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<p style="text-align:justify;">[[Agni]] is a responsible factor for digestion, transformation, and metabolism in the body. The term ‘dhatvagni’ means the fraction of [[agni]] that functions at various body components ([[dhatu]]) for nourishment and metabolism. It is responsible for the metabolic transformation of food consumed and its assimilation. [[Agni]] is the supreme physiological authority in the human body<ref>A. C. Bhaktivedanta Swami Prabhupāda, 1972. Bhagavad-gītā as it is. Purushottama Yoga, Chapter 15, Shloka No. 14, New York: Bhaktivedanta Book Trust, Page No.517</ref> and is of 13 types. Jatharagni is for digestion, five bhootagni for metabolism of [[panchamahabhuta]] components, and seven dhatvagni for metabolism of [[dhatu]] or tissues.[Chakrapani on Cha.Sa.[[Chikitsa Sthana]] 15] 
<br/>The dhatvagni assimilates and synthesizes the [[dhatu]] or tissues of the human body. It is located in the respective [[srotas]] of the particular [[dhatu]].<ref>Dhargalkar Nandini, Sarira Kriya Vidnana- A textbook of Physiology in Ayurveda, Packagni-Jatharagni,Acchapittam,Bhutagni,Dhatvagni, Part 2, Second edition 2010, Chaukhamba Sanskrit Series Office,Varanasi, Page No.123</ref>  Dhatvagni is responsible for the transformation of one [[dhatu]] into another.<ref>NAMASTE - Portal [Internet]. [cited 2022 Jul 9]. Available from: http://namstp.ayush.gov.in/#/sat</ref> This article describes the concept and applications of dhatvagni in medical sciences.
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{{Infobox

|title =  Dhatvagni
|label1 = Section/Chapter/topic
|data1 = Concepts / [[Agni]]/ [[Dhatvagni]]  

|label2 = Authors
|data2 = Bhojani M.K.<sup>1</sup>, Sharma Raksha <sup>1</sup>, Joglekar A.A.<sup>2</sup>

|label3 = Reviewer 
|data3 =  [[Gopal Basisht|Basisht G.]]<sup>3</sup>

|label4 = Editor 
|data4 = [[Yogesh Deole|Deole Y.S.]]<sup>4</sup>

|label5 = Affiliations
|data5 = <sup>1</sup> Department of Kriya Sharira, All India Institute of Ayurveda, New Delhi, India
<sup>2</sup>Department of Samhita Siddhant, All India Institute of Ayurveda, New Delhi, India
<sup>3</sup> Rheumatologist, Orlando, Florida, U.S.A.
<sup>4</sup>Department of Kayachikitsa, G.J. Patel Institute of Ayurvedic Studies and Research, New Vallabh Vidyanagar, Anand, Gujarat, India 
|label6 = Correspondence email
|data6 = meera.samhita@aiia.gov.in, carakasamhita@gmail.com 

|label7 = Publisher 
|data7 = [[Charak Samhita Research, Training and Development Centre]], I.T.R.A., Jamnagar, India

|label8 = Date of first publication:
|data8 = September 13, 2022

|label9 = DOI
|data9 = {{DoiWithLink}}
}}

==Synonyms==
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[[Dhatu]]-ushma [Cha.Sa.[[Chikitsa Sthana]] 8/39-40], dhatupaktru [Cha.Sa.[[Chikitsa Sthana]] 15/38], dhatupakta, dhatupachaka agni [A.S.Sutra Sthana 19/16]<ref name= Sangraha> Vridha Vagbhata, Ashtanga Sangraha. Edited by Shivaprasad Sharma. 3rd ed. Varanasi: Chaukhamba sanskrit series office;2012.</ref>
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==Classification==
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The management of diseases depends on correction of [[agni]] and restoration of well-formed [[dhatu]]. [Chakrapani on Cha.Sa.[[Sutra Sthana]] 30/28]. The dhatvagni is classified into seven types as below: 
*[[Rasa]] dhatvagni
*[[Rakta]] dhatvagni
*[[Mamsa]] dhatvagni
*[[Meda]] dhatvagni
*[[Asthi]] dhatvagni
*[[Majja]] dhatvagni
*[[Shukra]] dhatvagni
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==Physiology of dhatvagni==
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[[Dhatu]]s are the structural and functional units that act as [[dosha]] and [[mala]] seats. The functioning of dhatvagni (dhatvagnipaaka) includes overall nourishment and development of the body structures. Dhatvagnipaaka refers to the sequential changes undergone by the essence of food through the medium of seven dhatvagni entities.
[[File: Fig_1_Datu_agni.JPG|500px|'''Figure 1: Action of different agnis on their respective dhatus and their products '''|thumb]]
[[File: Fig_3_Datu_agni.JPG|500px|'''Figure 2: Process of Formation of different Dhatus '''|thumb]]

The seven dhatvagni act upon the respective [[dhatu]] by which each [[dhatu]] is metabolized into two parts i.e., essence (prasada bhaga) and by-products (mala bhaga). [Chakrapani on Cha.Sa.[[Chikitsa Sthana]] 15/15] [[Dhatu]] is metabolized by their inherent heat (ushma) or dhatvagni (transforming enzymes in the tissue elements). The nourishing fraction of [[dhatu]] (nutrient tissue elements) further nourishes the subsequent [[dhatu]] through their respective [[srotas]] (channels of circulation). For example, a poshaka [[rasa dhatu]] nourishes the [[rakta dhatu]].[Cha.Sa.[[Chikitsa Sthana]] 8/39] In this process, the formation of essence (prasad bhaga) can be correlated with anabolic pathways. The formation of metabolic wastes or by-products (kitta-paka) can be correlated with catabolic pathways.
 
The cell can carry on the metabolic process with the aid of enzymes (agnipitta), which are organic catalysts. A catalyst regulates the rate of a chemical reaction's acceleration without change in itself. Few enzymes, such as the digestive enzymes (comparable with jatharaagni), function outside the cell. Most enzymes are intracellular (comparable to dhatvagni and bhutagni). Enzyme oxidation that catalyzes an oxidation-reduction process is termed as ‘oxidase’. An enzyme concerned with the digestion of protein is a protease.<ref>Robinson PK. Enzymes: principles and biotechnological applications. Essays Biochem. 2015;59:1-41. doi: 10.1042/bse0590001. Erratum in: Essays Biochem. 2015;59:75. PMID: 26504249; PMCID: PMC4692135.</ref> This intracellular and extracellular metabolism can be perceived as the dhatvagnipaka.

'''Role of dhatvagni in pathogenesis:'''

The jatharagni essentially nourishes the respective [[dhatu]] in the form of dhatvagni residing in each of the [[dhatu]]. [A.H.Sutra Sthana 11/34]<ref name= Hridaya > Vagbhata. Ashtanga Hridayam. Edited by Harishastri Paradkar Vaidya. 1st ed. Varanasi: Krishnadas Academy;2000.</ref> The dhatvagni is responsible for the increase (vriddhi)/ decrease (kshaya) of the representative [[dhatu]].  The hypo functioning (saada) of the dhatvagni leads to the increase in the respective [[dhatu]]. While hyper functioning (atideepti) leads to diminished production (kshaya) of the [[dhatu]]. Thus, every [[dhatu]]'s metabolism depends on the functions of the dhatvagni, preceding and subsequent [[dhatu]]. 

Interaction of [[dosha]]-[[dhatu]] (samurchhana) is the basis of pathogenesis. The state of [[agni]] should be considered in the pathogenesis. Any derangement of [[dosha]], if not corrected properly, progresses deeper into the [[dhatu]]s and becomes more challenging to correct. Progressive pathogenesis in any [[dhatu]] should be controlled by specific measures, otherwise it affects other sequential [[dhatu]]s. [Su.Sa.Sutra Sthana 21]<ref name= Susruta> Sushruta. Sushruta Samhita. Edited by Jadavaji Trikamji Aacharya. 8th ed. Varanasi: Chaukhambha Orientalia;2005.</ref> So the role of dhatvagni is very important for metabolic disorders like dyslilipdemia (medoroga), obstinate urinary disease including diabetes ([[prameha]]), obesity (sthaulya). [[Agni]] and ultimately the dhatvagni are the basic concepts that are important to rule out the cause and treatment of any disease. The crucial aspects of concept of dhatvagni can be summarized as shown in Figure 1

This concept can also be depicted through the flowchart as given in Figure 2 [Dalhana on Su.Sa.Sutra Sthana 14/10]<ref name=Susruta/>

==Importance of concept of dhatvagni in physiology==
[[File: Fig_2_Datu_agni.JPG|500px|'''Figure 3: Dhatvagnipaka (intermediate metabolism)- Synthesis of constituents of sthayi (poshya) dhatu '''|thumb]]
Dhatvagni, in general, represents the process of tissue metabolism and assimilation. Different types of wholesome foods ingested in the form of eatables, drinkables, lickables and masticables stimulate digestion (antaragni). They are further digested by respective bhutagni (specific digestion per primary constituent or element). In due course of time, food gets transformed into different [[dhatu]] in the presence of dhatvagni (tissue-specific digestion and metabolism) [A.H.Sharira Sthana 3/62]<ref name=Hridaya/> and [[vata]] (vyanavayu) by the process of dhatvagnipaka. [A.S.Sharira Sthana 6]<ref name=Sangraha/> It nourishes the tissues through channels of circulation without interruption and produces plumpness, strength, complexion, health, and longevity. The tissues are sustained by getting fed by various nourishing factors (poshaka dhatu). Thus, it plays a vital role in maintaining the digestive physiology and assimilation in the body. [Cha.Sa.[[Sutra Sthana]] 28/3] Therefore, the whole genesis, metabolism, functioning and elimination of [[dhatu]] are dependent on this process of dhatvagnipaaka. [Cha.Sa.[[Sutra Sthana]] 28/3] Hence, it is the basis of the ksheeradadhinyaya (law of complete transformation of one substance to other like milk into curd) and kedarikulyanyaya (sequential transformation of tissues just like canals in a farm). This depicts the [[dhatu]] metabolism. [Chakrapani on Cha.Sa.[[Chikitsa Sthana]] 15/16] Thus, the systematic nourishment of [[dhatu]] (dhatusnehaparampara) is maintained through dhatvagni. [Cha.Sa.[[Chikitsa Sthana]] 15/19][Arunadatta on A.H.Sharira Sthana 3/70]<ref name=Hridaya/>

==Importance of the concept of dhatvagni in understanding disease pathology and disease treatment==

[[Agni]] is the physiological entity responsible for the status of [[dosha]]. [Cha.Sa.[[Chikitsa Sthana]]5/136] The dhatvagni being a part of this [[agni]] component, is thus equally responsible in the maintenance of health and even in the affliction of diseases. The dhatvagni is a determinant of the production and functions of [[dhatu]]. Hence its proper functioning is of utmost importance in health. Imbalance can lead to disease manifestation. For instance, in condition like [[raktapitta]], the excessive [[pitta]] is responsible for the overstimulation of [[agni]] and dhatvagni, leading to the depletion of quality of [[rakta dhatu]] and liquidity (dravana).[Cha.Sa.[[Chikitsa Sthana]] 4/8] Here the dhatvagni is overstimulated, leading to an imbalance in the tissue metabolism. Also, in conditions like obesity (sthoulya), the [[meda dhatu]] metabolism weakens, leading to excessive [[meda]] (fat deposition). Undernourishment of the remaining [[dhatu]] depicts the slow metabolism of meda (meda-dhatvagnimandya) in the body. [Cha.Sa.[[Sutra Sthana]] 21/5-8]

In the disease [[rajayakshma]], depletion of [[dhatu]] is observed. Dhatvagni plays a pivotal role in the pathological process.[Cha.Sa.[[Chikitsa Sthana]] 8/39-40] The text mentions the term 'ushma' in various instances while explaining the metabolism and formation of different [[dhatu]] ([[rakta dhatu]], [[mamsa dhatu]], [[asthi dhatu]]). [Cha.Sa.[[Chikitsa Sthana]] 15/28-31] This concept is also applicable in the pathogenesis of [[pandu]] roga, where the nourishment of [[dhatu]] is hampered leading to laxity and heaviness of [[dhatu]] (dhatushaithilya and dhatugaurava). The quality of the rasa-raktadi dhatu is hampered to a great extent in this condition.[Cha.Sa.[[Chikitsa Sthana]] 16/4-6] The dhatugata disorders are result of dysfunctions of dhatvagni. Dhatvagni is responsible for breakdown (bhinnasanghata), oxidation (dahana) leading to heat or energy generation (tapana).

==Recent researches on dhatvagni==

# A research work on the concept of dhatwagnipaka in an Ayurvedic perspective showed that prasadpaka can be compared with anabolic pathways and kittapaka with catabolic pathways.<ref>Vani G, Prasad JSRA. Concept of dhatvagnipaka in Ayurvedic perspective in comparison with tissue metabolism. Int J Res Ayurveda Pharm. 2016 May 5;7(2):92–7.</ref>
#In the research on role of dhatwagni in carcinogenesis, dhatvagni is related with gene mutation and disequilibrium (vishamaavastha) of [[agni]] leading to manifestation of cancer condition.<ref>Rao SD. Dhatwagni vyapara in carcinogenesis. Anc Sci Life. 1994;14(1–2):61–7.</ref> The study further states that disequilibrium of [[agni]] causes improper digestion and metabolism leading to decreased or increased or irregular formation of tissues. This is observed in carcinogenesis where intermediate by-products are formed in place of normal protein. The state of irregular dhatvagni is the root cause of tumor.
#In the work on location of physiological activities of dhatwagni and bhautikagni the physiological functioning of dhatvagni is described along with the pathologies in the respective [[dhatu]] due to the malfunctioning of dhatvagni.<ref>Kalpana D. Sathe.2016, Location of Physiological Activities of Dhatwagni And Bhautikagni. Int J Recent Sci Res. 7(2), pp. 9133-9136.</ref> This study concludes that the location of dhatvagni is in the respective tissue of particular [[srotas]] (transportation and transformation system) and cellular level.  Secondly, the dhatvagni activity and [[bhutagni]] activity can be correlated with catalyst of dhatusnehaparampara and dhatukshalan by bala production by bhautikagnipaka respectively.
#Dhatvagni is considered in the synthesis of new tissue and yielding of energy for the functioning of existent tissue.<ref>A Brief Mention of Agni In Ayurveda, GJRA - Global Journal For Research Analysis(GJRA), GJRA | World Wide Journals [Internet]. [cited 2022 Jul 8]. Available from: https://www.worldwidejournals.com/global-journal-for-research-analysis-GJRA/article/a-brief-mention-of-agni-in-ayurveda/MTEwOTg=/?is=1&b1=61&k=16</ref> Bhutagni acts on respective  [[mahabhuta]] portion and  dhatvagni acts on respective [[dhatu]]s for nutritional strength, complexion, and happy life.
#A study of dhatvagni with special reference to hypothyroidism depicted that abnormality at the level of [[meda dhatu]] (medodhatvagni vikriti) may be the cause of endocrinal disturbance related to thyroid gland functions. Secondly the excessive illumination of dhatwagni may cause rise in anabolism and catabolism.<ref>Sharma DV, Sharir MDK. Study of Dhatwagni vikriti W.S.R. to hypothyroidism. World Journal of Pharmaceutical Research. 10(5):10.</ref> Another study showed that the the clinical features of low dhatvagni functions (dhatvagnimandya) like slower metabolism (agninasha),  pallor (pandutwam), oligomenorrhoea (artavanasha), cold intolerance (sheetaasatmya) etc. can be correlated with symptoms of Hypothyroidism.<ref>Pawar VSD Deshpande DMS, Agni, Dhatwagnimandya, Hypothyroidism.2016;3.</ref>
#Selective production and transformation of [[dhatu]] is explained. Each dhatvagni synthesize and transform the constituents suitable to its particular [[dhatu]] as a part of selective action.<ref>Agrawal AK, Yadav CR, Meena MS. Physiological aspects of Agni. Ayu. 2010;31(3):395–8.</ref>  
#The inter-relationship between jatharagni and dhatvagni in the manifestation of different diseases is established. [[Agni]] are connected with each other and due to this relationship, vitiation of jatharagni results in vitiation of all the other [[agni]].<ref>Satani DKG, Raghvani H, Bhatt K. Interrelationship of Jatharagni and Dhatvagni in context to Dhatvagni Pradoshaj Vikaras. Journal of Ayurveda and Integrated Medical Sciences. 2017 Feb 28;2(01):180–5.</ref> 
#The inter relationship between the occurrence of [[ama]], dhatvagnimandya and their role in manifestation of diseases is observed in various diseases. In metabolic disorders like [[amavata]], medoroga, [[prameha]], sthaulya, etc. the role of [[ama]] and dhatvagni is very important.<ref>Shaikh JG, Burley AK, Deshmukh SG. Concept of Aama and Dhatvagni in Ayurveda. International Journal of Ayurveda. 2021 Feb 23;(0):15–7.</ref> 
#The role of dhatvagnimandya in the occurrence of various upadhatujanyavikara is discussed. Any kind  of  vitiation  to  the  status  of [[agni]] or dhatvagni, [[srotas]] and [[vata]] leads to manifestation of  upadhatupradoshajavikara.<ref>Gupta M. Understanding of Upadhatu Pradoshaja Vikara. Journal of Ayurveda and Integrated Medical Sciences. 2021 Sep 15;6(4):337–9.</ref>

==Contemporary approach==

Dhatvagni can be considered as an intermediate metabolism in contemporary light.<ref>C Dwarkanath, Digestion and Metabolism in Ayurveda, Section 2, reprinted 2010, Published by Chaukahmaba Krishnadas Academy, Varanasi, Page No. 126</ref> It is the conglomeration of sum of all intracellular chemical processes by which the nutritive material is converted into cellular matter.<ref>Veerappa S, McClure J. Intermediary metabolism. Anaesthesia & Intensive Care Medicine. 2020 Mar 1;21(3):162–7.</ref> Cellular energy is generated from aerobic oxidation of metabolic fuels (carbohydrates, fats, proteins) derived from the digestion of a meal or the breakdown of internal stores. These can also be compared with enzymes, the biocatalysts that speed up the biochemical reactions in living organisms.<ref>Robinson PK. Enzymes: principles and biotechnological applications. Essays Biochem. 2015 Nov 15; 59:1–41.</ref> The enzymes have varied actions depending upon the site of action and predicted function, also termed as the specificity of the enzyme.<ref>Hedstrom L. Enzyme Specificity and Selectivity. In: eLS [Internet]. John Wiley & Sons, Ltd; 2010 [cited 2022 Jul 14]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/9780470015902.a0000716.pub2</ref> Hence, the different types of enzymes have specific types of action based on the substrate diet taken. For instance, there are various enzymes like splitting enzymes (hydrolases), transferring enzymes (oxidases, reductases), and isomerases involved in the process of digestion.<ref>Patricia JJ, Dhamoon AS. Physiology, Digestion. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 Jul 14]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK544242/</ref> These can be compared with the functions of [[pitta dosha]] like breaking down particles (sanghatabheda), transformation (parinama), catalyst (pravritti) etc.<ref>C Dwarkanath, Digestion and Metabolism in Ayurveda, Section 2, Reprinted 2010, Chaukhambha Krishnadas Academy, Varanasi, pp.145.</ref> Dhatvagnipaaka can also be compared with the concepts of pilupaakavaada and pitharapaakavadaas put forth by the Nyaya-Vaisheshika philosophy. The pilupaka confers to the chemical transformation, while pitharapaka to the physical transformation.<ref>C Dwarkanath, Digestion and Metabolism in Ayurveda, Section 2, Reprinted 2010, Chaukhamba Krishnadas Academy, Varanasi, pp.112.</ref> The processes of metabolism, catabolism and anabolism are also closely related to the dhatvagnipaaka. The metabolism is a series of all the reactions that happen at the cellular level. Catabolism is the breakdown or the degradation of complex macromolecules, while anabolism synthesizes the macromolecules and tissues.<ref>Judge A, Dodd MS. Metabolism. Essays Biochem. 2020 Oct;64(4):607–47.</ref> More research on the relation between dhatvagni and specific digestive processes can provide new insights into understanding the physiology and management of diseases. 
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==Related chapters==

[[Vividhashitapitiya Adhyaya]], [[Sroto Vimana]], [[Rajayakshma Chikitsa]], [[Dhatu]], [[Grahani Chikitsa Adhyaya]], [[Trividhakukshiya Vimana Adhyaya]], [[Rasa Vimana Adhyaya]], [[Vividhashitapitiya Adhyaya]], [[Agni]], [[Agni mahabhuta]], [[Ahara vidhi]], [[Bhutagni]], [[Acid peptic diseases‎‎]], [[Deepana]], [[Pachana]] 

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