Review comments and Suggestions by Sabnis M.
Prameha is an important disease which is discussed in depth in all the samhitas. It seems that Prameha was prevalent disorder in samhita period were it was diagnosed in the light of turbidity of urine. All the samhitas has elaborated Prameha in the light of turbidity of urine and it seems that diagnostic criteria more over pointed towards the change in urine appearance and its metabolic contents. Frequency of Urine, alteration in consistency, change in volume of urine leads to the differentiation in the diagnosis of Prameha. Acharyas in those days definitely knew that these changes in urine were due to some metabolic changes in the body which can lead to complex disorders which can be fatal. As per the quotations in samhitas it is evident that any change in urine consistency was thought to serious disorder which was connected to change and vitiation of body tissues.
Modifications needed in the present text of chapter to improve it
Apparently the chapter is elaborated nicely. There are certain points which should be focused prominently. Observing the over all description of prameha in Samhita and specially in Charak Samhita this chapter of prameha has been described elsewhere in Sutra sathan apart from Nidansthan. It means that Charak wants to explore a different and complicated pathology which is different from routine samprapti . This topic is discussed in 17th Chapter of Sutra sthana where diseases of head and heart are discussed. It indicates that samprapti which is is mentioned in 17th chapter is more fatal than the samprapti elaborated in Nidana sthana. While discussing Nidan of prameha it is important to consider the pathogenesis from 17th Chapter which indicated the impact on oja due to prameha.
Discussing about the pathogenesis or samprapti of Prameha ,it can be broadly classified following types. Avarodhajanya samprapti, which is highly fatal and directly effects oja due to severe vitiation of Vata dosha. This is explained in 17th Chapter of Sutrasthan. The second type which is described in Prameha Nidan and has been broadly classified into 20 types depending on vitiation of Dosha. In Nidansathan again Prameha has been classified into two types that is
- Sthula Pramehi and Krusha Pramehi
- Krusha Pramehi.
Role of Kapha dosha
Prameha is primarily Kapha Dosha Disorder where kapha is vitiated due to its drava properties that is liquid property. In Prameha the drava property of kapha is excessively increased which leads to vitiation on Meda, mamsa,vasa, kleda and lasika. It is very important to note that Charak has specially mentioned that the vitiation of drava property of kapha dosha is specifically quantitative and not qualitative. This quantitative rise in kapha dosha vitiates the dushyas quantitatively . It has been mentioned in 17th Chapter of Sutra sthan that Kapha in normal status imparts strength to the tissues where as in vitiated states creates for waste products that is mala. Kidney and bladder are very close to Viseral fats, and Kleda and lasika which are in liquid state are quantitatively increased in Prameha . Due to quantitative increase in the volume of above tissues these get easily excreted through the kidneys and bladder causing turbidity ( Avila Mutrata ) in urine which is called as prameha.
The causes or Nidan explained by Charak in Prameha is very unique . Charak has emphasised on newly harvested grains. Its very important that the importance of old grains was known in those days. New grains are heavy to get digest and the proteins contents do not stabilize in newly harvested grains.
Classification of Prameha is also seen as per the physical make up of the person One is obese diabetic and second is thin Diabetic . This classification is more over intended towards the treatment. If obesity is predominating in pramehi person ,treatment should be subjected to weight reduction and then the treatment to pacify the doshas is to be advocated . Similarly for a thin person treatment should intend to harmonize the tissues. It is very important to note that deformity in meda dhatu in sthula pramehi leads to multiple disorders. Obese diabetic patient have multiple pathologies starting from mitochondrial dysfunction, insulin resistance, inflammation, change in gut hormones and fat derived peptides and deranged appetite control system. While treating sthula pramehi all the above pathologies are to be targeted . Inflammation at the tissue level, especially adipose tissue is very important when it comes to diabetes. Diabetes and Obesity are itself inflammatory disorders. As previously explained the quantitative rise in meda, mamsa should be considered as mitochondrial dysfunction leading to inflammation at cellular level of these particular tissues. Once mitochondrial dysfunction takes place inflammation occurs in these tissue where inflammatory markers gets secreted making the tissue more inflamed . These inflamed tissues also disturb cell to cell harmony and functions of these tissues decline causing malfunctioning of these tissues. Meda dhatu is the most important dushya in Prameha. Meda dhatu is vitiated in two ways.
- Abaddha meda dhatu
- Bahu drava meda dhatu.
In Abaddha meda the function of meda dhatu gets decline . Fats are considered as one of the important glands which secretes very important hormones like Adeponectin. Adeponectin is a protein hormone which in ectocrine in nature. Adeponectin imparts three important function
- Anti inflammatory
- Insulin sensitivity
- Anti atherogenic
When there is decline in function of meda dhatu specially in Sthula pramehi the above functions gets deranged and adeponectin resistance is developed due to inflammatory changes. This increases insulin resistance which is second important pathology apart from mitochondrial dysfunction in Diabetes. Resistin hormone which is an important inflammatory hormone is raised leading to more inflammation and atherogenic changes.
Deranged adiponectin levels leads to more lipogenic activity creating improper angiogenesis and oxidative stress in immature adipocytes leading to hypoxia and necrosis in adipose tissue. This immature adipogenesis can be analogue to bahudrava meda dhatu which creates important pathology in Prameha.
Mamsa Dhatu: Mamsa dhatu is one of the important dushyas in prameha. Looking towards the sequence of pathology in the tissues first Meda dhatu is vitiated which then infiltrates in mamsa dhatu. As explained that mamsa dhatu is vitiated in Kaphaja prameha as well as Avaranjanya Prameha,it is very essential to understand that smooth muscles as well as skeletal muscles are affected in prameha. Fatty infiltration in skeletal muscles and oxidized lipid deposition in endothelial layer of the arteries is the basic pathology observed in muscles. This pathology develops strong insulin resistance at skeletal muscle level and also develops alterations in GLUT hormones situated in skeletal muscles. This pathology develops strong insulin resistance creating more hunger pangs and increasing food demand. This pathology can be compared with hyper functioning of Agni due to Avaranjanya vata.
Rakta dhatu: The inflammatory pathology in muscles and derangements in fat derived hormones along with oxidative stress leads to changes in rakta dhatu increasing the atherogenic tendency in the blood. Due to certain causes explained in Pittaja Prameha the first impact or the first hit of the above said pathology is on hepatocyte creating strong insulin resistance and fatty infiltration at hepatocyte level. Liver is said to be seat of rakta dhatu. This changes in hepatocytes creates many enzymetic changes in liver which stimulates the production of intra cell adhesion molecules ( ICAM) and vascular cell adhesion molecules( VCAM ) which helps in plaque formation in the arteries . This is how bahudrava shelshma and abaddha shelshma can lead to changes in rakta dhatu creating dreadful complications of Prameha.
Vasa: Vasa is the fat situated in muscle especially skeletal muscle which can be called as Intra muscular adipose tissue. (IMAT) Vasa is considered is a sub tissue or upadhatu of mamsa dhatu. Vasa can be considered as storage of adipose tissue situated in between the muscle fibres. This includes the visible storage of lipids in adipocytes located between the muscle fibres and between muscle groups which can be called as inters muscular fats. There also exists a smaller group of adipose tissue which is called as inter myocellular lipids. These inter myo cellular lipids are seen in people who are regular endurance exercisers and also in insulin resistant people. It suggests that these inter myocellular adipose tissues are not harmful every time. It has been said that excess of kapha deranges meda dhatu and that can also derange vasa which can be compared with inter myo cellular adipose tissue. This excess of vasa or inter myo cellular adipose tissue can develop strong insulin resistance. These small adipose depots in muscle also interact with muscles making them weak and malfunction.
Kleda : Kleda is an physiological factor in the body which is essential for the proper digestion of food and getting food assimilated into dhatus. It is one of the important components of Ahar parniamkarak bhav. In normalcy its ease digestion and is retained by sweat and is excreted by urine. When vitiated it is known to induce laxity in body tissue decline their function. As it is in liquid form it is described that kleda also liquefies the dhatus quantitatively. It gives dampness to the tissues and creates laxity in it. It is related to vitiated kapha and Meda dhatu and is known to get excreted through urine. Rotting and putrefying are some of the meanings of it. It shows the decomposition of the tissues. Kleda in vitiated form can be one of the inflammatory factors responsible for creating laxity in tissues. Kleda can be ascribed as an inflammation creating factor at cellular level in meda dhatu. It can also be said that, kleda in vitiated state disturbs the micro environment of the tissues or dhatus. Considering prameha to be analogue of diabetes that glucose intolerance is a known cause of hyper tonicity and known correlate of obesity, glucose intolerance could confound or explain associations between hypertonicity and obesity. Kleda formation can be more observed in Kaphaja prameha or sthula pramehi due to excessive vitiation of kapha and meda. Kleda formation can be compared with plasma hypertonicity as a response to hyperglycemia. This hypertonicity dehydrates the cell and increase in intercellular fluid is observed which makes the cells and tissue weak and mal function. It is well known that the extracellular volume is maintained at the expense of the intracellular space. The altered fluid distribution which is in the form of kleda is recognized as a complication of lower metabolism at cell level . Relative over hydration vs cell dehydration, and abnormal fluid regulation vs normal adaptation to hyperosmotic stress could have different implications for obesity prevention and treatment Obesity and hypertonicity are associated with metabolic dysregulation, increased protein breakdown and glucose intolerance, decreased lipolysis, and negative outcomes including impaired physical performance, increased risk of incident diabetes and disability (Bratusch-Marrain and DeFronzo, 1983; Sawka, 1992; Berneis et al., 1999; Keller et al., 2003; Stookey et al., 2004a, b). Like obesity, hypertonicity is both cause and consequence of glucose dysregulation (Waldhausl et al., 1979; Wolfe et al., 1979; Bratusch-Marrain and DeFronzo, 1983; Burg and Kador, 1988; Komjati et al., 1989; Echegaray et al., 2001). As maximum fats are situated in abdomen in the form of visceral fats these extra cellular fluids can be excreted through kidney and bladder which increases the volume and turbidity of urine. It can be said that kleda formation is merely a out of chronic low grade inflammation at a cellular level which induces mal function of cell and increases the volume of urine making the tissue weaker and weaker.
Majja Dhatu : Chronic low-grade inflammatory reaction occurring in several organ tissues, including the adipose tissue. Infiltration of bone marrow derived leukocytes (granulocytes, monocytes, lymphocytes) into expanding adipose depots appears to be an integral component of inflammation in obesity. As kleda and kapha are the most important factors which disturbs the tissue environment in Prameha. Excess of glycation on bone marrow cells leads to micro angiopathy rendering the tissue to multiple array of disturbed metabolism of bone marrow. Due to inflammation and deposition of fats ( meda) in bone marrow tissue ( Majja) leads to ischemic condition and lack of nutrition to bone marrow which inhibits its functions. Vasa and Lasika are also said to be the dushyas in prameha.
Vasa is fat situated in muscle in normal condition and lasika is fluid in between two muscles as explained by Chakrapani .
लसीका मांसत्वगन्तरे उदकभागः| वक्ष्यति हि शारीरे- “यन्मांसत्वगन्तरे उदकं, तल्लसीकाशब्दं लभते” (शा.अ.७)
Vasa is a intramuscular adipose tissues. Factually intra muscular adipose tissues should be in specific limits. These are actually considered as ectopic fats and are supposed to be inflammatory stimulators. More intra muscular fats declines the muscle function and also muscle elasticity and flexibility and increases ageing in the muscles. Quantitative increase and liquefaction of vasa due to kleda and kapha also will decrease the muscle function and lead to muscle weakness. The inter muscular fluids are having important role in muscle turnover and its functions. Maintaining vascular volume, trans capillary fluid filtration which allows continuous turnover of water bathing tissue cells, provides the medium for diffusional flux of oxygen and nutrients required for cellular metabolism and removal of metabolic by products in muscles. Lasika or inter muscular fluids is driven by capillary filtration, is important for the transport of immune cells, tumor metastasis, and return of filtered fluid and extravasated proteins to the blood. In Prameha this inter muscular fluids are disturbed which interrupt muscle function creating a decline in muscular strength and activity.
मृजाव्यायामवर्जनं - Lack of Exercise & Sedentary Life style Mruja has been explained as Udavartan by Chakrapani.
Prameha is discussed in Samhitas very prominently. All the three samhitas have included Prameha in their Nidan and Chikitsasthan. In Asthang sangraha it has occurred after the chapter of Mutraghat. Charak has again discussed it in 17th Chapter of Sutrasthan in Kiyanta Shiraseeya Adhyaya .
Important concepts mentioned in the chapter
Charak has explained Prameha as a group of symptoms classifying them on the base of doshik predominance. The syndrome is more over attributed to the deformity of urine that is turbidity in the urine which can come due to the metabolic fault primarily in meda dhatu and mamsa dhatu. This is basically due to vitiation of kapha dosha which when excess along with kleda vitiates flaccid meda and mamsa creating an increase in body fluids which ultimately is excreted through urine making the urine more turbid. These symptoms are a big group of syndromes gradually landing into metabolic disorder. Inactivity and sedentary life style is said to be one of the prime cause of this disease. It is elaborated that inactivity can lead to many metabolic changes at a tissue level mainly Meda dhatu ( adipose ) and( Mamsa dhatu) muscle tissue which further can vitiate other tissues like Majja ( bone marrow ) and further tissue leading to vitiation to Oja . When Majja , Shukra and Oja gets vitiate the disease becomes irreversible and cannot be treated. Starting from the reversible form of prognosis in kaphaja prameha and leading to not treatable form of Vataja Prameha , the progression of disease is due to long and chronic exposure to dietary and life style factors. The concept that Prameha is a life style disorder and if not managed properly can lead to majority of tissue distortion which can create major complication and can be fatal. Most important thought elaborated in the samprapti of prameha is the involvement of Kleda which is said to be a major culprit in creating the deviation in tissue metabolism. While treating Prameha Obesity or Sthulata is given prime importance and and on the basis of management Prameha has been classified into a krusha ( thin Pramehi ) and Sthula ( Obese Pramehi ). While treating krusha Pramehi Charak has specially advocated bruhan ( proper optimum nourishment ) to the tissue which can induce qualitative change in the tissue where as in Sthula pramehi only weight reduction is not targeted but sanshodhan is advised to correct the metabolism of the dhatus and then to treat Prameha. While performing samshodhan decrease in weight and volume of the person can be the secondary outcome. Rather than treating the symptoms the main message is to correct the dhatus ( tissue metabolism ) and manage the hormony of doshas as well as dhatus and save the deterioration in oja.
There are number of important concepts which have been elaborated but unfortunately are not practiced in today’s era. नवानामतिवेलमतिप्रमाणेनचोपयोगः, Charak has clearly elaborated that navaanna that is newly harvested grains are one of the important cause of deviation of kapha dosha which can make adipose tissue and muscles flaccid. There are lot of change in old grains and newly harvested grains in their starch proportion, protein content and certain enzymes which may make them more hard to get digested which can even have high glycation effects. More research in this area is needed which can make understand the whole Ayurved and modern medical fraternity that along with sweets even newly harvested grains should be avoided. Newly harvested grains will not have a direct effect on increasing the sugar levels but can create a change in micro environment of gut creating lower grade inflammation. Unfortunately milk and milk products , consumption of newly harvested pulses like harenu (Pisum sativum Linn.) and masha (Phaseolus radiates Linn.), consumed with ghee; The meat of domesticated, marshy and aquatic animals; is not been said to be diabetogenic in modern literature. No diabetologist or dietician in large holds the consumption of the above said food in diabetic patients where these are the main causative factors in creating the syndrome in Prameha. Change in Glycemic index, change in microbiota and effect of new grains along with the above food substances in creating AGEs can be investigated so that the concept of prohibiting the above said food material will be strongly supported. Curd is also said to be one of the important dietary factor which is responsible to initiate the samprapti in Prameha. In today’s era Yogurt is widely used which is very different from curds. Properties of immatured curd can be attributed to yogurt. More work is needed in this area that weather substances like yogurt should be advised to people under metabolic syndromes on regular basis or not. As it has been discussed that prameha is tridoshaja vyadhi with kapha dosha predominance and has been classified into three types depending on the predominance of dosha ultimately landing into Madhumeha. This concept is very important for the prognosis of this disorder. Early diagnosis of kaphaja prameha can prevent a person landing into more complicated and incurable stage of the disease. It is observed that no diagnosis is made on the basis of the doshik classification in the regular OPDs regarding prameha. It can said that Kaphaja Prameha is pre pre diabetic stage where patients do not turn up in the clinics until they land into Madhumeha or do not get any bodily signal that lands into certain disorder. Certain sensitive and specific bio markers can be developed which may help for very early diagnosis of Prameha and classify them as Kaphaja , pittaja prameha. Depending on the body weight prameha has been classified in stula and Krusha Pramehi. Its very clear that the management of Sthula pramehi has way through proper weight management and hormonisation of the body tissues which is not routinely observed. Obese pramehi are at more risk to metabolic events and also are more prone for cardiac and cerebrovascular faults. This part of treatment which can correct the dhatus is qualitative and quantitative manner should be well developed and more focus on balancing meda dhatu should be developed.
Key research areas in the chapter
It has been ascribed that Kapha dosha deviates meda dhatu and mansa dhatu if it goes in excess. Kapha dosha in normalacy gives strength to dhatus and if vitiated creates mala or more waste products. It is very important to identify the stage of vitiation of dhatu like meda dhatu not only clinically but biochemically which creates laxity in tissue.
It has also been elaborated that Kleda is responsible for laxity or sluggishness in the dushyas in Premeha. Kleda has been literally translated as body fluids, but all body fluids do not cause laxity. This group of body fluids should be identified to make this concept clearer. Prameha is the only disease where lasika and vasa are involved in disease process. It shows that meda and mansa dhatu are excessively vitiated where its updhatu are also involved. This makes prameha very serious disorder of Meda and mamsa dhatu more over when the abnormalities in the dhatus goes to the extent of updhatu. It is very important to recognise the exact pathological change in meda and mamsa dhatu at a molecular level. A thought can be given weather this change in upadhatus can be attributed to mitochondrial dysfunction of that particular tissue. Unfortunately no work has been conducted keeping this Ayurved concept in mind regarding vitiation of Updhatus in the light of Prameha Samprapti .
Suggestions to make this work more user friendly and followed by scientific community
To follow this work by scientific community following we have develop certain strategies. Explore prameha chapter as a whole not only in the light of diabetes mellitus but as a syndrome of metabolic disorders where diabetes is one of the part of it. We have to focus more on the cellular pathology rather than targeting bio chemical parameters like blood sugar, cholesterol. This can develop an interest among scientific community. Prameha pidaka should be explored more precisely and the changes at a micro level in the tissues should be identified. The significance of fat derived peptides, inflammatory markers, endothelial inflammatory markers in prameha pidaka must be acknowledged so that diabetic complications at micro level shall be addressed properly and a strong thought of preventing the complications with a new vision can be developed. Modern society is completely ignorant regarding the hetus mentioned and diet advised for prameha More emphasis should be given in identifying the cause and effect of these specific hetus and dietary factors which can help in prevention of diabetes.