart!

Reply to Karthik Viswanathan: What is the link between psychologic stress, caffeine, sympathetic activity and ventricular ectopics?

Mohan Shanmugam, Anesthesia & Intensive Care, Abertawe Bro Morgannwg University NHS Trust, Swansea, UK; E-mail: mohan at intubator dot co dot uk

Received, accepted and published 27 April 2008

There appears to be adequate clinical, laboratory and cellular evidence that suggests that psychologic stress is arrhythmogenic. It is presumably related to the sympathetically mediated catecholamine surge [1-3]. Essentially, the mechanism is related to the activation of sodium-potassium-ATPase pump causing redistributional hypokalemia. The resulting hyperpolarisation of cardiac muscle cells predisposes to ventricular arrhythmias.

While a relationship between caffeine intake and ventricular ectopics is anecdotally presumed, there is inconsistent evidence in this area. It seems caffeine, when consumed in moderate amounts (~200 mg/day), causes a relatively insignificant increase in catecholamines [4].

The clinical management of ventricular ectopics and the current evidence base is very well summarised in a recent paper by Ng [5].

Conflict of interests: none declared.


References:

1. Tisdale JE, Patel RV, Webb CR, Borzak S, Zarowitz BJ. Proarrhythmic effects of intravenous vasopressors. The Annals of Pharmacotherapy. 1995; 29: 269-281 available online at http://www.theannals.com/cgi/content/abstract/29/3/269, accessed 27 April 2008

2. Clausen T and Everts ME. Regulation of the Na, K pump in skeletal muscle. Kidney International 1989; 35: 1–13. Full text article at http://www.nature.com/ki/journal/v35/n1/pdf/ki19891a.pdf accessed 27 April 2008

3. Macdonald JE and Struthers AD. What is the optimal serum potassium level in cardiovascular patients? Journal of the American College of Cardiology 2004; 43: 155-161; full text at http://content.onlinejacc.org/cgi/content/full/43/2/155 accessed 27 April 2008

4. Myers MG. Caffeine and cardiac arrhythmias. Chest 1988; 94: 4–5, full text at http://www.chestjournal.org/cgi/reprint/94/1/4.pdf accessed 27 April 2008

5. Ng GA. Treating patients with ventricular ectopic beats. Heart 2006; 92:1707-1712; extract at http://heart.bmj.com/cgi/content/extract/92/11/1707 accessed 27 April 2008

Reviewed by E.S.Prakash, Editor, Medical Physiology Online

What is the link between psychologic stress, caffeine, sympathetic activity and ventricular ectopics?

Read this post here

Karthik Viswanathan, Coronary Artery Disease Clinical Research Network Group, Leeds Institute for Genetic, Health & Therapeutics, Leeds, United Kingdom. E-mail: drkarthikv at gmail dot com

I see a lot of patients referred to us in the cardiology department with palpitations due to ventricular ectopics, and if there is no evidence of structural heart disease or coronary artery disease, we usually reassure and discharge these patients. Some of them have unifocal ventricular ectopics, some have multifocal ventricular ectopics, others have bigeminy or trigeminy. Few have pauses with compensatory tachycardia thereafter. Very often we get asked: Is there anything we can do to stop these symptoms? We usually say that reducing caffeine, alcohol, stress may help but I don't really know if there is any physiological basis for this recommendation. Is there any evidence that physiological ventricular ectopics are driven by increased sympathetic activity or by increased levels of stress, caffeine in susceptible people?

Conflict of interests: none declared

Read the response by Mohan Shanmugam

When ECF volume is measured, is transcellular volume also measured?

When we measure extracellular fluid volume, is transcellular fluid volume also measured? How is the total volume of transcellular fluid determined?

Dineash Kumar, Year 1 Medical Student, School of Medicine, Asian Institute of Medicine, Science & Technology, 08100 Bedong, Kedah, Malaysia; e-mail: dineashkumar at yahoo dot com

Conflict of interests: none

Read the response by E.S.Prakash

Is 5% dextrose an effective osmole?

Is 5% dextrose solution an effective osmole?

Ravivarma Rao Panirselvam, Year 1 Medical Student, School of Medicine, Asian Institute of Medicine, Science & Technology, 08100 Bedong, Kedah, Malaysia; e-mail: unicorn063 at hotmail dot com

Conflict of interests: none

Read the response by E.S.Prakash

On the real cause of pyloric stenosis of infancy

Read this article here

An interview with Ian Munro Rogers, School of Medicine, Asian Institute of Medicine, Science & Technology, 08100 Bedong, Kedah Darul Aman, Malaysia.

Correspondence to Dr. Rogers at irogers2000 at hotmail dot com

Interviewed by E.S.Prakash, Editor, Medical Physiology Online,
E-mail: medicalphysiologyonline at gmail dot com

[Interviewed 4 Feb 2008; manuscript received 6 Feb 2008; accepted and published 11 Feb 2008]

Abbreviations: PS – pyloric stenosis; ESP – E.S.Prakash; IMR – Ian Munro Rogers

Background: Dr.I.M.Rogers has put forth the hypothesis that the inheritance of a higher than normal parietal cell mass and the ensuing hyperacidity is the primary cause pyloric stenosis (PS) of infancy. See ref. [1] Rogers IM. The true cause of pyloric stenosis is hyperacidity. Acta Paediatrica 2006; 95: 132–136 [full text]. In this interview, Dr. Rogers answers some questions that come in the wake of this hypothesis.

1. ESP: If the hypothesis that hyperacidity is the ultimate cause of PS of infancy is correct, then, patients with pronounced hyperacidity (example, patients with Zollinger-Ellison syndrome) should also develop this complication. Your comments on this.
IMR: Patients with Zollinger-Ellison syndrome usually have acid-induced peptic ulcers – normally duodenal ulcers which perforate and bleed. Some of them will have PS or rather duodenal stenosis. I think newborns with hyperacidity are a different kettle of fish in the sense that the pyloric canal is very narrow, and even a small further reduction due to acid-induced pyloric sphincter hypertrophy would be enough to precipitate functional stenosis. At this point, other factors which further increase acidity begin to operate and a self-perpetuating process begins, culminating in PS. In a sense, this condition occurs because the rate of pyloric narrowing due to acid exceeds the rate at which age related widening of the pyloric canal occurs. This may be the reason why this condition presents within 3-4 weeks (a narrow interval indeed) of birth. Further, hypergastrinaemia, a phenomenon known to occur at this time (as alluded to my in my review [1]), is also likely to facilitate hypertrophy of the sphincter.

2. ESP: You have mentioned in your review [1] that in babies with PS, the negative feedback relationship between fasting gastrin and acid secretion is not evident until the third week of life. Is this also true for normal babies? If so, what does this indicate?
IMR: Yes, it is true for normal babies. In papers from Dr. MacGuigan’s laboratory, Florida, USA [2, 3], normal babies were found to have hypergastrinaemia without postprandial elevation in gastrin up to 2 months of age. Between 3-4 months, fasting gastrin levels had fallen and postprandial gastrin responses became evident. The implication is that from birth to 2 months of age, gastrin is maximally stimulated hence can not become higher when exposed to constitutional hyperacidity or after ingestion of a protein containing formula [2].

3. ESP: Are there any studies of plasma levels of secretin (the major humoral mediator regulating meal stimulated secretion of bicarbonate rich secretions from the gastrointestinal tract) in neonates with PS? The question comes as defects in neutralizing the effects of gastric acid might also predispose to the hyperacidity that you consider the prime pathogenetic mechanism in PS.
IMR: In 1975, we published a study [4] in which we evaluated the secretion of secretin in neonates. Curiously, the rise between day 1 and 4 was similar to that observed with gastrin. I know of no more investigations of secretin levels in neonates.

4. ESP: Is hyperacidity a consistent feature of PS of infancy?
IMR: Strangely, there have been very few studies of gastric acid secretion in PS. In 1979, I and my colleagues first reported basal hyperacidity in babies with PS compared to normal babies [5]. Heine et al [6] reported higher histamine induced gastric acid secretion in babies with PS before and 1 week after pyloromyotomy.

5. ESP: Is there evidence that a high parietal cell mass is inherited?
IMR: Babies with PS do secrete more acid than normal babies, and this persists after pyloromyotomy [6]. Supporting evidence for primary acidity is the observation that babies who are vomiting and are alkalotic at this age invariably have PS. The condition is strongly familial; it is much more common in males compared to females (4:1) as duodenal ulcers are in adults. Long term studies have documented problems with hyperacidity long after pyloromyotomy. Preterm normal male babies have been shown to secrete more acid than maturity matched female babies [7]. Thus, while there is no direct evidence of supernormal parietal cell mass, available evidence is indeed consistent with this theory.

6. ESP: Given your hypothesis, it is indeed surprising to me that the tumor does not disappear following gastroenterostomy; i.e., if hyperacidity were the primary cause of the growth of the pyloric sphincter, gastroenterostomy which allows drainage of acid should lead to a perceptible reduction in the size of the pyloric sphincter.
IMR: The extraordinary thing is that the pyloric tumour disappears within days of pyloromyotomy [8] and within weeks of successful medical treatment [9]. Regarding the failure of the tumor to regress following gastroenterostomy [1], it simply may be that unless the hypertrophied pyloric sphincter is divided, it can not relax or dilate with the passage of food. Further, a posterior gastroenterostomy may not drain the antrum well. A poorly drained alkaline antrum is a classical way of increasing gastrin levels - especially after vagotomy, and thus the continuing presence of trophic factors such as gastrin may in addition explain the persistence of the pyloric tumor following gastroenterostomy.

7. ESP: Alternate causes for pyloric stenosis have been proposed; for example, a relative deficiency of neuronal nitric oxide synthase at the sphincter [10] may be primary to the condition - something like in achalasia. Your comments on this:
IMR: Deficiency of nitric oxide explains the pylorospasm. It does not explain the predominance of this condition in males; neither does it explain spontaneous self-cure after a certain age. The failure of this condition to recur after simply dividing the sphincter and the very good response to adequate medical therapy is also not explained. How does it explain the persistence and complications of high acidity after pyloromyotomy?

8. ESP: The observation that rats with an artificially narrowed pylorus secrete more acid and gastrin in response to a meal and the fact that gastrin producing antral cells become hyperplastic [11] in this model is interesting but in this instance hypergastrinaemia and hyperacidity are secondary to pyloric stenosis not the cause of it. What is your opinion?
IMR: First, the hypothesis that primary hyperacidity is the cause of PS is based on the premise that all babies are potentially at risk of acid induced pylorospasm at around 3-4 weeks; however, babies who develop PS are most vulnerable because the burden of constitutional hyperacidity proves too great. Secondly, in my review [1], I cited the study by Omura et al [11] to suggest that once PS is established, there are mechanisms that maintain hyperacidity. The authors [11] demonstrated hypergastrinaemia secondary to PS. Furthermore, there is evidence for a gastrin independent pyloro-oxyntic local neural reflex [12] that can induce acid secretion. Indeed, Talbot [13] has reported improvement in symptoms in patients with peptic ulcer induced gastric outlet obstruction treated with proton pump inhibitors.

9. ESP: Please tell us what you believe would be the most important research questions that need to be investigated in the management of infantile hypertrophic PS?
IMR: To evaluate the benefit of intravenous proton pump inhibitors after making a diagnosis of PS and while awaiting surgery. Indicators of improvement would be reduced acid and volume loss from the nasogastric aspirate and a reduction in metabolic alkalosis. A period of 2 days is not unusual between diagnosis and surgery; this should allow an adequate appraisal. Retrospective data on patients undergoing surgery for PS on whom 2 acid base studies (preoperatively and intraoperatively) are usual would allow a comparison to be made with the acid base changes as a result of treatment with proton pump inhibitors. In adults who have high acidity and who vomit; i.e., adult pyloric stenosis, preoperative administration of proton pump inhibitors is standard therapy to reduce loss of fluids as well as acid. Indeed, in some instances, the alleged pyloric stenosis is functionally improved or cured by this treatment alone – so the question is why babies in whom acid base and volume homeostasis is less secure should be denied this treatment. I believe that the baby diagnosed early enough to have PS but without access to safe surgery would be advantaged by the sole temporary use of proton pump inhibitors while awaiting the enhanced possibility of spontaneous cure. That is my opinion.

ESP: Thank you very much Dr. Rogers for sharing your thoughts with us.
IMR: Thank you very much.

Conflict of interests: none declared.
Editor’s note: I invited this manuscript from Dr. Rogers, reviewed and edited it. Both Dr. Rogers and I work in the School of Medicine, Asian Institute of Medicine, Science & Technology, Malaysia, but I have no conflict of interests that would affect my review and disposition of this manuscript – E.S.Prakash, Editor, Medical Physiology Online.

References:
1. Rogers IM. The true cause of pyloric stenosis is hyperacidity. Acta Paediatrica 2006; 95: 132–136. [full text]

2. Rodgers BM, Dix PM, Talbert JL, McGuigan JE. Fasting and postprandial serum gastrin in normal human neonates. Journal of Pediatric Surgery 1978; 13: 13–16; [Abstract]

3. Moazam F, Kirby WJ, Rodgers BM, McGuigan JE. Physiology of serum gastrin production in neonates and infants. Annals of Surgery 1984; 199: 389–392. [Abstract]

4. Rogers IM, Davidson DC, Lawrence J, Buchanan KD. Neonatal secretion of secretin. Archives of Disease in Childhood 1975; 50: 120–122. [Abstract]

5. Rogers IM, Drainer IK, Dougal AJ, Black J, Logan R. Serum cholecystokinin, basal acid secretion and infantile hypertrophic pyloric stenosis. Archives of Disease in Childhood 1979; 54: 773–775. [Abstract]

6. 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]

7. Ames MD. Gastric acidity in the first 10 days of life of the prematurely born baby. American Journal of Diseases in Childhood 1960; 100: 252–256.

8. Yamataka A, Tsukada K, Laws YY, Murata M, Lane GJ, Osawa M, Fujimoto T, Miyano T. Pyloromyotomy versus atropine sulphate for infantile hypertrophic pyloric stenosis. Journal of Pediatric Surgery 2000; 35: 338–341. [Abstract]

9. Yamamoto A, Kuno M, Sasaki T, Kobayashi Y. Ultrasonographic follow-up of the healing process of medically treated hypertrophy pyloric stenosis. Pediatric Radiology 1998; 28: 177–178. [Abstract]

10. Vanderwinden JM, Mailleux P, Schiffmann SN, Vanderhaeghen JJ, De Laet MH. Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis. New England Journal of Medicine 1992; 327: 511–515. [Abstract]

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. [Abstract]

12. Debas HT, Konturek SJ, Walsh JH, Grossman MI. Proof of a pyloro-oxyntic reflex for stimulation of acid secretion. Gastroenterology 1974; 66: 526–532. Abstract

13. Talbot D. Treatment of adult pyloric stenosis: a pharmacological alternative? British Journal of Clinical Practice 1993; 47: 220–221. [Abstract]

Some rights reserved © IM Rogers, 2008. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by-nc-sa/3.0/

Ask a question: a new type of contribution to MPO

Letter from the Editor:

Dear readers:

I am pleased to inform you that we are inviting a new type of contribution to MPO. This new section is called "Ask a question". Quite often, we raise questions that we may not have an answer for. It is probably just a matter of asking that question to the right people and the answer will come from somewhere or at least we may know if nobody can answer our question.

Read more at

Which is more important in the genesis of tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis?

Type of contribution: Ask a Question

P. Pavithran, Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India. E-mail: pavithranpp at gmail dot com

Received 21 Jan 2008; accepted 22 Jan 2008

I have been reading some of the recent posts in MPO regarding tetanus and tetany. Mullin et al [1] have demonstrated that though tetany is a peripheral phenomenon, the concentration of Ca2+ ions in CSF plays an important role in inducing tetany. In contrast, there is a study by Edmondson et al [2] in which neither the rate of development of hypocalcemia nor CSF Ca2+ concentration were found to be directly involved although decreased serum ionized calcium and plasma alkalosis were found to interact synergistically in the etiology of tetany. Taken together, what do the results mean? Which is more important in the genesis of tetany: is it CSF hypocalcemia or serum hypocalcemia and alkalosis?

Acknowledgment: I am a student advisor for Medical Physiology Online.

References:
1. Mullin FJ, Hastings AB, and Lees WM. Neuromuscular responses to variations in calcium and potassium concentrations in the cerebrospinal fluid. Am J Physiol 1938; 121: 719-727 [Link]

2. Edmondson JW, Brashear RE, Li TK. Tetany: quantitative interrelationships between calcium and alkalosis. Am J Physiol 1975; 228: 1082-1086 [Link]

Reviewed by E.S.Prakash, Editor, Medical Physiology Online

Read the response by E.S.Prakash

Surface-potential theory for explaining the increase in sodium permeability seen in hypocalcemia

Type of article: Letter to the editor

Anand Bhaskar, Department of Physiology, Christian Medical College, Vellore, 632002, India. E-mail: anandbhaskar [at] sify [dot] com.

Received 23 January 2008; accepted 24 January 2008.

We are aware that hypocalcemia decreases the activation threshold of sodium channels. How does this happen? It can be explained on the basis of the surface-potential theory [1]. According to this theory, the outer surface of cells has a net negative charge. When calcium levels are high, these charges get neutralized by calcium and the electric field in the membrane is purely due to the resting potential. When there is low or zero calcium, the outer surface has a net negative charge and hence, a local negative potential or surface potential is created. The voltage sensor in the sodium channel will sense this change in electric field as depolarization. This results in the opening of sodium channels and thereby an increase in excitability.

Reference:

[1] Hille B. Chapter 13. Modifiers of gating; In: Ionic channels of excitable membranes, 1st edition, Sinauer Associates Inc, Sunderland, Massachusetts, 1984.

Conflict of interests: none declared.

Please cite this letter as Bhaskar A. Surface-potential theory for explaining the increase in sodium permeability seen in hypocalcemia. Medical Physiology Online, article 3.6, volume 1, 2008, available from http://medicalphysiologyonline.blogspot.com [Link]

Reviewed by E.S.Prakash, Editor, Medical Physiology Online.

Correction to the article: what is the difference between tetanus and tetany? by E.S.Prakash

Type of article: Correction

This correction refers to Prakash ES. What is the difference between tetanus and tetany? Medical Physiology Online [serial online] article 3; volume 1: 2008, available from http://www.medicalphysiologyonline.org.

The correct citation of the paper by Mullin FJ et al should be Am J Physiol 1938; 121: 719-727, and not Am J Physiol 1938; 121: 477-481 as mentioned in the original article. I thank P Pavithran, Student advisor for Medical Physiology Online for alerting me of this error.

What is the difference between tetanus and tetany?

Read this article here

Type of article: Point of View

E.S.Prakash, School of Medicine, Faculty of Medical and Health Sciences,
Asian Institute of Medicine, Science & Technology, 08100 Bedong, Kedah Darul Aman, Malaysia. E-mail: medicalphysiologyonline [at] gmail [dot] com

Submitted 1 Jan 2008; accepted 16 Jan 2008; published 16 Jan 2008.

Here is a common dialog between a physiology teacher and an undergraduate student during a physiology examination:
Teacher: What is the difference between tetanus and tetany?
Student: Tetanus is a disease caused by Clostridium tetani whereas tetany is a consequence of hypocalcemia.
Teacher: You are correct.

My comments: While there is nothing really wrong with the above dialog, it reads as though tetanus and tetany are two different things. My point is, in a mechanistic sense, there is little difference between tetanus and tetany but this is not commonly noted. Let me explain.

The clinical condition "tetanus", caused by Clostridium tetani, is characterized by painful muscle spasms and rigidity; this is because the toxin tetanospasmin which C. tetani produces is a powerful inhibitor of the release of glycine, an inhibitory neurotransmitter, from Renshaw cells in the spinal cord. When this happens, unrestrained high frequency discharge of alpha motor neurons results in sustained skeletal muscle contractions that we call tetanus.

Experimentally, for example with a frog sciatic nerve-gastrocnemius muscle preparation, we "tetanize" the muscle by stimulating the sciatic nerve supplying the muscle (or the muscle itself) at high frequencies (called tetanizing frequencies); in other words, we are exciting α-motor neurons supplying the muscle at high frequencies. Strictly speaking, a muscle is said to be tetanized completely if there is no relaxation between successive contractions. To be tetanized, skeletal muscle needs to be stimulated at a frequency greater than or at least equal to the reciprocal of the contraction period in seconds.

Hypocalcemia is said to increase neuromuscular excitability by reducing the magnitude of depolarization necessary to initiate changes in the Na and K conductance that produce an action potential [1]. The carpopedal spasm that occurs in hypocalcemia is evidence of increased neuromuscular excitability and must be due to increased discharge of motor neurons supplying the corresponding muscles. Indeed, Mullin and colleagues [2] have demonstrated the occurrence of opisthotonus, pleurothotonus, and rigidity of abdominal musculature in experimental dogs in which hypocalcemia was induced by injecting calcium poor solutions into the cisterna magna. Thus, the neuromuscular consequences of tetanotoxin and hypocalcemia are similar.

Conflict of interest: the author is the editor of Medical Physiology Online.

References:

1. Ganong WF. Chapter 2. Excitable Tissue: Nerve; In: Review of Medical Physiology, 22nd edition, Mc Graw Hill Co, New York, 2005.

2. Mullin FJ, Hastings AB, and Lees WM. Neuromuscular responses to variations in calcium and potassium concentrations in the cerebrospinal fluid. Am J Physiol 1938; 121: 477-481. [Link]

Please cite this article as: Prakash ES. What is the difference between tetanus and tetany? Medical Physiology Online [serial online] article 3; volume 1: 2008; available from http://www.medicalphysiologyonline.org

Some rights reserved © 2008 E.S.Prakash. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by-nc-sa/3.0/

Guest editor for this manuscript: Dr. Madanmohan, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India. E-mail: drmadanmohan123 [at] gmail [dot] com

Conflict of interest: E.S.Prakash invited me to review this manuscript. He was my student from 2001 through 2006. We have worked and published several articles together.

Correction: The correct citation of the paper by Mullin FJ et al should be Am J Physiol 1938; 121: 719-727, and not Am J Physiol 1938; 121: 477-481 as mentioned in the original article. I thank P Pavithran, Student advisor for Medical Physiology Online for alerting me of this error.

Restoring the joy in learning

Read this article here

Type of article: Point of View

Eugene A. Stead*, Jr. and C. Frank Starmer

Duke-National University of Singapore Graduate Medical School, Singapore 169547
E-mail: frank [dot] starmer [at] gms [dot] edu [dot] sg

*deceased

[Original source of this article: http://frank.itlab.us/stead/joy.html, accessed 16 Jan 2008]

Reproduced in Medical Physiology Online 16 Jan 2008 with permission from Dr Starmer.


Each time our grandchildren visit, we have the opportunity to observe what is exciting and what is boring. Up to the age of 10 or 12, they visit with a curiosity and energy that fills us with a bit of their energy and excitement. The visits are fun and we enjoy the opportunity to expand the fire of their curiosity.

Then something happens - as they enter the teenage years, their curiosity and excitement dwindles. Each of us has observed this with multiple grandchildren. The question for us, two individuals excited by the opportunities to grow the next generation of folks that will contribute to our social and economic fabric, is what happens to extinguish their curiosity?

We think back to our own youth and remember that we were part of an education system - something that was formal, structured and focused on pushing us to remember our arithmetic tables, correct spelling, and historical facts. One of us was a good memorizer (Gene) while the other was a poor memorizer (Frank) - but both of us struggled to find the fun in education and came to the conclusion that there is no fun in education - simply because it is the process of filling our heads with concepts and facts we may never use again. Where is the relevance? Fortunately, we were rebel enough to discover that there was another world - that of learning, and we had fun learning. Learning for each of us was experimental, we tried this and that; we disassembled a motor and could not correctly reassemble it. But our parents were fond of us and became our facilitators, helping us with reassembling a motor or radio or developing photographs or cooking a loaf of bread.

There are very few families today where there is one stay-at-home parent so that fueling curiosity is left to our public and private schools. They struggle with maintaining curiosity but are limited by the requirement that their classes must touch the least talented student while maintaining the excitement of the most talented student.

We believe that the attenuated curiosity of our grandchildren is a reflection of the averaging of the educational process that occurs in the traditional classroom. We believe, though, that with a little imagination, the averaging process can be abandoned in favor of what we call internet-centric learning.

The internet simply reflects electronic connections between computer memories located around the world. Because this memory is electronic, it has a degree of reliability far beyond that of our biological memory. So we ask, why do we insist that our grandchildren memorize the same information we memorized (but rarely used)? The internet levels the knowledge playing field. The curious student from a depressed region has access to the same information that the brightest Duke professor has. The only missing link is the facilitator.

We believe it is time to revisit our educational paradigm and question the utility of mastering facts we'll rarely use. We believe it is time to revisit the relationship between members of our educational programs. We prefer to dismiss the concept of education and replace it with learning. We prefer to dismiss the concept of faculty and students and replace it with a community of learners, senior (experienced) and junior (inexperienced) learners. We prefer to dismiss the concept of broad-based content mastery and replace it with mastery of essential core skills (reading, writing, arithmetic and searchology - the skilled use of google.com).

Educational reform starts in the home, where parents must equip their children with access to the world's information stores. Education continues in the schools where we can compress the 12 years of primary and secondary education required to memorize basic information to perhaps 6-8 years of understanding basic concepts and supplementing our human memory with the memory of the internet. Education continues within our universities and professional schools, where we can produce workers that can make significant contributions to society with less faculty and less time than at any time in the past. Why? Because the repetitive actions needed to memorize and then understand will be replaced by the repetitive actions needed to simply master concepts within the context of our internet memory. Moreover, forgetting is less of a problem. Many educators fail to understand that there is a sort of symmetry in learning and maintaining that which we learned. If we rarely use a concept or rarely recall a fact, we forget it. You can view a sort of forgetting curve [1] where the less frequently we use something, the more likely we are to forget it.

Our internet, our internet memory, our search engine skills, for the first time can address both the learning process and the forgetting process. By focusing our learning within a problem based framework, we know we are learning only that necessary to solve the problem, i.e. just-in-time learning. Thus forgetting is less an issue simply because we have not invested considerable time in learning things we rarely use.

Conflict of interests: none

Reference:
[1] The forgetting curve. http://frank.itlab.us/forgetting/index.html#curve accessed 16 January 2008

Some rights reserved © C Frank Starmer. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by-nc-sa/3.0/

Please cite this article as: Stead EA and Starmer CF. Restoring the joy in learning. Medical Physiology Online [serial online] article 2; volume 1: 2008. Available from http://www.medicalphysiologyonline.org and http://frank.itlab.us


Editor’s note: I wanted to reproduce this article in Medical Physiology Online. I am grateful to Dr C Frank Starmer for granting us permission to do so. Dr Starmer is a member of the advisory board of Medical Physiology Online. Please visit Dr. Starmer’s internet laboratory at http://frank.itlab.us. The web site of the late Dr. Eugene Stead now maintained by Dr Starmer is http://easteadjr.org. I have no conflict of interests to disclose.

E.S.Prakash, Editor, Medical Physiology Online

The power of pranayam

Read this article here

Type of article: Point of View

Madanmohan, Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India. E-mail: drmadanmohan123 [at] gmail [dot] com

Received 14 January 2008; accepted 15 January 2008; published 16 January 2008

Indian classical traditions including yoga emphasize the existence of pran, the infinite and omnipresent cosmic energy. This whole creation, Mother Nature is bountiful. So is pran. At the physical level, pran manifests as light and other forms of physical energy. In our body, pran is the vital force that energizes us. The science of pranayam (a yogic breathing technique) deals with the knowledge, control and enrichment of this vital force. The classical Upanishads which were written over 5000 years ago give us guidelines about pranayam. Prashn Upanishad (2:13) describes pran as the universal governing force that protects and enhances us like our mother. The Bhagavad Gita describes pran and pranayam in a number of verses. Patanjali’s Rajayog and many tantrik texts describe a number of graded practices including pranayams that help us understand and harness this infinite reservoir of energy. The popular complementary healing systems pranic healing and reiki are based on the concept of pranic energy. Indian yogis and ayurvedic physicians have used the power of pranayam for healing since time immemorial.

The mind and body are intricately interrelated. Besides wasting energy, irregular breathing is associated with a restless mind. In contrast, slow, deep and uniform pranayam breathing produces psychosomatic relaxation especially when it is associated with meditative awareness. During pranayam, one can follow the breath as it flows in and out. One can also visualize cosmic pran flowing into the body and mind with each inspiration enlightening the whole being. According to yogic texts, the practice of pranayam results in inner peace and joy, broadening of vision and development of positive emotions like unselfish love. Pranayam is described as a means to achieving divinity and perfection. According to Patanjali (Yoga Darshan, 2: 52–53) pranayam unfolds the inner light and improves the power of concentration.

We have previously reported [1] that savitri pranayam (slow, rhythmic and deep breathing with a ratio of 2:1:2:1 between inspiration, breath held in inspiration, expiration and breath held in expiration) produces a significant reduction in oxygen consumption and deep psychosomatic relaxation within 5 minutes. Telles and Desiraju [2] have demonstrated that a variant of pranayam breathing is associated with a 19% reduction in oxygen consumption. In a study on healthy children who underwent pranayam training for 3 months, Udupa et al [3] have inferred modulation of ventricular performance as indicated by systolic time intervals. In an 18-year old female with frequent premature ventricular complexes (PVC), Prakash et al [4] found that deep breathing at 6 breaths per minute abolished PVC; a significant reduction in the frequency of PVC during deep breathing at 6 breaths per minute has been reported in at least a subset of patients with unifocal PVC. The beneficial effect of deep breathing was suggested to be due to increased vagal modulation of sinoatrial and atrioventricular nodes. Ravindra et al [5] have shown that pranayam and relaxation training for 2 months reduced the frequency of palpitations in two patients with frequent PVC.

Given this evidence, I believe it is important to continue to investigate the physiologic effects of pranayam using scientifically valid methods and apply encouraging results to determine their effects on human health. The power of pranayam is there for all of us to harness. That is my opinion.

Conflict of interests: none

References:
1. Madanmohan, Rai UC, Balavittal V, Thombre DP. Cardiorespiratory changes during savitri pranayam and shavasan. The Yoga Review 3: 25-34, 1983.

2. Telles S and Desiraju T. Oxygen consumption during pranayamic type of very slow-rate breathing. Indian Journal of Medical Research 1991; 94: 357-363, abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1794892 accessed 15 Jan 2008

3. Udupa K, Madanmohan, Bhavanani AB, Vijayalakshmi P, Krishnamurthy N. Effect of pranayam training on cardiac function in normal young volunteers. Indian Journal of Physiology and Pharmacology 43: 27-33, 2003; full text available at http://www.ijpp.com/vol47_1/vol47_no1_orgn_artcl_1.htm accessed 15 Jan 2008.

4. Prakash ES, Ravindra PN, Madanmohan, Anilkumar R and Balachander J. Effect of deep breathing at six breaths per minute on the frequency of premature ventricular complexes. International Journal of Cardiology 111: 450-452, 2006; abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17004338 accessed 15 Jan 2008.

5. Ravindra PN, Madanmohan and Pavithran P. Effect of pranayam (yogic breathing) and shavasan (relaxation training) on the frequency of benign ventricular ectopics in two patients with palpitations. International Journal of Cardiology 108: 124-125, 2006; link to full text at http://www.ncbi.nlm.nih.gov/pubmed/16516708

Copyright © 2008 Madanmohan. Please cite this article as: Madanmohan. The power of pranayam. Medical Physiology Online [serial online] article 1; volume 1: 2008; available from http://www.medicalphysiologyonline.org

This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/ which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Editor’s note - conflict of interest: I commissioned, reviewed and edited this manuscript. I was Dr. Madanmohan’s student from 2001 through 2006. We have worked and published several articles together.

Please cite this article as: Madanmohan. The power of pranayam. Medical Physiology Online [serial online] article 1; volume 1: 2008, available from http://www.medicalphysiologyonline.org

E.S.Prakash, Editor, Medical Physiology Online.

Is hyperphosphatemia an independent cause of tetany?

Type of article: Letter to the Editor

Harsha Halahalli, Department of Physiology, KS Hegde Medical Academy, Mangalore, India

Received 20 January 2008; accepted 20 January 2008.

Singh has rightly pointed out [1] that hyperphosphatemia could also trigger muscular spasms. Hyperphosphatemia could result from several causes such as impaired renal function, tissue necrosis, rhabdomyolysis, tumor lysis syndrome, and exogenous administration of phosphate commonly in the form of laxatives. If phosphate builds up rapidly in such situations, it may be associated with features of tetany. However, in such cases the tetany is due to the hypocalcemia that results from the excess phosphate levels and in that sense, hyperphosphatemia may not be an independent cause for tetany [2].

Milk-alkali syndrome is not always accompanied by hyperphosphatemia [4]. Unfortunately, in the case report by Goetz [3], serum phosphate levels at the time of admission are not reported and those reported for the sixth day after admission are within normal limits. The tetany observed in this case despite the hypercalcemia could be attributed to the accompanying alkalosis which is known to reduce ionized calcium levels. It is possible that the level of ionized calcium which modulates membrane excitability is sufficiently low so as to cause tetany even though total serum calcium is moderately elevated.

Thus, my interpretation is that hyperphosphatemia could be associated with tetany only if it were also accompanied by reduced serum levels of ionized calcium.

Was the tetany in the case report by Goetz [3] due to hyperphosphatemia? Well, it is questionable.

Conflict of interests: none

References:

[1] Singh S. Milk alkali tetany. Medical Physiology Online 2008 [Link], accessed 20 January 2008

[2] Domico MB, Huynh V, Anand SK, Mink R. Severe hyperphosphatemia and hypocalcemic tetany after oral laxative administration in a 3-month-old infant.
Pediatrics. 2006; 118: e1580-1583.

[3] Goetz AA. Milk-alkali syndrome with jaundice and tetany. California Medicine 1958; 89: 136-139

[4] Felsenfeld AJ and Levine BS. Milk alkali Syndrome and the dynamics of calcium homeostasis. Clin J Am Soc Nephrol 2006; 1: 641–654.

Reviewed by E.S.Prakash, Editor, Medical Physiology Online.

Ill-conceived questions

Type of article: Letter to the Editor

Harsha Halahalli, Department of Physiology, KS Hegde Medical Academy, Mangalore, India.

Received 20 January 2008; accepted 20 January 2008.

I agree with the author [1] that, from a mechanistic point of view, little is achieved by differentiating the terms "tetanus" and "tetany". Tetany is best thought of as a clinical feature that may be seen in a variety of conditions including Clostridium tetani infections and hypocalcemia. The line of questioning that is referred to by the author does lead to the erroneous conclusion that tetany is a distinct condition that is attributable solely to hypocaclcemia. This is just one example of how ill-conceived and poorly framed questions could create flawed concepts in students. Having said this, it may however be noted that there is a difference in the pathogenesis of tetany resulting from tetanotoxin and hypocalcemia. While the site of action of tetanotoxin is pre-synaptic to the alpha-motorneurons in the spinal cord, hypocalcemia affects the motor neuronal membrane itself [2]. But the consequence of both is the increase in the firing rate of alpha-motoneurons resulting in the features of tetany.

Conflict of interests: none

References:

[1] Prakash ES. What is the difference between tetanus and tetany? Medical Physiology Online, article 3; volume 1: 2008; available from http://www.medicalphysiologyonline.org, accessed 17 January 2008

[2] Kandel ER, Schwartz JH and Jessel MT. Chapter 14: Transmitter Release; In: Principles of Neural Sciences, 4th Edn, Mc Graw Hill Co., New York, 2000.

Editor's note: I commissioned and reviewed this letter.
E.S.Prakash, Editor, Medical Physiology Online

Milk and alkali tetany

Type of article: Letter to the Editor

Satendra Singh, Department of Physiology, Pt Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, 124001, India. E-mail: dr.satendra [at] gmail [dot] com

Received 14 January 2008; accepted 16 January 2008

In agreement with the author [1], I would like to add that though hypocalcemia is a common cause of tetany, an excess of phosphate (high phosphate-to-calcium ratio) could also trigger muscular spasms. Milk-and-alkali tetany is an example of this imbalance. [2]

References:

[1] Prakash ES. What is the difference between tetanus and tetany? Medical Physiology Online [serial online] article 3; volume 1: 2008; available from http://www.medicalphysiologyonline.org, [link to the article] accessed 14 January 2008.

[2] Goetz AA. Milk-alkali syndrome with jaundice and tetany. California Medicine 1958; 89: 136-139.

Conflict of interest: none

Please cite this letter as: Singh S. Milk and alkali tetany. Medical Physiology Online [serial online] article 3.1; volume 1: 2008; available from http://medicalphysiologyonline.blogspot.com [Link]

Reviewed by E.S.Prakash, Editor, Medical Physiology Online.