Shat-kriyakala - modern time review ;
Acharya Sushruta has described the concept of Kriyakala which seeks to explain the incident of vrana in terms of dosha disturbance. Vrana in modern parlance may be described as inflammatory process which may lead on to suppuration and ulceration. The concept of Kriyakala describes the mode and stages of the development of diseases. A good understanding of Kriyakala is very essential for early diagnosis, prognosis and for adopting preventive and curative measurement.
The term Kriyakala means the time of action. Kala or time in this context signifies the avastha or stage of the process of diseases.
Kalo hi nityaga avasthika; tatra avasthika vikaram apekshate ||
Ca.Vi.1/229(6)
Kriya or action refer to the resort to measure-aushadha, ahara and charya-with a view to eliminate and correct the doshic disturbance.
Kriyakala therefore, means the (early) recognition of the avastha or the stage of the process of disease and the resort to appropriate measures to correct the same.
As described above shatkriyakala are explained in vrana prashna adhyaya where Dalhan the commentator clarifies vrana in this content is not wound but vatadi humor (dosha) which themselves are cause for dehotpatti (responsible for structural and functional activity of body). They are the one who maintain normalcy. They physiologically go through the phase of chaya prakopa and prashama. This 3 step process is essential for sharira dharan.
The same dosha when get vitiated are cause for destruction of sharir.
Ta eva cha vyapanna pralaya hetava ||
Su.Su.21/3
Destruction (vyapanna) in case of sharir refers to vikruti or disease which undergoes evolution in 6 phase viz chaya, prakopa, prasara, sthanasansraya, vyakti and bhedha.
Inflammation is the local physiological response to tissue injury. It is not in itself, a disease, but is usually a manifestation of disease. Inflammation may have beneficial effect such as the destruction of invading micro-organisms and the walling-off of an abscess cavity to prevent spread of infection. However, may also produce diseases; for example, an abscess in the brain wound act as space occupying lesion compressing vital surrounding structure, or fibrosis resulting from chronic inflammation may destroy tissue permanently.
Inflammation is a protective response that involves immune cells, blood vessels and molecular mediator. It is one among the reason why Acharya Sushruta in this context has accepted rakta (shonita) as fourth dosha. Inflammation is a generic response, and therefore it is considered as a mechanism of innate immunity as compared to adopted immunity specific for each pathogen/hetu. Thus one hetu can cause many diseases and many hetu can cause one disease.
Sanchayam ca prakopam ca prasaram sthana sansrayam II
Vyaktim bhedam ca yo vetti doshanam sa bhaveda bhisaka II
SANCHAYA: It is the first phase of shat kriyakala; it is the stage of accumulation or the stage which represents the inceptive phase of the disease wherein the dosha are stated to have accumulated and stagnated in its own place (Dosha sthanani yesu sanchiyate II Su. Su 21/28), instead of freely circulating as in its normal avastha or phase.
Dosha in this condition are in compact form (Samhati rupa vridhi chaya II Dalhan Su. Su. 21/18). Samhata or compactness can be understood by symptom of vata dosha, vata dosha chaya which is manifested as stabdha purna kostha i.e. stabdha kostha (sense of dullness in abdomen/ sense of reduced intestinal motility) and purna kostha (sense of fullness/ sense of heaviness in abdomen). To fill up the space is normal function of vata which is manifested in excess in sanchaya avastha.
Pitta chaya is manifested with yellow tinge (pittavabhasata). Yellow is normal colour of pitta which is manifested as excess.
Kapha manifest as low body temperature/ reduce temperature (manda ushmata), heaviness of a part or full body (anga gaurav) and languor (alasya). These symptoms are seen in sthan (seat) where chaya rupa vridhi is seen.
The process of acute inflammation is initiated by resident immune cells (sthanik dosha) already present in the involve tissue mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. Receptors named pattern recognition receptors (PRRs) recognize generic molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen associated molecular pattern (PAMPs). Thus cells undergo activation and recognize non self and mechanism of opposition is initiated which is manifested as pradvesho vridhi hetusu i.e. aversion towards similar and attraction towards contraries.
In case of fever it is the pyrogen which may be exogenous (bacterial substance lipopolysaccharide (LPS) present on bacterial cell wall) or endogenous (cytokines, Interleukin-1 and Interleukin-6 etc). These pyrogens enter the body and activate the immune cells (antigen presenting cell) for the formation of cytokines and other factors or due to endogenous cause too activation of immune system takes place.
Atherosclerosis, formally considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and ultimately, the thrombotic complications of atherosclerosis. Oxidised levels of LDL, increased level of VLDL are the initiation or triggering factor of atherogenesis.
Sanchaya is the early initiation of marker C-reactive Protein which prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors.
Thus new insights into inflammation in atherosclerosis not only increase understanding of disease but also have practical clinical application in risk stratification and targeting of therapy for this scourge of growing worldwide importance rightly said by Dalhan as prathama kriyakala aadya karmavasara.
PRAKOPA: In this stage dosha gets vitiated or aggravated or the dosha previously accumulated/ stagnated get swollen and excited. Vilayan rupa vridhi prakopa (Dalhan). Vilayana here means bonding (samhata) is loss and dosha gets released.
In case of acute inflammation release of inflammatory mediators responsible for the clinical signs of inflammation takes place.
In case of fever Exogenous factors contain immunological protein called lipo-polysaccharide binding protein (LBP) which binds to LPS. The LBP-LPS complex then binds to the CD14 receptors of a nearby macrophage. It causes synthesis and release of various endogenous cytokines factors such as IL-1, IL-6, Tumour Necrosing Factor alpha (TNFα).
In atherosclerosis C- Reactive Protein is elevated and noted in the blood test. Increased level of LDL, VLDL and intermediate lipoproteins activate inflammatory functions of vascular endothelial cells. During atherogenesis, inflammatory cells (eg, monocyte-derived macrophages) accumulate in arteries, releasing growth factors/cytokines (eg, platelet-derived growth factor [PDGF], transforming growth factor-beta [TGF-β], granulocyte-macrophage colony-stimulating factor). Whereas PDGF may stimulate cholesteryl ester (CE) hydrolysis in cells, TGF-β appears to cause a decrease in lysosomal CE hydrolysis. The latter could lead to a transient reduction in intracellular free cholesterol.
In case of Allergens pre-sensitized mast cells respond by degranulating, releasing vasoactive chemicals such as histamine.
Clinical knowledge of Acharyas is saluted by significant and pertinent observation made by Sushruta to rakta as the medium (or substrate) for the spread or dissemination of the morbific factors of the disease. The aggravation of the dosha goes together with the disturbed or agitated state of rakta.
Yasmad rakta……..
Dalhan says alone dosha are unable to get prakopita whereas they are always dependent (paratantra) on rakta. Therefore Acharya have mentioned vata, pitta and kapha dushita rakta. Modern Science too explains release of inflammatory mediators in blood. Vasodilation and its resulting blood flow cause the redness (rubor) and increased heat (calor), (paridaha).
Acute inflammation is an immune-vascular response to an inflammatory stimulus. Vascular response is compared with rakta prakopa and cellular/ immune response to vata, pitta and kapha.
Similarly upon contact with PAMPs, tissue macrophages and mastocytes release vasoactive amines such as histamine and serotonin, as well as eicosanoids such as prostaglandin E2 and leukotriene B4 to remodel the local vasculature. Macrophages and endothelial cells release nitric oxide. These mediators vasodilate and permeabilize the blood vessels, which results in the net distribution of blood plasma from the vessel into the tissue space.
PRASARA: The third phase signifies to spread which generally takes place with help of vata and rakta. Dosha are stated to spread over and extend to other parts of the body.
TESHAM VAYUGATIMATVAT PRASARAN HETU SATYA API ACHAITANYA I
RAJASCA PRAVARTANA SARVABHAVANAM II
The biomotor or motive force which keeps the rakta moving all over the body, through its own channels-srotas- is vata.
The doshas which have become prakupita expand and overflow the limits of their respective locations. This is explained with two analogues viz the overflow which occurs during the process of fermentation in which ferments rises acquiring new and unseen qualities and the later analogy refers to the overflowing in water dam due to an increased accumulation of water in it, resulting in the two sides of the dam being connected into one vast and continuous sheet of water. It explains the various pressure gradients which enable the vimargagaman of inflammatory mediators from vascular tract into another tissue space, organ system or tract. Pressure gradient cause permeability of srotas/ channels and due to unknown reason dosha do the dusti of rakta and prasar of dushit rakta takes place through 15 different ways as mentioned by Acharya Sushruta.
In case of fever the cytokine factors are released into general circulation, where they migrate to the circumventricular organs of the brain due to easier absorption caused by the blood–brain barrier's reduced filtration action there. The cytokine factors then bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, the arachidonic acid pathway is then activated. Prostaglandin E2 (PGE2) is released which is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase.
In acute inflammation the inflammatory mediators molecules alter the blood vessels to permit the migration of leukocytes, mainly neutrophils and macrophages, outside of the blood vessels (extravasation) into the tissue. Vimargagaman as explained by Sushruta. The neutrophils migrate along a chemotactic gradient created by the local cells.
Increased permeability of blood vessels results in the net distribution of blood plasma from the vessel into the tissue space.
Vasodilation occurs first at the arteriole level (prakopa) progressing to the capillary level, and brings about and increase in the amount of blood present causing the redness and heat of inflammation. Thus paridaha symptom is present in Prakopa and prasar stage of shatkriyakala.
In allergy vasoactive chemicals like histamine propagate an excessive inflammatory response characterized by blood vessel dilation and cytokine release into the blood which move alongwith blood.
Acharya Sushruta analogues that the manner in which rain loaded clouds downpour in specific area where they are taken with help of wind similarly dosha whether permeating the entire body or a part of it- ardha sharira or become confined to a particular part or a member of the body, may give rise to disease in the site of their transportation.
Further Sushruta has also explained how sometime simple cause trigger exacerbarated symptoms of disease. Sushruta says prakupita doshas when not sufficiently excited may remain quiescent, coating (lina dosha) the internal pathways- margas- of the body and exacerbate to cause disease, when they are subsequently excited by appropriate exciting factors.
The above quiescence can be easily understood when patient says previous night he had egg and from next day he started with bloody stools with increased frequency which was later on diagnosed as Ulcerative Colitis, an inflammatory bowel disease. Here egg is exciting factor whereas in patient body the dosha/ inflammatory mediators were already prakopita and waiting for exciting causes.
Allergic rhinitis, urticarial etc are example of lina dosha wherein vascular response secrete histamine which excitingly stimulates cellular immunity to show up sudden (achaya purvak) symptoms.
STHANASANSRAYA: It is prodromal phase or the phase of purvarupa wherein disease is yet to be manifested fully. The excited dosha having extended to other parts of the body become localized and it marks the beginning of specific diseases pertaining to those sthan/ structures. It is also known as the stage of disease augmentation. Sthana samshraya means taking shelter in a place.
In case of fever PGE2 is the ultimate mediator of the febrile response. PGE2 acts on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3). EP3-expressing neurons in the POA innervate the dorsomedial hypothalamus (DMH), the rostral raphe pallidus nucleus in the medulla oblongata (rRPa), and the paraventricular nucleus (PVN) of the hypothalamus. Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which evokes non-shivering thermo-genesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface. It is presumed that the innervations from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs.
In case of atherosclerosis sthansansraya takes place in myocardial vessel leads to angina/ myocardial ischaemia/ infarct. If it takes place in brain it leads to Cerebro Vascular Event and if it takes place in peripheral vessel it leads to peripheral vessel disease.
If the inflammatory mediators attack the component of muscle it leads to myopathy whereas if intestine are involved it leads to Inflammatory Bowel Disease.
With respect of atherosclerosis when plasma LDL concentrations become elevated, the vessel wall eventually becomes lipid-engorged because it is unable to traffic the large amounts of endocytosed LDL-CE. In addition, lipoprotein entrapment by the extracellular matrix can lead to the progressive oxidation of LDL because of the action of lipoxygenases, reactive oxygen species, peroxynitrite, and/or myeloperoxidase found in oxidized LDL particles. A range of oxidized LDL species is thus generated, ultimately resulting in their delivery to vascular cells through several families of scavenger receptors. These “molecular Trojan horses” and “cellular saboteurs,” once formed or deposited in the cell, can contribute to, and participate in, formation of macrophage- and smooth muscle–derived foam cells.
The accumulation of the WBCs is termed "fatty streaks" early on because of the appearance being similar to that of marbled steak. These accumulations contain living, active WBCs (producing inflammation) and remnants of dead cells, including cholesterol and triglycerides. The remnants eventually include calcium and other crystallized materials within the outermost and oldest plaque. The "fatty streaks" reduce the elasticity of the artery walls. However, they do not affect blood flow for decades, because the artery muscular wall enlarges at the locations of plaque. The wall stiffening may eventually increase pulse pressure; widened pulse pressure is one possible result of advanced disease within the major arteries.
Atherosclerosis is therefore a syndrome affecting arterial blood vessels due to a chronic inflammatory response of WBCs in the walls of arteries. This is promoted by low-density lipoproteins (LDL, plasma proteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high-density lipoproteins (HDL). It is commonly referred to as a "hardening" or furring of the arteries. It is caused by the formation of multiple atheromatous plaques within the arteries
Thus depending on srotovaigunya or khavaigunya or depending on organ/ system disease is caused.
In acute inflammation, after resultant movement of plasma into the tissue which lead to resultant stasis due to increase in the concentration of the cells within blood. Stasis allows leukocytes to marginate (move) along the endothelium, a process critical to their recruitment into the tissues.
VYAKTI: This stage may be stated to be that of manifestation of the fully developed disease- the resultant dosha dushya samurchana.
In case of fever the brain ultimately orchestrates heat effector mechanisms via the autonomic nervous system. It causes increased heat production by increased muscle tone, shivering and hormones like epinephrine (adrenaline) and also prevents heat loss by way of vasoconstriction.
In acute inflammation the increased collection of fluid into the tissue causes it to swell (edema). The main symptoms of the inflammatory response are as follows.
The tissues in the area are red and warm, as a result of the large amount of blood reaching the site.
The tissues in the area are swollen, again due to the increased amount of blood and proteins that are present.
The area is painful, due the expansion of tissues, causing mechanical pressure on nerve cells, and also due to the presence of pain mediators.
Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body, such as when inflammation occurs on an epithelial surface, or pyogenic bacteria are involved.
Granulomatous inflammation: Characterized by the formation of granulomas, they are the result of a limited but diverse number of diseases, which include among others tuberculosis, leprosy, sarcoidosis, and syphilis.
Fibrinous inflammation: Inflammation resulting in a large increase in vascular permeability allows fibrin to pass through the blood vessels. If an appropriate procoagulative stimulus is present, such as cancer cells, a fibrinous exudate is deposited. This is commonly seen in serous cavities, where the conversion of fibrinous exudate into a scar can occur between serous membranes, limiting their function. The deposit sometimes forms a pseudo-membrane sheet. During inflammation of the intestine (Pseudo-membranous colitis), pseudo-membranous tubes can be formed.
Purulent inflammation: Inflammation resulting in large amount of pus, which consists of neutrophils, dead cells, and fluid. Infection by pyogenic bacteria such as staphylococci is characteristic of this kind of inflammation. Large, localized collections of pus enclosed by surrounding tissues are called abscesses.
Serous inflammation: Characterized by the copious effusion of non-viscous serous fluid, commonly produced by mesothelial cells of serous membranes, but may be derived from blood plasma. Skin blisters exemplify this pattern of inflammation.
Ulcerative inflammation: Inflammation occurring near an epithelium can result in the necrotic loss of tissue from the surface, exposing lower layers. The subsequent excavation in the epithelium is known as an ulcer.
Atherosclerotic lesions, or atherosclerotic plaques, are separated into two broad categories: Stable and unstable (also called vulnerable). The pathobiology of atherosclerotic lesions is very complicated but generally, stable atherosclerotic plaques, which tend to be asymptomatic, are rich in extracellular matrix and smooth muscle cells, while, unstable plaques are rich in macrophages and foam cells and the extracellular matrix separating the lesion from the arterial lumen (also known as the fibrous cap) is usually weak and prone to rupture. Ruptures of the fibrous cap expose thrombogenic material, such as collagen, to the circulation and eventually induce thrombus formation in the lumen. Upon formation, intraluminal thrombi can occlude arteries outright (e.g. coronary occlusion), but more often they detach, move into the circulation and eventually occluding smaller downstream branches causing thromboembolism. Apart from thromboembolism, chronically expanding atherosclerotic lesions can cause complete closure of the lumen. Chronically expanding lesions are often asymptomatic until lumen stenosis is so severe (usually over 80%) that blood supply to downstream tissue(s) is insufficient, resulting in ischemia.
BHEDA: It is the stage in which the disease may become sub-acute and chronic or incurable. Different types or variant of disease gets manifested.
In case of fever signs like increased blood pressure, neck stiffness, headache, giddiness, unconsciousness etc are seen in this phase.
In case of inflammation the outcome is manifested as:
Fibrosis: Large amounts of tissue destruction, or damage in tissues unable to regenerate, cannot be regenerated completely by the body. Fibrous scarring occurs in these areas of damage, forming a scar composed primarily of collagen. The scar will not contain any specialized structures, such as parenchymal cells, hence functional impairment may occur.
Abscess Formation: A cavity is formed containing pus, an opaque liquid containing dead white blood cells and bacteria with general debris from destroyed cells.
Chronic inflammation: In acute inflammation, if the injurious agent persists then chronic inflammation will ensue. This process marked by inflammation lasting many days, months or even years, may lead to the formation of a chronic wound. Chronic inflammation is characterized by the dominating presence of macrophages in the injured tissue. These cells are powerful defensive agents of the body, but the toxins they release (including reactive oxygen species) are injurious to the organism's own tissues as well as invading agents. As a consequence, chronic inflammation is almost always accompanied by tissue destruction.
The importance of the scheme of kriyakala in early diagnosis and for adopting preventive and curative measures can be appreciated better by taking into consideration some of the recent trends in the modern medicine relating to the pathogenesis of disease.
Avoid hetu which are caused of dosha vridhi. Natural antioxidants (i.e. β-carotene, vitamin C, and vitamin E) have been used as a potential strategy to reduce damage caused by oxidized LDL in patients with or at high risk for CHD, but the majority of clinical trials have not shown reductions in CHD events with this approach. More clinically reliable markers of oxidative stress or the development of more effective antioxidant therapies might make this strategy more useful.
Rakta should always be given importance in all diseases. The mode of prasar should be assessed and managed at the same level.
Elevated values of circulating inflammatory markers such as CRP, serum amyloid A, IL-6, and IL-1 receptor antagonist commonly accompany ACS. Such elevations correlate with in-hospital and short-term adverse prognosis and may reflect not only a high prevalence of myocardial necrosis, ischemia-reperfusion damage, or severe coronary atherosclerosis but also a primary inflammatory instigator of coronary instability.
Non communicable disease are the main concerned in the 21st century, Metabolic Syndrome is among the main factor thus early diagnosis and prevention taken by changing the lifestyle can improve the health of society.
Study can be made by using specific antibiotics or specific medicine for each stage of evolution of disease. It will surely reduce the chances of drug resistancy and also control the vigorous use of drugs.
Study of shatkriyakala specifically sthanasansraya will help to understand kha vaigunyakar causes and help prevention of such hetus from causing the disease.
Conclusion: The utility of this shatkriyakala is to enable the treating physician to recognize the disturbances in its early formative stages and to enable to take necessary steps in time, to correct and eliminate the offending factors before they have caused sufficient damage.
Prof. Dr. Satyendra Narayan Ojha ,
MD (KC), Ph.D.
Director , Yashawant ayurveda college , Post graduate teaching and research center ,
Kodoli ,Panhala , Kolhapur..
drsnojha@rediffmail. com - See more at: http://infoayushdarpan.blogspot.in/2016/02/ginger.html#sthash.p9onK67z.dpuf
Acharya Sushruta has described the concept of Kriyakala which seeks to explain the incident of vrana in terms of dosha disturbance. Vrana in modern parlance may be described as inflammatory process which may lead on to suppuration and ulceration. The concept of Kriyakala describes the mode and stages of the development of diseases. A good understanding of Kriyakala is very essential for early diagnosis, prognosis and for adopting preventive and curative measurement.
The term Kriyakala means the time of action. Kala or time in this context signifies the avastha or stage of the process of diseases.
Kalo hi nityaga avasthika; tatra avasthika vikaram apekshate ||
Ca.Vi.1/229(6)
Kriya or action refer to the resort to measure-aushadha, ahara and charya-with a view to eliminate and correct the doshic disturbance.
Kriyakala therefore, means the (early) recognition of the avastha or the stage of the process of disease and the resort to appropriate measures to correct the same.
As described above shatkriyakala are explained in vrana prashna adhyaya where Dalhan the commentator clarifies vrana in this content is not wound but vatadi humor (dosha) which themselves are cause for dehotpatti (responsible for structural and functional activity of body). They are the one who maintain normalcy. They physiologically go through the phase of chaya prakopa and prashama. This 3 step process is essential for sharira dharan.
The same dosha when get vitiated are cause for destruction of sharir.
Ta eva cha vyapanna pralaya hetava ||
Su.Su.21/3
Destruction (vyapanna) in case of sharir refers to vikruti or disease which undergoes evolution in 6 phase viz chaya, prakopa, prasara, sthanasansraya, vyakti and bhedha.
Inflammation is the local physiological response to tissue injury. It is not in itself, a disease, but is usually a manifestation of disease. Inflammation may have beneficial effect such as the destruction of invading micro-organisms and the walling-off of an abscess cavity to prevent spread of infection. However, may also produce diseases; for example, an abscess in the brain wound act as space occupying lesion compressing vital surrounding structure, or fibrosis resulting from chronic inflammation may destroy tissue permanently.
Inflammation is a protective response that involves immune cells, blood vessels and molecular mediator. It is one among the reason why Acharya Sushruta in this context has accepted rakta (shonita) as fourth dosha. Inflammation is a generic response, and therefore it is considered as a mechanism of innate immunity as compared to adopted immunity specific for each pathogen/hetu. Thus one hetu can cause many diseases and many hetu can cause one disease.
Sanchayam ca prakopam ca prasaram sthana sansrayam II
Vyaktim bhedam ca yo vetti doshanam sa bhaveda bhisaka II
SANCHAYA: It is the first phase of shat kriyakala; it is the stage of accumulation or the stage which represents the inceptive phase of the disease wherein the dosha are stated to have accumulated and stagnated in its own place (Dosha sthanani yesu sanchiyate II Su. Su 21/28), instead of freely circulating as in its normal avastha or phase.
Dosha in this condition are in compact form (Samhati rupa vridhi chaya II Dalhan Su. Su. 21/18). Samhata or compactness can be understood by symptom of vata dosha, vata dosha chaya which is manifested as stabdha purna kostha i.e. stabdha kostha (sense of dullness in abdomen/ sense of reduced intestinal motility) and purna kostha (sense of fullness/ sense of heaviness in abdomen). To fill up the space is normal function of vata which is manifested in excess in sanchaya avastha.
Pitta chaya is manifested with yellow tinge (pittavabhasata). Yellow is normal colour of pitta which is manifested as excess.
Kapha manifest as low body temperature/ reduce temperature (manda ushmata), heaviness of a part or full body (anga gaurav) and languor (alasya). These symptoms are seen in sthan (seat) where chaya rupa vridhi is seen.
The process of acute inflammation is initiated by resident immune cells (sthanik dosha) already present in the involve tissue mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. Receptors named pattern recognition receptors (PRRs) recognize generic molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen associated molecular pattern (PAMPs). Thus cells undergo activation and recognize non self and mechanism of opposition is initiated which is manifested as pradvesho vridhi hetusu i.e. aversion towards similar and attraction towards contraries.
In case of fever it is the pyrogen which may be exogenous (bacterial substance lipopolysaccharide (LPS) present on bacterial cell wall) or endogenous (cytokines, Interleukin-1 and Interleukin-6 etc). These pyrogens enter the body and activate the immune cells (antigen presenting cell) for the formation of cytokines and other factors or due to endogenous cause too activation of immune system takes place.
Atherosclerosis, formally considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and ultimately, the thrombotic complications of atherosclerosis. Oxidised levels of LDL, increased level of VLDL are the initiation or triggering factor of atherogenesis.
Sanchaya is the early initiation of marker C-reactive Protein which prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors.
Thus new insights into inflammation in atherosclerosis not only increase understanding of disease but also have practical clinical application in risk stratification and targeting of therapy for this scourge of growing worldwide importance rightly said by Dalhan as prathama kriyakala aadya karmavasara.
PRAKOPA: In this stage dosha gets vitiated or aggravated or the dosha previously accumulated/ stagnated get swollen and excited. Vilayan rupa vridhi prakopa (Dalhan). Vilayana here means bonding (samhata) is loss and dosha gets released.
In case of acute inflammation release of inflammatory mediators responsible for the clinical signs of inflammation takes place.
In case of fever Exogenous factors contain immunological protein called lipo-polysaccharide binding protein (LBP) which binds to LPS. The LBP-LPS complex then binds to the CD14 receptors of a nearby macrophage. It causes synthesis and release of various endogenous cytokines factors such as IL-1, IL-6, Tumour Necrosing Factor alpha (TNFα).
In atherosclerosis C- Reactive Protein is elevated and noted in the blood test. Increased level of LDL, VLDL and intermediate lipoproteins activate inflammatory functions of vascular endothelial cells. During atherogenesis, inflammatory cells (eg, monocyte-derived macrophages) accumulate in arteries, releasing growth factors/cytokines (eg, platelet-derived growth factor [PDGF], transforming growth factor-beta [TGF-β], granulocyte-macrophage colony-stimulating factor). Whereas PDGF may stimulate cholesteryl ester (CE) hydrolysis in cells, TGF-β appears to cause a decrease in lysosomal CE hydrolysis. The latter could lead to a transient reduction in intracellular free cholesterol.
In case of Allergens pre-sensitized mast cells respond by degranulating, releasing vasoactive chemicals such as histamine.
Clinical knowledge of Acharyas is saluted by significant and pertinent observation made by Sushruta to rakta as the medium (or substrate) for the spread or dissemination of the morbific factors of the disease. The aggravation of the dosha goes together with the disturbed or agitated state of rakta.
Yasmad rakta……..
Dalhan says alone dosha are unable to get prakopita whereas they are always dependent (paratantra) on rakta. Therefore Acharya have mentioned vata, pitta and kapha dushita rakta. Modern Science too explains release of inflammatory mediators in blood. Vasodilation and its resulting blood flow cause the redness (rubor) and increased heat (calor), (paridaha).
Acute inflammation is an immune-vascular response to an inflammatory stimulus. Vascular response is compared with rakta prakopa and cellular/ immune response to vata, pitta and kapha.
Similarly upon contact with PAMPs, tissue macrophages and mastocytes release vasoactive amines such as histamine and serotonin, as well as eicosanoids such as prostaglandin E2 and leukotriene B4 to remodel the local vasculature. Macrophages and endothelial cells release nitric oxide. These mediators vasodilate and permeabilize the blood vessels, which results in the net distribution of blood plasma from the vessel into the tissue space.
PRASARA: The third phase signifies to spread which generally takes place with help of vata and rakta. Dosha are stated to spread over and extend to other parts of the body.
TESHAM VAYUGATIMATVAT PRASARAN HETU SATYA API ACHAITANYA I
RAJASCA PRAVARTANA SARVABHAVANAM II
The biomotor or motive force which keeps the rakta moving all over the body, through its own channels-srotas- is vata.
The doshas which have become prakupita expand and overflow the limits of their respective locations. This is explained with two analogues viz the overflow which occurs during the process of fermentation in which ferments rises acquiring new and unseen qualities and the later analogy refers to the overflowing in water dam due to an increased accumulation of water in it, resulting in the two sides of the dam being connected into one vast and continuous sheet of water. It explains the various pressure gradients which enable the vimargagaman of inflammatory mediators from vascular tract into another tissue space, organ system or tract. Pressure gradient cause permeability of srotas/ channels and due to unknown reason dosha do the dusti of rakta and prasar of dushit rakta takes place through 15 different ways as mentioned by Acharya Sushruta.
In case of fever the cytokine factors are released into general circulation, where they migrate to the circumventricular organs of the brain due to easier absorption caused by the blood–brain barrier's reduced filtration action there. The cytokine factors then bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, the arachidonic acid pathway is then activated. Prostaglandin E2 (PGE2) is released which is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase.
In acute inflammation the inflammatory mediators molecules alter the blood vessels to permit the migration of leukocytes, mainly neutrophils and macrophages, outside of the blood vessels (extravasation) into the tissue. Vimargagaman as explained by Sushruta. The neutrophils migrate along a chemotactic gradient created by the local cells.
Increased permeability of blood vessels results in the net distribution of blood plasma from the vessel into the tissue space.
Vasodilation occurs first at the arteriole level (prakopa) progressing to the capillary level, and brings about and increase in the amount of blood present causing the redness and heat of inflammation. Thus paridaha symptom is present in Prakopa and prasar stage of shatkriyakala.
In allergy vasoactive chemicals like histamine propagate an excessive inflammatory response characterized by blood vessel dilation and cytokine release into the blood which move alongwith blood.
Acharya Sushruta analogues that the manner in which rain loaded clouds downpour in specific area where they are taken with help of wind similarly dosha whether permeating the entire body or a part of it- ardha sharira or become confined to a particular part or a member of the body, may give rise to disease in the site of their transportation.
Further Sushruta has also explained how sometime simple cause trigger exacerbarated symptoms of disease. Sushruta says prakupita doshas when not sufficiently excited may remain quiescent, coating (lina dosha) the internal pathways- margas- of the body and exacerbate to cause disease, when they are subsequently excited by appropriate exciting factors.
The above quiescence can be easily understood when patient says previous night he had egg and from next day he started with bloody stools with increased frequency which was later on diagnosed as Ulcerative Colitis, an inflammatory bowel disease. Here egg is exciting factor whereas in patient body the dosha/ inflammatory mediators were already prakopita and waiting for exciting causes.
Allergic rhinitis, urticarial etc are example of lina dosha wherein vascular response secrete histamine which excitingly stimulates cellular immunity to show up sudden (achaya purvak) symptoms.
STHANASANSRAYA: It is prodromal phase or the phase of purvarupa wherein disease is yet to be manifested fully. The excited dosha having extended to other parts of the body become localized and it marks the beginning of specific diseases pertaining to those sthan/ structures. It is also known as the stage of disease augmentation. Sthana samshraya means taking shelter in a place.
In case of fever PGE2 is the ultimate mediator of the febrile response. PGE2 acts on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3). EP3-expressing neurons in the POA innervate the dorsomedial hypothalamus (DMH), the rostral raphe pallidus nucleus in the medulla oblongata (rRPa), and the paraventricular nucleus (PVN) of the hypothalamus. Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which evokes non-shivering thermo-genesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface. It is presumed that the innervations from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs.
In case of atherosclerosis sthansansraya takes place in myocardial vessel leads to angina/ myocardial ischaemia/ infarct. If it takes place in brain it leads to Cerebro Vascular Event and if it takes place in peripheral vessel it leads to peripheral vessel disease.
If the inflammatory mediators attack the component of muscle it leads to myopathy whereas if intestine are involved it leads to Inflammatory Bowel Disease.
With respect of atherosclerosis when plasma LDL concentrations become elevated, the vessel wall eventually becomes lipid-engorged because it is unable to traffic the large amounts of endocytosed LDL-CE. In addition, lipoprotein entrapment by the extracellular matrix can lead to the progressive oxidation of LDL because of the action of lipoxygenases, reactive oxygen species, peroxynitrite, and/or myeloperoxidase found in oxidized LDL particles. A range of oxidized LDL species is thus generated, ultimately resulting in their delivery to vascular cells through several families of scavenger receptors. These “molecular Trojan horses” and “cellular saboteurs,” once formed or deposited in the cell, can contribute to, and participate in, formation of macrophage- and smooth muscle–derived foam cells.
The accumulation of the WBCs is termed "fatty streaks" early on because of the appearance being similar to that of marbled steak. These accumulations contain living, active WBCs (producing inflammation) and remnants of dead cells, including cholesterol and triglycerides. The remnants eventually include calcium and other crystallized materials within the outermost and oldest plaque. The "fatty streaks" reduce the elasticity of the artery walls. However, they do not affect blood flow for decades, because the artery muscular wall enlarges at the locations of plaque. The wall stiffening may eventually increase pulse pressure; widened pulse pressure is one possible result of advanced disease within the major arteries.
Atherosclerosis is therefore a syndrome affecting arterial blood vessels due to a chronic inflammatory response of WBCs in the walls of arteries. This is promoted by low-density lipoproteins (LDL, plasma proteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high-density lipoproteins (HDL). It is commonly referred to as a "hardening" or furring of the arteries. It is caused by the formation of multiple atheromatous plaques within the arteries
Thus depending on srotovaigunya or khavaigunya or depending on organ/ system disease is caused.
In acute inflammation, after resultant movement of plasma into the tissue which lead to resultant stasis due to increase in the concentration of the cells within blood. Stasis allows leukocytes to marginate (move) along the endothelium, a process critical to their recruitment into the tissues.
VYAKTI: This stage may be stated to be that of manifestation of the fully developed disease- the resultant dosha dushya samurchana.
In case of fever the brain ultimately orchestrates heat effector mechanisms via the autonomic nervous system. It causes increased heat production by increased muscle tone, shivering and hormones like epinephrine (adrenaline) and also prevents heat loss by way of vasoconstriction.
In acute inflammation the increased collection of fluid into the tissue causes it to swell (edema). The main symptoms of the inflammatory response are as follows.
The tissues in the area are red and warm, as a result of the large amount of blood reaching the site.
The tissues in the area are swollen, again due to the increased amount of blood and proteins that are present.
The area is painful, due the expansion of tissues, causing mechanical pressure on nerve cells, and also due to the presence of pain mediators.
Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body, such as when inflammation occurs on an epithelial surface, or pyogenic bacteria are involved.
Granulomatous inflammation: Characterized by the formation of granulomas, they are the result of a limited but diverse number of diseases, which include among others tuberculosis, leprosy, sarcoidosis, and syphilis.
Fibrinous inflammation: Inflammation resulting in a large increase in vascular permeability allows fibrin to pass through the blood vessels. If an appropriate procoagulative stimulus is present, such as cancer cells, a fibrinous exudate is deposited. This is commonly seen in serous cavities, where the conversion of fibrinous exudate into a scar can occur between serous membranes, limiting their function. The deposit sometimes forms a pseudo-membrane sheet. During inflammation of the intestine (Pseudo-membranous colitis), pseudo-membranous tubes can be formed.
Purulent inflammation: Inflammation resulting in large amount of pus, which consists of neutrophils, dead cells, and fluid. Infection by pyogenic bacteria such as staphylococci is characteristic of this kind of inflammation. Large, localized collections of pus enclosed by surrounding tissues are called abscesses.
Serous inflammation: Characterized by the copious effusion of non-viscous serous fluid, commonly produced by mesothelial cells of serous membranes, but may be derived from blood plasma. Skin blisters exemplify this pattern of inflammation.
Ulcerative inflammation: Inflammation occurring near an epithelium can result in the necrotic loss of tissue from the surface, exposing lower layers. The subsequent excavation in the epithelium is known as an ulcer.
Atherosclerotic lesions, or atherosclerotic plaques, are separated into two broad categories: Stable and unstable (also called vulnerable). The pathobiology of atherosclerotic lesions is very complicated but generally, stable atherosclerotic plaques, which tend to be asymptomatic, are rich in extracellular matrix and smooth muscle cells, while, unstable plaques are rich in macrophages and foam cells and the extracellular matrix separating the lesion from the arterial lumen (also known as the fibrous cap) is usually weak and prone to rupture. Ruptures of the fibrous cap expose thrombogenic material, such as collagen, to the circulation and eventually induce thrombus formation in the lumen. Upon formation, intraluminal thrombi can occlude arteries outright (e.g. coronary occlusion), but more often they detach, move into the circulation and eventually occluding smaller downstream branches causing thromboembolism. Apart from thromboembolism, chronically expanding atherosclerotic lesions can cause complete closure of the lumen. Chronically expanding lesions are often asymptomatic until lumen stenosis is so severe (usually over 80%) that blood supply to downstream tissue(s) is insufficient, resulting in ischemia.
BHEDA: It is the stage in which the disease may become sub-acute and chronic or incurable. Different types or variant of disease gets manifested.
In case of fever signs like increased blood pressure, neck stiffness, headache, giddiness, unconsciousness etc are seen in this phase.
In case of inflammation the outcome is manifested as:
Fibrosis: Large amounts of tissue destruction, or damage in tissues unable to regenerate, cannot be regenerated completely by the body. Fibrous scarring occurs in these areas of damage, forming a scar composed primarily of collagen. The scar will not contain any specialized structures, such as parenchymal cells, hence functional impairment may occur.
Abscess Formation: A cavity is formed containing pus, an opaque liquid containing dead white blood cells and bacteria with general debris from destroyed cells.
Chronic inflammation: In acute inflammation, if the injurious agent persists then chronic inflammation will ensue. This process marked by inflammation lasting many days, months or even years, may lead to the formation of a chronic wound. Chronic inflammation is characterized by the dominating presence of macrophages in the injured tissue. These cells are powerful defensive agents of the body, but the toxins they release (including reactive oxygen species) are injurious to the organism's own tissues as well as invading agents. As a consequence, chronic inflammation is almost always accompanied by tissue destruction.
The importance of the scheme of kriyakala in early diagnosis and for adopting preventive and curative measures can be appreciated better by taking into consideration some of the recent trends in the modern medicine relating to the pathogenesis of disease.
Avoid hetu which are caused of dosha vridhi. Natural antioxidants (i.e. β-carotene, vitamin C, and vitamin E) have been used as a potential strategy to reduce damage caused by oxidized LDL in patients with or at high risk for CHD, but the majority of clinical trials have not shown reductions in CHD events with this approach. More clinically reliable markers of oxidative stress or the development of more effective antioxidant therapies might make this strategy more useful.
Rakta should always be given importance in all diseases. The mode of prasar should be assessed and managed at the same level.
Elevated values of circulating inflammatory markers such as CRP, serum amyloid A, IL-6, and IL-1 receptor antagonist commonly accompany ACS. Such elevations correlate with in-hospital and short-term adverse prognosis and may reflect not only a high prevalence of myocardial necrosis, ischemia-reperfusion damage, or severe coronary atherosclerosis but also a primary inflammatory instigator of coronary instability.
Non communicable disease are the main concerned in the 21st century, Metabolic Syndrome is among the main factor thus early diagnosis and prevention taken by changing the lifestyle can improve the health of society.
Study can be made by using specific antibiotics or specific medicine for each stage of evolution of disease. It will surely reduce the chances of drug resistancy and also control the vigorous use of drugs.
Study of shatkriyakala specifically sthanasansraya will help to understand kha vaigunyakar causes and help prevention of such hetus from causing the disease.
Conclusion: The utility of this shatkriyakala is to enable the treating physician to recognize the disturbances in its early formative stages and to enable to take necessary steps in time, to correct and eliminate the offending factors before they have caused sufficient damage.
Prof. Dr. Satyendra Narayan Ojha ,
MD (KC), Ph.D.
Director , Yashawant ayurveda college , Post graduate teaching and research center ,
Kodoli ,Panhala , Kolhapur..
drsnojha@rediffmail. com - See more at: http://infoayushdarpan.blogspot.in/2016/02/ginger.html#sthash.p9onK67z.dpuf
