ranjakapitta Ayurveda

Revalidation of the functions of Ranjaka pitta

www.ayurvedicmedicinalplants.com

REVALIDATION OF THE FUNCTIONS OF RANJAKAPITTA

Dissertation submitted to the Kannur University, Kerala,

In partial fulfillment of the regulations for the award of the degree of

DOCTOR OF MEDICINE (Ay)

In Kriyasareera

By

Dr. SUDHAGOPALAN V.S

Under the Supervision of

Dr. ANNY YOHANNAN. M.D. (Ay) Professor & H.O.D., Department of Kriyasareera

Govt. Ayurveda College

Thiruvananthapuram

DEPARTMENT OF POST GRADUATE STUDIES IN

KRIYASAREERA

GOVERNMENT AYURVEDA COLLEGE, KANNUR 670503 2007

AyurmitraDraft



List of Abbreviations .

List of Tables

List of Charts and Diagrams

Introduction

I Literary Review

Chapter 1- INTRODUCTION TO PITTA

Chapter 2- RAKTA DHATU

Chapter 3- RAKTA DHATWAGNI AND RANJAKA PITTA

Chapter 4- FACTORS INFLUENCING RANJAKA PITTA

II Clinical Study

Chapter 1- METHODOLOGY

Chapter 2- OBSERVATIONS AND ANALYSIS

III Discussion

IV - Summary

V - Conclusion

Bibliography

Appendix- Pro forma

Contents



Ayurveda, the science of life prescribes the ways and means of keeping

good health. This method of living emphasizes promotion of health and

prevention of diseases. It is designed and formulated for the well-being of the

world. Health in Ayurveda implies Harmony and there is really no end to the

degree of harmony we can achieve, if we set ourselves to the task.

The basic doctrine of ayurveda rests on tridosha siddhanta. Pitta is one

among the doshas, which is responsible for all the changes occuring in the

body, collectively referred as parinama. Reactions taking place during

digestion and metabolism, growth and maturation and the production of heat

and energy all these are under the control of pitta dosha. In terms of modern

physiology, all the reactions aided by the factors like hormones, enzymes etc

can be considered as pitta vyaparas.

Agni is an all pervading, uncontrollable, controlling force of the

universe. When comes to the living body, it is represented as pitta. The word

Pittoshma is comprising of two words- Pitta and Ushma which means ushma

contained in Pitta. Pitta acts as substratum for Kayagni. Agni resides in Pitta

owing to the agneya nature of pitta. Again, to be precise, the controlling force

of pitta is, termed as pachaka pitta. In other words, pachaka pitta controls all

Introduction



other fractions of pitta by its inherent agneya guna. Even if we can experience

its effects, it is not easy to identify it on a materialistic basis. Altogether, the

existence of life is maintained by its continuous action.

Ranjaka pitta is a division of pitta that is responsible for the formation of

rakta dhatu. Functions of ranjaka pitta are described in a vague fashion in our

classics. The details of description of ranjaka pitta which is instrumental in the

evolution of rakta dhatu is also very less.

Ranjaka pitta is originating from yakrit and pleeha so does raktadhatu.

The formation of ranjaka pitta and rakta dhatu shows some connections as an

asraya asrayi bhava i.e. the interdependence between dosha and dhatu exists in

the case of ranjaka pitta and rakta dhatu. According to asraya asrayi sambhanda

pitta is asraya to rakta and rakta is dependent of pitta mainly ranjaka pitta.

According to this doctrine when asraya increases asrayi also increases and

when asraya decreases asrayi also decreases. Ranjaka pitta when increased

shows the symptoms of pitta vridhi and when decrease show symptoms of

pittakshaya; as it is a part of pitta.

Rakta dhatu is special among other dhatus that it is treated with equal

status with doshas and is the only dhatu having agneya nature. It has an

important function jeevana. Rakta is formed from rasa dhatu which in turn is

formed from the nutrient portion of food i.e. ahara sara.



Significance of the study: -

Majority of research works were based on pachaka pitta. Ranjaka pitta

and its physiological importance are still not known clearly. To understand

rakta dhatu, the concepts involved in the genesis of rakta dhatu should be

understood with clarity. So this study is meant to understand the division of

pitta i.e. ranjaka pitta. Along with this an effort is made to quantify ranjaka

pitta and rakta sara.

Objectives of the study:-

To explore the concept of ranjaka pitta and to understand its functions in

a better perspective

To analyze whether food has any direct influence on ranjaka pitta

To study different steps in the formation of rakta dhatu and comparing

them with those in erythropoiesis

To identify rakta dhatvagni and to define its role in raktotpatti

To discuss the seat of ranjaka pitta.

Hypothesis

1. Null hypothesis: Ranjaka pitta does not play any pivotal role in the

transformation of the rasa dhatu into rakta dhatu



2. Alternate hypothesis: Ranjaka pitta plays pivotal role in the

transformation of the rasa dhatu into rakta dhatu

Study in a Nutshell

This descriptive study has been carried out in volunteers residing in

Orumanayoor Panchayath, Thrissur district, Kerala.

The total duration of the study is 18 months.

The ranjaka pitta status was quantitatively assessed by assessing

haemoglobin percentage and by RBC count.

A questionnaire assessing ranjaka pitta functions and its influencing

factors were made and data was collected from the healthy individuals.

Excellence of rakta dhatu was assessed by scoring method and was

assessed quantitatively.

Ranjaka pitta was analyzed and critically evaluated.

Statistical analysis, observation and interpretation are made, before

making the conclusion of the study.

Frame of this work

Unit-1 Introduction

Unit-2 Literal Abstraction



Contains literary data on pitta. rakta dhatu, ranjaka pitta and rakta

dhatvagni with modern comparison.

Unit-3 Clinical Research

Contains Research Methodology, Observations and Analysis.

Unit-4 Discussion

Contains Discussion on Literal Abstraction and on Clinical

Research.

Unit-5 Summary

Unit-6 Conclusion

Appendix



Even before finding the solution of a mystique, we ought to understand

the same in different perspectives. Insistent enthusiasm results in the

exploration of newer things or else adds the added edge to the existing things-

bearing this maximum in mind, to add a newer dimension to the available

concept of pitta, this immaculate literary work has been carried out on it.

This part of this research work unfolds the horizons of pitta like its

varieties, location either relevant or up to date, the way of execution of

physiological functions, pathophysiology and etc, with the work of art on

Ranjaka pitta.

More over, Ranjaka pitta, the second to none considering its

magnanimous physiological attributes deserves to be researched. Needless to

say, the outcome of this skilful work, irrespective of its impose on current

doctrines, will remain a helping hand for the future works on the similar track

which is not travelled by too many for so long.

Introduction To Pitta



A Review Of Pitta To Decipher Ranjaka Pitta

Introduction

In living body all the three humours work in a complementary way to

attain a state of equilibrium and control all physiological processes. The

second among the dosha triad, i.e. pitta, represents all the agents that are

responsible for the transformations taking place in the living system. Reactions

taking place during digestion and metabolism, growth and maturation and the

production of heat and energy all these are under the control of pitta dosha. In

terms of modern physiology, all the reactions aided by the factors like

hormones, enzymes etc can be considered as pitta vyaparas.

Nirukthi The term pitta is derived from root tap, which has 3 meanings-

Tap dahe - means burning. In living body daha is to be considered as

paka or parinama- conversion or transformation (1) . E.g. digestion,

erythropoiesis etc.

Tap santape(2) - means to generate heat. E.g. intermediate

metabolism

Tap aiswarye - means to enable or to attain eight fold nature of

animadi gunas



Pitta has been described as agni or fire as it performs actions similar to

fire. Theories of digestion and metabolism in our science are based on the

functions of agni which is impregnated in pitta in living body. Hence the

functions of pitta can be observed from GIT to cellular level.

In our classics there are five types of pittas- Pachaka, Ranjaka, Sadhaka,

Alochaka and Brajaka. Even though all pittas are same and the divisions are

done just to show specific functions of each, it is essential to understand pittas

in general in this context. As Pachaka pitta controls other pittas, proper

comprehensions of Pachaka pitta are a must in thorough knowledge of

Ranjaka pitta and Rakta dhatu.

Qualities of pitta

Physical qualities of pitta described in our classics are more or less

similar (3).

Table 1. 1 Qualities of pitta

Qualities Colour Taste Smell

Snigdha, Ushna, Teekshna, Sara, Laghu, Visada,

Drava

Neela, Peeta or any colour other than

white and red

Kadu, Amla Visra



Pitta is unctuous, hot, penetrative, mobile, light and clear. Colour is blue

or yellow or any colour other than red and white. Taste is hot or sour smelling

raw meat. According to Chakrapani pitta is of two varities -1.Sadrava &

Snigdha-natural-which control all physiological activities and 2.Nirdrava &

Rooksha that causes jwara and other diseases(4).

Quantity

Quantity of pitta is five Anjalis.

Location

Even though doshas are all pervading in the body, they have preferable

abodes according to our classics (5).

Table 1. 2 Pitta Locations

Charaka Susruta Vagbhata

Amasaya Pakwasaya madhya Amasaya & Nabhi

Rakta, Laseeka, Rasa Rakta Rakta, Laseeka, Rasa

Sweda Sweda Sweda

Chakshu, Sparsana



Hemadri defines laseeka as rasa mala which is like water and resides in

skin (6).According to Chakrapani laseeka is picha bhaga of udaka(7).Amasaya,

he says is the adho amasaya.

Functions

Functions attributed to pitta by different Acharyas are given below(8)

Table 1. 3. Functions of pitta

Susruta Vagbhata Charaka

Ragakrit- aids in production of normal colour

Prabha- production of lusture

Prakriti varna

Pakakrit- aids in digestion &metabolism

Pakti- digestion &metabolism

Pakti

Tejakrit- facilitate vision, light perception &colour

Darsanam- enables visual perception

Darsanam

Ojakrit-production of ojus

Ushmakrit- production of body heat

Ushma- production of body heat

Ushma

Kshut-cause hunger & appetite

Trit- cause thirst

Ruchi- promote desire for food

Tanumardavam- promote suppleness of the body



Medhakrit aid in the intellectual function.

Budhi- promote knowledge Prasadam-lucidity of mind

Medha -intellect Harsham-cheerfulness

Dhi-understanding

Dhairyam- courage &valour Souryam

Types

According to specific functions, the same pitta can be divided in to five

types-Pachaka, Ranjaka, Sadhaka, Alochaka and Bhrajaka(9)

As pitta is also synonymous with agni there are different types of agnis

also existing in our body.

Pitta and Agni

Agni in the body according to Ayurveda is implicit in pitta as pitta

performs functions like dahana (oxidation), pachana (chemical transformation)

etc like fire, pitta is spoken as internal fire(10).Chakrapani clarified the

implication of the term agni and states that pitta is not flaming fire but it refers

to the heat associated with pitta (11) .Susrutha has treated the pitta of the body

and agni as identical (12).

So pitta is used instead of agni and vice versa. There are mainly thirteen

agnis in our body viz Jataragni, five Bhutagnis and seven types of Dhatwagnis



(13). Food consumed is subjected to jataragni paka, bhutagni and dhatwagni

paka. Due to the difference in locality and functions they are separately

discussed in relation to digestion and metabolism. These sub groups are unified

in to a larger group because of their participation in nourishing the body and

also maintaining the health.

Dalhana commends that agni and pitta are not one and the same (14). In

Grahani roga nidana he states that the pitta is said to be vitiated by katu, vidahi,

amla, etc which will suppress agni. If both were one and the same pitta would

not have suppressed agni. Pitta and agni have dissimilar properties also. Pitta is

drava snigdha and adhogami, whereas agni is quite contrary to this and is

sukshma rooksha and urdhvagami. But in living body, the only dosha with

agneya properties, i.e. pitta performs all the functions and no other burning fire

is met with pitta is termed as agni. It does all dahana or paka in all living being.

Pachaka pitta

Human body is an out come of food and so as our diseases (15). Health

and diseases depends not only on nutrients of food but also on proper digestion

and assimilation. Importance of pachaka pitta is emphasized here and also by

the statement that every disease is due to the impairment of this factor.(16)

Kayachikitsa is termed as antaragni chikitsa (17). It is the main factor concerned

with digestion and the regulator of other pittas. Pachakagni, koshtagni,



antaragni, jataragni, kayagni and dehagni are synonymous with pachaka pitta.

Just the word agni is usually mentioned to indicate pachaka pitta. It is located

in pitta dhara kala.

Digestion of food is the main function of pachaka pitta. Food is then

divided in to sara and kitta. That is in GIT pachaka pitta acts on ingested food

and causes sanghatha bheda by breaking food in to different nutrients. After

absorption these nutrients are utilized for the synthesis of different dhatus and

production of energy.

As already stated, this pitta located between amasaya and pakwasaya is

responsible for the digestion of the four modes of food and drinks ingested.

By the virtue of its inherent power, it contributes to and augments the action

of pittas at other site (23). Vagbhata observes, koshtagni is the leader of all

agnis. Moieties of it are present ubiquitously in the dhatus. Increase of

pachakagni causes increase of dhatwagnis, but increase of dhatwagni results

in the decrease of dhatus(24).

Role of Pittadhara kala

Pittadhara kala is also known as Grahani (18). Under the stimulation of

samana vata pachaka pitta is produced from it. Pitta dhara kala provide

digestive juices which are collectively called pachakagni. Integrity of grahani



depends up on agni there fore impairment of agni involves integrity of grahani

and vice versa. Grahani retains food till it is completely digested (19).

This retention is affected by valve like arrangement located in

pakwasaya dwara due to the action of samana vayu (20). These references lead

to the fact that pitta dhara kala constitute an integral part of the structure of

annavaha srotas and is responsible for producing pachakagni for digestion and

nutrient factor is absorbed and transported through this kala for further

distribution (21).This kala can be comparable with the mucosal lining inside the

intestine.

Samana and Apana Vayu

The neural influence over the several functions of amasaya and

pakwasaya is attributed to samana and apana vayu. Samana vayu located near

agni is stated to move through out koshta. It has several functions.

1. Reception of food that is swallowed.

2. Stimulation of stomach and intestine to secrete digestive juices.

3. Digestion-directly or indirectly through digestive juices.

4. Storing of digested, indigestible food and excretory waste products.

5. Facilitate absorption of digested food and excretion of waste.



6. Control over sweating, water balance etc.26)

The functions similar to these are performed by intrinsic nerves of

stomach and intestine.

Pitta may be a group of substances and their main activity may come

into two different chemical processes of anabolism and catabolism. Pachaka

pitta is the controller of other pittas and is origin of other pittas. So functional

increase and decrease of pachaka pitta causes waxing and waning of other

pitas.

Ranjaka pitta

Rakta is as a special tissue and has treated in importance among other

dhatus mainly due to its function jeevana and also considering its importance

in pathological process of the body. This importance is also recognized by the

allotment of one of the sub division of pitta for the production of rakta dhatu,

that is the ranjaka pitta.

The term ranjaka is derived from the root ranj means to impart colour

(28).This pitta gives colour to rasa dhatu. It is the one and only function of this

pitta. As discussed earlier general function of pitta is to do dahana or paka

which means conversion. So this pitta converts rasa in to rakta by imparting

colour to rasa.



According to the concept of philosophy as well as Ayurveda, no

transformation can take place with out the aid of agni. Agni of any particular

type should be present at the site of transformation. Since Yakrit and Pleeha

are considered as the sites of the rakta formation, they have also regarded as

the site of ranjaka pitta according to Susruta Acharya. Here the

transformation is in the form of change of colour of the rasa when it is

converted into the rakta. As pachaka pitta is considered as the one which

endows its own strength to other types of pittas, the strengthening of ranjaka

pitta also can be attributed to the pachaka pitta.

Functions of Ranjaka pitta

As other pittas, ranjaka pitta is also panchabouthic and possesses a kind

of chemical action due to its agneya nature. The only function it does is rasa

ranjana-to provide coloration to rasa dhatu, a unique opinion by all acharyas

(40). But they differ in the opinion of the sthana of ranjaka pitta. So rasa ranjana

may take place in yakrit pleeha or in amasaya. According to Sargadhara there

is a substance called pitta srava present in yakrit and it helps in raktolpatana

(41) .Ranjana karma is a type of chemical process caused by agni.

The other divisions of pitta include sadhaka pitta, alochaka pitta and bhrajaka

pitta. They contribute to the functions intelligence, visual perception and skin

lustre respectively.



Rakta dhatu is special among other dhatus that it is treated equal status

with doshas and is the only dhatu having agneya nature. It has an important

function jeevana. It is synonymously used with blood, even though there are

certain differences. Rakta is formed from rasa dhatu which in turn formed from

nutrient portion of food. So in this context it is essential to review how food

consumed is transformed into body tissues-especially blood.

Importance of Rakta

Susrutacharya has given the importance of rakta as it is the origin or

foundation of body and body is maintained by rakta. So it has to be protected at

any costs (1) It is one among the ten seats of prana (2). Rakta is also considered

as one of the doshas by Acharya Susruta.He has endowed rakta with particular

importance both in physiological and pathological process and has given the

equal status to doshas (4). There is a special shodhana (raktamkosha) is

attributed to only one dhatu rakta because it the route through doshas spread.

universely rakta is not considered as dosha since it doesnt have the ability to

give rise to its own prakriti.

Rakta Dhatu



Nirukti

The word rakta is derived from the root ranj which means colour or

impart colour(5)

It has synonyms like raja, artava, rudhira, lohita etc

Colour

Normal blood appears bright red as Gunja phala or like petels of red

lotus or like blood of rabbit and bright as Indragopa - (6)

Qualities

Blood is drava or liquid (7). It has other qualities like anushnaseeta,

madhura, snigdha, rakta roopa, guru, and visra (8)

Though the rakta is predominantly agneya in nature, it shows many

qualities of other mahabhutas also

Panchabhoutic nature of rakta-(11)

Prithwi Visrata

Ap Dravata

Teja Ragata

Vayu Spandana

Akasa Laghuta



Quantity

The quantity of blood is 8 anjali(9)

The concept of shudha rakta

Purity of blood was determined by physical appearance such as(10)

Pure blood look like a bright Indragopa.

Like pure gold

Looks like Padma and Alaktaka.

Brightly reddish like Gunja Phala

According to Ayurveda the fluid that is circulating through vascular

system i.e. dhamanies, srotases and siras is both rasa dhatu and rakta dhatu. (12)

The circulating rakta is the medium of transport of ojus the factor

responsible for resistance to disease. It is also the medium of transport of

prakupita doshas through out the body, having it self involved in the process (13)

During circulation rasa dhatu exudes through the srotomukhas and fill up the

place between srotas and sthayi dhatus (interstitial space) nutrients passes into

sthayi dhatus and malas and kittas passes into rasa (lymph). and so rasa is

considered as kosta (14).



So circulating rakta is a complex fluid consisting of sthayi rasa (plasma,

serum) and sthayi rakta (erythrocyte), remaining astayi dhatus ,doshas, malas,

ojus etc. It perfoms the vital functions as jeevana(giving oxygen),provide

normal colour to skin, strength, health and happiness, nourishment of other

dhatus, tranquillity and life(15).

Rakta sara

When a dhatu in our body is in excellent condition that person is known

by that sarata. If one possesses pure rakta in excellence he has rakta sarata

.They are identified by following symptoms. They posses reddish ears, eyes,

face, tongue, nose, lips, palms, soles, nails, forehead, penis, etc and will be

glistening and attractive. They are happy, having good intelligence, mental

tranquillity and tenderness. They are more susceptible to stress and cannot

tolerate heat

Blood

Composition it consists of two parts formed elements and plasma

Blood cells and Plasma

Blood plasma consists of water: proteins including albumin, globulins

and fibrinogen; nutrients such as glucose, amino acids and fats; the blood



gases CO2 and O2;; weak acids / weak base buffer pairs; cations such as H+,

Na+, K+, Ca++; anions such as HPO4-2, HCO3- and Cl-; salts like NaCl;

hormones; vitamins; metabolic wastes like urea and ammonia; and,

complement enzymes. Serum is blood plasma without fibrinogen and other

clotting factors.

Plasma

Plasma is the straw-colored liquid in which the blood cells are suspended.

Table 2. 1. Composition of Blood plasma

Composition of blood plasma

Component Percent

Water 92

Proteins 68

Salts 0.8

Lipids 0.6

Glucose (blood sugar) 0.1

Plasma transports materials needed by cells and materials that must be

removed from cells:

Various ions - Na+, Ca2+, HCO3, etc.

glucose and traces of other sugars

amino acids



other organic acids

cholesterol and other lipids

hormones

urea and other wastes

Serum Proteins

Proteins make up 68% of the blood. They are serum albumin ,serum

globulins and fibrinogen

Serum Lipids

Table 2. 2. Serum Lipids

Lipid Normal values (mg/dl) Desirable (mg/dl)

Cholesterol (total) 170210



Red Blood Cells (Erythrocytes)

To transport hemoglobin, which in turn carries oxygen from the lungs to

the tissues is the major function of red blood cells also known as erythrocytes

.Hemoglobin When it is free in the plasma of the human being, about 3 per cent

of it leaks through the capillary membrane into the tissue spaces or through the

glomerular membrane of the kidney into the glomerular filtrate each time the

blood passes through the capillaries.

Therefore, for hemoglobin to remain in the human blood stream, it must

exist inside red blood cells. Besides transport of hemoglobin the red blood cells

have other functions also. RBC Contains a large quantity of an enzyme,

carbonic anhydrase that catalyzes the reversible reaction between carbon

dioxide and water to form carbonic acid increasing the rate of this reaction

several thousand fold.

The rapidity of this reaction makes it possible for the water of the blood

to transport enormous quantities of CO2 in the form of bicarbonate ion from the

tissues to the lungs, where it is reconverted to CO2 and expelled into the

atmosphere as a body waste product. Thus hemoglobin in the cells acts as an

excellent acid-base buffer.

Structure of Red Blood Cells



Normal red blood cells, are biconcave discs having a mean diameter of

about 7.8 micrometers and a thickness of 2.5 micrometers at the thickest point

and 1 micrometer or less in the center. The average volume of the red blood

cell is 90 to 95 cubic micrometers. The shapes of red blood cells can change

remarkably as the cells squeeze through capillaries. The red blood cell is bag

like and that can be deformed into almost any shape.

R B C Concentration in the Blood.

The average number of red blood cells per cubic millimeter is

5,200,000 (300,000) in normal men and in normal women, it is 4,700,000

(300,000). Persons living at high altitudes have greater numbers of red blood

cells.

Quantity of Hemoglobin in the Cells.

Red blood cells have the ability to concentrate hemoglobin in the cell

fluid up to about 34 grams in each 100 milliliters of cells. The concentration

does not rise above this value, because this is the metabolic limit of the cells

hemoglobin- forming mechanism. Furthermore, in normal people, the

percentage of hemoglobin is almost always near the maximum in each cell.

However, when hemoglobin formation is deficient, the percentage of

hemoglobin in the cells may fall considerably below this value, and the volume

of the red cell may also decrease because of diminished hemoglobin to fill the



cell. When the hematocrit (the percentage of blood that is cellsnormally, 40

to 45 per cent) and the quantity of hemoglobin in each respective cell are

normal, the whole blood of men contains an average of 15 grams of

hemoglobin per 100 milliliters of cells; for women, it contains an average of 14

grams per 100 milliliters.

Each gram of pure hemoglobin is capable of combining with 1.34

milliliters of oxygen. Therefore, in a normal man, a maximum of about 20

milliliters of oxygen can be carried in combination with hemoglobin in each

100 milliliters of blood, and in a normal woman, 19 milliliters of oxygen can be

carried.

Leukocytes (White Blood Cells)

The leukocytes, also called white blood cells, are the mobile units of the

bodys protective system. They are formed partially in the bone marrow and

partially in the lymph tissue. After formation, they are transported in the blood

to different parts of the body where they are needed. The real value of the white

blood cells is that most of them are specifically transported to areas of serious

infection and inflammation, thereby providing a rapid and potent defense

against infectious agents.



General Characteristics of White Blood Cells.

Six types of white blood cells are normally present in the blood. They

are polymorphonuclear neutrophils, polymorphonuclear eosinophils,

polymorphonuclear basophils, monocytes, lymphocytes, and, occasionally,

plasma cells. In addition, there are large numbers of platelets, which are

fragments of another type of cell similar to the white blood cells found in the

bone marrow, the megakaryocyte. The first three types of cells, the

polymorphonuclear cells, all have a granular appearance, for which reason they

are called granulocytes, or polys because of the multiple nuclei. The

granulocytes and monocytes protect the body against invading organisms

mainly by phagocytosis. The lymphocytes and plasma cells function mainly in

connection with the immune system;

Concentrations of the Different White Blood Cells in the Blood.

The adult human being has about 7000 white blood cells per micro liter

of blood of the total white blood cells, the normal percentages of the different

types are approximately the following:

Neutrophils - 62.0%

Eosinophils -2.3%

Basophils - 0.4%



Monocytes - 5.3%

Lymphocytes -30.0%

The number of platelets, which are only cell fragments, in each

microliter of blood is normally about 300,000.

Life Span of the White Blood Cells

The life of the granulocytes after being released from the bone marrow

is normally 4 to 8 hours circulating in the blood and another 4 to 5 days in

tissues where they are needed. In times of serious tissue infection, this total life

span is often shortened to only a few hours because the granulocytes proceed

even more rapidly to the infected area, perform their functions, and, in the

process, are themselves destroyed. The monocytes also have a short transit

time, 10 to 20 hours in the blood, before wandering through the capillary

membranes into the tissues. Once in the tissues, they swell to much larger sizes

to become tissue macrophages, and, in this form, can live for months unless

destroyed while performing phagocytic functions.

Lymphocytes enter the circulatory system continually, along with

drainage of lymph from the lymph nodes and other lymphoid tissue. After a

few hours, they pass out of the blood back into the tissues by diapedesis. Then,

still later, they re-enter the lymph and return to the blood again and again; thus,

there is continual circulation of lymphocytes through the body.



The lymphocytes have life spans of weeks or months; this life span

depends on the bodys need for these cells.

The platelets in the blood are replaced about once every 10 days; in

other words, about 30,000 platelets are formed each day for each microliter of

blood.

Neutrophils

Neutrophils are multilobed and have a diameter of10-12 micron,

develops from stem cell and as the cell grows it begins to acquire granules

primary and secondary granules. Most important function of neutrophil is to

attack and destroy the invading bacteria.

Eosinophils

The eosinophils normally constitute about 2 per cent of all the blood

leukocytes. Eosinophils are weak phagocytes, and they exhibit chemotaxis.

Eosinophils, however, are often produced in large numbers in people with

parasitic infections, and they migrate in large numbers into tissues diseased by

parasites. Although most parasites are too large to be phagocytized by

eosinophils or any other phagocytic cells, eosinophils attach themselves to the

parasites by way of special surface molecules and release substances that kill

many of the parasites in several ways:



By releasing hydrolytic enzymes from their granules, which are

modified lysosomes;

Also by releasing highly reactive forms of oxygen that are especially

lethal to parasites; and

By releasing from the granules a highly larvacidal polypeptide called

major basic protein.

Eosinophils also have a special propensity to collect in tissues in which

allergic reactions occur, such as in the peribronchial tissues of the lungs in

people with asthma and in the skin after allergic skin reactions. This is caused

at least partly by the fact that many mast cells and basophils participate in

allergic reactions,. The mast cells and basophils release an eosinophil

chemotactic factor that causes eosinophils to migrate toward the inflamed

allergic tissue.

The eosinophils are believed to detoxify some of the inflammation-

inducing substances released by the mast cells and basophils and probably also

to phagocytize and destroy allergen-antibody complexes, thus preventing

excess spread of the local inflammatory process.



Basophils

The basophils in the circulating blood are similar to the large tissue mast

cells located immediately outside many of the capillaries in the body. Both

mast cells and basophils liberate heparin into the blood, a substance that can

prevent blood coagulation. The mast cells and basophils also release histamine,

as well as smaller quantities of bradykinin and serotonin. Indeed, it is mainly

the mast cells in inflamed tissues that release these substances during

inflammation.

Monocytes

Monocytes accounting for about 2-8% of leukocytes in the peripheral

blood.Then they leave the blood and enter the tissues where they are known as

tissue macrophages. Tissue macrophages and blood monocytes together

considered as reticulo endothelial system.The major functions of monocytes are

phagocytosis, secretions which kill bacteria, role in lymphocyte mediated

immunity and also in tissue repair.

Lymphocytes

Lymphocytes are of three types. They are

T lymphocytes

B lymphocytes

Natural Killer cells or non T non B cells



Besides there are memory cells that can be T memory cell or B memory

cells. Lymphocytes are present in the blood, lymph nodes, spleen, lymphoid

follicles and red bone marrow.

Platelets

Platelets are cell fragments produced from megakaryocytes.

Blood normally contains 150,000350,000 per microliter (l) or cubic

millimeter (mm3). This number is normally maintained by a homeostatic

(negative-feedback) mechanism If this value should drop much below

50,000/l, there is a danger of uncontrolled bleeding because of the essential

role that platelets have in blood clotting. It may be due to

Certain drugs and herbal remedies;

Autoimmunity.

When blood vessels are cut or damaged, the loss of blood from the

system must be stopped before shock and possible death occur. This is

accomplished by solidification of the blood, a process called coagulation or

clotting. A blood clot consists of

A plug of platelets enmeshed in a

Network of insoluble fibrin molecules.



At any one time, about two-thirds of the body's platelets are circulating

in the blood and one-third is pooled in the spleen. There is constant exchange

between the two populations. The life span of platelets is between 8 and 12

days. They are destroyed by macrophages, mainly in the spleen and also in the

liver are cell fragments of the giant megakaryocyte cell in red bone marrow;

they are important in forming blood clots

Rakta karmas

Functions of Rakta are

Jeevana,

Varna prasaadana

Mamsa poshana

Jeevana

Jeevana is the foremost function of rakta. It is the assignment that gives

life to the body parts (16). The word jeeva is synonymous to atma (17) or life. So

the main function that rakta has to do is supplying life or life saving

constituents to all body parts. Susrutacharya has stated that jeevana is that

principle by which a living thing upholds life(19). It is the duty of rakta to give

life to tissues by supplying oxygen and nutrients to all cells. Rakta is some

times called jeeva rakta(18) indicating its capacity to perform the jeevana

functions.



Functions of the blood

Blood performs two major functions:

Transport of

Oxygen and carbon dioxide

Food molecules (glucose, lipids, amino acids)

Ions (e.g., Na+, Ca2+, HCO3)

Wastes (e.g., urea)

Hormones

Heat

Defence of the body against infections and other foreign materials. All

the WBCs participate in these defences.

Oxygen Transport

In adult humans the hemoglobin (Hb) molecule consists of four

polypeptides with two alpha () chains of 141 amino acids and two beta ()

chains of 146 amino acids. Each of these is attached with the prosthetic group,

i.e. heme. There is one atom of iron at the centre of each heme. One molecule

of oxygen can bind to each heme.



The reaction is reversible

Under the conditions of lower temperature, higher pH, and increased

oxygen pressure in the capillaries of the lungs, the reaction proceeds to the

right. The deoxygenated haemoglobin of the venous blood becomes the

oxyhemoglobin of the arterial blood.

Under the conditions of higher temperature, lower pH, and lower oxygen

pressure in the tissues, the reverse reaction is promoted and oxyhemoglobin

gives up its oxygen.

Carbon Dioxide Transport

Carbon dioxide (CO2) combines with water forming carbonic acid,

which dissociates into a hydrogen ion (H+) and a bicarbonate ion:

CO2 + H2O H2CO3 H+ + HCO3

95% of the CO2 generated in the tissues is carried in the red blood cells:



It probably enters (and leaves) the cell by diffusing through

transmembrane channels in the plasma membrane. (One of the proteins

that form the channel is the D antigen that is the most important factor in

the Rh system of blood groups.)

Once inside, about one-half of the CO2 is directly bound to hemoglobin

(at a site different from the one that binds oxygen).

The rest is converted following the equation above by the enzyme

carbonic anhydrase into

v bicarbonate ions that diffuse back out into the plasma and

v Hydrogen ions (H+) that bind to the protein portion of the

haemoglobin (thus having no effect on pH).

Only about 5% of the CO2 generated in the tissues dissolves directly in

the plasma.

When the red cells reach the lungs, these reactions are reversed and

CO2 is released to the air of the alveoli.

Mamsa poshana

Rakta, as all other dhatus, offer necessary nutrients to its succeeding

dhatu - mamsa. As in the case of every other dhatu in a living body, the basic



nutrients of mamsa dhatu are also derived from the ahara i.e. the food

consumed. Food we consume in different form should be converted in to

body tissues for that it is transformed by digestion and metabolism (paka).

Paka is chemical reaction and is the function of pitta.

Depending upon the agni which carry out the paka, there are three

different levels of ahara paka.

Jataragni paka

Bhutagni paka

Dhatvagni paka

Jataragni paka

Here jataragni has the major role in the parinaama of ahara. This

process is also known as avastha paka. As a result of jataragni paka, the food

ingested gets divided into two portions- sara and kitta. The sara portion

undergoes bhutagni paka where as kitta portion contribute to the formation of

pureesha and mutra.

Bhutagni paka

After jataragni paka ahara, sara which is pancha bhoutic is again dealt

with bhutagnis for further digestion and each bhutha digested by same fraction

of agni (30). All structural and functional constituents of the body are composed



of panchamahabhutas at fundamental level. The panchaboutic constituents of

body are given below (31).

Table 2. 3. Panchaboutic composition of doshas and dhatus

Pachaboutic composition

Functional

And structural

factors

Pritwi

Ap

Tejas

Vayu

Akasa

Vata +

Pitta + + +

Kapha + + +

Rasa + +

Rakta + + +

Mamsa + +

Medas + + +

Asthi + + +

Majja + +

Sukra + +

Mutra + + +

Purisha + +

Sweda + +

Artava + +

Sthanya + +

Dhatwagni paka-

Sara bhaga that comes out after bhutagni paka is subjected to the action of

dhatvagnis. Seven kinds of dhatwagnis corresponding to seven kind of dhatus

are rasagni, raktagni, mamsagni, medogni, asthiagni, majjagni and sukragni.



They bring about transformation of appropriate nutrient substances in ahara

rasa into corresponding poshaka or astayi (precursor) dhatu, before it is build

up poshya or stayi dhatu. This paka is done by the ushma present in each

dhatus the datwagnis. The process involved in dhatwagni vyapara is seemed

to comprise of two pakas prasada and kitta pakas.

Prasada paka as described yield seven kinds of posaka dhatus and kitta

paka yield kitta or waste products (33). Posaka dhatus are transported to

respective poshya dhatus through srotases(34). Upadhatus are formed as a by

product of prasada paka. They include sthanya, raja, kandara, vasa, twak,

snayu, etc(35). The product of kitta paka on the other hand said to contribute to

the formation of sweda, mutra, pureesha, vatha, pitta, shlesma etc.

Dhatwagnipaka can be summarised in the following table

Table 2. 4. Summarisation of Dhatvagni paka

Nutrients for rasa

+ Rasagni- Posaka rasa + kapha Stanya,artava

Nutriens for rakta

+ Raktagni Posaka rakta + pitta Kandara, sira

Nutrients for mamsa

+ Mamsagni Poshaka mamsa

+ karna, akshi, nasika, asya lomakupa prajanana mala

Nutrients for medas

+ Medogni Poshaka medas

Sweda



Nutrients for asthi

+ Asthi agni Poshaka asthi Kesa, smasru, loma, nakha

Nutrients for majja

+ Majja agni Poshaka majja

Akshi, vit, twak sneha

Nutrients for sukra

+ Sukra agni Poshaka sukra

ojus

Dhatwagnis are very specific that they take part in the formation of

particular dhatus only. Rasagni form rasa from apya materials, raktagni form

rakta from apya and agneya materials and so on. These posaka dhatus are

transported to sthayi dhatus by their particular srotases. Dhatu vaha srotases are

extremely subtle; they transport nutrients undergoing metabolic transformation

to corresponding sthayi dhatus. Pattern of distribution of nutrients to tissue

elements present all over the body through the three well known hypothesis -

khseera dhadhi, kedara kulya and khale kapota nyaya,and sthayi dhatus in order

are formed rasa, then rakta etc

The mamsa poshana performed by the rakta dhatu can be explained by

the ksheera dadhi nyaya. This nyaya is also called the sarvatma parinaama

paksha. According to this analogy, the process of dhatu parinaama is

comparable to the process of souring of milk, in which entire milk is converted

into curd; similarly the entire rasa dhatu substrate evolves as rakta dhatu and

rakta dhatu to mamsa dhatu and so on by the action of the respective dhatvagni.



This process of conversion is further explained by chakrapani, based on

the concept of modification at the level of panchabhuta. According to this, the

rakta formed by the modification of rasa is accompanied by vayu, jala, tejas

and ushma and attains compactness and gets transformed into mamsa dhatu.

Varna prasadana

The varna prasadana is an important function of raktha dhathu. A well

formed raktha is essential for charming skin with radiant appearance.This can

also be illustrated through the concept of raktha sara.Sara represents the

exellence of dhatu and the features of raktha sara includes the healthy radiant

appearance of skin.Making colour to an appealing nature is done by rakta.

Ranjaka pitta impart colour to rakta and this rakta make the skin bright. In the

excellent state of rakta dhatu, the skin of the person appear to be radiant.

Colour of skin depends on thickness and amount and quality of blood in

capillaries. Pallor occurs in a person with thick or opaque skin. Pale yellow

colour of skin is seen in haemolytic jaundice and dark yellow in obstructive

jaundice.

Cyanosis occurs in reduced haemoglobin. The factor that responsible for

such changes in colour is rakta.



The sub papillary venous plexus is parallel to the surface of the skin

therefore, the color of the skin depends upon the flow in capillary loops as well

as sub papillary plexus. When the anastomosing channels are fully open, the

skin become hot and reddish in hue. Thus, the functions attributed to rakta can

be related to the modern physiology summarised above.



Rakta dhatwagni and ranjaka pitta are two entities that are concerned

with the formation of rakta dhatu. Both of them are agnis or pittas and these

terms are treated synonymously. Both have similar function the formation of

rakta dhatu. Description in our classics are very few and that also in an

indistinct manner. When comparing with western medicine production of blood

is evident and clear that it is produced from bone marrow, but this is not

mentioned by our acharyas. So a deeper understanding is needed to understand

them properly

Sites of formation of rakta dhatu

Ayurveda mention that essence of food become rasa dhatu and when this

rasa passes through yakrit and pleeha it gets coloured and rakta is formed.

A variety of medas sarakta medas is mentioned may be equalent to red

bone marrow, but it is not mentioned as a site for production of rakta.

Yakrit

It is included under koshtangas (visceral organ) and is functionally and

structurally an extension of adho amasaya. It is the main seat of rakta dhara

kala (1) and seat of rakta and pitta (2). It is stated that rasa acquires colour while

Rakta Dhatvagni and Ranjaka pitta



traveling through yakrit and pleeha. The liver has a wide variety of functions

and many of these are vital to life. Hepatocytes perform most of the functions

attributed to the liver, but the phagocytic Kupffer cells that line the sinusoids

are responsible for cleansing the blood. It also synthesise the plasma proteins

Pleeha

Pleeha is also considered as one among kostangas. It is the seat of pitta

and rakta and is the organ where rasa is coloured.

There are three different tissues within the spleen.

Reticuloendothelial tissue- concerned with phagocytosis of erythrocytes

and cell debris from the blood stream. This same tissue may produce

foci of hemeopoiesis when RBC's are needed.

Venous sinusoids -along with the power of the spleen to contract,

provides a method for expelling the contained blood to meet increased

circulatory demands in certain animals.

White pulp-provides lymphocytes and a source of plasma cells and hence

antibodies for the cellular and humoral specific immune defence

Functions of spleen

helps in immunity (protection against infection)



stores blood for the body and releases it when needed

destroys bacteria

destroys worn out and damaged platelets

destroys worn out and damaged red blood cells

It is interesting to note that the liver and spleen take up erythropoietic

functions in an adult if the necessity is extremely intense. Thus the rakta

formation function explained by Acharyas is substantiated.

Vagbhata quoted amasaya as the seat of ranjaka pitta (3).

Amasaya

It is included under koshtanga.(4) Adho amasaya is agni stana (5) . Stomach

plays a vital role in the synthesis of intrinsic factor that is extremely needed for

blood formation. Vitamin B12-IF complex deficiency leads to megaloblastic

anaemia. This proves the role of amasaya in the formation of rakta dhatu.

Concept of Sarakta medas

It is stated that majja inside long bones are red in colour and is termed

sarakta medas. But any where in our classics or in its commentaries it is not

stated as a production site of rakta or any relation with the formation of blood

Site of production of blood



Site of production of blood according to modern science is different

according to age.

Hemopoietic cells first appear in the yolk sac of the 2-week embryo.

By 8 weeks, blood making has become established in the liver of the embryo,

and by 12-16 weeks the liver has become the major site of blood cell

formation. It remains an active hemopoietic site until a few weeks before

birth. The spleen is also active during this period, particularly in the

production of lymphoid cells, and the foetal thymus is a transient site for some

lymphocytes.

The highly cellular bone marrow becomes an active blood making site

from about 20 weeks gestation and gradually increases its activity until it

becomes the major site of production about 10 weeks later. At birth, active

blood making red marrow occupies the entire capacity of the bones and

continues to do so for the first 2-3 years after birth.

The red marrow is then very gradually replaced by inactive, fatty,

yellow, lymphoid marrow. The latter begins to develop in the shafts of the

long bones and continues until, by 20-22 years, red marrow is present only in

the upper ends of the femur and humerus and in the flat bones of the sternum,

ribs, cranium, pelvis and vertebrae. However, because of the growth in body

and bone size that has occurred during this period, the total amount of active



red marrow (approximately 1000-1500 g) is nearly identical in the child and

the adult.

Adult red marrow has a large reserve capacity for cell production. In

childhood and adulthood, it is possible for blood making sites outside marrow,

such as the liver, to become active if there is excessive demand as, for

example, in severe hemolytic anaemia or following hemorrhage.

Red marrow forms all types of blood cell and is also active in the

destruction of red blood cells.

Red marrow is, therefore, one of the largest and most active organs of

the human body, approaching the size of the liver in overall mass although as

mentioned it is distributed in various parts of the body. About two-thirds of its

mass functions in white cell production (leucopoiesis), and one-third in red

cell production (erythropoiesis). However as we have already seen there are

approximately 700 times as many red cells as white cells in peripheral blood.

This apparent anomaly reflects the shorter life span and hence greater turnover

of the white blood cells in comparison with the red blood cells.

Formation of Blood

Rakta is formed from rasa dhatu. Actual method of transformation was

not clear. It is only said that rasa while travelling through the sites of blood i.e.



yakrit and pleeha accrue red colour and rakta is formed (6).Charaka observed

that from ahara rasa, rakta dhatwagni absorb more agneya amsa and transform

into rakta(7).

Step by step formation of rakta from rasa is given in the commentary of

sargadharasamhita.

Varnaparivartana in the stages of formation of rakta dhatu (8)

In the deepika commentary of sargadhara samhita it is stated that blood

is formed in seven days by gradual change taking place in its colour.

1. Sweta

2. Kapota

3. Haridra

4. Padma

5. Kimsuka

6. Alaktaka

7. Rasaprakhya/indragopa

Formation of Blood Cells



Blood cells are produced in the bone marrow (some 1011 of them each

day in an adult human). All types of blood cells arise from a single type of cell

called a hematopoietic stem cell an "adult" multipotent stem cell.

These stem cells

Are very rare (only about one in 10,000 bone marrow cells);

Are attached (probably by adherens junctions) to osteoblasts lining the inner

surface of bone cavities;

Express a cell-surface protein designated CD34;

Produce, by mitosis, two kinds of progeny:

v More stem cells (A mouse that has had all its blood stem cells killed by

a lethal dose of radiation can be saved by the injection of a single living

stem cell).

v Cells that begin to differentiate along the paths leading to the various

kinds of blood cells.

Differentiation of the stem cells is regulated by the need for more of that

type of blood cell which is, in turn, controlled by appropriate cytokines and/or

hormones. They include,



Interleukin-7 (IL-7) is the major cytokine in stimulating bone marrow

stem cells to start down the path leading to the various lymphocytes

(mostly B cells and T cells).

Erythropoietin (EPO), produced by the kidneys, enhances the

production of red blood cells (RBCs).

Thrombopoietin (TPO), assisted by Interleukin-11 (IL-11), stimulates

the production of megakaryocytes. Their fragmentation produces

platelets.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), as

its name suggests, sends cells down the path leading to both those cell

types. In due course, one path or the other is taken.

v Under the influence of granulocyte colony-stimulating factor (G-

CSF), they differentiate into neutrophils.

v Further stimulated by interleukin-5 (IL-5) they develop into

eosinophils.

v Interleukin-3 (IL-3) participates in the differentiation of most of

the white blood cells but plays a particularly prominent role in the

formation of basophils (responsible for some allergies).



Stimulated by macrophage colony-stimulating factor (M-CSF) the

granulocyte/macrophage progenitor cells differentiate into monocytes,

macrophages, and dendritic cells (DCs).

1. Red Blood Cells

Red Blood Cells or erythrocytes enucleated cells filled with

hemoglobin, a protein with quaternary structure. R.B.C.s are made in the red

blood marrow cavities of the long bones. They live for approx. 120 days and

die, their materials usually recycled by the spleen or liver. The Fe2+ iron

returned to the red bone marrow by transferrin, some Fe2+ and Fe3+ iron are

excreted in bile. The part of the

heme group that does not

contain iron makes

bilirubin. It is excreted by the

liver into bile, then to the

feces where its breakdown

product stercobilin colors the

feces. Fe+2 ion is bluish

green (like deoxygenated blood), and Fe+3 ion is red (oxygenated). Fe+2 is

oxidized by bacteria in the gut.



Red blood cells are first formed from stem cells that develop into

erythroblasts. The erythroblast loses its nucleus; therefore, the RBC is

enucleate. Reticulocytes, usually only present in the red marrow and having a

faint intracellular net pattern, move into the blood stream after maturation.

Mature red blood cells develop from hemocytoblasts. This development

takes about 7 days and involves three to four mitotic cell divisions, so that each

stem cell gives rise to 8 or 16 cells.

Development of RBC can be tabulated as follows

Table 3. 1. Development of RBC

Cell Cell diameter

(In micrometer)

Nucleus

Cytoplasm Mitosis

Pronormoblast 15-20 Big and strongly basophilic

Very scanty and basophilic. No Hb

+

Early normoblast

Smaller than pronormoblast

Smaller than that of pronormoblast

Still scanty & basophilic. No Hb

+

Intermediate normoblast

10-12 Smaller than that early normoblast

Hb has now apppeared, so that cytoplasm

becomes polychromatophilic

+

Late normoblast

8-10 Nucleus very small and deeply

stained

Plentiful cytoplasm, Hb present in fair amount:

cytoplasm is eosinophilic

_



Reticulocyte Almost same as that of matured

erythrocyte

Absent Some RNA still present in the cytoplasm

_

Matured erythrocyte

7.5 Absent Hb ++ _

The young red cell is called a retlculocyte because of a network of

ribonucleic acid (reticulum) present in its cytoplasm. As the red cell matures

the reticulum disappears. Between 2 and 6% of a new-born baby's circulating

red cells are reticulocytes, but this reduces to less than 2% in the healthy adult.

However, the reticulocyte count increases considerably in conditions in which

rapid erythropoiesis occurs, for example following hemorrhage or acute

hemolysis of red cells. A reticulocyte normally takes about 4 days to mature

into an erythrocyte.

In health, erythropoiesis is regulated so that the number of circulating

erythrocytes is maintained within a narrow range. Normally, a little less than

l% of the body's total red blood cells are produced per day and these replace an

equivalent number that have reached the end of their life span.

Factors influencing erythropoiesis

Erythropoiesis is stimulated by hypoxia (lack of oxygen). However,

oxygen lack does not act directly on the hemopoietic tissues but instead



stimulates the production of a hormone, erythropoietin. This hormone then

stimulates hemopoietic tissues to produce red cells.

Erythropoietin is a glycoprotein. It is inactivated by the liver and

excreted in the urine. It is now established that erythropoietin is formed within

the kidney by the action of a renal erythropoietic factor erythrogenin on plasma

protein, erythropoietinogen. Erythrogenin is present in the juxtaglomerular

cells of the kidneys and is released into the blood in response to hypoxia in the

renal arterial blood supply.

Various other factors can affect the rate of erythropoiesis by influencing

erythropoietin production.

1. Thyroid hormones: Thyroid hormones, thyroid-stimulating hormone, adrenal

cortical steroids, adrenocorticotrophic hormone, and human growth hormone

(HGH) all promote erythropoietin formation and so enhance red blood cell

formation (erythropoiesis). In thyroid deficiency and anterior pituitary

deficiency, anaemia may occur due to reduced erythropoiesis. Polycythemeia is

often a feature of Cushing's syndrome. However, very high doses of steroid

hormones seem to inhibit erythropoiesis.

2. Sex hormones: Androgens stimulate and oestrogens depress the

erythropoietic response. In addition to the effects of menstrual blood loss, this



effect may explain why women tend to have a lower hemoglobin concentration

and red cell count than men.

3. Oxygen availability: Plasma levels of erythropoietin are raised in hypoxic

conditions (low oxygen levels). This produces erythrocytosis (increase in the

number of circulating erythrocytes) and the condition is known as secondary

polycythemeia. A physiological secondary polycythemeia is present in the

foetus (and residually in the new-born) and in people living at high altitude

because of the relatively low partial pressure of oxygen in their environment.

Secondary polycythemeia occurs as a result of tissue hypoxia in diseases such

as chronic bronchitis, emphysema and congestive cardiovascular abnormalities

associated with right-to-left shunting of blood through the heart, for example

Fallot's tetralogy.

2. Granulocytes

Granulocytes is the collective name given to three types of white blood

cell. Namely these are neutrophils, basophils and eosinophils.

In terms of their formation (granulopoiesis) they all derive from the

same type of committed stem cells called myeloblasts. After birth and into

adulthood granulopoiesis occurs in the red marrow.



The process of producing granulocytes is characterised by the

progressive condensation and lobulation of the nucleus, loss of RNA and other

cytoplasmic organelles, for example mitochondria, and the development of

cytoplasmic granules in the cells involved.

The development of a polymorphonuclear leukocyte makes take a

fortnight, but this time can be considerably reduced when there is increased

demand, as, for example, in bacterial infection. The red marrow also contains a

large reserve pool of mature granulocytes so that for every circulating cell there

may be 50-100 cells in the marrow.

Mature cells pass actively through the endothelial lining of the marrow

sinusoid into the circulation. In the circulation, about half the granulocytes

adhere closely to the internal surface of the blood vessels. These are called

marginating cells and are not normally included in the white cell count. The

other half circulate in the blood and exchange with the marginating population.

Within 7 hours, half the granulocytes will have left the circulation in

response to specific requirements for these cells in the tissues. Once a

granulocyte has left the blood it does not return. It may survive in the tissues

for 4 or 5 days, or less, depending on the conditions it meets.



The turnover of granulocytes is, therefore, very high. Dead cells are

eliminated from the body in feces and respiratory secretions and are also

destroyed by tissue macrophages (monocytes).

No precise mechanisms for the control of granulocyte production have,

so far, been found. However, in health, the count remains relatively constant so

it is likely that homeostatic control mechanisms operation

3. Monocytes

Monocytes are produced in the bone marrow, developing from nucleated

precursors, the monoblast and promonocyte. Mature cells have a life in blood

of approximately 3-8 hours and, like granulocytes, there is a circulating and

marginating pool.

Monocytes are actively phagocytic (engulf other cells) and, on migration

into the tissues, they mature into larger cells called macrophages (Derives from

the Ancient Greek: macro = big, phage = eat), which can survive in the tissues

for long periods. These cells form the mononuclear phagocytic cells of the

mononuclear phagocytic system (reticuloendothelial system) in bone marrow,

liver, spleen and lymph nodes.

Tissue macrophages (sometimes called histiocytes) respond more slowly

than neutrophils to chemotactic stimuli. They engulf and destroy bacteria,



protozoa, dead cells and foreign matter. They also function as modulators of

the immune response by processing antigen structure and facilitating the

concentration of antigen at the lymphocyte's surface. This function is essential

in order that full antigenic stimulation of both T and B lymphocytes can take

place.

4. Lymphocytes

Lymphocytes are round cells containing large round nuclei. The

cytoplasm stains pale blue and appears non-granular under light microscopy.

However, some cytoplasmic granules and organelles are present.

Morphologically, lymphocytes can be divided into two groups: the more

numerous small lymphocytes, with a diameter of 7-10 mm; and large

lymphocytes, which have a diameter of 10-14 mm. Lymphocytes are produced

in bone marrow from primitive precursors, the lymphoblasts and

prolymorphocytes. Immature cells migrate to the thymus and other lymphoid

tissues, including that found in bone marrow, and undergo further division,

processing and maturation.

5. Platelets

Platelets are produced in bone marrow by a process known as

thrombopoiesis. They are formed in the cytoplasm of a very large cell, the



megakaryocyte. The cytoplasm of the megakaryocyte fragments at the edge of

the cell. This is called platelet budding. Megakaryocytes mature in about 10

days, from a large stem cell, the megakaryoblast.

It is likely that there are thrombopoietic feedback mechanisms as the

platelet count remains fairly constant in health, and platelet production is

reduced following an infusion of platelets and increased following removal of

platelets.

Fate of RBC

When RBCs are terminally differentiated; they lose their power to

multiply. The life span of erythrocytes is about 120 days and then they are

ingested by phagocytic cells in the liver and spleen. Most of the iron in their

hemoglobin is reclaimed for reuse. The remainder of the heme portion of the

molecule is degraded into bile pigments and excreted by the liver. Some 3

million RBCs die and are scavenged by the liver each second.

Ayurvedic concept

There are at least three factors which play major role in the formation of

any dhatu. They are:

Poshaka dravya



Srotas

Agni

Poshaka dravya of rakta dhatu

According to Ayurveda, shad rasayukta ahara is advised. such food is

capable of developing all dhatus in equal quantity and good quality and this

may be called as a balanced diet.

According to Ayurveda concept, the rakta dhatu is formed as a product

of transformation of rasa dhatu. This transformation from rasa to rakta is

explained by various nyayas by Chacrapani. They are kshreera dhati nyaya or

conversion of one dhatu to next as milk to curd like that rasa is converted,

kedara kulya nyaya or transportation of nutrients from one dhatu to another.

Nutrients for rasa are first absorbed then pass on to rakta etc one after other and

khale kapota nyaya or selective attainment of nutrients i.e. rasa absorb nutrients

it want and rakta also absorb its nutrients only, as parrots take their own food

(9).

To trace the site of rakta dhatwagni it is indispensable to have a deep

acquaintance about rakta vaha srotas.

Rakta vaha srotas



The term srotas means channel. It comprises of channels of different

kinds. They may be stula (gross or macroscopic), sukshma (subtle) or anu

(microscopic) (10).This internal transport system of body has been given a

fundamental importance in ayurveda in health and disease. It is said that when

the integrity of srotases are impaired both stayi and astayi dhatus become

involved and the morbidity spreads by one dhatu to another (11). They are the

transporters of factors that cause prakopa (exitation) or samana (alleviation) of

doshas (12). Anatomically they resemble in colour and form to the dhatus they

transport. Functionally they are different from siras and dhamanies and the

function of srotases are to exudates or to ooze out.

Vagbhata told that rasa spread through out the body through fine

dwaras (pores) of srotases which are distributed through out the body be fond

of lotus stem (13). According to Charaka srotases represent internal transport

system and nutrients are made available to dhatus through them (14).

Chakrapani has further explained that these pores have both ayana and mukha

and nutrients are given to dhatus and malas are returned back (15). Even though

Charaka has said there are numerous srotases in the body, important thirteen

ones are described with its origin, course and how they become vitiated.

Amongst them rakta vaha srotas is very important.

Rakta vaha srotas have moola stana in liver and spleen (16). They have an

influence over whole rakta.



Factors which vitiate rakta are intake of food and drinks that are irritants

(vidahi), more unctuous, hot in potency and more liquid in consistency. Rakta

get vitiated when a person is over exposed to sun or fire (17). When this srotas is

vitiated skin diseases, erysipelas, boils, hemorrhoids, menorrhoegia,

suppuration in anus, penis and mouth, spleen enlargement, abscess, gulma,

nilika (blue pimples), vyanga, jaundice, leucoderma, urticarial patches,red

patches, etc results(18).

Raktadhara kala

According to Susruta kalas are the structures that separate dhatus from

their asayas (19). It is compared with epithelium. They are seven in number and

rakta dhara kala is one among them. Raktadhara kala support or protect rakta

and is seen inside mamsa, inside sira especially that in yakrit and pleeha but

does not have any role in the rakta dhatu formation.

Agni concerned with the rakta formation

There are two agni factors which have direct influence on the rakta

formation. They are

Ranjaka pitta

Rakta dhatvagni

Ranjaka pitta



Pancha bhoutic structure of ranjakapitta is assessed by the study of

panchabhoutic dominance of rasa, pitta and rakta as ranjaka pitta plays

amongst those three.

Table 3. 2. Panchabhoutic status of rasa, pitta and rakta

Prithvi Ap Teja Vayu Akasa

Rasa - + + - - -

Pitta - + + + - -

Rakta - + + + - -

As rasa of apya nature is converted to rakta of ap-tejo nature by the ranjaka

pitta, it can be assumed that the ranjaka pitta also has the agneya quality in

predominance.

Formation of ranjaka pitta

Ranjaka pitta is originating from yakrit and pleeha so does raktadhatu.

The formation of ranjaka pitta and rakta dhatu shows some connections as an

asraya asrayi bhava i.e. the interdependence between dosha and dhatu exists in

the case of ranjaka pitta and rakta dhatu. According to asraya asrayi sambhanda

pitta is asraya to rakta and rakta is dependent of pitta mainly ranjaka pitta.

According to this doctrine when asraya increases asrayi also increases and



when asraya decreases asrayi also decreases. Pitta has asraya in rakta. It not

only means pitta resides in rakta but it depend rakta for its formation and

nourishment.

Ranjaka pitta when increased shows the symptoms of pitta vridhi and

when decrease show symptoms of pitta kshaya.

Rakta dhatwagni

The special agni that is concerned in the production of rakta is rakta

dtatwagni. The dhatwgnis are located in respective dhatus. Dhatus attain

nurture through the srotases by their agni. Dhatwagni vyapara begins after

bhutagni vyapara.

Rasa dhatu on reaching yakrit and pleeha, is subjected to paka by rakta

dhatwagni which is already present there. It absorbs nutrients taijasa amsa and

also with the help of ranjaka pitta, rasa ranjana is done and conversion of rasa

to rakta is completed.

Every dhatwagnis have two duties. One portion help in absorption of the

nutrients they want, while the other fraction engage in converting the dhatu to

succeeding one. Rakta dhatwagni also absorb nutrients from aharasara (iron

etc) and employ in formation of rakta, while a portion converts rakta in to

mamsa.So when there is a decrease in rakta dhatwagni (being pathological),



there will be a quantitative raise of rakta dhatu as it is not properly formed and

not converted to mamsa (20).

If there is an increase of rakta dhatwagni, either quantitative decrease in

rakta dhatu happens or rakta dhatu not capable of performing jeevana karma

properly is produced. So both conditions are pathological. Raktagni is very

similar to ranjaka pitta at a glance

Similarities between rakta dhatwagni and ranjaka pitta

v Both of them are pitta or agni

v Both of them have similar functions

Differences between them

v Ranjaka pitta is a dosha, one among five pittas and rakta dhatwagni

is one among seven dhatwagnis which is a portion of pachakapitta.

v Even though both take part in the formation rakta, ranjaka pitta is

clearly told to impart colour to rakta dhatu and production of rakta

from rasa is the function of rakta dhatwagni

v Site of ranjaka pitta is told differently in different situations but rakta

dhatwagni is not clearly mentioned

So we can see that ranjaka pitta and rakta dhatwagni are not one and the

same. Rakta being a special and important dhatu it is included with equal status

of dhosas and a special sodhana is also attributed to it- the rakta moksha. So



ranjaka pitta may be a group of substances helping in formation of RBC or

specifically heam which is the colouring agent. It resides in liver and spleen

as many hemopoitic factors are stored there. Being a dosha it can travel to any

sites in body, it may be traveling to site of production of cells through any

srotases as the whole body is srotas to doshas. Rakta dhatwagni on other hand

receive agneya materials and form blood cells.

Ranjaka pitta may supply coloring materials simultaneously in it and

thus formation of rakta is completed. This can be related to heme synthesis in

particular.

Metabolism of Heme:

Metabolism of heme has two aspects; the synthesis of heme and the

catabolism of heme.

Synthesis of heme

Synthesis of hemoglobin begins in the proerythroblasts and continues

even into the reticulocyte stage of the red blood cells. Therefore, when

reticulocytes leave the bone marrow and pass into the blood stream, they

continue to form minute quantities of hemoglobin for another day or so until

they become mature erythrocytes. First, succinyl-CoA, formed in the Krebs

metabolic cycle binds with glycine to form a pyrrole molecule. In turn, four



pyrroles combine to form protoporphyrin IX, which then combines with iron to

form the heme molecule. Finally, each heme molecule combines with a long

polypeptide chain, a globin synthesized by ribosomes, forming a subunit of

hemoglobin called a hemoglobin chain

Porphyrins

The porphyrins are complex structures consisting of 4 pyrrole rings,

united by "methyne" bridges (or methylidene bridges)

The nitrogen of 4 pyrrole rings can form complex with metallic ions

such as Fe++and Mg++. They form the prosthetic groups of conjugated proteins,

viz.

v Hemoglobin of mammalian erythrocytes

v Myoglobin of muscle

v Erythrocruorins of some of the invertebrates, which occur in blood and

tissue fluids.

v Cytochromes: respiratory enzymes in electron transport chain.

v Catalase and peroxidase enzymes and

v Oxidative enzyme like tryptophan pyrrolase. All the above contain Fe-

porphyrins as prosthetic groups.

v Chlorophyll, occurring in plants, contain Mg-porphyrin as the prosthetic

group.



Biosynthesis of Porphyrins

Porphyrins are synthesized partly in the mitochondrion and partly in

cytosol of aerobic cells like developing erythrocytes and hepatic cells.

Stages of Biosynthesis:

Arbitrarily the synthesis of porphyrins can be divided into three stages

for understanding.

Stage I: Synthesis of -Amino Laevulinic acid (ALA), which occurs in

mitochondria.

Stage II: Synthesis of coproporphyrinogen III (major series) and

coproporphyrinogen I (minor series) which occurs in cytosol.

Stage 111: Synthesis of protoporphyrin IX, - which occurs in mitochondria

again.

Stage I: Synthesis of -Amino Laevulinic Acid -ALA (Intramitochondrial)

Biosynthesis begins with the condensation of 'succinyl CoA' ("active"

succinate) and glycine to form ' -amino-- Ketoadipic acid".

-amino-- Ketoadipic acid acid then undergoes decarboxylation to produce -

ALA.



Both the reactions are catalyzed by the enzyme -ALA-synthetase, which

requires pyridoxal-P (B6-P) and Mg++ as coenzymes. In liver cells, the

synthesis occurs in the mitochondrion. Panthothenic acid is also required at this

stage being a constituent of CoA-SH.

Mechanism of Action:

v Glycine first combines with "Enz. - B6 - complex" to form enzyme

bound "schiff base".

v The above then condences with Succinyl-CoA forming a "Ternary

complex", -amino--ketoadipic acid + B6P + Enz and CoA-SH is

liberated.

v -amino--ketoadipic acid then loses a mol. of CO2, liberating -ALA in

free form from the complex.

-ALA Synthetase Enzyme and its Regulation

-ALA synthetase enzyme is: Very unstable, Low in concentration in tissues,

Main rate-limiting enzyme in the synthetic pathway.

Regulation:

v Many erythropoietic substances including hormones stimulate heme

synthesis by inducing the production of the enzyme.



v End product 'heme' inhibits the enzyme by "feedback" inhibition.

v Heme also causes a repression of the synthesis of the enzyme, "end-

product repression".

Stage II: Synthesis of coproporphyrinogen III and I (cytosolic):

1. formation of Porphobilinogen

v -ALA comes out of mitochondrion into the cytosol. Two molecules of

-ALA condense further to form a molecule of "porphobilinogen",

which is the precursor of 'pyrrole' ring.

v The reaction is catalyzed by the enzyme -ALA deliydratasc, for which

Cu** is required as a cofactor. It is a Zn-containing enzyme.

Regulation:

This is a second rate-limiting enzyme, which is inhibited by 'feedback'

inhibition by end product Heme.

2. formation of Uroporphyrinogen I and III:

I. Uroporphyrinogen I (minor series):

v In presence of a porphobilinogen deaminasc (also called

uroporpliyrinogen-1 synthetase), 4 moles of porphobilinogens condense,



losing 4 mols of NH3 and forms "Uroporphyrinogen I" (minor series), in

which the acetic acid and propionic acid side chains alternate.

v In formation of Uroporphyrinogen I, as above, "Di-pyrroles" and

"tetrapyrroles" may be formed as intermediates.

v Oxidation of uroporphyrinogen-I, produces uroporphyrin I, which may

be excreted in urine in small amounts normally.

II Uroporphyrinogen III (Major series):

v Concomitant operation of an isomerase (also called as

Uroporphyrinogen III cosynthetase with deaminase, results in reversal

of one porphobilinogen residue, so that the cyclization results in the

formation of "Uroporphyrinogen III" (major series). In this, in IV

pyrrole ring, acetic acid and propionic acid side chains are "reversed",

(cf. Uroporphyrinoge

ranjakapitta Ayurveda

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