Point of View: What is the difference between tetanus and tetany?
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.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.
Reference: [1] Ganong WF. Chapter 2. Excitable Tissue: Nerve; In: Review of Medical Physiology, 22nd edition, Mc Graw Hill Co, New York, 2005.
Please cite this article as: Prakash ES. What is the difference between tetanus and tetany? Medical Physiology Online, 16 Jan 2008; available from http://www.medicalphysiologyonline.org
Copyright © 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.
Prepublication record: The prepublication record for this manuscript MPO-001-2008 containing the draft manuscript, readers and editor’s comments can be accessed from http://www.medicalphysiologyonline.org
Medical Physiology Online 
ASK A QUESTION:
Which is more important in the genesis of tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis?
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, published 29 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
[2] Edmondson JW, Brashear RE, Li TK. Tetany: quantitative interrelationships between calcium and alkalosis. Am J Physiol 1975; 228: 1082-1086.
Please cite this as: Pavithran P. Which is more important in the genesis of tetanus and tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis? Medical Physiology Online, 29 Jan 2008, available from http://www.medicalphysiologyonline.org
Reviewed by E.S.Prakash, Editor, Medical Physiology Online
P Pavithran
January 29, 2009 at 10:59 AM
Reply to P Pavithran: Which is more important in the genesis of tetany: CSF hypocalcemia or serum hypocalcemia and alkalosis?
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
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, 29 Jan 2008 available from http://www.medicalphysiologyonline.org
[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
E.S.Prakash, Editor, Medical Physiology Online
Note: This submission was not peer reviewed.
E.S.Prakash, Editor, Medical Physiology Online
May 11, 2008 at 11:08 AM
Surface-potential theory for explaining the increase in sodium permeability seen in hypocalcemia
Anand Bhaskar, Department of Physiology, Christian Medical College, Vellore, 632002, India. E-mail: anandbhaskar [at] sify [dot] com.
Received 23 January 2008; accepted and published 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.
Reviewed by E.S.Prakash, Editor, Medical Physiology Online.
Please cite this letter as: Bhaskar A. Surface-potential theory for explaining the increase in sodium permeability seen in hypocalcemia. Medical Physiology Online, 16 Jan 2008, available from http://www.medicalphysiologyonline.org
Anand Bhaskar
January 24, 2008 at 10:51 AM
Correction to the article: what is the difference between tetanus and tetany? by E.S.Prakash
This correction refers to Prakash ES. What is the difference between tetanus and tetany? Medical Physiology Online, 16 Jan 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.
E.S.Prakash, Editor, Medical Physiology Online
E.S.Prakash
January 21, 2008 at 10:00 AM
Ill-conceived questions
Harsha Halahalli, Department of Physiology, KS Hegde Medical Academy, Mangalore, India.
Received, accepted and published 20 Jan 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, 17 Jan 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.
Reviewed by E.S.Prakash, Editor, Medical Physiology Online
Please cite this letter as Halahalli H. Ill conceived questions. Medical Physiology Online, 20 Jan 2008, available from http://www.medicalphysiologyonline.org
Harsha Halahalli
January 20, 2008 at 10:48 AM
Reply to ‘what is the difference between tetanus and tetany’
Selvakumar Balakrishnan, Final year undergraduate medical student, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India. E-mail: selvasriram87 [at] gmail [dot] com
Received, accepted and published 17 January 2008.
The message from this article [1] is clear enough for anyone to understand; i.e., the terms “tetanus” and “tetany” are not as different as we assume them to be. This deeper understanding is a refreshing experience and inspires us to stop and assimilate medical literature rather than reading it as such, a common practice these days. But it is also true that both the terms are not the same. In my opinion, “tetany” is a state of hyperexcitability in which a muscle can contract non-stop, and this is the final pathogenetic mechanism by which Clostridium tetani causes the disease “tetanus”. Maybe that is why the disease was named tetanus in the first place!
Acknowledgment: I am a student advisor for Medical Physiology Online.
Reference:
[1] Prakash ES. What is the difference between tetanus and tetany? Medical Physiology Online, 16 Jan 2008; available from http://www.medicalphysiologyonline.org
Editor’s note: I commissioned and reviewed this contribution from Selvakumar. We have learnt a lot together and have recently published an article together.
Please cite this letter as: Balakrishnan S. The difference between tetanus and tetany. Medical Physiology Online, 17 Jan 2008, available from http://www.medicalphysiologyonline.org
S Balakrishnan
January 17, 2008 at 10:32 AM
Milk and Alkali Tetany
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 and published 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, 16 Jan 2008; available from http://www.medicalphysiologyonline.org
[2] Goetz AA. Milk-alkali syndrome with jaundice and tetany. California Medicine 1958; 89: 136-139.
Conflict of interest: none declared
Reviewed and edited by E.S.Prakash, Editor, Medical Physiology Online
Please cite this letter as: Singh S. Milk and alkali tetany. Medical Physiology Online, 17 Jan 2008, available from http://www.medicalphysiologyonline.org
Satendra Singh
January 16, 2008 at 10:25 AM
Is hyperphosphatemia an independent cause of tetany?
Harsha Halahalli, Department of Physiology, KS Hegde Medical Academy, Mangalore, India
Received, accepted and published 20 January 2008.
Singh [1] has rightly pointed out 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.
Please cite this letter as: Halahalli H. Is hyperphosphatemia an independent cause of tetany? Medical Physiology Online, 20 Jan 2008, available from http://www.medicalphysiologyonline.org
Harsha Halahalli
January 20, 2008 at 10:29 AM