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Monday, August 31, 2009

C rporate Banking Transformation Banking Frontiers organized a roundtable at the Sahara Star Hotel in Mumbai on 11 June 2009 on the topic 'Corporate B


Manoj: We have terms like nano seconds nowadays and that is part of business language and not just technology language. Given the economic scenario in the competition, corporates wants things faster and faster. So, how are bankers accelerating corporate banking services?
Vipul Acharya: Today MNC banks give a lot of technological advantage to the corporates, and hence most of the corporate big houses are with MNC banks. But now Indian banks are also competing with them· in terms of service and pricing. People banking is slowly shifting to electronic medium. India is evolVing and I think we will not have clearing system any more and everything will be done through electronic banking only. In 3 to 4 years, all the banks will have ERr integration. So once a company goes for ERr integration with one bank, it is very difficult to move that customer from one bank to another bank.
Vispi: The move is in the right direction. In the days to come, we see payments to be the driver as far as cash management or transaction banking business is concerned. In two years time, all-India clearing will get centralized or it will get divided into four zones only. With just cheque truncation and speed clearing taking shape, we see collection as a dying product two years down the line. It's all going to end up with payments and the banks who get integrated with corporate ERr are going to create a stickiness because this is one business which is highly sticky - no customer wants to move out for a small advantage unless you are able to offer something that is mind-boggling and going to make his life very different from what it is today. The other thing that we see emerging these days among large corporates is the shared service centre concept, where the corporates are trying to centralize the receivables, payments and collections - all this at the group level.
Rajamani: You will see that most of the organizations inIndia are ITenablingthemselves through ERr deployment. What they are looking forward is how much they can connect themselves with the external world, particularly with financial institutions. Right now banks are their daily life and they cannot survive without the banking industry, so they see lot of value in decreasing the cycle ti me of various transactions. With RTGS and NEFT in place, they see lot of value in automation of transactions and that really brings the question of how do we establish the last mile connectivity between the corporate and

• BRGB has provided financial assistance to 15 projects with financial outlay of Rs 53.70 lakh under Venture Capital Scheme for Dairy.

computerization of the bank's business already completed and further initiatives, including implementation of CBS, (ii) NRE/NRO business being started shortly, (iii) undertaking pension business as sub-agent of sponsor bank, (iv) augmenting non farm sector advances especially MSME
in collaboration with German Financial Corporation, (v) branch expansion -opening of 5 new branches, (vi) WomenDevelopmental Cell for empowering rural women, (vii) social banking, (viii) solar energy project, (ix) debt swap scheme for freeing the families from the clutches of money lenders, (x) financial inclusion for rural empowerment - 835 villages including one district fully covered and (xi) Promotion and revitalization of farmers clubs. This year's motto of the bank is 'Maximization of Profit through Rural Empowerment and Technology Upgradation' and in order to translate the spirit of the motto into reality, the bank has proposed to pursue the following prime corporate objectives and business strategies to achieve the same.

OBJECTIVES & STRATEGIES
Garg said that corporate objectives are to increase gross profit by 50'K" bring down gross NPA to less than 2.5% and NPA to less than 1 %, 2291' growth in deposits (Rs 2,330 cr), 25U/c, growth in advances (Rs 1,474 cr), to attain per branch productivity of Rs 13.63 cr, to attain per staff productivity off Rs 3.40 cr, implementation of CBS in 80 urban, semi urban and other centers, all branches to be a profit making unit, substantial increase in non interest income, recovery of at least Rs ] cr in written off accounts, increase the clientele base to two million, opening of 5 new branches - 3 semi-urban and 2 rural, increasing share of low cost deposits to 58% and achieve cross sell ratio of 2.
l3RG l3 has multiple strategies to achieve its corporate objectives.
The bank plans to maximize its profits by low cost deposit mobilization, diversify loan portfolio with high yielding advances, maintaining asset quality with no slippages, reduction in NPA level at least by 30% through cash recovery and up gradation, at least 20'}(, cash recovery in written off accounts, doubling of non interest income, inter alia, by canvassing non fund business such as bank guarantee and sale of third party products, increasing staff

LOOK IT SHOWS 105 KG-So LAST WEEK IT S~WED 100·

WHICH CAN MEAN ONL'( ONE 1H1NG-.
productivity, bring down the controllable expenses through cost discipline, preventing revenue leakages. Another objective is rural empowerment which will be done through programs for financial inclusion, financial literacy, micro finance,

women development cell and formation of farmers club. As regards technology, CBS will be implemented in the first phase 80 branches in urban and semi­urban areas, covering 51% of business of the bank.

GROWTH POTENTIAL OF RAJASTHAN
The pace of financial inclusion has proved to be a good tool for banking extension in the state. BRGB has covered 835 villages under 100% financial inclusion with coverage of whole district of Dungarpur under 'Dungarpur Project' in collaboration with its sponsoring bank, Bank of Baroda. BRGB has associated with its sponsor bank as 40% partner in its endeavor towards 100% financial inclusion and Total Integrated Rural Development of Dungarpur, a tribal district in its area of operation. The 100% financial inclusion has already been achieved by coverage of 250 Villages. The bank has provided financial assistance of Rs 486.20 lacs to 2287 families for dairy, spices cultivation, vegetable production and to rural artisan besides forming 51 Farmers Club and 731 SHGs, Credit Linkage of 442 SHGs and issuing] 951 KCCs.

POTENTIAL SECTORS
Garg added that in terms of potential sectors in the state for banking, there is ample scope in minor irrigation, land development, water management, soil conservation, farm mechanization, horticulture, forestry, waste land development, bio-fuel crops, rural non farm sectors - agro processing, agri exports, contract farming which can be explored for augmenting credit dispensation. Besides there is vast potentials in marble, cement, mica, limestone, mineral crushing, cotton, textile industry which can be explored to add to the economy of Rajasthan state, added Garg.

State Bank of Bikaner and Jaipur (SBBJ) has a strong network of 698 branches in Rajasthan. the largest network among all banks operating in the state.

Arun Shandilya: SBB) has a strong network of 860 branches. Of these, 698 branches are in Rajasthan which is the largest network among all banks operating in the state. Of these, 524 branches are located in rural and semi-urban areas, which play an important role in rural development and poverty alleviation in the state. Even in terms of number of customers, about 93% of them emanate from Rajasthan. The percentage of SBB) customers (both deposits and advances) is about 9.8% of total population and about 19% of the adult population of the state, which is the highest amongst all banks in Rajasthan. Over the last few years, the bank has made significant progress towards financial inclusion and providing services to hitherto un-banked population of the state.
What are the major changes observed in the pattern of savings, fixed deposits, loan taking, etc, over a period of time?
The interest rates have generally gone up in the financial system (barring the last six months when policy rates have been cut aggressively to combat the economic slowdown). As a result, there has been an increasing preference of our customers towards the term deposits which provides better return to depositors. Between March 2005 and March 2009, the share of term deposits in total deposits of the bank has gone up from 56.9% to 62.2%. The share of savings and current deposits has correspondingly gone down, although in quantitative terms, even CASA deposits have grown by over 80% between March 2005 and March 2009. Likewise in case of advances, over the last few years there has been substantial upscaling of advances in commercial and institutional (C&I) segment particularly by financing of infrastructure sector projects. Accordingly, the proportionate share of C&I segment in total advances has gone up from 36.1% in March 2005 to about 50.4% in March 2009. The share of personal segment and small scale industries has correspondingly gone down, although in quantitative terms advances to these segments too have gone up significantly over the last few years.
Is the NRls' contribution in your bank increasing'? \\ hat is the percentage of the NRls' clientele?
The bank has a customer base of nearly 70,000 NRls. The deposits from NRls have increased from Rs 637 crore in March 2005 to Rs 813 crore in March 2009.
What are the major projects currently at ')BBF
SBB) is amongst the first few public sector banks in the country with all branches on core banking. One of the major projects at hand is to optimize the usage of technology to offer value added services to customers. Amongst the major objective is to migrate more and more customers towards alternate delivery channels particularly internet banking and ATMs. The bank is also implementing BPR exercise whereby most of the bank office functions are being centralized so that branches can focus more on improving customer service, sales and marketing. We are endeavoring to boost non-interest income by cross selling life and non-life insurance, mutual funds and credit cards, besides expanding the coverage of online share trading facility launched during 2008-09.
How does your bank compete with other banks, especiallv cooperative banks, in the statl?
AU branches are on core banking solution and the bank has satellite connectivity even in the remotest corner of the state. Today SBB) offers multiple products and delivery channels which include internet banking at all branches, online funds transfer, B2B payments, utility and other biH payments, online tax payments, railway freight payments, etc. The bank has about 500 ATMs which are connected to State Bank group ATM network. Overall, SBB) is far ahead in terms of network, business size and technology particularly compared to cooperative banks in the state.
Can you explain the strategy of business growth and expansion plans of your bank? What are the targets for 2009-1 O?
Notwithstanding the global economic slowdown, SBB) has maintained a healthy growth in business and profitability in 2008-09 with net profit growth of 28.1%. For the year 2009­10, the bank is targeting a business growth of Rs 18,600 crore, as against the growth of Rs 9,885 crore in 2008-09. For the purpose, special emphasis is being laid on the retail segment, particularly agriculture, housing, education and SMEs. Branch expansion shaH also be pursued Vigorously keeping in view the potential at select centers.

themselves. The three leading banks that did well were SBl, ICICI Bank followed by Central Bank of India. What we did was display a notice board at th

advertise their personal messages on the board - anything that they may want to advertise. This has happened 10 years ago.
PK Nair: But the point is that you may 2000 branches and it is hard to replicate the same across all the branches.
Rajesh: What I am trying to say is that informally the PSUs are already doing it. They interact with so many customers daily that it is easy for them to bounce off the information to customers. For instance, if a customer purchases a car and is unhappy with his choice, the bank on hearing about this could pass on the information to other prospective customers. They can then make it formal.
PK Nair: Do you offer the car loan from a branch or do you offer it from a retail asset group?
Asha: It is now a centralized retail asset hub. But the leads are sourced through the branch. When 1 have a wide network of 2000 branches, why do I need to centralize it? Some banks do not have the advantage of a network.
Narayanan: The question is whether your marketing is information driven or transformation driven. Information driven marketing may be able to give you volumes but not values, especially in an era which is either customer convenience or affinity. What is required is to reach the headlines or the heartlines. That's what going to count. If you manage to hit the heartlines of the customer, there is no need to hit the headlines. Information may help you to reach the headlines, but unless your personal relationship at the touchpoint of the customer will only help you to reach the heartlines. And when you reach the heartlines, your relationship with the customer gets strengthened. And that's why it's the greatest relationship for banking because it is almost relationship driven.
Manoj: Heart to heart commerce?
PK Nair: If you analyse the set of customers today, how many of them would be the younger generation and what is the kind of products and services they would ask for in the next five years? Do you have a set of products and services you think you will introduce three years from now? So what happens to that next set of products and services which that generation is going to demand? Where's that coming from?
Venkatramaiah: True to the younger generation today, all banks offer internet banking, mobile banking,
Sunder Rajan: For the Nano car booking loan, we went in for marketing face-to-face. We did not depend much on internet and website. At the branch level, we were driving the branch people to interact with the customers. The results spoke for
themselves. The three leading banks that did well were SBl, ICICI Bank followed by Central Bank of India. What we did was display a notice board at the branches and we encouraged the staff to ask customers whether they were interested in booking the Nano. We even offered tips. Some customers were fussy and don't want to buy a low-end car. So we suggested that they buy it as a gift for their son or wife - a second car. We did well. We also had a relationship with some dealers with whom we exchanged information.
PK Nair: What Tata Motors did was created a mini website within their website and in that they had a series of discussions. What they wanted to find out was whether it should be positioned as a second car for customers or a safety car because the world is increasingly going green. They used the internet as a medium as it can be accessed immaterial of the location. From a banker's perspective, we would be mainly interested in the booking amount and the fee amount. For Tata, it helped them immensely to get better feedback on how to segment the car and the customer segment to target and also the additional functionalities they need to bring. Normally they would have done a huge market research exercise that would have cost them crores of rupees. Here they have got the feedback for free which the customer has come and given to them. That's the differentiation you can bring and the trend we are seeing.
Srinivas: You are aware that the public sector banks are becoming tech-savvy and providing lots of facilities, etc. But we believe that human interaction is more important. Earlier RBI pushed for customer satisfaction; from here they have now moved to customer excellence. Now the buzzword is customer ecstasy. We should be in a position to offer services to customers that they are not expecting. This could be in the form of mutual funds, insurance, etc.
Manoj: 1 am sure all of you must have moved house some time or the other in the past. This means changing addresses with banks, insurance, mutual funds. [ am just wondering whether banks be the agents for various other segments such as mobile phones and others?
Hegde: Even the bank pass book is accepted as one of the proof of address.
Taneja: 1 think there are two aspects to this especially when you are engaging with a client whose contact information or address keep changing regularly. First part is there are some ways in which we can anticipate what is going to happen. As a bank, I will accept change in contact numbers through various channels including the phone, internet banking, etc. The address on the account will not change till the customer gives me a letter because that is the KYC. Customers who like to keep in touch with the bank or like to receive alerts will probably update their phone numbers first because it will be done qUickly because typically banks will accept such requests over the phone, or through email or the internet. Whenever that happens, it is an alert by itself. It could also suggest that the customer has shifted the location itself. Maybe as a bank what I can do is ask the customer whether he has shifted his residence too. Other indicators are that might have stopped issuing cheques which were earlier happening on a monthly basis. The other point raised here is whether banks can help the customer change his address in respect to other things such as magazines, mobile phone operators, etc. I think as far as

Wednesday, August 19, 2009

When the concentration of serum hormone is high, the color will be more intense and vice versa. ELISA technic may be used to measure the peptide hormo

the intensity of color is measured with a spectrophotometer. When the concentration of serum hormone is high, the color will be more intense and vice versa. ELISA technic may be used to measure the peptide hormones as well as some steroid hormones (eg, progesterone, recall progesterone circulates in the blood being bound with a serum protein). LISA technic can be used to measure any protein in the serum, provided the protein is antigenic. By ELISA technic a screening may be made to detect sufferers from AIDS. Regarding the technology, other variants (other than the mentioned above) of ELISA are also available. Further, a new technic, closely related to ELISA is EMIT (not described here). By EMIT technic, trace quantities of protein (having low molecular wt, hence unsuitable for ELISA) can be measured. 3. Flurimetric analysis Plasma cortisol can be estimated by this method The analysis requires a flurimeter. This is currently the method of choice for plasma cortisol estimation. 4. Cytochemical assay More sensitive than RIA, the method is unfortunately very complicated and requires great expertise. However, its potentiality is great. 5. Dynamic tests In cases, where the endocrine malfunction is only very mild, estimation of concentration of the hormone level in blood may not give clear clue. In such case, a drug, which either stimulates or depresses the hormone's secretion may be given and after the drug administration the hormonal concentration measured. Such tests are called dynamic tests. An example is metyrapone test (chap. 4, sec. VI, in assessment of 'adrenocortical status'). Some older methods 1. Estimation of the urinary metabolites : Progesterone is metabolized and part of the metabolites appear in the urine as pregnanediol. Urinary pregnanediol can be estimated by column chromatography followed by colorimetry. Therefore, from a 24 hour urinary sample, daily secretion of progesterone in the body can be assessed. This method of assessment of progesterone status in the body is still somewhat popular, but similar others are not so. For example, estimation of urinary metabolites of suprarenal cortical hormones (e.g., 17 ketogenic steroids, 17 ketosteroids), for assessment of suprarenal status in the body, was very popular till the 1960s but are now practically obsolete, because superior methods are now available. 2. Whether an endocrine gland is hyper or hypo functioning, or functioning normally, car, be assessed (i.e , endocrinal status determinated) by many indirect methods. Examples are : serum cholesterol/BMR estimation, to assess the thyroid status. With the introduction of the modern methods, importance of the indirect methods have fallen considerably. HORMONE DEGRADATION A portion of the hormone is degraded in the target organ Apart from this, liver is the principal site of hormone degradation and the degraded hormones are often removed via the kidney through urine and are called urinary metabolites of the hormone. SUMMARY & HIGHLIGHTS Hormones may be (i) peptide, (ii) steroid and (iii) amines. Receptors for (i) peptide hormones are in the target cell membrane whereas (ii) those for steroid and thyroxine are in the cytosol or nucleus Membrane receptors combine with the hormone→activate G protein (coupling unit)→activate the catalytic unit --3- now a 2nd messenger is produced. The 2nd messenger ultimately produces the biological effect. However, some peptide messenger hormones are, till now, not known to produce 2nd messenger. cAMP, DAG, Ca++ etc. are examples of 2nd messenger. Adenyl cyclase, PLC etc are examples of catalytic unit. Steroid hormones and thyroxme do not prduce 2nd messengers. Instead they cause increased production of RNA → more proteins (= enzymes and/or structural proteins). Clinically blood concentrations of most hormones can be measured by RIA or ELISA technics. Normally, hormones are present in exact quantities, neither more nor less. Very often, hormones, regulation is achieved by (i) hypothalamus, (ii) ant. pituitary both of which are influenced by feed back (-ve, usually). However, some feed backs do not operate on the hypothalamus. Control of some other hormones (eg. insulin, PTH) is achieved by feed back by blood constituents (glucose, Ca++). I. Functional anatomy 2 Chemistry 3. Bio synthesis 4. Carriage of the thyroid hormones in the blood. 5. Functions 6. Mechanism of action 7. Control of secretion 8. Degradation of thyroid hormones 9. Applied physiology : (a) Hypofunction. (b) Hyperfunction (c) Goiter (d) Drugs used (e) Assessment of the thyroid function (status). FUNCTIONAL ANATOMY The thyroid (from Gk. thyroid, meaning a shield, because it shields the trachea) gland, first described by Wharton in the 19th century, weighs around 20 gms in adult. On its posterior side, there are four parathyroid glands. (Removal of thyroid gland therefore can cause unintended removal of the parathyroid glands as well, this is of clinical significance). The gland is very vascular and the blood vessels receive sympathetic supply. The thyroid begins to function from the midterm of fetal life. Food iodine deficiency in the mother's diet may lead to hypofunction of the thyroid in the fetus and its consequent hazards. Microscopically the gland contains about 3 million follicles (fig 6.2.1), diameter of each follicle being about 200 uM Each follicle contains a structureless material called 'colloid'. Each follicle is lined by epithelial cells When the activity of the gland is low or moderate, the epithelial cells are cuboidal and the amount
FILE NO. 74185325

. FUNCTIONS OF HORMONES. OVERVIEW All the functions can be classified under few headings (see Table No. 6.1.3 - previous page). ESTIMATION OF HORMONES

of serum acts directly on parathyroid glands lo conlrol parathormone secretion. FUNCTIONS OF HORMONES. OVERVIEW All the functions can be classified under few headings (see Table No. 6.1.3 - previous page). ESTIMATION OF HORMONES AND HORMONAL STATUS Because of the fact that most hormones occur in the blood in exlremely small quantities, conventional chemical analysis (colorimetric estimation) are usually of no avail. It is only in the tast two and half decades, newer and newer technics have been developed and as a result, an explosive amount of informations has been gathered in recent times. The well known modern melhods of hormone estimation are given below. 1 .Radioimmunoassay (RIA). Originally developed by Bershon and Yalow in around 1960, for which they were subsequently awarded a Nobel Prize, the melhod is as follows: For peptide hormones: The peplide hormone is isolated, purified and repealedly injected into an animal's (which belongs to a different species) body. In the recipient animal's body, because of the fact, that the injected hormone is a foreign protein, antibody development begins and attains high liter with time. Blood of this animal is now col-lected, the antibodies isolaled and purified, and stocked. This anlibody can combine with the peptide hormone in question, selectively and with great affinity. Let this sample be called, A Again, a sample of pure peptide hormone in question is obtained and radiolabelled. Let this sample be called B. Such purified specific anybodies (A) and radiolabelled peptide hormones (B) are readily available from big commercial firms, as well as, for India, from 'BARC' (Bhava Atomic Research Center). The anybodies are now mixed with the patient's serum and radiolabelled hormone. If the palient's serum (sample C) contains excess of the hormone, then, on mixing A, B and C, large amount of radiolabelled hormone will remain un combined. Reverse will be the case, when the serum contains too little amount of the hormone. (These anlibodies can combine with the hormones of both the sources, viz, B & C.). Now the uncombined hormone is separated from the combined ones by cenlrifugation (or by eleclrophoresis). In the supernatant solution, thus obtained (containing uncombined hormone) the intensity of the radioactivity is measured by a suitable counter. From the result thus obtained, estimation of the hormone in the patients serum can be made In short, both the radiolabelled hormone (acting as antigen) and the hormone in patient's serum (also acting as antigen) compete with each other and try lo bind with Ihe antibodies. If serum contains more hormone then more radiolabelled hormone will be unbound. The bound hormone, being heavier particles, can be precipitated and removed. With the introduction of RIA, there has been a revolutionary change in the clinical endocrinology. Diagnosis of many endocrmological disorders, today, can be made with impunity. Steroid hormones and Ihyroxine Steroid hormones and thyroid hormones do not elicit antibodies when injected into a different species of animal (not 'antigenic). However, in the blood, these hormones circulate as bound with some proteins. Thus, there are CBG (cortisol binding globulin), TBG (thyroxine binding globulin) and so on, destined to bind cortisol and thyroxine respectively. These proteins are highly specific and elicit antibodies ('antigeinc). Therefore, such proteins (which bind hormones) are used as antigen and the rest of the procedure remains same. However, one inherent flaw of the RIA is this : it measures the amount of immunologically similar molecules. Now, it is possible that a 'prohormone' or a fragment of a hormone is immunologically same as the hormone in question and yet does not otherwise (biologically) behave as the hormone. In such instances, the RIA value will not reflect the biologically active amount of the hormone. Almost all the peplide hormones and many of the steroid and other non-protein hormones, today can be measured by the RIA technic. Because of the simplicity of the procedure, this melhod is extremely popular in clinical endocrinology. 2. ELISA (enzyme linked immuno sorbent assay) technic So far as the principle is concerned, it resembles closely with that of the RIA However, it does not require a counter for measuring the radio activity (inslead only a spectrophotometer to measure the color is sufficient) and therefore, this technic can be used in smaller towns of India. In short, ultimately, instead of measuring the radioactivily (as in RIA), one has to measure the intensity of the color of the final product. Three samples, viz, A, B, C will be required A conlains the slocked highly, purified antibody (obtainable from commercial firms, in the form of 'kit'), B is the serum of the patient containing the hormone which acts here as the an-tigen (whose concentration is to be measured), and C is a purified antigen (ie, a purified specimen of the hormone which is chemically identical in nature with the hormone in B), but conjugated with horse raddish peroxidase. A, B, and C are mixed together. Some of the horse raddish peroxidase leaves C and conjugates with the complex formed by A and B (recall, in the mean time, the antigen of B combines with the antibodies in A so that a complex of A and B is formed). The complex of A and B is now isolated, and washed to remove extraneous materials finally the complex of A & B is stained with a suitable dye, called ABTS (diammonium 2, 2' azino bis (3 - ethyl benzothiozolene 6 sulfonate)] in presence H20
FILE NO .74185324

. Thus sleroid hormones are not stored. In the blood the steroid hormones combine with a prolein, synthesized by the liver. For example, cortisol bind

mones are immediately released from the cell. Thus sleroid hormones are not stored. In the blood the steroid hormones combine with a prolein, synthesized by the liver. For example, cortisol binds with the cortisol binding globulin, CBG. A part of the circulating hormone, however remains free (= unbound). For example, about 90%, the circulating cortisol remains bound with CBG, but the rest of the cortisol (ie, 10%) remains free. lt is the free cortisol that is active (ie, can bind with the receptor of the target cell). Thus in some conditions (eg, pregnancy) the circulating steroid hormone concentration may be higher than normal but the concentration of the free hormone (say, per ml of blood) remains same and thus no sign of excess mrtisol activity is presented by the subject. [NB. It is imporiant to note that in some forms of malignancies of non endocrinal tissues, peptide hormones may be secreted (eg. peptide hormone secreting lung cancers). This is unknown with steroid hormones]. CONTROL OF HORMONE SECRETION Recall, hormones are one of the fundamental agents of achieving the homeostasis. Therefore, exactly that much hormone is released for circulation which is exactly needed by the body, neither more nor less. That is, only the eustate of secretion is permitted, but not the hyper (excess) nor the hypo (deficient) state of secretion is allowed in the healthy slable states. Question is how this becomes possible ? Answer is, by the feed back mechanism (fig. 1.3.1, chap 3 sec I). As stated there, there are two varieties of feed back, (i) the -ve, and (ii) the +ve feed back. Table 6.1.2 gives a summarized version of control of hormone secretion in general. Explanation of table 6.1.2 Note, there are 4 major controlling agents or factors. Short explanatory note follows : (1) Anterior pituitary controls (a) thyroid, (b) suprarenal cortex and (c) gonadal (= testicular or ovarian) hormones through their 'tropic' (also spelt, trophic, by the British authors) hormones. Thus, there are thyrotropic, gonadotropic, adrenocorticotropic (ACTH) hormones causing stimulation of thyroid, gonads and adrenal cortex respectively. (2) Hypothalamus. 7 This part of brain is on the under surface of the brain (fig. IOD.1.1) and from hypolhalamus hangs the anterior pituitary. The vascular connection (chap 5 sec VI) that exists between the hypothalamus and the anterior pituitary is a portal syslem, ie, it starts (in the hypothalamus) as capillaries, and ends (in the anterior pituitary) as capillaries. Many hormones called hypothalamic releasing factors are produced by the hypothalamic neurons enter the capillaries (of the portal circulation) of the hypothalamus reach the capillaries at the level of anterior pituitary comes out of the blood vessels, to enter the cellular masses of anlerior pituitary. In this way, by a forward flowing blood flow, the hypothalamic hormones reach the anterior pituitary and either stimulate or inhibit their cells (who in turn secrete the tropic and other hormones of the anterior pituitary). A retrograde flow also occurs , that is, hormones of anterior pituitary enter Ihe capillary blood by diffusion reach the hypothalamic level hypothalamic neurons where they (= the anterior pituitary hormones) exert an inhibitory effect; this is also called short loop feed backfrom the anterior pituitary. In short the hypothalamus controls (= stimulates/ inhibits) the anterior pituitary by its releasing hormones (releasing factors of the yesleryears). For details see chap 5, sec VI. (3) Some of the endocrinal secretions (notably the cortisol and the ACTH) occur vigorosly at a predetermined hour of the day and the rate of secretion drops sharply at another given hour of a 24 hr, day night cycle. For example cortisol and ACTH are secreted very vigorosly in the early morning, whereas their secretion is greatly reduced in the night. This occurs in most persons and occurs without any obvious cause (though some cellular level explanations have recently been forwarded, see chap 4, sec VI). This is called circadian rhythm. (4) Stress. As mentioned already (chap 3, sec I) anything which tries to destabilize homeostasis is called a stress. Thus, physical injury, menial injury, disease, sharp changes in the environmental temperature are examples of stress. It is now known, several hormones viz, ACTH, cortisol adrenalin, ADH and thyroxine are secreted in increased rate during stress. Some further details Feed back. The general fealures of feed back mechanism have been described in chap 3 sec I. In endocrinology, most of the feed back mechanism belong to the variety of-ve feed backs allhough +ve feed backs (eg, LH surge) are also known. In -ve feed back mechanism (fig. 1.3.1) as in, say, the control of cortisol secretion, level of plasma hormone (cortisol) is the signal the signal reaches and operates at, usually two levels, anlerior pituitary and hypothalamus higher level of blood cortisol causes inhibition of release of both anterior pituitary tropic hormone(= ACTH) as well as hypolhalamic releasing hormone (= CRH) ultimately low level of anterior pituitary tropic hormone (= ACTH) withdrawal of stimulation on the adrenal cortex. Reverse occurs when the blood hormone level is low. Plasma or blood level of hormone is not the only signal. Feed back signals may be constituted by other conslituents of blood Further, such signals can also operate on glands other than anterior pituitary or hypothalamus. Thus blood sugar levels act as signals and act on a and β cells of islets of pancreas controlling glucagon and insulin secretions. Na+ and K+ levels of serum ultimately act as signals which control the aldosterone secretion by feed back. Ca++ level
FILE NO. 74185323

The RLC eventually causes opening up of channels in the cell membrane (fig. 1.1.2) entry of various ions within the cell biological effects. The recep

rmed. The RLC eventually causes opening up of channels in the cell membrane (fig. 1.1.2) entry of various ions within the cell biological effects. The receptors of these hormones contain an enzyme lyrosine kinase incorporated within them. The RLC formation causes phosphorylation of the protein tyrosine kinase which leads to the final biological effects [There are strong evidences to suspect that the enzymes having tyrosine kinase activty are involved in growth as well as cancer formation]. WHEN THE R IS IN THE CYTOSOL OR IN THE NUCLEUS (Steroid hormones) Events are as follows : 1. The receptors (R) are present within the cytosol. 2. The R has a special domain called "DNA binding domain" which contains Zn++. 3. The steroid hormone molecules [recall, all steroid hormones conlain a CPP ring structure; being lipid, all steroid hormone molecules can pass through the cell membrane by 'lipid diffusibility', (chap 1 sec I), because cell membrane itself is oily in nature. Also compare this phenomenon with that seen with peptide hormones : peptide hormones cannot cross the cell membrane. Therefore, their receptors must be present in the cell membrane to suit the concept of teleology] enter the cytosol by crossing the cell membrane. 4. The ligand (L), ie, the steroid hormone molecule now binds with the R and RLC is formed. 5. Formation of the RLC causes the DNA binding domain of the R to expose itself fully and to become active. 6. The RLC moves to the nucleus (therefore, these receplors are also called mobile receptors) and the DNA binding domain gets itself attached to a specific region of a specific DNA (this portion of the DNA is called 'enhancer') 7. This attachment with the DNA binding domain and enhancer causes the enhancer to become active and increased transcription of messenger RNA (mRNA) occurs. 8. These mRNAS, in turn, increases the synthesis of their corresponding proteins, which can be either enzymes or structural proteins. The enzymes also can be either degrading enzymes or synthetic enzymes. 9. Now, the biological effect (s) occurs. Eg : Cortisol (steroid hormone) increase in synlhesis oftransminase degradation of amino acids and enhancement of gluconeogenesis. N.B : (i) Sleps 7 and 8, taken together constitute genetic expression. Therefore, the popular phrase, 'the steroid hormone acts by regulating genetic expression' should now be clear. They say regulating (not increasing) because, the genetic expression, with some ligands may be inhibited (instead of accelerated) too. (ii) estrogen and thyroid (recall, thyroid is not a steroid hormone) receptors are also situated within the cell, but these Rs are situated right on the nucleus (not in the cytosol). However, otherwise, estrogen and thyroid hormones behave similarly with the corticosteroids (iii) studies suggest that the DNA binding domain of the R might have strong intrinsic affinily to combine with the enhancer. It is because of the presence of the rest of the R, this intrinsic affinity (to unite with the enhancer) is kept inhibited. The combination of the hormone molecule with the receplor causes withdrawal of this inhibitory effect and the DNA binding domain becomes free to combine with the enhancers. (iv) Sleroid receptors are often, for obvious reasons, called 'gene active' receptors. HORMONE SYNTHESIS GENERAL PRINCIPLES Peptide hormones. In short, peptide hormones are synthesized just as other prolein molecules are. Therefore, from DNA the mRNA (messenger RNA) is transcribed the corresponding peptide hormone produced (for details see protein synthesis, chap 12 sec VII). The special points for peptide hormone synthesis can now be noted 1 Within the cell of the endocrmal gland the peptide molecule prepared first, is usually a much bigger (bigger than the matured peptide hormone molecule) molecule and is called 'preprohormone'. Thus, we have preprohormone for insulin called, preproinsulin. 2. The preprohormone is decimated, a portion, usually called signal sequence, is removed What remains is called a prohormone leg. Preproinsulin proinsulin, chap.6, sec VI). 3. Prohormone is further decimated and a mature hormone molecule is released into the blood. ( However, sometimes, little prohormone may also escape into the blood, see insulin synthesis chap 6 sec VI. These pro hormones of blood have clinical importance, see chap 6, sec VI). This is not the end of the story. Some so called mature hormones may again be further allered at the cellular level and this altered molecule may be the final active agent. Thus, the so called mature hormone, testosterone, in some tissues (eg. proslate) is converted into dihydrotestosterone. For such tissues (prostale), dihydmtestosterone is the final hormone and testosterone is the prohormone. Steroid hormones. Only the salient features will be outlined. The steroid hormone synthesizing cells (eg, cells of the zona glomerulosa or fasciculata of suprarenal cortex) have LDL (low density lipoproteins, LDL conlain cholesterol) receplors. LDL molecules (see chap 8 sec VIII) of the blood plasma get attached with these LDL receptors cholesterol of LDL crosses the cell membrane enters the biosynthetic pathway of steroid hormone synthesis (= steroidogenesis), eg, cholesterol cortisol or aldosterone. Alternatively, steroidogenesis may start from a cholesterol molecule which has been synthesized from active acetate by the cell itself; but this is less preferred. The rate limiting step is the conversion of cholesterol (C27 structure) to pregnanelone (C21 structure) by the enzyme desmolase (table 6.4.1). Once formed, the steroid hor
FILE NO. 74185322

A phosyhorylates the corresponding enzyme (phosphorylation of enzyme protein either inhibits or stimulates Ihe enzyme, depending upon the nature of Ih

stimulaled protein kinase A phosyhorylates the corresponding enzyme (phosphorylation of enzyme protein either inhibits or stimulates Ihe enzyme, depending upon the nature of Ihe enzyme) the corresponding biochemical reaction is either depressed or stimulated biological effect. What are the chemical events that occur between the combination of R and the L (the 1st messenger) and production of the cAMP (the 2nd messenger) ? Answer is as follows: recall, the R has two domains (i) the ligand bin ding site and (ii) the active site. Also recall, that the RLC formation occurs in the ligand binding site. Once the RLC has formed, the chain of events will be, RLC (ligand binding site) the active site now recognizes that the L of the RLC is an agonist (not antagonist) RLC now stimulates a protein, called Gs (G slimulatory) prolein, situaled close to the RLC and situated within the membrane (fig.6.1.1). Gs is now activated he activated Gs now stimulates an enzyme, adenyl cyclase (also called adenylate cyclase, but adenyl cyclase is more popular), abbreviated AC, also situated in the membrane (fig. 6.1.1) and hence called membrane bound AC AC now acts on ATP to form cAMP cAMP stimulates protein kinase A stimulated protein kinase A phosphorylates enzyme proteins the enzyme(s) is (are) either stimulated or inhibited allered metabolism = biological effect (see also below) More serious readers can note that the Gs protein, when inac tive, remains bound with GDP (guanosine diphosphate) but when the GDP is replaced by GTP (guanosine triphosphate) the Gs becomes active (fig. 6.1.3). The active protein kinase A can, instead of phosphorylating an enzyme, cause opening up of channels present in the cell membrane (fig. 1.1. 2) -> ions enter or leave the ICF. This, therefore, is another biological effect of cAMP. Components of hormone sensitive adenyl cyclase Note (fig. 6.1.1) that the formation of cAMP from ATP requires three components, (i) receptor (ii) Gs prolem (iii) adenyl cyclase. Gs protein is called the coupling unit (as it couples the R with the AC). Adenyl cyclase is called the catalytic cyclase (abbr. C). The three components, viz the R, the coupling unit and the C taken together, is called the membrane bound (hormone sensitive) adenyl cyclase system. Fig. 6.1.1. Mechanism of action at molecular level, of hormones which ad by generating cAMP. For his works on cAMP and for establishing the concept of sec-ond messenger Earl Sutherland was awarded Nobel Prize in 1970. Degradation of cAMP (fig. 6.1.2) The enzyme phosphodiesterase (PDE) degrades the cAMP to 5' AMP. There are several varieties of phosphodiesterases (PDEs). The drugs caffeine and theophylline oppose the PDEs and thus prolong the action of cAMP. Gr. 8. Hormones (fig. 6.1.4) The hormones of this group bind with the R in the target cell membrane and RLC is formed RLC now activates a G protein (present in the membrane) called Gp prolein. Gp protein thus, here, is the coupling unit Gp protein now stimulates a catalytic unit named phospholipase C (PLC) Phospholipase C now hydrolyses phosphalidyl inositol diphosphate (PIP2) forming mositol triphosphate (IP3) and diacylglycerol (DAG). Both IP3 & DAG are 2nd messengers. DAG now activates protein kinase C. Prolein kinase C is an intracellular enzyme. Also IP3 is formed within the cell membrane —> diffuses into the cytosol. Subsequent events are as follows: Fig. 6.1.4. IP3, DAG & Ca++ are 2nd messengers Role of released Ca++ ions Concentration of Ca++ is high in the ECF but very low in the ICF. However, normally the Ca++ ions cannot enter the cell. But when the chemical signal like angiotensin II acts and the membrane bound PLC becomes active, IP3 is formed within the cell membrane diffuses inlo the cylosol triggers off release of Ca++from endoplasmic reticulum. Ca++ entry (from the ECF) into the ICF is also facilitated. The free Ca++ ions, thus available within the cylosol, now bind with a prolein called calmodulin to form what is known as calcium calmodulin complex. This calcium calmodulin complex (C - Ca++ complex) now activates many processes that culminate in various biological effects, like, (i) contraction of muscle, (ii) synaptic transmission, and (iii) glycogenolysis. [ NB. Calmodulin is closely related to the contractile protein in the muscle, troponin C, see figs 5.1.7 and 5.2.1 ]. The G proteins Thus, we have come across with two types of G proteins, viz, (i) Gs and (ii) the Gp proteins. They are coupling units, present in the cell membrane and are also called 'nucleotide regulatory proteins', (because they control the formation of nucleotides like cAMP). They link the RLC with the membrane bound catalytic units like adenyl cyclase phosphohpase C (PLC). Various other G proteins are also known, eg, Gi (i for inhibitory, as s in Gs stands for stimulatory), Gt and Gk. They will however be not described in this text. The 2nd messengers cAMP, Ca++, DAG, IP3 have been described above. Other well known 2nd messengers include cGMP (involved in the action of ANP, atrial natrinretic protem which is a hormone released from the atrium and broadly speaking, opposes the action of renin angiotensin axis). Gr C Hormones Insulin and the various growth factors, like, (i) IGF (insulin like growth factor), (ii) EGF (epidermal growth factor), (iii) PDGF (plalelet derived growth factor), as well as vasopressin fall in this calegory. These hormones bind with_the_R in the_membrane to form the RLC, but no 2nd messenger is formed, or at least, no 2nd messenger is known to be fo
FILE NO. 74185321

Sunday, August 2, 2009

MECHANICAL PRESSURE ON NERVES OR ROOTS OR REFERRED PAIN-1. In the spinal cord - Tumours of cauda aquina, arachnoiditis, rarery thrombosis, haemorrhag


detail Treatment - Minor symptoms can be relieved by appropriate physiotherapy, but progressive neurological deficit calls for
surgical interference. (2) MALIGNANT INFILTRATlON -of brachial plaxus may resut from either upward extension of apical lung carcinoma, or local metastalic spread from mammary carcinoma. Pain and sensory loss in medial aspect of forearm and slowly progressive weakness which starts in the small hand muscles. (3) BRACHIAL NEURALGIA (Neuralgic amyotrophy) -may follow injury, operation, inoculation or specific fever. Pain is usually the first symptom, often severe and of sudden onset, followed after several days or few weeks by weakness and wasting of muscles, especially those innervated by C5 and C6 cord segments. Sensory loss is mild or absent and there are usually few or no constitutional symptoms. Recovery is slow 4. Fibrositis. periarthritis and arthritis of the shoulder - Diseases of shoulder joint and its surrounding structures should be considered. Pain referred to the shoulder, to arm, or to region of elbow, associated with loss of range of movement or pain on movement. Treatment - None specific. In acute stage arm should tie supported in a sling. Physiotherapy as soon as pain subsides. 5. Lesions of median nerve - Carpal tunnel syndrome (See p. 477). 6. Vascular conditions - Those producing sensory disturbances in arm include occlusion of brachial artery due to embolus, or ischemia from polyarteritis nodes a, scleroderma and other conditions grouped under' the term Raynaud's phenomenon. Inspection of the skin, changes in temperature and colour of the limb, and inadequate pulse at the wrist facilitate diagnosis. Coronary insufficiency may be responsible for pain in the ulnar aspect of arm and forearm. THE LUMBOSACRAL PLEXUS Sciatica Defination -Pain in ihe distribution of the sciatic nerve or its component nerve roots. The syndrome is now accepted as being caused by lumbar disc prolapse. However, sciatic nerve lesions can occur due to pressure in the buttock or upper part of thigh. Causes -1 TRUE SClATIC NEURITIS - Leprosy, polyarteritis nodosa, nerve injury due to infections or trauma, post-herpetic neuralgia. II. MECHANICAL PRESSURE ON NERVES OR ROOTS OR REFERRED PAIN-1. In the spinal cord - Tumours of cauda aquina, arachnoiditis, rarery thrombosis, haemorrhage or infection irritating meninges of the cord. 2. In the cord space - Protruded intervertebral disc. extramedullary tumours. 3. In the vertebral column - Arthritis. Tuberculosis, spondylolisthesis. ankylosing spondylitis. primary bone tumours. secondary carcinoma 4. In the back - Fibrositis of posterior sacral ligaments. Compression where the nerve leaves the pelvis in those who he immobile on a hard surface for long time (a form of Saturday nignt palsy). 5. In the thigh and buttock - Fibrositis, sacro-sciatic band, hip joint or sacroiliac joint disease, neurofibroma, haemorrhage within or adjacent to nerve sheath in blood dyscrasias and anticoagutant therapy, misplaced therapautic infection 6. In the pelvis - Sacroiliac arthritis or strain, hip disease, infection of prostate or female genital tract, rectal impactions, tumors of lumbo-sacral plaxus. INVESTIGATION OF A CASE OF SCIATICA I. History - Of irauma, exposure to damp or cold, sphincter control and history of previous attacks. Typs of radiation whether nerve root type or vaguely localised deep aching pain. Paraesthesia will occur in pain from sensory pathways but not in referred pain. Pain down the leg on coughing in root lesions and also acute extraneural disease of spine, pelvis and sacroiliac joints. II. Physical examination - 1. LUMBAR SPINE - Shape, mobility, muscle -spasm, list to one or other side on standing (sclatic scoliosis), local tenderness and presence of trigger points in back and limbs. Sciatica may be the first symptom of spinal caries. 2. SPECIAL SIGNS - (i) SLR test -Restriction of straight leg raising is usually much more marked in lesions affecting the nerve roots than in purely skeletal affections. SLR test gives a useful indication of the severity of the sciatica, and increased capacity for painless SLR is objective measure of improvement. (ii) Tenderness of nerves (iii) Intensification of pain in back and lag during rotatory extension of lumbar spine very suggestive of ruptured disc. (iv) Popliteal compression - Radiating pain can often be aggravated by pressure over the course of the tibial narve through the popliteal fossa. It is an additional finding in favour of root compression. (v) Testing of the sacroiliac joints by pressure on the two anterior superior iliac spines. (vi) Estimation of range and painlessnees or otherwise of hip joint by passive stretching. (vii) Muscle power in the lower limb tested against resistance. (viii) Knee and ankle jerks - When L4 root is involved knee jerk is depressed and there is likely weakness of tibialis anterior muscle. L5 root lesions, both knee and ankle ierks usually brisk but there may be weakness of dorsiflexion of the toes particularly of extensor hallucis longus. S1 root ankle jerk lost and weakness, when present involves the calf muscles (ix) Tone and size of gluteal muscles judged by asking patient to contract both buttocks, in upper sacral root lesions marked wasting may be clearly visible. 3. SENSATIONS -impairment of perception of pin-prick commonly found on dorsurn of foot if implication of 5th lumbar and 1st sacral nerve roots .4.

MEASUREMENT OF BP I. In human subjects in routine clinical practice, BP is determined by the sphygmomanometer, an instrument devised by Riva - Rocci,


od is, mean BP = DBP + 1/3 pulse pressure. For example, in the above mentioned subject, the mean BP is about 93 mm. Hg. Fig. 5.9.1. Recording of BP in man by the usual method (Riva-Rocci manometer). MEASUREMENT OF BP I. In human subjects in routine clinical practice, BP is determined by the sphygmomanometer, an instrument devised by Riva - Rocci, and subsequently improved by Von Recklinghausen. The sphygmomanometer is essentially a mercury manometer. However, instead of the classical U tube of the manometer, only one of its limbs is long the othar is very short, and acts as a raservoir of mercury (figure 5.9.1). The reservoir is, via a rubber tube, connected with an arm 'cuff the cuff, in turn is, via rubber tube, connected with a hand pump. Air can be introduced into the cuff by pumping the hand pump, a process called 'inflation'. Air from the cuff can be driven out by unscrewing the pump ('deflation'). The determination. The subject lies flat on his back, the cuff is wrapped round his arm (preferably the left arm, as the left subclavian artery unlike the right one, is a direct branch of the aorta). The heart sphygmomanometer and the arm should be at same horizontal plane. Then inflation is started by pressing the pump and the radial arterial pulse palpated concomitantly. A time comes when the radial pulse disappears. 'The height of mercury column at this stage is noted in the side scale. Then the cuff is deflated fully. The ball of the stethoscope is placed lightly on the brachial artery near the elbow. The cuff is again inflated and inflation continued for sometime even after the column of mercury has attained the previous height where the radial arterial pulse disappeared. Then deflation is started, at a rate of 2-3 mm/sec, neither more nor less. At first there is no sound heard by the stethoscope ('grave yard silence), after the deflation has reached a particular stage. a 'tap' sound is heard and this marks the SBP the reading at the side scale (of the height of the mercury column) is noted, deflation continued, till all sounds disappear. Between the 'tap' sound and the, reappearance of silence, a series of sounds, called Korotkov sounds, are heard as follows: For a long time, there was a raging controversy, viz, which phase corresponds, to the true diastolic pressure. Some said it was phase IV ('muffled' sound), some others said, disappearance of all sounds., (phase V). The true diastolic pressure is between the phase IV and phase V, but nearer the phase V of Korotkov sounds. Therefore it is now the official policy to regard phase V as the diastolic BP* According to an American heart association subcommittee report in 1967, it is desirable to mention the readings of both the IVth and Vth phases. Thus, if the SBP is 120 and the readings at phases IV and V be 80 and 70 mm Hg,the BP should be expressed as 120/80/70 mm Hg. Dependability of the clinical method. The precautions. In the same subject, the BP can be measured simultaneously in one arm by the above mentioned clinical method and in the other arm by the direct method. It has been found that, usually the SBP, as measured by the clinical (spliygmamanometric) method, is considerably lower (the difference is usually between 10-25 mm Hg) than the value obtained by the direct method. Further, if the IVth phase (of the sphygmomanometric method) is regarded as the DBP, the clinical method gives about 8 mm higher figure than that obtained by the direct method whereas if the Vth phase is regarded as the DBP, the differences of the values obtained by the two methods is almost nil "Dollery, CT: Arterial Hypertension, in Wyngarden. J 3 dc Smith, LH (Ed), Cecil Text Book of Medicine. Chap. 47 Saunders, 1985. The above method is called, 'auscultatory method' BP can also be determined by palpatory method: inflate the cuff and simultaneously also continue to palpale the pulse. A time comes when the pulse can no longer be felt, continue to inflate for still some time, keeping the fingers an the radial artery. Now begin to deflate the cuff. A time comes when the pulse can again be felt. Note, the value (on the side scale of the mercury column) where the pulse reappears. This is the SBP as recorded by the palpatory method. But the SBP recorded by this method is a trifle lower than that obtained by the auscultatory method. Moreover, by palpatory method, only the SBP (but not the DBP) can be recorded. Auscultatory gap. This is seen sometimes in patients suffering from high blood pressure. A subject has a BP of say, 200/100 mm Hg. The first sound of Korotkov, the 'tap' sound, appears at 200 mm height as expected, but as deflation proceeds all sounds disappear. The sound reappears again at a lower pressure. Thus, in this example, the sound disappears, say, at 190 mm of Hg and reappears, again at 170 mm Hg, the Vth phase (disappearance) remaining at 100 mm Hg. Thus, if the inflation is made only upto say, 180 mm Hg, and a simultaneous palpation of pulse is not done, the clinician will record the BP as 170/100 mm Hg and rhe patient and the clinician may develop a false sense of security. The silent zone, mentioned above, viz. 190 mm Hg to 170 mm Hg is the auseutatory gap. The pulse however can be felt throughout the zone. Of auseultatory gap'. The BP, as will be shown later, is affected by many factors like, excitement, anxiety, exercise, meal and exposure to cold. It is expected that the clinician remembers these factors while determining the BP, and ensures that while recording BP, his subject is at rest (mentally and physically), in a comfortable climate and has not taken a heavy meal

The sympathetic stimulation produces some well known signs of shock, like pallor and sweating


C sympathetic stimulation elevation of BP and tachycardia perfusion of the tissues is restored. (ii) Sympathetic stimulation also causes carotid chemo receptor stimulation by causing vasoconstriction of the artery feeding the carotid chemoreceptors. Further, hemorrhagic shock produces hypoxia which also causes chemoraceptor stimulation (particularly if the subject is restless). Chemoreceptor stimulation in turn, produces VMC stimulation. Fall of BP, if of sufficient degree, results in ischemia of the VMC and in turn produces stimulation of VMC (CNS ischemic response, chap. 8 sec. V, see also fig 5.8.1). Stimulation of VMC causes stimulation of sympathetic system elevation of BP restoration of perfusion. Also sympathetic stimulation causes redistribution of blood flow, the cutaneous, splanchnic and muscle blood flow are greatly cut down and the blood thus made available are flown to the brain and heart. Recall sympathetic stimulation, (i) has no effect on brain blood vessels, and (ii) causes coronary dilatation. The sympathetic stimulation produces some well known signs of shock, like pallor and sweating (pallor, because of the cutaneous vaso constriction. sweat glands are supplied by the sympathetic fibers, therefore sympathetic stimulation may lead to sweating and cold clammy skin). Endogenous substances like adrenalin are also liberated (as hemorrhage produces 'stress' and stress causes adrenalin secretion). Adrenalin reinforces the sympathetic activity. II. Tissue fluid shift As the BP falls the capillary blood pressure also falls. However, there is no fall of the colloidal osmotic tension. This causes stoppage of flow of fluid from the capillary to the tissue, or if the fall of BP is greater, the return of the tissue fluid to the capillary is enhanced (see Starling's hypothesis, fig. 1.1.9). This corrects the hypovolemia within the vascular compartment increase in cardiac inflow, and the real follows. III. Conservation of body water Fall of BP leads to lowering of perfusion pressure of the kidney production of renin production of angiotensin production of aldosterone [for details, see chapter on aldosterone, chap. 4 (control of sacretion) sec VI] sodium retention body water retention. It is now known, in stress, the hormone ADH is also secreted in greater amount. This reduces the volume of the urinary output body water conserved hypovolemia corrected. [Cardiovascular shock is a farm of stress. Recall, any deviation from homeostasis is a stress (chap 3 sec I). In massive hemorrhage, massive amounts of ADH is secreted. ADM in high concentration acts as vasopressin which is a powerful visoconstrictior. In addition, local autoregulatory mechanisms are also important. Even if the BP is falling for considerable period. the blood flow of the brain or heart does not fall, although blood flow in the other organs are falling. This is called autoregulation, whose mechanisms have been discussed earlier (chap. 6 sec V, see also fig. 5.10.2). However, if the fall of BP is severe, agtoregulation cannot manage. Compensatory mechanisms are often called 'negative feed back mechanisms', negative, because the results (effects) are in the opposite direction of the causes(chap. 3 sec I). For example, withdrawal of baroreceptor stimulation is caused by the fall of BP but effect of the withdrawal of baroreceptor stimulation is rise of BP A -ve feed back mechanism restores homeostasis, whereas a +ve feed back destabilizes the homeostasis irreversible shock if the shock continues and is not treated promptly, the stags of 'irreversible shock, develops, when the patient dies despite the (late) institution of the correct treatment. It will be seen afterwards, the term irreversible is rather misleading, a better term will be advanced stage of shock'. Causes of the irreversibility. At this stage some +ve feed back mechanisms appear in the scene with the result that there develops a vicious cycle [a cycle of 'vices' or sins; example, an individual begins, say, gambling loses money his financial situation deteriorates with a hope to improve his monetary position, he does more gambling further loss of money). These are: (a) Cardiac damage (i) Even normally, the subendocardial region of myocardium is susceptible to anoxia. When the BP is falling, this danger increases and ultimately subendocardial damages occur further fill of cardiac output (due to subendocardial damage) the vicious cycle operates (ii) A factor called, myocardial depressing factor, is suspected to appear in the circulation during advanced stages of shock. This reduces cardiac contractility vicious cycle, (iii) In advanced stages of shock, the acidosis (see below) develops and depresses the myocardial contractility still further further fall of BP vicious cycle. (b) Acidosis Tissue anoxia leads to accumulation of lactic acid acidosis. The fall of pH causes relaxation of the arteriolar and precapillary sphincter muscles vasodilatation operation of vicious cycle. (c)vToxemia Prolonged spasm oar the splanchnic vessels (which develops as a result of compensatory mechanism) intestinal mucosal damage due to lack of 02 massive entry of the intestinal bacteria (through the damaged mucosa) which liberate toxin relaxation of the vascular smooth muscles due to the effect of the bacterial toxin. (Recall, during sympathetic simulation, powerful splanchnic vasospasm develops). (d) VMC ischemia Slight ischemia stimulates the VMC, but massive ischemia kills it. When VMC death sets in, there is sympathetic paralysis precipitate fall of BP. (e) Elderly people generally have artherosclerotic lesions in their coronary"

Urinary reaction in some types of renal disorders. the ability secrete H* is reduced and as a result surfficiently acd urine cannot be formed

reduced and as a result surfficiently acd urine cannot be formed, causing renal acidosis This may be esiabtehed by adminstratlon of NH4 Ci

symptoms, that the kidneys have started to fail. Some test of kidney (e.g. blood analysis) may or may not reveal the incipient failure

well as the likely information (s), which can be obtained from a particular test, should be clearly understood. Very often, in the early stages of some renal diseases. it is not apparent from the signs and symptoms, that the kidneys have started to fail. Some test of kidney (e.g. blood analysis) may or may not reveal the incipient failure. However, more sophisticated tests (e.g. clearance tests) may reveal the incipient failure at this stage and the pnysician and the patient, both now being alive to the incoming danger, can take appropriate action. The tests of the kidney functions are Urine examination. Chemical examination of blood. Clearance tests. Concentrating power of the kidney, Radioiogicai and imaging investigations. Udrine examination Features of normal urine have already been deserbed (chap 2, sec VIII) The outstanding features which may be obtaned in a case of kidney dysfunction are mentioned below 1. Volume : Normally the volume, of urire per. day is f. 500 ml (range 800 lo 2,500 ml/day) if he volume is less than 500 ml/day (severe ollguria) waste product cannot be satisfactcrity excreted and they atcurnlate In blood. Conversety, in polyuria, so much water and Na may be lost that symploms may be produced Oliguna may be produced try severe lacK of drinking water, acute giornerlonephritis. cardavastilar shocK cardiac insufficiency and other conditions Diabetes mellitus, diabetes insipidus and chrome pyelonephritis are some of the well known causes of polyura}. 2 Specific gravity (Sp. gr) Very low and fixed sp.gr. (i.e where the kidineys have lost-the power to concentrate the urine) may be obtained r chrome nephrite Very high sp grof urine is found incases ofgtycosuna Proiemuna causes onfy a margnainge of ( HYPERLINKhttp//sp.gr) of urine. 3.

In certain areas of the world, drinking water is deficient in flurine. That is why fluoride ion is added to the water


water. In certain areas of the world, drinking water is deficient in flurine. That is why fluoride ion is added to the water supply to the extent of 1 ppm (part per million) in some countries. FIBERS AND ROUGHAGE Leafy vegetables containing a cellulose or hemicellulose coating, are indigestible in hunan intestine. Hence if such substances are present, they tend to increase the bulk of the feces and mass peristalsis' (chap. 3.7. defecation) is favored, and constipation can be avoided. Great amounts of leafy vegetables however can produce diarrhea. Plant components (cellulose/nemicellulose/pectins/lignins etc) which cannot be digested by the enzymes of our digestive tract are collectively called fibers. Strong evidences indicate that, lack of fibers in the diet predispose colorectal cancer, breast cancer, diverticulosis and coronary heart disease. Grams, peas and dal contain good deal of indigestible vegetable fibers. FOOD HABITS, TABOOS, COST. Food habits must be considered. Thus a Bengalee likes fish and rice whereas a North Indian non-vegetarian likes wheat and meat. Religious taboos are too well known. Thus, a Hindu nonvegetarian wil not take beef whereas a Muslim will not touch pork. Many Hindus (including Jains and some Sikhs) are strict vegetarians, although most of them take milk. Such religious flats should be remembered and respected while formulating the diet and alternatives to the tabooed food should be priscribed. Cost also is to be consid-ered. Animal proteins in general are costly products. Many fruits are expensive although they have no special advantage over the cheaper fruits. LOSS Cooking, particularly in Indian way, causes much wastage. The classical Bengalee cooking deserves more condemnation. The habit of discarding the water after boiling rice (thus causing loss of water soluble vitamins, some quantities of aibumin and starch). extensive discarding or the skin of vegetables, hard frying in oils all cause variable loss of food vitamins. Digestibility is another important consideration. Some proteins, particularly dal and peas lose some of thaeir values because of lack of easy digestibility. In an average menu, loss due to cooking and indigestibility together may account for about 10% of the food value. THE BALANCED DIET CHART with the background mentioned above, a diet chart for a healthy young adult male may be set as an erample. The term balanced diet means a diet which is complete in all respects. (i e . it is not lacking in any respect) at the same time it contains no excess of any item that may cause harm to the body. The following should be noted :The calorie requirement varies from person to person and in the same person from time to time. To adjust the, carbohydrate (rice, wheat, potato, sugar, jaggery and so on) and fats and oils (butter, ghee, cooking oil) should primarily be adjusted whereas. ordinarily, protien should not be considered for adjustments of calories. SOME COMMON FOODS. Common articles of food may be divided as follows. I. Meat, fish, egg Sources of animal protein (meat about 20%, fish same as meat, egg about 14%). Proteins are of very high quantity. Disadvantage is high cost. However, because of the Government policy of encouraging poultry in most states of India, price of egg is not high. The associated fat (in ordinary butcher's cut of meat) is however saturated and its ingestion predisposes to atherosclerosis. II. Milk, milk products (excludrig ghee/butter). Milk is almost a complete food, very high quality protein (though not as high as in Gr. I), for details, see later. III. Grains (cereal) :Rice and wheat. Rich in starch and contain between 7 to 10% protein. Protein is of good quality. Deficient in fat, cheap. Table 7.16.1: Balanced diet (for non rich and moderately working man) Food vegetarian. Non vegetarian lacto vegetarian gms/day gms/day. Cereals rice/wheat 350 350 Pulses (dal), gram 90 60 Meat/fish . 60 Milk 300 100 vegetables (pulbul, ladies finger, cauliflowers, 100 100 carrot, brinjal etc. Potato 75 75 Green leafy vegetables 100 100 Egg one (about 60 gms) Fats and oils (crooking oil, butter/ghee, fat 50 40 associated with meat) Sugar and jaggery 40 40 Lemon one one Seasonal fruits some helps some helps N.B.: Values are approximate only. Important. See that, (othere is enough fibers in the diet (to prevent colorectal cancer, breast cancer, antherosclerosis), (ii) plenty of carotenoids are taken (to prevent cancer lung, breast cancer). (iii) fat, particularly saturated fat intake is low (iv) NaCl is restricted and finally (v) sugar intake is low. IV. Pulses (dal) and legumes. Dal. Rich in protein but poor in fat. Protein is somewhat less digestible and of lower qualify. It is the most important protein supplier throughout whole of lndia excepting marginal areas of North East india. Because of its impotance to the nation, the Government of India is trying very hard to improve the national yield of dal Protein content of the dry dal is between 20% to 25%, cheap. Byumes, usually the dried peas and beans are meant. Soyabean is also a kind of legume. They contain high amount of vegetable protein. The major protein supplier in Latin American counties is, kidney bean, which they consume in large quantity. Soyabean contains approximately 40% protein and 17% fat V. Nuts (peanuts, alrnonds, walnuts, ground nuts, etc) :very rich in fat (about 40%) and protein (about 25%) content is amost equal to dal. IV. Roots and tubers :Potato and sweet potato are examples oftubers.: They are rich in starch but poor in fat. Carrot and beet roots are examples of roots. Beet is a rich source of sugar like sucrose but not of starch. Protein content is very low. Carrot has protective effects against lung and breast cancers. VII. Green vegetables :Green leafy vegetables are primarily taken to increase the bulk of food and to avoid constipation. Other vegetables Iike brinjai, pulbul,lady's finger etc. are low in calories. MILK Milk is almost a complete food containing protein, carbohydrate and fat as well as the important vitamins and minerals. Milk however. is deficient in iron. Old people living in isolation and depending mostly on milk and bread (not fortified with iron) can thus develop anemia. which is sometimes called 'milk injury'. The protein of milk is of very high biological value(i.e., high quality protein). The composition of milk varies from species to species. Thus,

The small remnants of chylomicron* particles now go to liver where they will be further catabulued

small remnants of chylomicron* particles now go to liver where they will be further catabulued. The enzyme lipoprotir irpase (clearing factor lipast) is present in the walls of the capillaries of blood and therefore present in sufficient amount in large number of organs which 31 e rich in capillaries. This enzyme is different from (and therefore should not be confused with) the adipose tissue (also called, hormone sensitive") hpase Hepann injection causes release of the plasma hpoprorem lipase from the endothehal cells of capillary walls [Hepann also causes release of another hpase. from The liver, called, heparin releasable hepatic Ijpcprolem It-past, whose function is largely obscure] Applied biochemistry of plasma hpoproteins Disorders of lipid metabolism and lipoproieint Many disorders of lipid metabolism an aitociatid with changes of plasma lipoproteina. Thus atherosclerosis/ coronary heart diseases (CHD) are associated with changes of plasma lipid values as well as llpoprotem pattern, changes include increase of plasma cholesierol values (hypercholesteremia) and rise of p llpoprotem ((JLP) Further, in atheroscleiosis the ratio of pLP/ a LP increses. This 19 underslandable, inspection of Tsble 7 t2 will show that most of the cholesterol is present in the aLP (= LDL) fraction of The hpoproletns Kamholesma is also assoculpd with increase of pLP Idiopalhic
'hyperlipemia. diabetes mellitus. myixedema. nephrotic syndrome are also characterized by rise of plasma hpid values Importance of lipoproiem estimation in diseases in the late 1950s and 60s it began to be suspected strongly that for diagnostic (as well as prognostic) purposes in disorders of lipid metabolism (atheraselerosis. xantholesma. Thanhauser's disease etc J over and above the estimation of plasma cholesterol and triglycendes, estimation of plasma lipoproleins is also imptrative it was suggested N B (i) Sf = Svedberg's ftotation unit Higher the Sf value greater is tha tendency to float in the solution (a) Some authors recognize two furthtr vanties, (a) chylormcron remnants (s*« fool note previous page), (b) IDL, in between LDL and VLDL that value of plasma cnuTesierol may remain almost normal but the ratio of p LP/ a LP might increase. However, now it is usually conceded lhat for routine clinical purposes, estimation of serum (or plasma) cholesterol and Inglycende is reasonably enough, lipoproiem estimation does not give much additional informations. Rectnrly however, estimation of the different types of apohpoprotein, for predicting the possibility of CHD. is becoming popular Further, it is now agreed that persons who have a high cholesterol HDL ratio are specialty prone id atheraseter-asis. Therefore, like smoking, obesily. drabetes and hypertension, bad cholesterol HDL ratio is also a risk factor Free tally acids. The FFA accounts for about 5% of the lotal plasma lipids But because of the exlremely rapid lumover rate, this is a very important sechon of
.plasma lipids FFA in plasma remains bound with plasma albumin (and thus becomes soluble} Within the cells, There is a protein called Z protein (also called. fatty acid binding protein), which binda with the FFA Z protein is thus.tha caunltrpvt of albumin. Fatlora influencing plasma lipid valuta. A Hormones Insulin reduces plasma lipid values (Old standing diabetics nave sometimes abnomially high values of plasma Lipids which however may not always be controlled by insulin and diet control (sec chap 7. 9, diabetes and lipid merabolism)insulin promotes fatty acid synthesis by stimulating HMP which causes
generation of NAOPH. and the H atoms of NADPH can subsequently be utilzed for fitly acid synthesis. Insulin inhibits
inhibiting hormone sensitive Ijpoprolein hpase m adipose tissue and Thus Ihe FFA co

substances including coenzymes which must be present in many eniymatic

substances including coenzymes which must be present in many eniymatic reactions, in their absence the enzymatic reaction cannot proceed) Thus apo I is a cotactor of lecilhm cholesterol acyl transtecase (LCAT) ativity, CM acts as a cofactor for lipoprotein lipase activity Genetic absence of CM in a family causes the disease familial hypercholesTeremia (b) bin from the pom! of view of medical students the most important fact is that because of the presence of these apoli pop roleins, the hpoproteins can combine with their specific race plots of the largal cells (and subsequently metabolized) Thin apo B binds with LDL and the LDL now can bind with its receptor it is hightly possible that abnormalities of these of such diseases like atherosclerosis and hyperchotesteremia. Structure of a lipoprolein [NB To keep the discussion simple, only 4 classes of lipoproteins have been mentioned above Most authors now include IOL {intermediate density lipoprol em) in addition lo the above 4 categories) Upoprotem lipase. After a meal very rich in fat. the plasma becomes milky. This milkiness is due ret the presence of exces s amount of chylomicron particles In the plasma In due time, or following a heparin injection, the plasma is cleared of its milkiness. This clearing is due to the activity of a clearing factof (.an enzyme] called plasma lipoproiem hpate As a result or the action of this enzyme, the Inglycenda portion of the lipoprotein is hydrulyzed to glycerol and free fatty acids (FFA) Most of the FFA rhus formed enter the ertrahepatic tissues (like the muscles, where they are catabolized) This causes clearing of the plasma. The anginal chylomrcron panicle therefore now becomes much smaller, and contains tha protein cholesterol and phospholipid portions but practically no Inglyceride

specially notable are the neurons, heart, liver, skeletal muscles, adipose tissues, mammary gland) converted

mammary gland) converted into T3 HR (hormone receptor) complex is formed within The nucleus HR attachment with DMA occurs more mRNA production synthesis of more proteins biological action One single biochemical action of T4 (rather T3) at Ihe molecular level cannot explain all the actions of thyroid hormones (TH) Thus, (i) as stated already (see above), trie idea that TM causes 'uncoupling of oxidative phasphorylaiion' has bsen discarded, (ii)the idea, that. Na+K+ ATPase enzyme is vigorosly synthesized so that TH causes calori genesis, (although still very popular), does not explain all. (iii) TH causes mcreass in the synthesis of many proteins (including enzymes) which explains some of The effects of thyroxine (growth ol neuron/rise in myocaidial contractilily/lung development in tadpoles etc etc ) CONTROL OF THE THYROID SECRETION There are three major ways of controlling [he ihyroid secretion, viz. (i) Tha anterior pituitary, (ii) the hypolhalmus, and (lii) auloregulation Fig.6.2.4 gives a diagramatic representation of the mode of working of the first two factors Besides, some other factors like (iv) sympathetic stimulation (v) exposure to cold are also important. Fig. 6.2.4 Conlrol of Thyroid Secretion. TSH of the anterior pituitary Some details have been discussed previously (in this chapter) in connection with the biosynthesis of Ihe thyroid hormones. Additional details have been given in connection with the antenor pituitary hormones. In short, thyroid stimulating hormone, TSH. is secreted by Ihe specialized cells, tailed thyrotrophs' of the antenor pituitary, (i) TSH stimulates almost all the major steps of Thyromne biosynthesis as well as the release of thyroid hormones Hence, more TSH = more secretion of thyroid. (2) in addition, it causes increased vascuiarity and cellular growth of the thyroid gfarrd. These are the two major actions of the TSH. TSH is controlled by negative feed back mechanism eierted by T4 and T3. The circulating T4 is converted into T3 at the level of the anterior pituitary and thus both T4 and TB are active. Therefore, when Circulating T4 is in high concentration. the pituitary Ihyrolroph is inhibited so that TSH secretion is depressed, resulting in correction of excess T4 in blood Reverse occurs when T4 concentration of blood is low Hence, more T4 =less TSH TSH is the single most important regulator ef the thyroid secretion Hypothalamus From the hypolhalamus, thyrotropin releasing hormone. TRH is secreted (NB. Ihyrotropin = TSH). TRH acts on pituilary thyrc-trophs and stimulates them to secrele TSH Hence more TRH = more TSH Probably T4 and T3 do not operate at the level of the hypolhalamus level for the feed back mechanism Thyioxine and TRH both act at the level of thyrotrophs of ant pituitary where they antagonize each other. Another hormones called somatostatin inhibits the TSH secielion. Somatostatin, in this case, is released from the hypothalamus [somatoslatin is also secreted by the islets of Langerhans and slornach) Autoremulation of thyroid If there is deficiency of the food iodine, The iodine trapping mechanism of The follicular cells become super efficient. Therefore, unless there is frank (severe] food iodine deficiency, supply of iodine to the follicular cells, for synthesis of T4 and T3 continues satisfactorily Conversely, if there is evcess of the food rod

According to some recent works. thyroxine causes increased Ca++

owever have challenged this idea. According to some recent works. thyroxine causes increased Ca++ ATPase activity of myosin (which in turn may be due to increase in the bulk of myosin in heart muscle due to thyroxine) increased contractility of myocardium. In short, excess thyroxine excess myosin in the myocardium increased contractility of the heart. (ii) Central nervous system In the neonatal slags, up to the age of approximately 1 year, normal amount of thyroxine is required for the satisfactory development of the neive fibers and their myelination. If sufficient thyronine is not available at this stage. the bram becomes small. The child grows in chronological age but his mental development does not occur. On the other hand, if thymune becomes deficient after the full development of the CNS, some mental signs like mental stowing still develops but can be completely cured by thyroid administration. This is not so in the case of hypolhyroidism in the neonatals If the hypolhyroidism is not corrected within about 1 year of birth, no matter how vigoros is the subsequent treatment, satisfactory brain development will not occur( iii) On skeletal system. ThyroHine is required for the growth and maturation of epiphyseal cartilage so that in the absence of this hormone, linear skeletal growth does not occur. Excess thrioxnine causes osleopoiosis because of calcium drainage from the bone (iv)On reproductive system Lack ofthyromne in adult woman of reproducing age usually causes menorrhagia (= excessive menstrual bleeding) but the explanation is not definitely known HypoIhyioidism may be associated with infertility also. (v)0n digestive system. Excess thyrocxine causes increased motitrty of the gastrc intestinal trad (and thus causing diarrhea) and/or, increased appelite. Lack of thyroxine causes reverse symptoms. (vi)0n blood In hypothyroidism a normoeytic normochromic anemia is seen MECHANISM OF ACTION As stated already (chap i, ssc VI, Mechanism of action. Thyroid hormones), thyroid hormones act somewhat like the steroid hormones. The free (not the TBG bound] T4 enters the target cell (almost all tissues are target cells of T4 ,

The TL value can now be determined in human sublets (halthy and diseased) fig

Illustrating the P02 ai different levels (see also Fig4.4.1) OXYGEN CARRIAGE AND UNLOADING 1 Introduction 2 Oxygen dissociation curve, biological advantages of the aigmoid curve 3. Unloading of 02 in the tissues, coefficient of utilization. 4. Myoglobm 5 A-V 02difference, VQ2 max Introduction In a healthy man, at sea level, the artenal blood contains aboul 19m1 of 02/1O0 ml, of which 0.3 ml is in physical solution and trie rest, i e 18.7 ml is in combination with Hb Therefore, 02 is earned in the blood in two forms; (1)in physical solution, and (ii) as oxyhemagtobin (Hb02) The lension of a gas in blood is produced by only mat portion of gas which is in physical solution it follows that the Hb02 is not directly responsible For the tension produced by 02 (i.e. Pa02) When anenal blood reaches the tissue level, rt is exposed to a Ptissue O2 level which is very low, say <>

pulmonary capillary but the Hb within it becomes saturated with in about 0.3 sec, that is this 1 sec is more than sufficient for full

however, be quickly formed or dissociated The actual exchange of CO2 therefore, occurs more, From this compound. Time required for oxygen uptake At real, an RBC stays for only about 1 sec in a pulmonary capillary but the Hb within it becomes saturated with in about 0.3 sec, that is this 1 sec is more than sufficient for full oiygenation of Hb During exercise, when the circulation speed is high, the transit time of the RBC may be as low as 0.3 sec. but even this Time as shown above, is sufficient SHUNTS Fig. 4. 4.2 shows that PO2 of oxigenated pulmonary capillary blood is practically same (100 mm Hg) as that of alveolar PO2, yet The PO2 of systemic arterial blood (PaO2) is little lower (95 mm Hg) How to explain this fall Answer is (i) various venous blood, that is. deoxygenated blood, gets mixed with the pulmonary venous Wood Such veins are bronchial veins and the bisian venous system, both carrying de oxygenated blood, (ii) Moreover in some areas of the lung, the alveoli are very poorly ventilated but perfusion of These alveoli (by the blood) is alright Pulmonary capllary blood, draining these poorly ventilated alveoli contains poor quantities of O2 and they too drain in the pulmonary veins All these factors lower the P02 of pulmonary venous blood slightly The total reduction of P02, due to these causes, in health, is only 5 mm Hg. All these factors, collectively, constitute the shunt APPLIED PHYSIOLOGY Pulmonary edema, bronchopneumonia and lobar pneumonia increase the resistance lo the alveolo capillary diffusion by bringing fluid into the alveolo capillary membrane Various industrial hazards like asbestosis. pneumoconiosis etc. also increase the thickness of the alveolocapillary membrane to produce alveolocapillary block. To overcome the block. O2 Therapy may be given For further details, see chapter 6 of section IV Gaseous enchange in the peripheral tissus. Some special problems. Diffusion of 02 and C02 at the level of peripheral capillaries are governed, as in the case of that at lung alveolar level, by Fick's law One important difference is that. the distance between, capillary blood and needy tissue (T in the Fick's law, see earlier this chapter] is usually much greater and therefore oxygenation of peripheral tissues, on theoretical grounds, should nol be easy Yet, the tissues normally show no anona. To explain this, it has been, proposed that there is a facilitated diffusion' of 02 (chap 1 sec I) at this level and myoglobin acts as the earner. Gunng euercise owever many capillaries open up( recruitment) and the vlaue of T therefore falls Perfiiaion inefficiency (reduction of puknonary blood flow) can also lead to hypoxemie. Thus pulmonary embolism is an important cause of this arveolocapillary block ultimately leads lo hyponemia (low P02 in the artenal blood) end hypercapnia (excess PC02 In the artenal blood) with their train of aitendent symptoms (see chapter 6 of sec. IV) SUMMARY The transfer of 02 or C02 across the alveolo capillary barrier is governed by the Fick's Law of diffusition of gases across a membrane. The transfer, normally, almost wholly, depends upon the diffusion, biological processes are not involved to any appreciable extent. All conditions ensling between the alveoli and pulmonary capillary favor a diffusion Provisions also exists so that total volume of transfer of gas (TL) can increase sufficiently during exercise in vanous diseases of the lung or heart, the abilrty lo exchange gas deienorales and symptoms develop.

therefore, is, more vigorous is the respiration, speedier are the venous returning (cardiac inflow) This suction action of respiration is called the r

therefore, is, more vigorous is the respiration, speedier are the venous returning (cardiac inflow) This suction action of respiration isThe muscle pump When the skeletal muscles contact they exert a squeezing action on the veins Because of the presence of valves in them, when the veins are squeezed, blood moves only towards The heart. Conclusion is. when the skeletal muscles are working hard (e.g. muscular exercise) the venous rectum increases. 4. Gravity On assumption of erect posture. the venous drainage from head and neck is facilitated by gravity where as the same from the inferior extremity is opposed by gravity. 5. Vasomotor tone Veins are supplied by the sympathetic fibers When the sympathetic fibers are stimulated, the vein undergo constriction and The blood within it is driven towards the heart more speedily. Therefore sympathetic, stimulation leads to venison striation and greater cardiac inflow In some organs, veins normally hold great quantities of blood On sympathetic stimulation, the venous blood from these organs are evacuated and Thus the cardiac inflow increases Such organs are called reservoirs of blood ANATOMICAL CONSIDERATIONS AND THE STRUCTURE FUNCTION INTER RELATIONSHIP 1. The Major Division of the Vascular Tree. 2. General Structure of the Vascular Tree. 3. The Individual Segments of the Vascular Tree their functions and structural peculiarities The Vascular tree' begins at the beginning of the aorta. continues at branches of the aorta The branch repeatedly give rise to further branches, which are narrower and narrower and ultimately they become arterioles The areoles eventually open into the capelins. the capillaries into The venues (= very delicate veins) The venues unite with other venues To form veins. the veins unite with other veins and ultimately two great veins, via, the superior and inferior vane cave (singular, vena cava} are formed which open into the right atrium This portion of the vascular tree is called the systemic circuit, and its circulation called greater or systemic Circulation From the right ventricle, arises the main pulmonary artery, which divides into two branches. The right and the left pulmonary arteries, destined to supply the right and the left lung respectively Blood from the two lungs are eventually drained by the four pulmonary veins which open into the left atrium. This portion of The vascular tree is called the pulmonary circuit. and its circulation called, lesser or pulmonary circulation For descriptive purposes end viewed from functional point of view, the vascular tree is usually subdivided into following divisions (segments) or regions (fig. 5.10.4.). 1. Windless vessels', also called elastic arteries. 2. Precapillary resistance vessels' or the arterioles, also called, muscular arteries. 3. precapiltary sphincters .'4. 'Exchange vessels' or capillaries. 5. "Post capillary resistance vessels'chtefly the venues .6. Large veins or the 'capacitance vessels' A term 'microcirculation' is very popular amongst the physiologists and clinicians Micro circulation includes the precapillary sphincter region, capillaries and the smallest venues The name (i.e. 'microcirculation') owes its origin to the fact That they can be seen only under the microscope GENERAL STRUCTURE OF THE VASCULER TREE To start with. a big artery. e.g. the aorta, may be considered Such an artery has three coats, via (I)ton called the respiratory pump

This equilibrium point is relatively viable For example, let at a given moment

mm Hg. This equilibrium point is relatively viable For example, let at a given moment. I, the CVP is suddenly raised The first heart beat after the , because of the Frank-Starting mechanism, will have a greater stroke volume But because of this greater stroke volume, translocation of blood from the venous side to the arterial side will be greater and so the CVP will be somewhat lesser in the following beat Therefore, immediately after .the equilibrium point will shift no doubt, but it will try. to return to the original point gradually. Fig. 5.5.5. To show that when cardiac output rises, the rap' falls Fig. 5.5.6. See text FACTORS INFLUENCING VENOUS RETURNS 1. When the cardiac output rises, the velocity of circulation raised which results in greater cardiac inflow (= venous return to the. heart) per unit time Explanation (I) as the cardiac output rises, as explained above, the central venous pressure falls hence pressure in the peripheral veins also falls. (II) as the cardiac output rises, a little extra blood is pushed into the arterial system per beat As the arterial system resists distension even a slight increases in blood volume in it (the arterial system). causes a sharp rise of arterial BP When the above two factors, vast (I) and (ii) are considered together, it becomes obvious that the pressure gradients between the arterial and venous system (= the difference between arterial BP and venous BP) rises. This increase in the pressure radiance results in greater rate of flow of blood from the arterial to the venous side, stated simply this means greater venous return per unit time. 2. The respiratory pump During inspiration, the intrapleural pressure as well as (he intrathoracic pressure as a whole becomes more negative The intra abdominal pressure however rises due to the descent of the diaphragm Because of the increasing negativity, the diameters of the vane cave increase, and the BP within them falls So the pressure radiance (the difference of BP s between the intra abdominal part of the inferior vane cava and The right atrium) increases — flow of blood towards the right atrium increases. Conclusion,

in question. if a person has behaved normally previously. and then show behavioural abnormalities.

a casual relationship. (b) Disruption in multiple areas of life such as work, friendship, marriage, finance etc. 5. BORDERLINE PERSONALITY DISORDERS - The long-term functioning of such persons is characterised by preserve of self-damaging impulsivity. unstable interpersonal relationships, undue and inappropriate outbursts of anger, doubts about one's personal identity, variable moods or aftective instability, intoleranca of being left alona, and chronic feelings of emptiness or boredom. 6. SCHlZOTYPICAL PERSONALITY DISORDER - Characteristics include - (a) Magical thinking (superstioness. clairvoyance telepathy. etc.) (b) Social isolation. (c) Referantial thinking in sispiciousness (d)Oddspeech -vague, digressive. overelaborate or metamorphical (e) Recurrent illusions, (f) Undue social anxiety or hypersensitivity to real or imagined critism and (g) being emotionally 'cold' 7. NARCISSISTIC PERSONALITY DISORDER - Grandiose sense of salt importance and preoccupation with fantasies of unlimited success, power or intellectual brillance. They seek attention from others but show few warm Feelings in return These individuate tend to exploit othars for their own salfish needs and seek favours which they do not retum. 8 DEPENDENT PERSONALITY DISORDER - Such persons suffer from lack d self-confidence and passively allow others to assunme responsibillity for major areas of Iife because of their inabillty to functlon Independently Such people appear weak-willed and unduly compliant, falling in passively with the wishes of others. 9. AVOIDANT PERSONALITY DISORDER -Prominent features are - {a) Hypesensitivity to rejaction (b) Unwillingness to enter into Interpersonal relationships (c) Social withdrawal (d) Desire for affection and acceptance and (a) Low self -esteem. 10 COMPULSIVE PERSONALITY DISORDER -Rigid, perfectionstic, unduly conventional. formal. sitngy, undecisive "they show excessive devotion to work to the exclusion of pleasure and the value of interpersonal relationships. 11. PASSIVE-AGGRESSIVE PERSONALLY DISORDER - This term Is applied to those persons, who, when demands are made upon them for adequate performance respond with passive resistance.

constitutional. endocrinal and metabolic dastutbances also contribute to the development of these candhions

responsible agents but genetic. constitutional. endocrinal and metabolic dastutbances also contribute to the development of these candhions. In an individual case, one or more of these factors may be of greater importancethen the others. It is the complex interactions of all these varied etiological factors which result in a psychosomatic condition. This view has a very important bearing in the treatment procedures of these diseases. Treatment Careful attention has to be given to the emotional and the psychological factors contributing to these illnesses or better therapeutic results, short term as well as long term In this respectT an internist with good orientation Inthe principles of psychological medicine will prove a better physician tothese sutteters. A psychiatrist would have to be included In the medical team managing these patients Paychiatric treatment of the underlying emotional and personality factors may necessitate the use of psychotropic drugs, psychotherapy, behaviour therapy, biofeadback. etc. Treatment of the organic dysfunction by appropriate mathods should be undertaken concurrently. 5 PERSONALITY DISORDERS Definition: The term personality refers to the unique characteristics of an indvidual which predispose to his typical or recurring patterns of behaviour. The presence of certain personality traits make some individuals more vulnerable to develop behavioural abnormalities when faced with stressful events With this degree of vulnerability, abnormal behaviour occurs only in response to environmental stress. In certain other personalities, unusual behaviour occurs even in the absence of stressful events. The latter group is referred to as personality disorders Central to this concept of personality disorders is the duration of abnormal or unusual behaviou

Aden late cycles is activated D camp accumulates intracellular the camp, ultimately speaking

acts on the cytoskeleton of these cells (for details of cytoskeleton, see chap I sec I) ultimately this causes development of fine intra cellular channels within the cells communicating with the extensor (the tubular lumen) through which water passes for reassertion Control of ADH secretion there are Iowa major means by which the body controls the ADH secretion as described below 1 Amorality of blood Whittle body develops water deprivation (e g . no drinking water for long Time) the osmotic tension of the blood becomes higher than normal, the hypertonic blood stimulates the osmoreceptyors present in the hypothalamus the osmoreceptors now send nerve impulses to the (supraoptic nuclei of the) hypothalamus and the hypothec amuse secretes the ADH the concept of osmoreceptors was first developed by E D Emery of England in the 1940s Subsequently, Verne showed that these oamoreceptois are situated in the regions of supraoptic and par a ventricular nuclei of the hypothalamus Normal values osmolafty of plasma is about 290 m ormolus/kg. Only a slight rise of the amorality from this value triggers off the mechanism to stimulate the secretion of ADH This means as the body is dehydrated even slightly, the osmotic tension of plasma becomes higher, the osmoreceptore then are stimulated D ADH secretion Occurs water loss through the kidney is reduced, i e . body water conserved disturbances in water homeostasis is checked. If there is hypervolemia of the blood, ADH secretion is slopped Mechanism is as follows . the hypervolemia causes distension in the. atnum. the stretch receptors in the atria wall are stimulated and the afferent impulses from these stretch receptors reach the hypo helium* and ADH secretion is stopped This means, during hypervolemia (say due to excess saline transfusion), there is stoppage of ADH dilute and large volume urine is passed correction of hypervolemia Fig6.5.4 Control oath Many other factors can stimulate and inhibit ADH secretion Some such factors are diagrammatically sum married in fig6.5.4 it should be understood, a vary large number of drugs can influence ADH secretion, although they have not been shown in fig 6. 5. 4. Oxytocin its chemistry and biosynthesis

E rises when the concentration of 02, (02). in the inspired air becomes 12% Or lessi. at sea Level Mechanism Fall of PI02 (and thus of Pa 02) causes

at sea Level Mechanism Fall of PI02 (and thus of Pa 02) causes stimulation of 'peripheral chimoreceptors'(PC')' neural impulses arising fromthese PCa cells go to the RC stimulation of -respiration What causes stimulation of PC? Low Pa O2 is the most important example. Fall of blood pH is another. Rise of Pa C02 also stimulates. Some anatomical (and histological details) of PC can now be discusseld there are two sets of PCs, (l) the caotided body chemreeeptors (fig. 4.3.6) and (ii) The aortic body chemoreceptores. Between them, the carolid body chemoreceptors havt between studied much more extentsively,, no doubt, because of thir easy accessibility But it is safe to presume that the behaviores of and functions of the carotid body (CB) are more or lass same as those of aortic body chemoreceptores. CB At bffurcation of each common carotid artery (fig 4. 3.5), withen the vascular andothelium, in direct contact with the blood, lise the CB. The CB can analyze the Pa 02 f Pa Co2 / H+ concentration if there is )ow Pa 02 or high Pa C02 or low blood pH the CB cells an stimulated nauiral impulses art art up medulary RC stimulated increased repiration homeostasis regained the aortic bodies also behave similar ways (i.e. they also analyze the above mentained chemicals send signals achive homeostasis). The neural from the CB also called glomus caroticum ) travel via nerve Of Hering (a branch Of glossophryngeall or the IXh nerve) the IXlh nerve (fig. 4. 3. 5) 4 medullary RC. Whereas, from the aortic bodies, impulses travel up via (afferent) vagal fiberes medullary R.C There are altogether two CB. one On each side (fig 4.3.5.) There are two types Of Cells in the CB.' type 1 and (ii) Type II cells. Type I cells contain large vesicles and sensory nerve fibers (which eventually constitute the nerve ofHering) emerge from the type I cell Probably the type I cells themsellves or the begining of these nnerves are the detectlores (= receptors ) of the chemical sensation (e.q. anoxial). Three neurotransmitter chemicals are involved in the above mention detection of chemical senses as well as their' tranimiision. They are, (i) dopamine (DA), (ii) subttance P, and (iii) acetyl choline Ach) Of them DA and substance P are present in the vesicles of type I cells Proba- bly DA causes blunting of the sensivity of the chemoresepter cells. whereas substance P increases it. ACh might probably be the neurotransmitter involved in the transmission between the type I cell and the emeging nerve fiber. Thai it, stimutation of lypt I call releaser (locally) ofACh stimulation of the afferent nerves. Molecular level mechanism(s) of action of tha CB (glomius caraticum)
is uncertain and contraversial. Some very popular (and mutually comphmentary) ideas are given below .Any one or all of them may be correct. I
. The CB cells (glomus cells) are metabolically axtremely active Therefore, inspite oft the fact that the CB it tremendously vascular. there.are normally. areas. where there is some hypoxia Of these
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