in this condition, blood flow per minute, in the pulmonary circglalion increases( EMBED Equation 3 )grealer axtraction

02 (= partial pressure of CO2 in It blood) begins to fall because of The hyperventilation This causes withdrawal of The respwatory drive some decrease in Ihe hyprvenlilatron 2 Soon, there develops Hyperkinesia of tha circulatory systen Benefits of hyrperkinetic circulation are as follows Hyperkmetic circulatory state means a state where the velocity of the blood circtilalion is high, tachycardia and cardiac stimulation are present Obviously, in this condition, blood flow per minute, in the pulmonary circglalion increases( EMBED Equation 3 )grealer axtraction of 02 from the alveolar air by the blood, thus, is now possible Cause of this hyperkiunsia is increased sympathetic activrty which in turn, is due to vaso motar center (VMC) stimulation due to hypoxia Recall, when the blood feeding the VMC is mildly or moderately hypoiemit the VMC is stimulated (gross hypotemic blood, however, causes death of VMC{ EMBED Equation 3 )sympathetic paralysis] The blood pressure (BP) however may fall or may rise of may show no change This is because, the BP is subjected to two opposing forces, (a) vasconstndion due to VMC overacrrvity (h) vasodilatalian due to local anoxia The resultant of these two opposing forces determine the outcome In addition, the concomitanl polycythernia also raises the BP 3 Thare is erythropoielin elaboration (for details, see chap 1 sec ll{ EMBED Equation 3 }rise of RBC count This also aids in extraction of greater 02 from the lung alveoli 4 Besides the above, kidneys also contribute But this is Largely to counteract, the (ill) side effects of hyperventrtation, as follows hypervenilation {EMBED Equation 3 } loss ofC02 from the body { EMBED Equation 3 ) loss of H2CO3 or rather H+ ions ( EMBED Equation 3 threatened alkalosis But gross alkalosis does not develop because the kidneys remove the HCO-3ions and the hnmeoslasis regarding the acid base balance is not disturbed 5 At this stage. role of 2, 3. DPG can be taken up Normally, within the RBC, glucose is catabolized by the glycotytic pathway; (also called the Embden Meyerhof pathway, EMP) to pyruvic acid (T 7.6.1, sec VII chip 6) On its way, in the EMP, one of the miermediate products is 1,3 diphosphoglycerate, (1.3 DPG.T7.6.1) The 1,3,DPG normally is first converted into 3 PG and then into pyruvic acid Sometimes nowever. 1.3. DPG is attacked by an enzyme 'diyhosphoglycerate rnutase' which converts the 1,3, DPG into 23, DPG This 2,3. DPG has some mportant effects Normally, 2.3. DPG is again converted into 3 phosphogtycerate (3 PG) (EMBED Equation 3 )pyruvic acid, a phenomenon called reentry of2,3, DPG mlo EMPcycle For-mation of 2.3 DPG therefore, occurs via a biochemical shunt which is also called The Papaport Bulbrmg Shunt' 2, 3r DPG shifts the O2 dissoc-anon curve to the rig ht That is. it lowers the affinity of Hb for ovygen so that 02 unloading at the hssue level becomes easier (P.50 increases) After about 2 days at a madertfely high attiude (eg, 15000 ft above the sea level), the 2.3. DPG concerntration in RBCs nses (EMBED Equation 3 } 02 unloading at the penpheral tissues facilitated Bui this rise (of2,3, DPG) also causes difficulty in catching 02 at The alveofar level Therefore rise of 23. DPG cannot be viewed as a pure unmixed advantage [ N B (1) Recall, 2, 3, DPG also rises in stored blood in blood bank and is one of the prsservaiion injuries' 2,3. DPG also rises in muscular exercise (2) Note, in table 4.6.1, that hypoxia hypoxia is the only type of hypoxia which causes arterial hypoxia (that is. a condition characterized by low Pa O2 )] Anemrc hypoxia This is seen, in (1) anemia and (ii) in CO poisoning In anemia, the concentration of Hb is deficient whereas in CO poisoning (recall that CO binds with Hb so that 02 cannot bind with Hb Further, the affinity for Hb of CO is about 250 times stronger than thet of 02 Therefore the combination of CO and Hb is very difficult to dissociate) the Hb. although physically present, is not functionally available, hence it is anemic hypoxia In anemic hypoxia, the O2 contenl of artenial blood is lew but Pa02 is normal (that is, 02 tension of attend blood is normal) This is because, there is no obstacle to the development of physical solution of 02 in the plasma Because ol the fact that Pa02 is normal. The carotid bodies are not stimulated and there is no (or very little)dyspnea in anemia (unless it 13 very severe) at rest However, dyspnea is quick to appear on exertion (Recall, the carotid bodies are susceptible. only to Pa02 values and nor the oxygen conten) Compsnsatory mechanism (ij Hyperkinesia oirculation, as dsscnbed under hypoxia hypoxia is also seen here (ii) There is increase o' 2.3. DPG within the R8C causing a shrft to ihe right of the O2 dissociation curve, (m) the Q2 lack slimulates rhe production ol erythropoietm. which in Turn raises the PBC count WHEN carbonmoonxide) is inhaled, the CO combines with the Hb to form carboxyhemoglobin (carboxy Hb, COHb) The affinity of CD for Hb it tome 250 times higherthanthat of 02 (see above) Therefore once COHb is formed, it is not dissociated easily As 02 competes for the same site. Hb02 thus, cannot be formed Conclusion therefore, in. in CO poisoning, the Pa02b is normal bul 02 saturation of Hb is very poor As the dissolved 02 alone is unable to meet the demand of the body.the symptoms and signs of hypoxia develop Trealment consist of high pressur* 02 therapy which raises the dissolved O2 (= PaO2) as will at by mass action replaces

This pacemaking and conducting system structures are composed of myocardiai cells although

ed arborising fibers of Purkmje It should be clearfy borne in mind That these structures, viz. tha SAN, AVN, bundle of his and Purkinje's fibers, together from a system, whose function is to create impulse (pace making) and convey the impulse (conduction of impulse} lo every part of the heart. This pacemaking and conducting system structures are composed of myocardiai cells although their functions have become highly specialized, viz. pace making and conducting the impulse These speuahzed cells, thus, do not have sufficient contractility The muscle of the heart (including the above mentioned pace making and conducting system) are called myocardium. Pericardium The entire heart is enclosed by a sac called pentardium In between the two layers of pencardium. a cavity called pencardial cavity exists which contains a very small quantity of fluid If there is an acute enlargement of heart the pericardium may oppose the enlargement However, if the cardiac enlargement is chronic. the pencardium also grows and therefore does not oppose the expansion of hear! The heart valves AV valves Each orifice between atnum and the corresponding ventricle, contains alriovernncular (AV) valves Thus, There are two AV valves, right and the left. These valves function in such a way that blood can tow from atrium to ventricle but not from ventncle to atnum .Therefore, these valves are open during ventncular diastole bul are closed during ventncufer systole The right AV valve consists of three cusps or leaflets (fig 5 1 2) whereas the left consist of two cusps and hence they are known as tricuspid and bicuspid (mitral) valves respectively During ventncular systole, Ihe free margins of the cusps meet each other and seal off the orifice so efficiently that no blood can escape from the ventricle into the corresponding atrium /I the ventricular side of the cusps, strong chord like structures, catted chordae tendmeae (fig 5.1 3) are attached These chords arise from muscular structures (looking lika muscle bellies) tailed 'papillary muscles', which in tum. arise from the vanrncutir myocardium That is. these papillary muscles and chordae tendmeae run through Ihe cavities of the ventricle and get attached with the undersurlace of the AV valves. Fig 5 1 2 The cusps of the different waives When venlncilar systole (contraction of tha ventncle) occurs. the papillary muscles also contract and thereby rhey exert a pull on the cusps of the AV valves This pull ensures that there is no prolapse of the valve due to high pressure (during ihe ventncular systole)L into the atrium The chordae lendmeae and the papillary muscles may therefore be viewed as different members of a single system, aimed to prevent the prolapse of Ihe valves as mentioned above For studymg the mechanical properties of heart muscle, and the effects of drugs on them. The erpenmental physiologist or pharmacologist usually chooses isolated papillary muscles of a mammalian heart Semilunar valves.Aortic and pulmonary valves are known as temilunar valves They are present in The beginning or aorta and pulmonary artery respectively. Both the aortic and the pulmonary valves contain three cusps These valves allow one way traffic of blood from the right ventricle to the pulmonary artery, or from the lefl ventricle to the aortaj but not in the reverse direction',. Ventricular muscles As stated already, the left ventricular musculature is quite heavy, the right ventricular one is comparatively thin. The muscles of Ihe venlncles take their origin from the atnoxentncular fibrous rings (annull fibrosi) of the heart (fig 5 1 2) There are four Fibrous rings (annull fibrosi) m the heart, situated at Ihe amoventricular orifices as wall as in the regions of pulmonary and aortic valves (Tig.5 1.2) Fig 5 13. Chordae landmae Because of these nngs, the musculature of the atria and those of the ventricles are competely separaled from each other. The only communication between the atria and the venlncles being The atnoventncular bundle of His This issue needs to be carefully understood Although, we do not say nowadays that anatomically hear! is a syncylium (vide infra), from the physiological point of view, tha heart muscle slill can be regaided at father, a sort of syncytium However the atrinventricular rings cornplately cut off tha continuity of the atrial and ventricular musculature Ultimilaly, tharafore. tha two atria togethei may be viewed at if acting as a single cell and the two ventricles acting as another single cell. The ventricular muscles, at already stated, take their origin from the AV rings [Vanous bundles of muscles, have been described by some authors, but many authors consider these to be artifacts and will not be discussed here any morel ) is more important to understand the effects of contraction of ventricular muscles. When the left ventricle contracts and the muscles are allowed lo shorten (isotmmc contraction), the main directions in which tha left ventricle shortens are, (i) base to apex. thal is the base moves towards the apex and the vertical diameter is reduced, and (ii) side to side, that is, the distance between the inlervanlncular septum and The lataral watt rjf the left ventricle is reduced As a result, the contracting left venlncle greatly squtezes on its content (The blood) The blood cannot escape into the left atrium (owing To the firm closure of the mitral valve) and so the blood forces open The aortic valve and escapes into Ihe aorta The right ventricle mainly shortens m ils transverse diameter There is another factor, called, left ventricular aid. This mechanism is produced by the bulging of the intervent

FUNCTIONS OF THE LOOP OF HENLE AND THE DISTAL NEPHRON the tunctions of this portion* of the nephron are Concentration of urine

load. [ N.B (i) TG feed back must not be confused with glomerulo tubular balance. (ii) The TG feed back, thus, also controls the glomerular blood flow and may cause renal autoregul ation] FUNCTIONS OF THE LOOP OF HENLE AND THE DISTAL NEPHRON the tunctions of this portion* of the nephron are Concentration of urine. Further reabsorplion of Na+, C!- and water. Acidification of urine Secretion of K+ and some drugs Some of these functions are Interdependent. Therefore, concentraticn of urine, electroyte and water absorption will be constiered together Concentration of urine. Countercurrent multiplier exchange system Some facts are restated at the onset. These are; 1. There are two classes of nephrons. Most of the (about 85% in man) nephrons belong to the class of cortical nephrons, whereas the rest (about 15%) belong to the class of juxta rnedullary nephrons. 2. The anatomical features (fig.8.1.2.) of these two class of nephrons are fairly different. The important differences are: (a) the loop of Henle in the Juxta medullary nephron, very long and the U-bend of the loop lies at the tip of the renal papilla, whereas the loops of Henle of the corticaI nephrons are short and end in the parts of the medulla dose to the cortex (that is, superficial parts of the meduia). (b) the blood vessels also show differences in the cortical nephrons, the efferent arteriole from the glomerulus breaks up into peritubular capillaries which remain in the cortex but n case ofthe juirla medullary nephrons, the efferent arteriole floes not break up in peritubular capillaries; instead, it gives rise to long delicate walled vessels (which are basically capillaries) called vasa recta (flg. 8.2.4) which follow the course of me loop of Henle and remain within the medulla. (c) the juxta medullary nephrons have, even in their ascending limb of the loop or Henle, a thin segment (fig 8.1.2). The actual mechanism of concentration of the tubular fluid (concentration of the urine) occurs by a process called counter current multiplier exchange system. The details are as follows A term, distal segment has been used In this book and means, loop of Henle + distal nephron (p. 465) 1. At its beginning, the descending limb the loop of Henle receives, from the pars recta of the proximal tubule, a fluid which is isotonic with plasma. The approximate composition of the fluid is : osmolalita 300 m osmcl/kg, NaC12 80 m mol\kg, urea 20 mmol\kg Fig. 8. 24. To show the difference of vascular supply between cortical and juxta medullary nephrons. 2. In the interstitium, that is in the pentubular spaces (ie, space which lies in between the tuoules) of medulla, the osmokality of the fluid, at this zone, called the outer zone of medulla, (fig. 8.2.5.) is between 300 to 600 mosm\kg Further deep into the medulla, that is, in the deeper zone, the osmolality rises more and more, till it becomes maximum at the level of the'U-bend where it beomes nearly 1200 mosmol/kg. Therefore, the medullary osmolality continuously rises from the outenmost zone to the deeper zone, and this phenomenon s called "medullary gradient 3. Concentration of the tubular fluid occurs rather spectacularly in the juxta medullary nephrons alone, therefore, the events which will be deseribed below occur only typically in a loop of Henle of a Juxtamedullary nephron but somewhat smilar events (Out In a law key) also occur in the cortical nephrons. 4. Assume that the flow of the fluid in the descending Iimb (of Henle s loop) is slopped for a while. The osrnolalty of the fluid in the peritubulr space (medeulary inter-stitium) is higher than that or the tubular fluid, Further, the descendig limb is freely permeable to water, but not to the electrolytes (Na* and CI-) As a result, the water moves out from the descending Iimb to enter the peritubular space and the fluid of the descending limb becomes concentrated in electrolytes (fig. 8.2 .5.). Then the fluid in the descending limb resumes movement and moves forward and, as s result, another small quantity of isotonic fluid from pars recta Is delivered into the descending Iimb. at the next moment, the forward movement of The fluid stops again and the process of concentration as mentioned above is repeated. By repeated repetitions of the whole process, there is intense concentration of the fluidi in the descending tubule, the fluid becoming more and more concentrated as it moves more and more to the U turn (fig 8,2.5). As the interstrtium is also becoming more and more hyperosmo laI (the meduIary gradient, see above), The outward movement of water continues. This mechanism results in multiplication of the effect that isr it causes multiplication (- intensification or amplification) of the concentration. further, the fluid In the ascending and descending limb moves In the opposite (countercurrent) direction. Hence the whole process is called countercurrent multiplier- system Fig 8 .2 .5 Medullary gradient Because of presence of this gradient, tubular fluid tn me descending loop of Henle Becomes very concentrated in sodlum and. as a result, the Na removal from the ascending limb involves much less energy, 5 Nest the fluid enters the ascending Iimb. As we are distussing juxtamedulary nephron. this part of the loop of Henle is also a thin segment. At this segment ie in the ascending limb, the tubule becomes impermeable to water but permeable o Na* and C-. The Na* is actively transported out from The ascending limb to the fluid of trie peritubular space which Is already rich In Na* However, thanks to the countercurrent multiplier system mentioned above, the Na* concentration within the ascending limb near the U bend b also (qiute heavy and so the work done (for transporting the Na* against concentration gradient) is not too great. Minimisation of work done for the active. Transport of the Na* from the ascending limb to the peritubutar space appears, on teleological ground. To be one of the fundamental aims of the counter current mutiplication. 6. Thus, the tubular fluid now. eventually, reaches the thick part of the ascending limb of the loop of Henle Na* and Cl- ions continue to be transported out from this part also, to the pentubular space bul this part e also totally impermeable to water (so water remains within the tubule) The results in hypolonicity of the fluid and the fluid delivered from the thick ascending Iimb to the distal nephron, in a juxtameduiary nephron, Is always hypotonic. The Na+ reabsorption at this segment follows. The Clreabsorption. Thus, the Cl reabsorption here, is pimary and Na* reabsorption is secondary (see 'chloride driven Na transport' earlier in this chapter) Similar events occur In the cortical nephrons also but as the length af the loop of Henle in the cortical ne phrons is short, the

A proportion of the active ingredients(s) is usually deposited on the inner surface of the actuator,

pressure in a seated container and are released as a fine mist of spray upon activation of a suitable valve system They are intended either for inhalation for local action in the lungs or for systemic absorption through the alveoli or for topical application to [he skin or various body onf ices Inhalation aerosols are metered dose preparations which provide controlled amounts of the active ingredient(s) The basic components of an aerosol system are the container, the propellant. the concentrate containing the active ingredient(s), the valve and the actuator Aerosols are of two types, the two-phase system consisting of gas and bquid or the three-phase system consisting of gas, liquid and solid or liquid The two-phase aerosol comprises a solution of active ingredient(s) in liquefied propellant and the vaporised propellant. The solvent is usually the propellant or a mixture of the propellant and co-solvents such as ethanol.propylene glycol and polyethylene pjycote The three-phase aerosol consists of a suspension or emulsion of the active ingredient(s) and the vaporised propellants in the suspension the ingredient(s) may be dispersed in the propellant system with the aid of suitable pharmaceutical aids such as wetting agents, solubilismg agents, emulsifying agents, suspending agents and lubricating agents to preveni clogging of valves Foam aerosols contain an emulsion of the active ingredient(s). surface-active agents, aqueous or non-aqueous liquids and the propellents Active ingredients For satisfactory bioavailability the active ingredient(s) should have the majonty of particles under 10 gin in size in the case of inhalation aerosols and not more than 100 gm for other types of aerosols Propellants Propellants perform the essential function of expelling the material from the container by supplying the necessary pressure within the aerosol system They are liquefied or compounded gases fiavmg vapour pressures exceeding atmospheric pressure The commonly used propellants in aerosol systems are hydrocarbons, especially the fIuorochloro-derivatives of methane and ettane. the butanes and pentanes and compressed gases such as nitrogen and carbon dioxide Mixtures of propellnts are often employed to obtain the necessary delivery and spray characteristics of the aerosol Vafces The vatve regulates Uie flow of the active inp/edientfs) and propeltent from the container and determines the spray charactensto of the aerosol It must be manufactured from materials which are inert to the contents of the aerosol The common^ used matenais are rubber, plastic, aluminium and stainless steel For topical products vatves capable of providing continuous spray operation are suitable However, products for oral or nasal inhalation require metered-dose vafves which ensure delivery of a uniform quantity of spray and an accurate dose of the active ingredient(s), both within specified tolerances, with each activation of the valve Metered valves may need priming before use if the aerosol packages have not been stored properly or have not been used for long periods of time Actuators The actuator or adaptor which is fitted to the aerosol valve stem is a device which on depresston or other movement opens the valve and directs the spray to the desired area The design of the actuator which incorporates an orifice of varying size and shape and expansion chamber is very important in influencing the physical charactenstics of the spray or foam, particularly in the case of inhalation aerosols, where the active ingredent(s) must be delivered in proper particule size range A proportion of the active ingredients(s) is usually deposited on the inner surface of the actuator, the amount available is therefore less than the amount released by actuation of the valve Containers Aerosol containers are made of metal (stainless steel, aluminium or tin-plated steel), glass or plastic or acombination of these materials The containers must be so designed that they provide the maximum in pressure safety and impact resistance Preparation of aerosols Aerosols are commonly prepared by filling under pressure and sometimes by filling after refrigeration to temperatures below 0* infilling under pressure, the requisite volume of the concentrate of the active ingredient(s) is filled in the container and either the propellant is forced under pressure through the valve orifice after the valve is sealed, or the propellant is allowed to flow under The valve cap and (he valve assembly is sealed in either case, the air in the container must be evacuated by means of vacuum or displacement with a small amount of the propellant Aerosol products should be manufactured under stritly controlled conditions and subjected to process controls which include propellant and medicament fill weights, pressure test and leak test of the finished product Inhalation aerosols should be manufactured in conditions designed to minimise mcrobial

biosynthesis and source Histamine is amine of the amino acid histidine Histamine is synthesized by enzymatic decarboxylation of histidine

this book Many illustrious personalities (physiologist /pharmacologists/ clinicians) have worked on histamine some prominent names being Dale. Laidlaw, Best and Lewis. Chemistry, biosynthesis and source Histamine is amine of the amino acid histidine Histamine is synthesized by enzymatic decarboxylation of histidine. the enzyme beinq histidine decarboxylase In our body histamine can be obtained from many tissues but most notably from the mast cells of the tissues and the blood basophilc. Other important sources are gastro intestinal mucosa and CNS. In the mast cells, histamine is completed with heparin and the heparin histamine complex is dissociated to cause, release of pharmacologically active histamine In allergic states following the contact of the antigen with a mast cell, the mast Cell is diegranulated (= mast cell granules are lysed) Dhistarnme is released from the mast celt Certain bee venom and stings ol certain insects are rich in histamme Actions The actions of hrstamine cart be divided into two major categones. (A) On smooth muscles, and (B) On exocnine glands of stomach Besides hislamine has (C) some other (miscellaneous) action. Actions on smooth muicles 1 It causes relaxation of Ihe anenoles and probably also of [he smooth muscles of precapillary sphincter, leading la engorgement of the capillaries This action used to be designated as "capillary dilatation* by our forofathers, but now it is known that true capillaries are devoid of muscles and hence active dilatation is not possible in them. 2. Hislamine causes contraction of bronchial (specially in susceptible persons) and intesimal smooth muscles leading to bronchospasm and diarrhea. Recall, mast cells occur plentifully in mucous membrane tracheobronchial tree. An injection of histarmne therefore can produce a shafp fall of blood pressure and violent attack of asthma, theie may also be uflicaria Fall of BP is due to acute dilaiation of the artenoles (Ihe 'resistance vessils) Urticaria (as well as Inple response', see chap 10, sec V, cutaneous circulation), is due to transudatB of fluid from the capillary to the tissue which in turn is due to capillary engorgement Ultimately, speaking, histamine injection in susceptible persons can produce, anaphylactic shock, characterized by severe fall of BP and asthma Action on secretion of eiocnne glands The tote of nisiamirie in gasinc acid secretion has been discussed in chap 3. sec III. In short, histamme stimulates the parietal calls of the stomach and thus increases the secretion of MCI Miscellaneous action 1 In addition, histamme also is related to the pain and itching sensation. 2. Some rapidly growing tissues produce hrstamine in large amounts Thus, embryos, regenerating liver and rapidly healing wounds produce histamme It is possible. 1. hat for (he smooth functioning of the raprdty growing (issues, histamme is necessary 3 Some neurons of the brain are hisiammergic. ie. 1har neurotransmitters is histamine Such histaminergic neurons play a role m therrnoregulalion by hypolhalamus Drugs and histamine Many drugs, especially in susceptible individuals liberate histamine Such drugs, when consumed by these individuals, produce vanous allergic manifestations on shin, like urticaria, itching and triple response after ilchmg Such drugs, presumably on coming in contact with mast cells cause membrane perturbation n degranulation Histamme receptors There are at least two sub lypes of hotamine receptors on the cellular membrane H1 and 22 receptors 1 Contraction or relaxation of the smooth muscles ate due to combination of hisiamme and HI receptor Therefore, drugs which are HI receptor therefore, drugs which ire h1 anlagonists, oppose tftese actions (e g urticaria, triple response following itching elc ) of histamme Such drugs are called classical anlmisiammics and include diphenhydremine (benadryl). iripelennamine (pynbenzamme), promelhazine (phenergan), and chlorpheniramine 2. Oxyntic cells of the stomach contain H2 receptors and when H2 blockers are used, gasinc HCI secretion is mhibrled (for details see chap 3, sec III) Cimetidine and ranitidme are very popular H2 antagonists and are used evtensively in the treatment of paptic ulcer rt is possrbta that There are more than Two Types erf receptors for histamine, further. apart rlomlhi giitnc glands, H2 receplon are present in other sites also, however their functions are not clear) EICOSANOIDS AND PAF Introduction Burr and Bun m the 1920s discovered the essential fatly acids (Iinoletic. linolenic and the arachidonic acids, all of them are long chain fatly acids having more than one double bonds. Hence they are known by the generic name 'polyunsaturaled fatly acids). In the 1930s Kurzok and Uele of USA discovered that semen contains a subitance that tan cause contraction of uterus Sometime after the great US von Euler studied Ihe chemistry and some of the functions of this compound and named it 'prustaglandin', because the source of this matenalwas supposed to be the prostate (gland) Researches on prostaglandin became almost explosive since the 1960s and a large number of new compounds, (occurring naturally), were discovered As a result, as the things stand, todays position is as follows. The parent material in our body (= human body) is usually arachidonic acid (a C 20, polyunsaturated, ie, eicosanoic, acid) There are two great classes of compounds which can be synthesized in our body from the

The Windkessel action is most spectaculars aorta but is also seen in its branches too In old age (and some times in young persons too)

ries Their functions areas follows . As the heart pumps out its stroke volume into the aorta (which already contains some blood), an additional 70 ml or so (= the stroke volume) is thrust into it (aorta) The aorta is therefore suddenly more distended This means a part of the energy released by the heart during the ventricular systole is stored as potential energy in the walls of the aorta. in the next moment, during diastole, the aortic wall recoils due to its elasticity and the potential energy is re leased into the blood, causing it to surge forward with a renewed' vigor This is called Windkessel Effect' Because of this Wmdkessel Eflect. the velocity of blood is reduced to some eilent during systole but the velocity of blood during diislole is increased (owing to the elastic recoil of aorta), where the Windkessel Effect is deficient (as in arteriosclerosis, see below), the systolic velocity or blood is very high and the aorta becomes more empty in distole( The Windkessel Effect, reduces the requirement of energy expenditure by the heart dunng the systole The pumping action of heart the elastic recoil, of the aorta, taken together, is the driving force which drives the blood forward and is called Vis a tergo' Vis a largo is the most important factor for the onwar movement of blood Evidently, the magnitude of the elastic recoil depends upon the presence of sufficient number of elastic fibers in the aorta and its branches. The Windkessel action is most spectaculars aorta but is also seen in its branches too In old age (and some times in young persons too) the aorta becomes the seat of the disease called atherosclerosis In this disease there is lipid deposition in the tunica itima and media and subsequently there is calcification. There is much loss of elastic tissue. As a result of all these events. The arterial walls become hardened ('arteno-sclerosis) and The aorta loses its elasticity In such cases, owing to the lack of stretchability of the aorta, the systolic BP be comes very high but as the eitra blood leaves these vessels very quickly, the diastolic pressure is low Clinically, such cases are called systolic hypertension, the condition is characterized by high systolic, and a normal or subnormal diastolic pressure (e.g. ,200/70 mm Hg) and a high pulse pressure. This may be thus, viewed as a type of 'water hammer pulse' (chap 9 sec V, pulse', for details) The Windkessel vessels do not offer any serious resistance to The flow of blood (fig. 5 .7. 4.) Any change in their diameter has only a negligible effect on the total penpheral resistance. II Precapillary resistance vessels in short, this means the arterioles Most of the peripheral resistance encountered by the advancing column of blood is at the level of arterioles (fig. 5.7.4.) Therefore, arterioles are aften spoken of as the 'seal of the peripheral resistance' NB In the disease, essential hypertension, the arterioles are narrowed -4 BP increases. The walls of the ariterioles, practically speaking do not contain any elastic tissue, hence they are also called muscular arteries. They are richly supplied by the sympathetic system, There is a basic tone of The smooth muscles, on the top of which there is the added effects of the sympathetic nerves. Further, the sympathetic nerves themselves discharge Tonically. Due To the action of the sympathetic nerves (and also due to The actions of such naturally occurring vasoactive agents like adrenalin) the diameter of the artenoles after from time to time which in turns causes change of total peripheral resistance from time to time Some special points in relation to the artenoles are discussed below. 1. Critical closing pressure (of Burton) it can be shown by arguments that there is a critical diameter for every blood vessel, and if the diameter is Further reduced [below this critical diameter (due to the achon of sympathetic or vesopressor agent), the blood vessel will totally collapse. Evidently, arterioles therefore face the possibility of closing when subjected to The excessive action of vasoconstrictors Explanation: Recall the Laplace's law (fig. 5. 12.1 ) however the mathematical expression of Laplace's law for cylinder like arteriole is little different from that of a sphere, but this may be ignored for the time being). Smaller the radius, r. of the cylinder (or sphere) greater is The transmural pressure, P (which here is due to the tone of the arteriolar muscle) at a low perfusion pressue the arteriole collapses. If the vascular tone is constant, lower the BP. greater is the propensity to collapse (Here. the BP is the P1 of fig. 5.12.1) 2. Autoregulation Apparently it appears that if the perfusion pressure in the aorta falls there will be reduction of blood flow in the individual organs and vice versa. In practice, at least in some organs (brain, heart, kidney) the blood flow does not after unless the perfusion pressure is severely changed That is. minor or even moderate rise or fall of perfusion pressure does not affect the perfusion of the organ This ability of the individual organ to keep its blood flow reasonably constant, despite fair degree of changes in the perfusion pressure, is called autoregulation Mechanism of autoremulation is not clear Some popular the ones are discussed below (i) One of the widely believed theories is as follows Suppose the perfusion pressure in the feeding artery of the organrises — This causes more stretch of the arterial wall. In the arterioles. this leads To stretch of the smooth muscles in the well — vigorous contraction of the smooth muscles, (because a property of the smooth muscles of arterioles is that when it is stretched, it risponds to the stretch by contracting). This theory, called myogenic Theory is not new

about 0.8,Appendix 5.5.C A 1% w/v solution is acid to methly red solution D Melts between 121° and 123*, Appendix 8.8 Clarity

about 0 4 g and dissolve in a mixture of 25 ml of hydrochlonic acid and 50 ml of water Cool to 10° and carry out the nitrite tiration. Appendix 344 Each ml of 0 1M sodium nirtrite is equivalent to 0.01652 9 of C9 H11 NO2 BENZOIC ACIDCaltgory Antifungal agent, pharmaceutical aid (antimicrobial preservative) Description Colourless, light Crystals, scales or needles, odour, Slight and charactenstic Solubility Freely soluble in ethanol (9S%)h in chloroform and in ether: slightly soluble in water but soluble in boiling water It is soluble in fixed oils Storage Store in well-closed containers STANDARDSBenzoic Acid contains not less than 99 5 per cent and not more than 100 5 per cent of C7H6O2, calculated with reference to the anhydrous substance Identification A Warm gently 02 g with 20 ml of water, add 1 ml of IM sodium hydroxide and filter To The filtrate add ferric chloride test solution, a buff coloured precipitate is produced.B The light absorption in the range 220 to 360 nm of a 0 001% w/v solution in methanol exhibits a maximum only at about 225 nm, absorbance at about 225 nm. about 0.8,Appendix 5.5.C A 1% w/v solution is acid to methly red solution D Melts between 121° and 123*, Appendix 8.8 Clarity and colour of solution A 5% w/v solution in ethanol (95%) is clear, Anpendix 6 1, and colorless Appendix 6 2. Arsenic Mix Win 5 g with 3 g of anhydrous sodium carbonate, add 10 ml of bromine solution and max thoroughly Evaporate to dry ness on a water-balh, gently ignite and dissolve the cooled residue in 16 ml brominated hydrochloric acid and 45 ml of water Remove the excess of bromine with 2 ml of stannous chloride AsT. The resulting solution complies with the limit lest for arsenic. Appendix 3.9 (2 ppm) Heavy metals Not more than 10 ppm, determined by (the following method Dissolve 20 g in 25 ml of acetone and add 2 ml of water and 10 ml of hydrogen sulphide solution, any colour produced is nol more intense than that of a solution prepared wrth 25 ml of acetone. 20 ml of lead standard solution (10 ppm Pb) and 10 ml of hydrogen sulphide solution Readily oxidisable substances Add 1 ml of sulphuric acid to 100 ml of water, heat to boiling and add dropwise 0 1M potassium permanganate until the pink colour persists for 30 seconds Dissolve exactly 1 g in the hot solution and titrate'wrth0.1 IM potassium permanganate to a pink colour that persists for 15 seconds, not more than 0.5 ml of 0 1M potassium permanganate is required Readily carbonisable substances Dissolve 0 50 g 5 ml of sulphunc acid and allow to stand for 5 minutes The colour of the solution is not more intense than that of reference solulion YS5. Appendix 6.2 Cinnarnic acid Warm 0 .1 9 with 0 1 g of potassium permanganate and 5 ml of dilute sulphuric acid, no odour of benzaldehyde is developed Chlorinated compounds. Dissolve 0 33 g in 5 ml of 0 5M sodium carbonate evaporate to dryness and heat Ihe residue until completely charred, keeping the temperature below 400* Extract the residue with a mixture of 10 ml of waler and 12 ml of dilule nitric acid and filter, the filtrate complies with the limit test for chlorides, Appendix 3 10 Sulphated ash Nol more than 0 1%, Appendix 3 .22 Water Not more than 0 .7% w/w. determined on 0. 25 g and using a mixture of I volume of methanol and 2 volumes of pyridine as the solvent, Appendix 3.24. Assay: Weigh accurately about 1.0 g and dissolve in 15 ml of warm ethanol (9S%) previously neutralised to phenolphthale in solution. Add 20 ml of water and titrate with 0. 5M sodium hydroxide using phenolphthalein solution as indicator Each ml of 0.5M sodium hydroxide is equivalent to 006106 g of C7O2COMPOUND BENZOlC ACID OlNTMENTBenzoic and Salicylic Acids Ointment, Whirtheld's Ointment"Compound Banzoic Acid Ointment is an ointment containing 6.0% w/w of Benzoic Acid -and 30% w/w of Salicylic Acidin a suitable ointment base. Other strengths may also be prepared with Benzoic Acid and Salicylic Acid being in the ratio of about 2. to 1. Category Antifungal (topical) Storage; Store in well-closed containers at a temperature not exceeding 30° STANDARDS Com pound Benzoic Acid Ointment contains not less than 5.7 per cent and not more than 6.3 per cent w/w of benzoic acid, C7 -H6O2, and not less than 2.85 par cent and not more than 3.15 percent w/w of salicylic acid C7H6O3 Identification Carry out the method for thin -layer chromatography, Appendix 4.6, using silica gel GF254 as the coating substance and a mixture of 80 volumes of toluene and 20 volumes of glacial acetic acid as the mobile phase. Apply separately to the plate 2 ul of each of the following solutions For solution (1) warm 1 g of the ointment with 10 ml of chloroform, cool and filter Solution (2) contains 06% w/v of benzoic acid and 0.3% w/v of salicylic acid in chloroform. After removal of the plate, allow it to dry in a current of air and examine under ultra-violet light (254 nm). The two principal spots in chromatogram obtained with solution (1) correspond to those in the chromatograrn obtained with solution (2) Examine the plate under ultra violet light (365 nm) A blue fluorescent spot in the chromatogram obtained with solution (1) corresponds m colour and position to the one in the chromatogram Obtained with solution (2) Spray the plate with feme chloride test-solution. The chromatogram obtained with solution (1) shows a purple spot corresponding in position to the blue fluorescent spot observed under ultra-violet