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Active transport can occur against an electrochemical gradient antibiotics for uti make you sleepy buy noroxin 400mg visa, but it does not mean that it only occurs against such gradients in the body. Endocytosis is also a type of active transport and it will prove prudent to revise the various transport mechanisms described in Chapter 1. Tubular mechanisms, patterns of renal handling of substances and concept of renal clearance Tubular mechanisms. As mentioned earlier, the two main tubular mechanisms involved in renal handling of a substance are tubular reabsorption and tubular secretion. Small proteins and peptide hormones are reabsorbed in the proximal tubules by endocytosis. Active secretion of substances occurs into the tubular fluid with the help of certain nonselective carriers. It is because of the common carrier that probenecid can block secretion of penicillin and maintain its plasma concentration for a longer time. I mportant N otes the ensuing discussion includes the list and mechanism of the substances reabsorbed and/or secreted in different segments of renal tubule (page 496). Such substances that are both filtered across the glomerular capillaries and secreted from the peritubular capillaries into urine have the highest renal clearances. In such circumstances, depending upon which of the two process is dominant, there may be net reabsorption or net secretion of the substance. Many organic compounds are bound to plasma proteins and are therefore unavailable for ultrafiltration. From the above, the renal clearance can be defined as the volume of plasma that is cleared of a substance in 1 min by excretion of the substance in the urine. It is the amount of a substance entering the renal tubule by glomerular filtration per unit time. The excretion rate (Eo) can be calculated by multiplying urine flow rate (V) and the urinary concentration of the substance (Ux). Reabsorption of a substance is said to occur when the filtered load exceeds the excretion rate. The net secretion of a substance is said to occur when the excretion rate is more than the filtered load. Under such circumstances, the secretion rate is calculated by subtracting filtered load from the excretion rate, that is: Renal tubular transport maximum (T m). Renal tubular transport maximum Tm refers to the maximal amount of a solute that can be actively transported (reabsorbed or secreted) per minute by the renal tubules. Therefore, it is important to note that Tm pertains to solutes that are actively transported only and the substances that are passively transported. Maximum tubular secretory capacity (Ts) is the highest attainable rate of secretion. Maximal tubular reabsorptive capacity (Tr) is the highest attainable rate of reabsorption. Threshold concentration is defined as the plasma concentration at which a substance first appears in the urine. Thus, its concentration in tubular fluid is determined solely by how much water remains in the tubular fluid. Transport across different segments of renal tubule the substances transported across the different segments of renal tubules are described below and enlisted in Table 6. The brush is composed of thousands of villi which increase the absorptive surface area of each cell 20-fold. The substances absorbed are transferred to the peritubular capillaries from the basolateral membrane of the cells. Sodium reabsorption the process of sodium reabsorption in proximal tubule is isosmotic, i. Mechanism of Na+ reabsorption in the early proximal tubule and late proximal tubule is different. In early proximal tubule, Na+ is reabsorbed by cotransport with H+ or organic solutes (glucose, amino acids, phosphate and lactate). The glucose and other organic solutes that enter the cell with Na+ leave the cell across the basolateral membrane by passive transport mechanism. Values above 100 indicate that relatively less of substance than water was absorbed; and values below 100 indicate that relatively more of substance than water was reabsorbed. In the late proximal tubule the Na+ is reabsorbed primarily by chloridedriven sodium transport mechanism across both the transcellular and paracellular pathways. So the fluid entering the late proximal tubule contains very little of these substances but contains a high concentration of Cl- (140 mEq/L) compared with that in the early proximal tubule (105 mEq/L). This high Cl- (140 mEq/L) concentration in the lumen of late proximal tubule and comparatively low concentration (105 mEq/L) in the interstitium creates a concentration gradient which favours the diffusion of Cl- from the tubular lumen across the tight junctions into lateral intercellular space. Movement of negatively charged Cl- causes the tubular fluid to become positively charged relative to the blood. Water reabsorption Approximately 67% of the filtered water is absorbed in the proximal tubule by osmosis in response to a transtubular osmotic gradient established by the solute reabsorption. Protein reabsorption Normally, only a small amount of proteins is filtered by the glomerulus (40 mg/L). Normally, the proteins are completely taken into the cells of proximal tubules by the process of endocytosis. Once inside the cells, enzymes digest the proteins and peptides into their constituent amino acids which exit across the basolateral membrane and return to the blood in the peritubular capillaries. When the amount of filtered proteins increases (due to disruption of glomerular filtration barrier in kidney diseases), the reabsorbing mechanisms saturate and the proteins may appear in the urine (proteinuria). The cells of proximal tubule, in addition to reabsorbing solutes and water, also secrete organic anions and organic cations, which include some end products of metabolism circulating in plasma, exogenous organic compounds and certain drugs Table 6. This mechanism is driven by the magnitude of the voltage difference (negative potential) across the basolateral membrane. Transport across loop of henle About 20% of filtered Na+ and Cl-, 15% of filtered water and cations such as K+, Ca2+ and Mg2+ are reabsorbed in the loop of Henle. Reabsorption occurring in different parts of the loop of Henle is: Thin descending limb of loop of henle. Water absorption occurs passively (because of hypertonic interstitial fluid) exclusively in this part of loop of Henle. It is accompanied by diffusion of sodium ions from interstitial fluid into tubular lumen. Because of impermeability to water, the fluid leaving this limb is hypotonic relative to plasma. This limb is impermeable to water but is involved in the reabsorption of 20% of the filtered Na+, Cl- and other cations. Some of Cl- absorption in thick ascending loop of Henle occurs with Na+, K+ and Ca2+. Gene mutation of this channel is associated with Ca2+ containing renal stones and hypercalciuria, is known as Dent disease. Because of the unique location of transport proteins in the apical and basolateral membranes, the tubular fluid is positively charged relative to the blood. As a result, tubular fluid Na+ and tubular fluid osmolarity decreases to less than their concentration in plasma. Further, Na+ reabsorbed from this segment is the main driving force behind the countercurrent multiplier system which concentrates Na+ and urea in medullary interstitium. Early distal tubule (initial segment of distal tubule) reabsorbs Na+, Cl- and Ca2+, and is impermeable to water. Cl- is driven by the lumen negative charge generated by the diffusional influx of sodium. Like other steroid hormones, the action of aldosterone takes several hours to develop because new protein synthesis is required.

Diseases

• Norrie disease
• Anorexia nervosa binge-purge type
• Thyroid carcinoma, papillary (TPC)
• Hyperkeratosis palmoplantar with palmar crease hyperkeratosis
• Neural tube defects X linked
• Chromosome 9 inversion or duplication
• Radiculomegaly of canine teeth congenital cataract
• Adducted thumb club foot syndrome
• Homologous wasting disease
• Nephrotic syndrome, idiopathic, steroid-resistant

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In such states antibiotics for dogs uti cheap noroxin 400 mg otc, the flow and apparently the pressure in micro-circulation increases with an increase in cerebral perfusion pressure. Role of intracranial pressure in regulation of cerebral blood flow the intracranial pressure level regulates cerebral blood flow by following two mechanisms: i. However, practically it does not occur so because due to gravity the venous pressure and intracranial pressure are also decreased, and so the pressure on the vessels is decreased. When intracranial pressure is increased and becomes equal to the arterial pressure, it compresses the arteries in the brain and blood supply to vasomotor area is compromised. The rise in blood pressure is proportionate to rise in intracranial pressure up to a certain limit, beyond which cerebral circulation ceases. The resultant increase in blood pressure also causes reflex bradycardia via baroreceptor response. Nervous regulation of cerebral blood flow the cerebral blood vessels are innervated by noradrenergic vasoconstrictor fibres and cholinergic vasodilator fibres. The precise role of these fibres in regulation of cerebral blood flow is still a matter of debate. However, under normal conditions vasomotor nerves do not regulate the cerebral blood flow. These nerves may act indirectly by release of substances from the astrocytes which act paracrinally and regulate vasomotor tone. The meta-arterioles subdivide into capillary loops, which provide a large surface area for heat exchange. These vessels are wide, low-resistance connections that serve as shunts and allow blood to bypass the superficial capillary loops and play major role during control of body temperature. The metabolic rate of the skin is relatively small so that a minimal amount of blood flow to the skin can supply the nutritive function. Maximum cutaneous blood flow that occurs on heat exposure imposes a heavy circulatory load on the heart. That is why persons working under maximal heat loads may simply collapse with circulatory failure unless supervised adequately. During heat stress, the blood flow to the area with rich A-V anastomoses increases much more (about 75 ml/100 g/min) compared with the rest of the skin (about 25 ml/min/100 g tissue). The colour of skin is basically determined by the pigment present; however, the amount of blood and degree of oxygenation also affect the skin colour tinge which may be reddish, bluish or some shade in between. Therefore, in contrast to most other tissues, the cutaneous blood flow is predominantly regulated by the nervous control instead of metabolic control. Neural control mechanisms the cutaneous blood flow is regulated by following neural control mechanisms. The bradykinin produced by the secretory activity of the sweat glands acts locally as a powerful vasodilator and increases blood flow to skin. All the above mechanisms combinedly may increase the cutaneous blood flow to as high as 150 ml/min/100 g tissue. The increased blood flow carries heat to the surface of the body, where it is dissipated by radiation, evaporation and conduction to the environment. If the environmental temperature is higher than the body temperature, heat can only be dissipated by means of evaporation of sweat; under these conditions radiation and conduction would cause the body to gain heat. Consequently, cutaneous blood flow is markedly decreased to as low as 1 ml/min/100 g. Thus, total blood flow to skin during exposure to cold stress may be even less than 50 ml/min. In this way, heat conservation is accomplished by markedly diminishing the rate of blood flow to skin. Baroreceptor-mediated reflex Cutaneous blood vessels participate in baroreceptor-mediated reflexes during conditions of circulatory stress such as exercise and haemorrhage. They exhibit considerable vasoconstriction and act as compensatory mechanism to divert blood from periphery to the central pool. Cortical control mechanism the emotions affect the cutaneous circulation through corticohypothalamic pathway. The impulses are relayed from the corticohypothalamic centres to the thoracolumbar sympathetic cell bodies and thence to the skin vessels. It is supposed to be the result of bradykinin (a potent vasodilator) release, secondary to a brief corticohypothalamically controlled discharge of sympathetic cholinergic fibres to the sweat glands. White reaction White reaction refers to appearance of a pale stroke line when a pointed object is drawn lightly over the skin. This occurs due to the fact that the mechanical stimulus initiates contraction of the precapillary sphincter, and blood drains out of the capillaries and small veins. Triple response Triple response is three-part response, consisting of the red reaction, wheal and flare, which occurs as a normal reaction to the skin which is more in intensity than that simply causes white reaction. In other words, even when the skin is stroked more firmly with a pointed instrument, instead of white reaction, there occurs triple response. The red reaction refers to the red line which appears at the site of injury in about 10 s. The dilation of the precapillary sphincters is not mediated by nerves but is produced by histamine and/or some polypeptides such as bradykinin released from the damaged skin. The flare refers to the diffusely spreading and irregularly outlined redness of the skin surrounding the red line. Wheal refers to the swelling or localized oedema that develops within the area of flare when the stroke stimulus is strong enough. The use of effective nonapeptide antagonist to substance P reduces extravasation of the fluid, thus prevent wheal formation. Dermatographia Dermatographia refers to striking triple response that occurs as an unusual reaction in some individuals. Thus, in the prone individuals anything drawn on the skin even with a blunt point becomes conspicuous within a few minutes. Possibly, it is due to excessive release of the histamine from the involved skin area. Reactive hyperaemia Reactive hyperaemia is a phenomenon by which the vessels control blood flow to the organ after a period of ischaemia following occlusion of the artery to an organ or tissue. This response of the blood vessels occurs in many organs but is visible in the skin. Due to this phenomenon, the blood flow exceeds the control level when the occlusion is removed. For example, when the blood supply to a limb is occluded, the cutaneous arterioles below the occlusion dilate. When the circulation is re-established, blood flowing into the dilated vessels makes the skin fiery red. Oxygen diffuses a short distance through the skin, and reactive hyperaemia is prevented if the circulation of the limb is occluded in an atmosphere of 100% O2.

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Cerebellar nystagmus occurs during damage to flocculonodular lobes and occurs at rest (when neither the person nor the visual scene is moving) virus pictures discount 400mg noroxin. Dysarthria or scanning speech occurs due to inco-ordination of various muscles and structures involved in speech. Clinical tests for cerebellar dysfunctions Clinically cerebellar dysfunctions can be demonstrated by following tests: 1. The patient has great difficulty in promptly bringing the finger of outstretched arm to touch the tip of his nose. This is because the intention tremors become more severe as the hand approaches the face. When the patient attempts to do a movement against a resistance, and if the resistance is suddenly removed, the limb moves forcibly in the direction towards which the effect was made. When the patient is asked to walk on a straight line, he is unable to do so (even with eyes open); he follows a zigzag path due to disturbance of equilibrium. Lying in a supine position, the patient is asked to place his heel on opposite knee, and then slide his heel up and down the shin between knee and ankle. Basal ganglia Physiological anatomy Components of basal ganglia According to anatomic definition, basal ganglia are subcortical nuclear masses which include corpus striatum (amygdaloid body and claustrum). It is divided almost completely by the fibres of internal capsule into two parts: i. Phylogenetically, the caudate nucleus and putamen are of more recent origin and hence called neostriatum or striatum in short. Caudate nucleus is separated from the lentiform nucleus almost completely by the fibres of internal capsule, except lower part of its head where it is continuous with putamen nucleus (part of lentiform nucleus). The tail of caudate nucleus ends by becoming continuous with putamen and lies in close relation to the amygdaloid body. It is shaped like a biconvex lens and is triangular in both coronal and horizontal sections. The striatum has four types of neurons; 95% are Gabanergic medium spiny neurons, and remaining 5% striatal neurons are nonspiny, which include: large (cholinergic), medium (somatostatinergic) and small (Gabanergic) Subthalamic nucleus Subthalamic nucleus (body of Luys) is a biconvex mass of grey matter, which is situated lateral to red nucleus and dorsal to substantia nigra in the mesencephalon. Subthalamic nucleus is separated from the ventral nuclei of thalamus by a thin sheet of grey matter known as zona inserta. Substantia nigra Substantia nigra is a sheet made up of small unpigmented and large pigmented nerve cells. It appears dark in unstained sections as neurons within it contain the pigment neuromelanin. Pars compacta of the two sides are continuous with each other across the ventral tegmentum. Afferents or input to striatum the striatum (caudate nucleus and putamen) is regarded as the input side of the basal ganglia receiving following afferents. These originate from all parts of the cerebral cortex (premotor, supplementary motor cortex and primary somatosensory) and terminate in striatum. These originate from the pars compacta, part of substantia nigra and terminate in the striatum. Raphe striate fibres are serotoninergic fibres received by the striatum from raphe nuclei in the reticular formation of brainstem. Locus coeruleus striate fibres are noradrenergic fibres received by the striatum from the locus coeruleus. Striatum (caudate nucleus and putamen) which receive most of the afferents gives robust projection to both segments of globus pallidus. Efferents or output from globus pallidus the pallidum (globus pallidus) is the output side of basal ganglia. Functional neuronal circuits or loops Physiologically, the connections of basal ganglia are best understood in term of functional circuits or loops. Cortex-basal ganglia-cortex neuronal circuit, provides a negative feedback loop to control the activity of motor cortex Parts. The primary feedback loop (cortex-basal ganglia-cortex neuronal circuit) consists of two parts, i. Caudate loop plays a role in cognitive control of motor activity (thinking process of brain). Functions of basal ganglia Control of voluntary motor activity Basal ganglia control the voluntary movements, which are initiated by the motor cortex. During lesions of basal ganglia, the controlling mechanism is lost and so movements become inaccurate and awkward. Physiological studies have shown that neural discharge in basal ganglia, like cerebellum, begins well before the movements begin. The cognitive control of motor activity is executed by the basal ganglia through the feedback loops (functional neuronal circuit). As described on page 943, the caudate loop is primarily involved in the cognitive control of motor activity. In higher animals, the basal ganglia act as important co-ordinating centre of extrapyramidal system. In the absence of basal ganglia, the timing and scaling function becomes very poor. Basal ganglia subconsciously execute some movements during the performance of trained motor activities, i. Control of clutch and brake while driving (constant attention is required during initial stages; however, they are carried out subconsciously by basal ganglia as they become routine). By subconscious control of activities, the basal ganglia relieve cortex from routine acts so that cortex can be free to plan its actions. As described on page 943, the putamen feedback circuit is concerned with control of subconscious execution of some movements, during the performance of trained motor activities as listed above. Control of reflex muscular activity the basal ganglia exert inhibitory effect on spinal reflexes and regulate activity of muscles, which maintain posture. The co-ordination and integration of impulses for these activities depend upon basal ganglia. Control of muscle tone Muscle spindles and the gamma motor neurons of spinal cord (which are responsible for maintaining the tone of the muscles) are controlled by basal ganglia, especially substantia nigra. Pathway includes projection from cortical inhibitory area-striatumpallidum-substantia nigra-reticular formation-spinal cord. Role in arousal mechanism Globus pallidus and red nucleus are involved in the arousal mechanism because of their connections with reticular formation.

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It causes depolarization of the cell membrane causing openings of voltage-dependent calcium channels and an increase in intracellular calcium antibiotics for acne uk buy noroxin overnight delivery. They themselves are weak androgens but are converted to the more potent androgen testosterone in peripheral tissues. It is important to note that normal human adrenal cortex does not secrete physiologically effective amounts of testosterone and oestrogen. Synthesis the adrenal sex steroid precursors are synthesized in the zona reticularis. The 17-hydroxylated derivates of pregnenolone and progesterone are the starting points for synthesis of androgen precursors. The circumstances that lead to impairment of cortisol synthesis at any point beyond this step, cause accumulation of 17-hydroxypregnenolone and 17-hydroxyprogesterone leading to greatly increased androgen synthesis. Plasma levels, contributiontowards sex steroids, metabolism and excretion Plasma levels. However, they may be partly responsible for development of male sex organs in childhood. In prepubertal males, occurrence of such tumours produces precocious pseudopuberty. In prepubertal or in adult females, they cause development of secondary male sexual characteristics. The metabolism of androgens, in general, involves reduction of the 3-ketone group and the A-ring in the liver. These metabolites are not specific for the adrenal gland, as they also arise from the gonadal androgens. The stretching of abdominal skin due to excessive subcutaneous fat deposition causes rupture of subdermal tissues producing reddish-purple striae. Hyperglycaemia occurs due to gluconeogenesis and inhibition of peripheral utilization of glucose. Hirsutism and menstrual irregularity may occur due to increased adrenal androgens. Susceptibility to osteoporosis and bone fracture is increased due to protein depletion and bone resorption. It is important to note that marked hypernatraemia and oedema do not occur because Na+ excretion is soon normalized despite hypersecretion of aldosterone (escape phenomenon, see page 752). Adrenogenital syndrome As mentioned earlier, the androgen precursors secreted by the adrenal cortex are of little biological importance under normal circumstances. Hypoactivity of adrenal cortex Adrenocortical deficiency (insufficiency), depending upon the site of lesion, can be divided into two types: i. Characteristic features occur due to chronic deficiency of hormones secreted by all the three zones of the adrenal cortex: 1. Glucocorticoid insufficiency produces weight loss, malaise, anorexia, nausea, vomiting, weakness and diarrhoea. Oral prednisolone 20 mg in the morning and 10 mg in the evening is the drug of choice. Secondary and tertiary adrenal insufficiency Secondary and tertiary hypoaldosteronism is usually milder than primary adrenal insufficiency. Isolated cases of aldosterone deficiency have also been reported in patients with renal disorders and low circulating renin. Pseudohypoaldosteronism occurs when aldosterone secretion is normal but there is resistance to its action. Characteristic features occurring because of above pathophysiological changes are virilism and excessive body growth. In boys, adrenal hyperplasia leads to a congenital condition known as macrogenitosomia praecox. Hormones of adrenal medulla the adrenal medulla secretes catecholamines, which include epinephrine, norepinephrine and dopamine. About 80% of adrenal medullary catecholamine is epinephrine and the rest is norepinephrine. Apart from catecholamines, the adrenal medulla also contains small amounts of dynorphins, neurotensin, encephalin, somatostatin and substance P. Epinephrine circulating in the blood is almost exclusively produced in the medulla, with smaller amounts synthesized in the brain. Humans who have undergone bilateral adrenalectomy excrete practically no epinephrine in the urine, confirming the fact that the medulla is the sole source of circulating epinephrine. Norepinephrine is normally a neurotransmitter, but in select circumstances may also function as a hormone. It is widely distributed in neural tissues, which in addition to the medulla include sympathetic postganglionic fibres and central nervous system. In the brain, the concentration of norepinephrine is the highest in the hypothalamus. The norepinephrine content of tissue reflects the density of its sympathetic innervation. Except for the placenta, which is devoid of nerve fibres, norepinephrine has been demonstrated in almost all tissues. Urinary levels of norepinephrine remain within normal limits even after bilateral adrenalectomy, indicating thereby that the norepinephrine originates from extra-adrenal sources. Synthesis and storage of catecholamine hormones Synthesis of catecholamines Epinephrine and norepinephrine are synthesized in different cells. The biosynthetic pathway originates with L-tyrosine, which is derived from the diet or from the hepatic hydroxylation of L-phenylalanine by phenylalanine hydroxylase. The enzyme tyrosine hydroxylase is found only in those tissues which synthesize catecholamines. Moderate doses of dopamine results in rise in systolic blood pressure but no effect on diastolic pressure. I mportant N ote Dopamine is useful in treatment of traumatic and cardiogenic shock, because it causes renal vasoconstriction and relaxes mesangial cells and thus maintains glomerular filtration rate. This enzyme is exclusively present in the granules of these tissues which synthesize catecholamines. In about 20% of chromaffin cells, the norepinephrine is the end product and the sequence ends here with its storage. Its activity is induced by glucocorticoids (cortisol), which are found in high concentration only in the adrenal portal blood draining the adrenal cortex and supplying the medulla. The epinephrine formed in the cytoplasm is then taken back by the chromaffin granules, in which it is stored as the predominant adrenomedullary hormone. The portal circulation system subserves this action, because blood from the cortex has a high concentration of cortisol and it directly perfuses the chromaffin cells.

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Thrombosis: the incidence of thrombosis increases because the blood flow through peripheral vessels becomes sluggish antibiotic infusion buy cheap noroxin 400 mg line. These indices are calculated from the values of packed cell volume, the haemoglobin concentration and the red cell count. The white blood cells and platelets which constitute only about 1% of the volume of blood are seen as a thin white layer called buffy coat on the top of the red cell mass. It is calculated because even if the red cells are fully packed, about 2% of plasma is trapped in between the cells. It is calculated because the haematocrit is estimated from the venous blood whose haematocrit is greater than the whole body. It is calculated by dividing the amount of Hb in 1 L of blood by the red cell count in 1 L of blood. It is calculated by dividing the amount of Hb in g/dL by the volume of packed cells in 100 ml of blood and then multiplying by 100. Therefore, it has been long abandoned and is not used for any diagnostic purposes. The discoid shape and protein coating of red cells play a major role in Rouleaux formation. Rouleaux formation does not occur in normal circulation under physiological conditions, as the moving cells show little or no tendency to adhere. However, within a blood vessel, in the absence of significant flow and when the blood is taken out, the red cells tend to form Rouleaux. It should not be confused with agglutination where the cells are irreversibly clumped. Increased tendency of Rouleaux formation raises the erythrocyte sedimentation rate. A pplied A spects Abnormalities in the amount or structure of spectrin cause hereditary spherocytosis or elliptocytosis. Hereditary spherocytosis is a genetic disease transmitted as an autosomal dominant trait, which affects about 1: 5000 North Americans. Hereditary elliptocytosis is also a genetic disorder similar to hereditary spherocytosis. The red cell membrane is a semi-permeable membrane, allowing some substances to pass through and preventing some. Almost half of the lipids are bounded to the protein forming a lipoprotein complex known as elenin (Calvin). The active haemopoietic bone marrow is red in colour due to marked cellularity and hence is called red bone marrow. However, during this period, there occurs a progressive fatty replacement throughout the long bones converting red bone marrow into the so-called yellow bone marrow. In adults, exc ept ends of long bones and axial skeleton, all sternum and pelvis) and long bones in c hildren. The monophyletic theory of haemopoiesis is now widely accepted, according to which all blood cells originate from a single ancestral cell called pluripotent or multipotent stem cell. Morphologically, the progenitor cells present in the bone marrow cannot be differentiated from the stem cells, as they both lookalike. However, they can be differentiated by immunological techniques, taking advantage of the different types of molecules present on their cell membrane. Further details of erythropoiesis are discussed in this chapter and details of development of other blood cells are discussed in the relevant chapters. About 75% of the cells are immature white cells and about 25% of the cells are immature red cells, thus forming a ratio of 3:1; while in peripheral blood the ratio of white and red cells is 1:600. This vast difference is because the lifespan of red cells is far greater than that of the white cells. Control of haemopoiesis the growth of different blood cells from the stem cells is controlled and regulated by the haemopoietic growth factors, which in general are called cytokines. Cytokine is a general term used to denote the proteins released by cells that act as intercellular mediators. Pronormoblast or proerythroblast is the earliest recognizable cell of the erythroid series seen in the red bone marrow. Intermediate (polychromatic) normoblast (polychromatic erythroblast) is the next maturation stage in the erythroid series. Late (orthochromatic) normoblast (orthochromatic erythroblast) is the last nucleated cell of the erythroid series. Reticulocyte is the last stage in the formation of erythrocytes, which is why it is also called young red cell. The mature red cell has lost its nucleus, as well as the ribosomes and mitochondria. The immature cells in various stages of development are found outside (around) the blood sinusoids of the bone marrow. This is seen when the rate of erythropoiesis is very high, as occurs in haemolytic anaemia and following the treatment of deficiency anaemias. The reticulocytes in the peripheral blood are distinguished from mature red cells by a slightly basophilic hue in the cytoplasm, similar to that of an orthochromatic normoblast. Reticulocytes can be counted in the laboratory by vital staining with dyes, such as new methylene blue or brilliant cresyl blue. Till the reticulocyte stage, it takes 5 days and to become a matured red cell from the reticulocyte, it takes 2 days. In the stage of late normoblast when haemoglobin synthesis is almost completed, cytoplasm is stained by acidic dye. From the stage of late normoblast onwards, the mitosis ceases and the cell only matures. Erythropoietin is mainly (85%) produced by the juxtaglomerular apparatus of the kidney. Extrarenal sources like the liver and cells of the tissue macrophage system produce about 15% of erythropoietin, especially when hypoxia is marked. A certain basal level of the hormone is necessary for the normal rate of erythropoiesis. Therefore, whenever, there is hypoxia or a decrease in the number of red blood cells. Thus, the levels of erythropoietin vary with degree of hypoxia or the number of circulating red blood cells. This explains how polycythaemia (increased red blood cell count) is observed in hypoxic states such as in normal individuals residing at high altitude or in patients suffering from cardiopulmonary disorder. Erythropoietin increases erythropoiesis by acting at the site of erythropoiesis (It may be yolk sac, liver, spleen and bone marrow depending upon the age). Vasoconstrictor drugs produce renal hypoxia, which in turn increases erythropoietin secretion. The main general factors necessary for the process of erythropoiesis are optimum level of the hormone erythropoietin and the efficient feedback mechanism controlling the secretion of erythropoietin. All the factors (including hypoxia) affecting erythropoietin and feedback mechanism have been discussed in the regulation of erythropoiesis. Special factors which are essential for maturation of a red blood cell include vitamin B12, intrinsic factor of Castle and folic acid.

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Regulation of sex differentiation and development From the above discussion it is apparent that the normal sex differentiation and sexual development proceeds sequentially: first chromosomal sex is established at fertilization that determines gonadal differentiation antibiotic withdrawal buy cheap noroxin 400 mg online. The genital differentiation (phenotypic sex) is dependent on gonadal differentiation. It is quite obvious that Y chromosome plays key role in testicular differentiation or male development. The absence of testicular differentiation results in ovarian differentiation or female like development. Then level starts declining and by the age of puberty and afterwards its level is very low. Testosterone causes unilateral virilization of the Wolffian duct into vas efferens, epididymis, vas deferens, ejaculatory ducts and seminal vesicles by its local paracrine action (by maintaining local high concentrations). The local high concentration of testosterone is maintained because testosterone has great affinity for androgen-binding protein released from Sertoli cells. In the bound form, testosterone flows along the Wolffian duct and released from the binding protein at its site of action. Dihydrotestosterone is the most potent natural androgen and is therefore, it is necessary for virilization. Castration (removal of foetal testis) in an early embryonic stage prevents the formation of male genitalia and thus results in female-like development. However, castration of male foetus at a later stage does not affect male differentiation. Trisomy Chromosomal abnormalities usually arise during gametogenesis due to nondisjunction of sex chromosomes. The presence of extra X or Y chromosome gives rise to many syndromes; associated with abnormal development, mental retardation and abnormal growth. However, there is nothing super about them, because there is poor sexual development (infantile), scanty menstruation and mental retardation. It is the most common sex chromosome disorder, has an incidence of 1 in 500 males. The classical form is due to chromosomal nondisjunction phenomenon during gametogenesis (meiotic nondisjunction). The mosaic form occurs due to chromosomal nondisjunction after fertilization when zygote undergoes mitotic division hence also called mitotic nondisjunction. Down syndrome (also known as mongolism) is an example of autosomal chromosomal trisomy of (21 chromosome). Though there is female type of sexual development but it is characterized by scanty menstruation, amenorrhoea (no menstruation), primary infertility and amastia. The characteristic features are webbed neck (folds of skin on the side of the neck present), face is peculiar with low hair line, ptosis (drooping of eyelids), epicanthus (low set ears), micrognathia (small jaw) and co-arctation of aorta. The condition of monosomy is very lethal and leads to intrauterine death of the foetus. The disorders with these chromosomal patterns are recognized by severe mental retardation. Triploidy Sometimes gametes have diploid number of chromosomes, therefore, the zygotes so formed at the time of fertilization will have 46 + 23 = 69 chromosome. Mosacism During cell division normally the centromere splits longitudinally so that each chromatid splits longitudinally so that each chromatid becomes separate chromosome, but sometimes centromere splits transversely, thus producing two dissimilar chromosomes. Such types of chromosomes are also called isochromosomes (mosacism) and individuals with such chromosomal defects show various types of abnormalities. In this procedure, amniotic fluid is collected by inserting a needle into the amniotic cavity through anterior abdominal wall. Chorionic villus sampling: In early pregnancy, the foetal cells are obtained by a needle biopsy of chorionic villi. The most common developmental disorders due to hormonal abnormalities is pseudohermaphroditism. Pseudohermaphroditism Pseudohermaphroditism means individual having genotype (gonads) of one sex (either testes or ovaries) and genitalia of other sex. In all the above-mentioned conditions there is exposure to increased levels of androgens to the genetic female foetus. Androgen resistance means androgen levels are normal but cannot exert their full effect on the target tissue. The effect varies from mild defect to complete loss of responsiveness of receptors to androgens. This condition cannot be diagnosed until patient seeks consultation for primary amenorrhoea. The testicular and adrenal androgens are formed from pregnenolone; hence, this congenital blockade of pregnenolone formation is associated with male pseudohermaphroditism. Various other non-hormonal anomalies are also associated with male pseudohermaphroditism. Puberty and adolescence Introduction Puberty and adolescence are the phases of growth between childhood and adulthood. Since these two phases (adolescence and puberty) of growth are overlapping, hence the terms are interchangeable. Components of puberty the two principal components of puberty are: sudden spurt of physical growth and appearance of secondary sex characters. Sudden spurt of physical growth During sudden spurt of physical growth there is increase in height, muscle mass and muscle strength of an individual. The muscle mass and muscle stregnth also increases in both the sexes but the increase is far greater in boys as compared to in girls. Appearance of secondary sex characters Stages of development of secondary sex characters. The sequence of events of puberty which occurs in 3 to 5 years period have been discussed in 5 stages Table 9. The secondary sex characters are almost fully developed by the stage 5 of the puberty both in male and females. Psychological Lower Lower 5 to 10% higher than female Higher Begins Absent Girls are more emotional, shy, introvert and sexually attrac ted Behaviour is more aggressive, extrovert, c ompetitive, towards males and interested in opposite sex Hormonal changes during puberty Besides ovaries and testes, other endocrinal glands (adrenal, thyroid and anterior pituitary), also grow in size and their activity increases at the onset of puberty. In prepubertal stage, the gonadrotropin secretion is not under the check of gonadal hormones (oestrogen and testosterone). There may be possibility that different genes are involved for inhibitory effect in prepubertal stage and stimulatory effects during pubertal stage.

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Retention of salt and water bacteria images trusted 400 mg noroxin, waste metabolites and electrolytes (rise in creatinine and urea) in blood and extracellular fluid can lead to oedema and hypertension. Excessive retention of potassium (hyperkalaemia) is a serious threat to a patient with acute renal failure. Kidneys are unable to excrete hydrogen ions resulting in metabolic acidosis and that itself is a fatal condition and also aggravates hyperkalaemia. In severe cases of acute renal failure, oliguria or complete anuria occurs and the patient may die unless kidney functions are restored. Management during the oliguria phase is directed with the sole aim of keeping the patient alive with appropriate measures till diuretic phase sets in: 1. Dialysis is frequently needed in cases with oliguria, hyperkalaemia, or acidosis or fluid overload (for details see page 556). Common causes which lead on to slow, progressive nephron loss and ultimately chronic renal failure can be grouped as under: 1. Atherosclerosis of the larger renal arteries leads to hypertension and involvement of smaller arteries (interlobular arteries and efferent arterioles) results in thickening of vessel walls due to deposits of fibrinoid tissue (nephrosclerosis), eventually leading to constriction (ischemic injury). Chronic glomerulonephritis: injury to glomeruli can be caused by several diseases. Injury to renal interstitium can be caused by bacterial infection (called as pyelonephritis) or as a result of vascular, glomerular and tubular damage by poison and toxic drugs. Chronic renal failure, like acute renal failure, also occurs in a wide variety of diseases, but the end result is reduction of functional nephrons and deterioration of the kidney function to the point, where the patient must be placed on dialysis treatment or transplanted with a functional kidney for survival. Differentiating features of acute and chronic renal failure are summarized in Table 6. Measures to limit the adverse effects of uraemia and to prevent further progression include: - Control of infection, - Control of hypertension, - Control of diet as regards proteins, Na+, K+, water and Mg+ content, - Control of anaemia, - Control of metabolic acidosis and - Maintenance of electrolyte and water balance. A wide variety of disease processes including immunological disorders, toxic injuries, metabolic abnormalities, biochemical defects and vascular disorders involving glomeruli contribute to development of the nephrotic syndrome. Minimal change nephrotic syndrome is a condition in which there is no abnormality of the glomerular capillary membrane. Minimal change nephropathy is associated with loss of normal negative charges from the basement of the glomerular membrane resulting in easy passage of albumin. Normally, negative charges in the basement membrane repel negatively charged plasma protein molecules. Plasma protein concentration usually falls below 2 g/L, leading to a decrease in colloidal osmotic pressure (<10 mmHg). Therefore, a large amount of fluid leaks out from the capillaries all over the body into the tissue, causing oedema Specific tubular disorders Specific tubular disorders There are many tubular disorders due to abnormal transport of individual or groups of substances through the tubular epithelial membrane. These disorders mainly occur due to an absence of enzyme, deficient or mutations of genes encoding carrier proteins required for transport. Classification Depending upon their efficacy, the diuretic drugs can be classified as: 1. They abolish the urine concentrating ability of the nephron and, therefore, are also classified as high efficacy diuretics. Thiazide diuretics act on this cortical diluting segment and have medium efficacy, because only a small part of the filtered solute load reaches this part of the tubule. The increased concentration of osmotically active molecules cause an increase in osmotic pressure resulting in reduced water reabsorption. Increased concentration of sodium and bicarbonate in tubular fluids acts as osmotic diuresis. In addition to the above described drugs, following other substances also act as diuretics. Renal function tests Renal function tests are carried out to assess the functional capacity of the kidneys. The main aim of these tests in clinical medicine is the detection of renal impairment as early as possible in its course and the quantitative measure of change in function with time. However, it must be remembered that about two-thirds of renal tissue must be functionally damaged to show any abnormality by these tests. Analysis of urine Analysis of urine helps, of course, to a limited degree, to assess kidney functioning. In patients with suspected renal disorder, the urine analysis should be performed for volume, specific gravity, osmolality, pH, abnormal constituents, microscopic examination and bacteriological finding. Abnormalities of urine volume include polyuria, oliguria and anuria (see page 544). The normal light yellow colour of the urine is due to the presence of urochrome pigment (a compound of urobilin and urobilinogen with peptide). Normal urinary osmolality varies from 50 to 1200 mOsm/kg and specific gravity from 1. If the early morning urine sample after an overnight fast has an osmolality of >600 mOsm/kg H2O (and specific gravity > 1. Intake of high protein nonvegetarian diet shifts the urinary pH towards the acidic side, while vegetarian diet shifts it towards the alkaline side. Other causes of glomerular proteinuria are acute glomerulonephritis, pyelonephritis and toxaemia of pregnancy. Other sugars like galactose and fructose may also be present in urine in certain inborn errors of metabolism. Ketonuria refers to presence of ketone bodies (aceto-acetic acid, hydroxybutyric acid and acetone) in the urine. Ketonuria occurs in patients suffering from ketosis due to severe diabetes mellitus or prolonged starvation. Bilirubinuria refers to appearance of bilirubin in the urine in patients with elevated conjugated bilirubin levels, in hepatic or posthepatic jaundice. Its excessive excretion in the urine is one of the characteristic features of haemolytic jaundice. They have cylindrical shapes, broken ends and various shapes corresponding to the tubule in which the formed casts may be cellular or noncellular. Crystals are usually present in normal urine and thus have no pathological significance.

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It is made of interneurons that receive terminals of vestibulospinal and reticulospinal tracts bacteria reproduce buy generic noroxin 400 mg on line. It contains alpha and gamma motor neurons (that give off efferent fibres to skeletal muscles) and several internuncial neurons. It forms the grey matter around the central canal and consists mostly of neuroglial cells. Tracts of spinal cord are described along with the tracts of the brainstem (see page 908). The dorsal nerve root is formed by several rootlets which are attached to the surface of the spinal cord along a vertical groove called the posterolateral sulcus. Each dorsal nerve root is marked by a swelling called dorsal nerve root ganglion or spinal ganglion. Dorsal root ganglion is composed of T-shaped unipolar neurons with peripheral and central processes. Each rootlet just before entering the spinal cord divides into medial and lateral divisions. Ventral nerve root is formed by various rootlets which are attached to the anterolateral aspect of spinal cord opposite the ventral grey column. The ventral nerve root is composed of axons of motor neurons present in the ventral grey horn. These are upward continuation of the fibres of the medial division of the dorsal nerve roots of the same side. These tracts mediate sensations of fine touch, tactile localization and discrimination, pressure, vibration sense, sense of position and sense of movement. Autonomic functions Visceral afferent impulses in spinal cord travel through dorsal nerve roots to lateral horns of T1 to L2 and S2 to S4 spinal segments. In other words, spinal cord helps in maintaining the optimal internal environment of the body through its autonomic function. Medulla oblongata Gross anatomy the medulla oblongata is conical in shape and connects the pons above to the spinal cord below. These are composed of bundles of nerve fibres that originate in large nerve cells in the precentral gyrus of the cerebral cortex. The pyramids taper below, and have most of the descending fibres which cross over to the opposite side, forming the decussation of pyramids. The medulla oblongata forms the main pathway for the ascending and descending tracts of spinal cord. Pons Gross anatomy the pons is situated on the anterior surface of the cerebellum below the midbrain and above the medulla oblongata. Internal structure the main features of internal structure of pons can be best studied by transverse sections at the level of facial colliculus, i. The most prominent ascending tracts are the four lemnisci: medial, trigeminal, spinal and lateral. The pontine nuclei receive corticopontine fibres and their axons from the middle cerebellar peduncles which serve as a connecting pathway between cerebral cortex and cerebellum. Joining station for medial lemniscus with fibres of 5th, 7th, 9th and 10th cranial nerves. Contains pneumotaxic and apneustic centres for regulation of respiration (page 443). Midbrain Gross anatomy the midbrain is a narrow part of the brain that connects forebrain to hindbrain. Each superior colliculus acts as subcort ical centre for visual reflexes and is connected to the lateral geniculate body by a raised band known as superior brachium. Each inferior colliculus acts as subcortical centre for auditory reflexes and is connected to medial geniculate body by an elevated band known as the inferior brachium. Internal structure the main features of internal structure of midbrain can be studied by making two transverse sections-one at the rostral level through the superior colliculi, and the other at the caudal level through the inferior colliculi. Tectum refers to the part of midbrain lying behind a transverse line drawn through the cerebral aqueduct. Cerebral peduncles (right and left) constitute the part of midbrain lying in front of the line passing through the cerebral aqueduct. It consists of large mass of vertically running descending fibres from cerebral cortex which include frontopontine fibres (occupying medial one-sixth of crus), corticospinal and corticonuclear fibres (occupying intermediate two-third of crus) and temporopontine, parietopontine and occipitopontine fibres (occupying the lateral one-sixth of crus). Physiologically, the red nucleus is a part of basal ganglia and is involved in regulation of posture (see page 1062). Tracts of spinal cord and brainstem the tracts that transmit sensory impulses to the brain are termed ascending tracts, and the tracts which are responsible for transmission of motor impulses from the brain to motor neurons reaching muscles and glands are termed descending tracts. There are numerous ascending and descending tracts in the spinal cord and brainstem. Ascending tracts Ascending tracts convey impulses arising in various parts of body to different parts of the brain. Fasciculus gracilis and fasciculus cuneatus occupy the posterior white funiculus of the spinal cord, and are, therefore, often referred to as the posterior column tracts. Note, sensory decussation and position of medial lemniscus at various levels of brainstem. The fibres derived from the lowest ganglia are situated most medially, while those from the highest ganglia are most lateral. Some fibres of the medial division of the posterior nerve root descend through the posterior white funiculus in the form of fasciculus interfasciculi or comma tract of Schultze. The neurons of nucleus gracilis and nucleus cuneatus form the second-order sensory neurons. Their axons form the internal arcuate fibres which run forwards and medially to cross the midline. The fibres of medial leminiscus terminate in ventral posterolateral nucleus of thalamus. The fibres of medial lemniscus synapse with the third-order sensory neurons located in the thalamus. Axons of the third-order neurons pass through the internal capsule and corona radiata to reach the somatosensory areas of cerebral cortex. These fibres carry sensations of some components of touch, vibration and proprioception to the cortex and thus help in following functions: 1.

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The corticorubro-spinal tract thus formed may act as an alternate route of pyramidal system to exert influence on lower motor neurons antibiotic resistant germs order noroxin pills in toronto. In humans, the red nucleus is relatively small and the rubrospinal tract reaches only the upper three cervical segments of the spinal cord. Fibres to cervical segments arise from the cranioventral part, those to thoracic segments from the central part and those to lumbosacral segments from the dorsocaudal part of lateral vestibular nucleus. Vestibular nucleus receives afferents from vestibular apparatus mainly from utricles. This pathway is principally concerned with adjustment of postural muscles to linear acceleratory displacements of the body. Lateral vestibulospinal tract mainly facilitates activity of extensor muscles and inhibits the activity of flexor muscles in association with the maintenance of balance. This tract descends through the anterior funiculus (within the sulcomarginal fasciculus). This part of the vestibular nucleus receives signals from the vestibular apparatus mainly from the semicircular canals. Functionally, medial vestibulospinal tract is the donor connection of medial longitudinal fasciculus. This tract provides a reflex pathway for movements of head, neck and eyes in response to visual and auditory stimuli. Reticulospinal tracts There are two reticulospinal tracts: the medial (pontine) reticulospinal tract and lateral (medullary) reticulospinal tract. The fibres of this tract originate from the gigantocellular component of medullary reticular formation. The reticular formation of the brainstem receives input mostly from the motor cortex through the corticoreticular fibres which accompany the corticospinal tracts. Thus, the cortico-reticulospinal tracts form additional polysynaptic pathways from motor cortex to spinal cord. These tracts are concerned with control of movements and maintenance of muscle tone. The reticulospinal tracts, probably, also convey autonomic information from higher centres to the intermediate region of spinal grey matter and regulate respiration, circulation and sweating. In contrast to other tracts of extrapyramidal system, the fibres cross the midline in the lower part of segmental of the midbrain forming dorsal segmental decussation. This tract forms the motor limb of the reflex pathway for turning the head and moving the arms in response to visual, hearing or other exteroceptive stimuli. The tract fibres descend and terminate ipsilaterally in the anterior horn cells of the spinal cord. Inferior olivary nucleus receives afferent fibres from cerebral cortex, corpus striatum, red nucleus and spinal cord. It is also related to the fibres of 7th nerve (as they wind round the abducent nucleus), and to some fibres arising from the cochlear nuclei. Below this level, the fibres run along with the fibres of medial vestibulospinal tract. Along with the fibres of the medial vestibulospinal tract, the fibres of this tract make connections with ventral horn cells that innervate the muscles of neck. These arise from the cerebral cortex along with the corticospinal tracts (see page 913). These fibres descend along with corticospinal tract fibres as part of corona radiata and then pass through posterior limb of the internal capsule. In the brainstem, they cross to the opposite side at various levels and end by synapsing with cells of the cranial nerve nuclei, either direct or through interneurons. The nuclei of cranial nerves that supply skeletal muscles are functionally equivalent to ventral horn cells of the spinal cord. This pathway consists of the fibres arising in the cerebral cortex of the frontal, temporal, parietal and occipital lobes. Axons of the neurons in the pontine nuclei form the transverse fibres of the pons. These fibres cross the midline and pass into the middle cerebellar peduncle of the opposite side and reach the cerebellar cortex. This pathway forms the anatomical basis for control of cerebellar activity of cerebral cortex. Spinal shock refers to cessation of all the functions and activity below the level of the section immediately after injury. Effects depend on the site of injury; complete transection in cervical region (above C5) is usually fatal, because of cutting of connections between respiratory centre and respiratory muscles leading to paralysis of respiratory muscles. In quick transection of spinal cord, the patient feels as it has been cut into two portions, the upper portion (higher centres and mind) is unaffected, but the whole body below the level of injury is deprived of all the sensations and motor activity. Cause of stage of spinal shock (also called stage of flaccidity) is not known, but it is related to cessation of tonic neuronal discharge from upper brainstem or supraspinal pathway. In higher animals, the entire nervous system is integrated as a functional unit; therefore, damage to any part of the nervous system disturbs its smoothness of working and the functional failure is more severe. Depending upon the site of lesion, when both lower limbs are paralyzed (transection between cervical and lumbosacral enlargements), it is called paraplegia and when all the four limbs are affected (transection below C5), it is called quadriplegia. Fall in blood pressure is less marked as the section shifts more distally towards L2 segment. Absence of movements due to paralysis of muscles further retards the circulation and also the venous return producing cold and blue (cyanotic) extremities. It is important to note that after paralysis of the muscles, the body temperature becomes subnormal (as muscular contraction is a major source of heat production). When hot bottles are given to raise the body temperature, under such circumstances bed sores develop. If the patient survives the stage of spinal shock, gradually he/she gains few functions. After about 3 weeks period, depending largely upon the general health of the patient, the reflex activity begins to return to the isolated segments of spinal cord below the level of lesion. Various developments which take place, in a chronological order, in this stage are: 1. Smooth muscles regain functional activity first of all, and urinary bladder becomes automatic, i. Recovery of muscle tone is reflex in character and is produced by impulses entering the spinal cord from the muscles. No wasting of muscles is seen, because though the muscles are paralyzed for voluntary movements, they are in constant reflex activity. Recovery of reflex excitability is due to the development of denervation hypersensitivity to the mediators released by the remaining spinal excitatory endings and the growing of collaterals from existing neurons with the formation of additional excitatory ending on interneurons and motor neurons. Generally, about 6 months after the occurrence of transection, marked activity appears in the extensor arcs. This results in exaggerated extensor reflexes with the appearance of extensor spasms.