Changes

Concept of analytical knowledge: The concept of analytical knowledge or detailed knowledge of the body elements that is described here is very much similar to the concept of systems biology in contemporary science.

Concept of analytical knowledge: The concept of analytical knowledge or detailed knowledge of the body elements that is described here is very much similar to the concept of systems biology in contemporary science.

Systems biology studies biological systems by analyzing them (biologically, genetically, or chemically), by monitoring the gene, protein, and informational pathway responses, integrating these data and ultimately, formulating mathematical models that describe the structure of the system and its response to individual variations. Systems biology does not investigate individual genes or proteins one at a time. Rather, it investigates the behavior and relationships of all of the elements in a particular biological system while it is functioning. Thus, the systems biology theory understands the importance of the constituent units of the body as well as their networking. (Timothy Galitski, 2001)[1]

Systems biology studies biological systems by analyzing them (biologically, genetically, or chemically), by monitoring the gene, protein, and informational pathway responses, integrating these data and ultimately, formulating mathematical models that describe the structure of the system and its response to individual variations. Systems biology does not investigate individual genes or proteins one at a time. Rather, it investigates the behavior and relationships of all of the elements in a particular biological system while it is functioning. Thus, the systems biology theory understands the importance of the constituent units of the body as well as their networking. (Timothy Galitski, 2001)<ref> Timothy Galitski, and Leroy Hood. A new approach to decoding life: Systems Biology Annu. Rev. Genomics Hum. Genet. 2001; 2:343–72 </ref>

A simple example that can illustrate System biology approach is of sickle cell anemia. This disease is caused by a single point mutation at position 6 of the β-chain of hemoglobin, which changes hemoglobin’s oxygen affinity and promotes polymerization under hypoxic conditions. However, individuals with sickle cell disease can present with variety of symptoms which include hemolysis, inflammation, cell adhesion and end-organ ischemia-reperfusion injury and infarction. Patients also experience intermittent painful episodes due to acute vascular obstruction. (Mack KA) [2] There are many reasons for these different clinical manifestations, including the presence of other genes modifying the disease modifying genes (e.g., hemoglobin F). Hence, this example indicates that the knowledge of single gene is not sufficient to understand the disease. There is need to consider other genes or in other words other constituents of the body.  (verse 3)  

A simple example that can illustrate System biology approach is of sickle cell anemia. This disease is caused by a single point mutation at position 6 of the β-chain of hemoglobin, which changes hemoglobin’s oxygen affinity and promotes polymerization under hypoxic conditions. However, individuals with sickle cell disease can present with variety of symptoms which include hemolysis, inflammation, cell adhesion and end-organ ischemia-reperfusion injury and infarction. Patients also experience intermittent painful episodes due to acute vascular obstruction. (Mack KA) <ref> Mack KA, Kato GJ. Sickle cell disease and nitric oxide: A paradigm shift? Int J Biochem Cell Biol. 2006; 38(8): 1237–1243. </ref> There are many reasons for these different clinical manifestations, including the presence of other genes modifying the disease modifying genes (e.g., hemoglobin F). Hence, this example indicates that the knowledge of single gene is not sufficient to understand the disease. There is need to consider other genes or in other words other constituents of the body.  (verse 3)  

==== Definition of ''sharira'' and disequilibrium in body elements ====

==== Definition of ''sharira'' and disequilibrium in body elements ====

Cow’s urine and ''kapha dosha'' share similar physical properties i.e. both are liquid. Still cow’s urine reduces ''kapha'' because of differences in other attributes, viz. ''katu'' (pungent), ''ushna'' (producing heat in the body), ''ruksha''(dry, desiccating) etc. Thus, it can be inferred that more than the physical nature (''jati''),the attributes (''guna'') are responsible for the increase or decrease of ''dhatu'', and to reiterate this, the term ''guna'' has been added as a suffix to ''viparita'' (opposite) in the text.

Cow’s urine and ''kapha dosha'' share similar physical properties i.e. both are liquid. Still cow’s urine reduces ''kapha'' because of differences in other attributes, viz. ''katu'' (pungent), ''ushna'' (producing heat in the body), ''ruksha''(dry, desiccating) etc. Thus, it can be inferred that more than the physical nature (''jati''),the attributes (''guna'') are responsible for the increase or decrease of ''dhatu'', and to reiterate this, the term ''guna'' has been added as a suffix to ''viparita'' (opposite) in the text.

The concept explained here is simultaneous changes happening in two or more ''dhatus'' having mutually opposite attributes. An etiological or causative factor can cause an increase or decrease in different body elements disturbing the equilibrium. It is possible that the introduction of the etiological or causative factor may be catalyzing a cascade of events either independent or related to the ''dhatu'' bringing changes in them. This concept can be further understood by the concept of “cross-organ talks” explained in modern medicine. When there is change in status of any organ, there can be changes seen even in the distant organs through cellular networks.  For example, adipose tissue is an endocrine organ. The tissue produces and secretes a wide range of mediators regulating adipose tissue function in an auto-/paracrine manner and important distant targets, such as the liver, skeletal muscle, the pancreas and the cardiovascular system. The enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines in metabolic disorders such as obesity. Adipose tissue dysfunction has a central role in the development of insulin resistance, type 2 diabetes, and cardiovascular diseases. (Romacho T). [3]

The concept explained here is simultaneous changes happening in two or more ''dhatus'' having mutually opposite attributes. An etiological or causative factor can cause an increase or decrease in different body elements disturbing the equilibrium. It is possible that the introduction of the etiological or causative factor may be catalyzing a cascade of events either independent or related to the ''dhatu'' bringing changes in them. This concept can be further understood by the concept of “cross-organ talks” explained in modern medicine. When there is change in status of any organ, there can be changes seen even in the distant organs through cellular networks.  For example, adipose tissue is an endocrine organ. The tissue produces and secretes a wide range of mediators regulating adipose tissue function in an auto-/paracrine manner and important distant targets, such as the liver, skeletal muscle, the pancreas and the cardiovascular system. The enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines in metabolic disorders such as obesity. Adipose tissue dysfunction has a central role in the development of insulin resistance, type 2 diabetes, and cardiovascular diseases. (Romacho T).<ref> Romacho T, Elsen M, Röhrborn D, Eckel J. Adipose tissue and its role in organ crosstalk.Acta Physiol(Oxf).2014; 210(4):733-53. </ref>

==== Objective of therapy ====

==== Objective of therapy ====

The child is characterized by two fundamental facts- development and growth. Development refers to the increase of functional capacity in perfect form resulting from production of specialised tissues from unspecialised ones.

The child is characterized by two fundamental facts- development and growth. Development refers to the increase of functional capacity in perfect form resulting from production of specialised tissues from unspecialised ones.

Growth means increase in the size of various parts and organs of the body by multiplication of cells and intercellular components during the period commencing from fertilization to physical maturity. Changes in size are outcomes of three underlying cellular processes: (a) an increase in cell number or hyperplasia; (b) an increase in cell size or hypertrophy; and (c) an increase in intercellular substances or accretion. Hyperplasia, hypertrophy and accretion all occur during growth. This increase in body size is limited by predetermined constitutional and hereditary factors. It is however influenced by exogenous factors like diet, climate, race, environment etc.[4]

Growth means increase in the size of various parts and organs of the body by multiplication of cells and intercellular components during the period commencing from fertilization to physical maturity. Changes in size are outcomes of three underlying cellular processes: (a) an increase in cell number or hyperplasia; (b) an increase in cell size or hypertrophy; and (c) an increase in intercellular substances or accretion. Hyperplasia, hypertrophy and accretion all occur during growth. This increase in body size is limited by predetermined constitutional and hereditary factors. It is however influenced by exogenous factors like diet, climate, race, environment etc.<ref> Bose Kaushik. Concept of Human Physical growth and development.[monograph on the Internet].[last accessed on 15th October 2015]. Available from: http://nsdl.niscair.res.in/bitstream/123456789/243/1/PDF+5.5CHAPTER+ON+HUMAN+GROWTH+FOR+CSIR.pdf </ref>

==== Effect of season ====

==== Effect of season ====

During the year, there are periods of more rapid growth when growth rate is three times greater than the time of slowest growth. These periods of growth rate are synchronized with the seasons, and most rapid growth occurs in spring. (Marshall,1971)[5] Climate is also affected by high altitude, where people exposed to lower oxygen saturation in the air have a shorter stature.(Eveleth PB,1990).[6]

During the year, there are periods of more rapid growth when growth rate is three times greater than the time of slowest growth. These periods of growth rate are synchronized with the seasons, and most rapid growth occurs in spring. (Marshall,1971)<ref> Marshall WA. Evaluation of growth rate in height over periods of less than one year. Arch. Dis. Child.46:414-420. </ref> Climate is also affected by high altitude, where people exposed to lower oxygen saturation in the air have a shorter stature.(Eveleth PB,1990).<ref> Eveleth PB, Tanner JM. Worldwide Variation in Human Growth. Cambridge University Press, Cambridge, 1990. </ref>

==== Effect of nutrition ====

==== Effect of nutrition ====

Malnutrition results in failure to grow, involving both weight and height. Increased growth hormone secretion occurs in protein malnutrition, presumably inducing mobilization of the remaining fat tissue. On the other hand, growth hormone levels are decreased in calorie malnutrition. When malnutrition is corrected, the affected children soon recover, and when this reversal occurs at a young age, most children will attain a complete remission in height and weight to equal their siblings before puberty. (Henriette A,1993)[7]

Malnutrition results in failure to grow, involving both weight and height. Increased growth hormone secretion occurs in protein malnutrition, presumably inducing mobilization of the remaining fat tissue. On the other hand, growth hormone levels are decreased in calorie malnutrition. When malnutrition is corrected, the affected children soon recover, and when this reversal occurs at a young age, most children will attain a complete remission in height and weight to equal their siblings before puberty. (Henriette A,1993)<ref name=ref7>Henriette A., Delemarre-van de Waal. Environmental Factors Influencing Growth and Pubertal Development: Environmental Health Perspectives Supplements.101 (SuppL 2): 39-44 (1993) </ref>

==== Effect of stress ====

==== Effect of stress ====

Acute stress elicits a burst of growth hormone secretion, but chronic exposure to stress such as is caused by psychosocial deprivation suppresses growth hormone secretion, resulting in failure to grow. Once the stress is removed, growth hormone secretion rapidly returns to normal and then there is a period of catch-up growth. Postnatal growth is affected by nutrition, socioeconomic factors, disease, urbanization, psychosocial stress, and physical activity. There is a complex interaction among these different factors, and periods of retardation can be compensated by ensuing catch-up growth if the adverse factors are remedied. (Henriette A,1993)[7]Excellence of mind:

Acute stress elicits a burst of growth hormone secretion, but chronic exposure to stress such as is caused by psychosocial deprivation suppresses growth hormone secretion, resulting in failure to grow. Once the stress is removed, growth hormone secretion rapidly returns to normal and then there is a period of catch-up growth. Postnatal growth is affected by nutrition, socioeconomic factors, disease, urbanization, psychosocial stress, and physical activity. There is a complex interaction among these different factors, and periods of retardation can be compensated by ensuing catch-up growth if the adverse factors are remedied. (Henriette A,1993)<ref name=ref7/>Excellence of mind:

The sympathetic nervous system regulates the function of the immune system primarily via adrenergic neurotransmitters released through neuronal routes. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. Glucocorticoids are the main effector end point of this neuroendocrine system and, through the glucocorticoid receptor, have multiple effects on immune cells and molecules.(Webster JI,2002)[8]. (13)

The sympathetic nervous system regulates the function of the immune system primarily via adrenergic neurotransmitters released through neuronal routes. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. Glucocorticoids are the main effector end point of this neuroendocrine system and, through the glucocorticoid receptor, have multiple effects on immune cells and molecules.(Webster JI,2002)<ref> Webster JI, Tonelli L, Stenberg EM. Neuroendocrine Regulation of Immunity. Annual Review of Immunology. Vol. 20: 125-163.2002 </ref>. (13)

==== Factors responsible for transformation of food ====

==== Factors responsible for transformation of food ====

==== Fetal development ====

==== Fetal development ====

According to contemporary science, it has been observed that after the formation of the zygote, the cells further divide and form into a ball of cells called blastocyst. Once this blastocyst reaches the uterus, it buries itself in the uterine wall. The blastocyst sticks tightly to the wall of the uterus and receives nourishment from the mother's blood. Further the embryonic cells multiply and start to take on specific functions. This is called differentiation. Blood cells, kidney cells, and nerve cells all develop. Simultaneously the brain, spinal cord, heart and gastrointestinal tract begin to develop. Further the arm, leg buds, cranial nerves, main vessels, lungs and other begin to develop. [9, 10]

According to contemporary science, it has been observed that after the formation of the zygote, the cells further divide and form into a ball of cells called blastocyst. Once this blastocyst reaches the uterus, it buries itself in the uterine wall. The blastocyst sticks tightly to the wall of the uterus and receives nourishment from the mother's blood. Further the embryonic cells multiply and start to take on specific functions. This is called differentiation. Blood cells, kidney cells, and nerve cells all develop. Simultaneously the brain, spinal cord, heart and gastrointestinal tract begin to develop. Further the arm, leg buds, cranial nerves, main vessels, lungs and other begin to develop. <ref> Cunningham FG, Leveno KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham FG, Leveno KL, Bloom SL, et al, eds.Williams Obstetrics. </ref>  <ref> Ross MG, Ervin MG, Novak D. Placental and Fetal Physiology. In: Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics: Normal and Problem Pregnancies. </ref>

Hence it may be appropriate to accept Dhanvantari’s view that all the organs start developing simultaneously. (21)

Hence it may be appropriate to accept Dhanvantari’s view that all the organs start developing simultaneously. (21)

The presently accepted cephalopelvic position correlates well to the position of the foetus explained in the classics.(22)

The presently accepted cephalopelvic position correlates well to the position of the foetus explained in the classics.(22)

Modern embryology supports that the fetal blood flows through villi in which the capillaries are covered only by fetal tissue. It bathes directly in the intervillous space in a pool of flowing maternal blood. The transfer, processing and synthesis of nutrients under the influence of maternal, fetal and placental hormones is carried by various parts of the placenta through several modes. Lipid soluble molecules such as respiratory gases, anesthetic agents, several drugs and unconjugated bilirubin cross easily by penetrating the cell membrane.  Small water soluble molecules such as urea and water also cross easily by diffusion or osmosis. A specific carrier molecule facilitate transfer of glucose. Specific carrier mediated processes are carried to transport most amino acids, calcium, potassium and phosphorous from mother to fetus. This consumes energy leads to active transport leading to higher concentration in fetal than in maternal plasma. IgG, iron and vitamin B12 are transported by means of a receptor mediated mechanism into the fetal circulation. Any changes in the rate of blood flow hardly affect permeability of lipid insoluble substances. Their passage is ‘membrane limited’ and control of their transfer is largely by a change in placental tissue carrier mechanisms. Large increases in placental blood flow as gestation proceeds are important so that the transport of respiratory gases can be increased to meet the needs of the growing fetus. This mechanism of transport is similar to ''upasneha'' and ''upasweda nyaya'' described in this chapter. [11] (23)

Modern embryology supports that the fetal blood flows through villi in which the capillaries are covered only by fetal tissue. It bathes directly in the intervillous space in a pool of flowing maternal blood. The transfer, processing and synthesis of nutrients under the influence of maternal, fetal and placental hormones is carried by various parts of the placenta through several modes. Lipid soluble molecules such as respiratory gases, anesthetic agents, several drugs and unconjugated bilirubin cross easily by penetrating the cell membrane.  Small water soluble molecules such as urea and water also cross easily by diffusion or osmosis. A specific carrier molecule facilitate transfer of glucose. Specific carrier mediated processes are carried to transport most amino acids, calcium, potassium and phosphorous from mother to fetus. This consumes energy leads to active transport leading to higher concentration in fetal than in maternal plasma. IgG, iron and vitamin B12 are transported by means of a receptor mediated mechanism into the fetal circulation. Any changes in the rate of blood flow hardly affect permeability of lipid insoluble substances. Their passage is ‘membrane limited’ and control of their transfer is largely by a change in placental tissue carrier mechanisms. Large increases in placental blood flow as gestation proceeds are important so that the transport of respiratory gases can be increased to meet the needs of the growing fetus. This mechanism of transport is similar to ''upasneha'' and ''upasweda nyaya'' described in this chapter. <ref> Mother and Child Nutrition in the Tropics and Subtropics. Nutrition in Pregnancy and Growth of the Foetus. Chapter 4:pp 104-105 </ref> (23)

''Kalayoga'' is interpreted as ‘attainment of proper time’ e.g. development of body in adolescence (seventeen years of age and onwards). The seasons of the year are also considered. ''Swabhava'' means the invisible factor of nature. ''Avighata'' is the absence of inhibiting factors such as excessive sexual act, mental stress etc. ''Avighata'' to ''ahara'' and thus interprets in restricted sense as ‘non-antagonism of dietary factors’. (12)

''Kalayoga'' is interpreted as ‘attainment of proper time’ e.g. development of body in adolescence (seventeen years of age and onwards). The seasons of the year are also considered. ''Swabhava'' means the invisible factor of nature. ''Avighata'' is the absence of inhibiting factors such as excessive sexual act, mental stress etc. ''Avighata'' to ''ahara'' and thus interprets in restricted sense as ‘non-antagonism of dietary factors’. (12)

''Ushma'' takes part directly in the digestion of food and the remaining factors take part indirectly. ''Vata'' transports food to the site of ''agni'' to facilitate and stimulate digestion (Cha.Chi.15/6,17). (Cha.Chi.15/17). Apart from this, specific time is required to complete the digestive process. The detail process of digestion and metabolism is described in fifteenth chapter of [[Chikitsa Sthana]](Cha. Chi.15/6-11).(15)

''Ushma'' takes part directly in the digestion of food and the remaining factors take part indirectly. ''Vata'' transports food to the site of ''agni'' to facilitate and stimulate digestion (Cha.Chi.15/6,17). (Cha.Chi.15/17). Apart from this, specific time is required to complete the digestive process. The detail process of digestion and metabolism is described in fifteenth chapter of [[Chikitsa Sthana]](Cha. Chi.15/6-11).(15)

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===References ===

===References ===