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By H. Rune. Viterbo College.

A radioimmunoassay (RIA) is a laboratory test to deter- length of long bones purchase 8 mg aceon mastercard. Excessive growth hormone secretion in an mine the concentration of hormones in blood and urine buy aceon 8 mg lowest price. Other adult does not cause further growth in bone length because the blood tests include the protein-bound iodine (PBI) test to deter- epiphyseal plates have already ossified best aceon 8mg. A urinalysis can be important in the diagnosis of several en- docrine disorders aceon 4mg low cost. A high level of glucose in a fasting patient in- dicates diabetes mellitus. A patient who has diabetes insipidus will produce a large volume (5–10 L per day) of dilute urine of low specific gravity. Certain diseases of the adrenal glands can also be detected by examining for changes in urine samples col- Simmonds’ disease: from Morris Simmonds, German physician, 1855–1925 lected over a 24-hour period. Endocrine System © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 Chapter 14 Endocrine System 481 (a) (b) (c) FIGURE 14. This disorder affects body fluids, causing edema and increasing Symptoms of this disease include polyuria (excessive urination), blood volume, hence increasing blood pressure. A person with polydipsia (consumption of large amounts of water), and severe ionic myxedema has a low metabolic rate, lethargy, sensitivity to cold, imbalances. This condition is treated with thyroxine or triiodothyronine, both of which are taken orally. Disorders of the Thyroid Endemic Goiter and Parathyroid Glands A goiter is an abnormal growth of the thyroid gland. When this is a result of inadequate dietary intake of iodine, the condition is Hypothyroidism called endemic goiter (fig. An affected child usually appears normal at birth levels of thyroxine secretion. Endemic goiter is thus associated because thyroxine is received from the mother through the pla- with hypothyroidism. The clinical symptoms of cretinism are stunted growth, thickened facial features, abnormal bone development, mental retardation, low body temperature, and general lethargy. If cre- Graves’ Disease tinism is diagnosed early, it can be successfully treated by admin- Graves’ disease, also called toxic goiter, involves growth of istering thyroxine. Endocrine System © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 482 Unit 5 Integration and Coordination FIGURE 14. Type I, or insulin-dependent diabetes mellitus, is hyperthyroidism is produced by antibodies that act like TSH and caused by destruction of the beta cells and the resulting lack of stimulate the thyroid; it is an autoimmune disease. Type II, or non-insulin-dependent diabetes quence of high levels of thyroxine secretion, the metabolic rate mellitus (which is the more common form), is caused by de- and heart rate increase, there is loss of weight, and the auto- creased tissue sensitivity to the effects of insulin, so that increas- nomic nervous system induces excessive sweating. Treatment of advanced diabetes mellitus requires adminis- tering the necessary amounts of insulin to maintain a balanced Disorders of the Parathyroid Glands carbohydrate metabolism. If excessive amounts of insulin are Surgical removal of the parathyroid glands sometimes uninten- given, the person will experience extreme nervousness and tionally occurs when the thyroid is removed because of a tumor tremors, perhaps followed by convulsion and loss of conscious- or the presence of Graves’ disease. This condition, commonly called insulin shock, can be roid hormone (PTH) causes a decrease in plasma calcium levels, treated by administering glucose intravenously. Hyperparathyroidism is usually caused by a tumor that secretes excessive amounts of Reactive Hypoglycemia PTH. This stimulates demineralization of bone, which makes the bones soft and raises the blood levels of calcium and phosphate. People who have a genetic predisposition for type II diabetes As a result of these changes, the bones are subject to deformity mellitus often first develop reactive hypoglycemia. In this condi- and fracture, and stones composed of calcium phosphate are tion, the rise in blood glucose that follows the ingestion of carbo- likely to develop in the urinary tract. This can result in weakness, changes in personality, and exophthalmos: Gk. Endocrine System © The McGraw−Hill Anatomy, Sixth Edition Coordination Companies, 2001 Chapter 14 Endocrine System 483 Disorders of the Adrenal Glands ple with chronic inflammatory diseases receive prolonged treat- ment with corticosteroids, which are given to reduce inflamma- tion and inhibit the immune response. These tumors cause hypersecretion of epinephrine and norepinephrine Usually associated with Cushing’s syndrome, this condition is whose effects are similar to those of continuous sympathetic ner- caused by hypersecretion of adrenal sex hormones, particularly vous stimulation.

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Because the three-dimensional integrity of the tissue is maintained order 8mg aceon with amex, they can also be used to study modulation of transmitter release by heteroceptors (see below) aceon 4 mg otc. One approach generic aceon 4 mg, and the first to be adopted discount 8 mg aceon amex, is to study transmitter release from slices which have been preloaded with radiolabelled transmitter. This involves comparing the effects of a test drug on the amount of transmitter released in response to a reference pulse and a second identical test pulse. As with 86 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION synaptosomes, however, it cannot be assumed that incubation of slices in a medium containing radiolabelled transmitter results in its even distribution throughout the slice. Also, the problem of continuous dilution of the radiolabelled store with newly synthesised (unlabelled)transmitter must be borne in mind. Modern sensitive chromatographic and voltammetric techniques now make it possible to estimate the release of unlabelled endogenous transmitter from slices of brain tissue (commonly the hippocampus and striatum)or spinal cord (Fig. However, whatever analytical method is used, the thickness of the slice is paramount. It is important to maintain the balance between preserving the integrity of the tissue (the thicker the slice, the better)against maintaining tissue viability by perfusion with oxygenated aCSF (the thinner the slice, the better). TECHNIQUES IN VIVO The cortical cup The cortical cup has been used for many years to monitor changes in transmitter release induced by physiological and pharmacological stimuli (Fig. In the past, it was used most commonly to study release of amino acids and acetylcholine. Measurements by HPLC and fluorescence detection after reaction of amino acids with o-phthalaldehyde: 1, aspartate; 2, glutamate; 3, asparagine; 4, serine; 5, glutamine; 6, histidine; 7, homoserine (internal standard); 8, glycine; 9, threonine; 10, arginine; 11, taurine; 12, alanine; 13, GABA; 14, tyrosine. Glutamate concentration is almost 1 pmol/ml which represents a release rate of 30 pmol/min/mg tissue NEUROTRANSMITTER RELEASE 87 Figure 4. For the rat, the overall diameter is 6±7 mm and a typical flow rate is 50 ml/min been adopted in studies of peptide and purine release as well (e. Transmitters released from neurons near the surface of the brain accumulate in the cup and their concentration in the aCSF can be used as a crude index of release rate. The importance of this technique is that it enabled, for the first time, the monitoring of transmitter release in freely moving animals. Microdialysis This is a modification of the earlier push±pull cannula which could be used in anaesthetised animals only. The microdialysis probe which has an outside diameter of about 250 mm (Fig. Solutes (including neurotransmitters)in the extracellular fluid of the brain diffuse down their concentration gradient into the probe. By taking samples of the effluent dialysate at regular intervals it is possible to monitor changes in transmitter release. This technique has been used for several years to study release of monoamines (e. Sharp, Umbers and Gartside 1997)but is now used to harvest acetylcholine and amino acids as well. Since the molecular cut-off of the dialysis membrane is in the region of 6±20 kDa (depending on the type of membrane used), this technique can also be used to measure release of some small neuropeptides (e. One advantage of microdialysis is that it enables the study of transmitter release in specific brain areas or nuclei. To ensure its correct placement, the probe is implanted, under anaesthesia, by sterotaxic surgery. Another advantage is that the probe can be anchored in place with dental cement and experiments carried out later, in conscious freely moving animals once they have recovered from the anaesthetic. Indeed, comparison of results from studies carried out on both anaesthetised and freely moving subjects has revealed drug interactions with anaesthetics that can affect transmitter release: anaesthetic-induced changes in the regulation of noradrenaline release by a2-adrenoceptors is a case in point. It is also possible to carry out long-term 88 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Figure 4. The length of membrane below the probe support can be altered (1±10 mm)to suit the size of the animal and the brain area being studied. Flow rates are normally below 2 ml/min or repeated studies on the same animals but this requires a slight modification of the technique. Unfortunately, for a variety of reasons, each microdialysis probe can be used for only a few hours and so it has to be replaced each day. However, the presence of the guide cannula makes this a relatively straightforward process that requires only light sedation of the animal.

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The downhill (energetically substances fall (glucose cheap 2 mg aceon overnight delivery, amino acids cheap aceon 2mg line, HCO3 ) buy aceon 4mg online, others rise speaking) movement of Na into the cell drives the uphill (inulin purchase 2mg aceon with amex, urea, Cl , PAH), and still others do not change transport of these solutes. By the end of the proximal convoluted tubule, acids, phosphate, and so on are reabsorbed by secondary only about one-third of the filtered Na , water, and K re- active transport. Na is also reabsorbed across the luminal main; almost all of the filtered glucose, amino acids, and cell membrane in exchange for H. The Na /H ex- HCO3 have been reabsorbed, and several solutes destined changer, an antiporter, is also a secondary active transport for excretion (PAH, inulin, urea) have been concentrated in mechanism; the downhill movement of Na into the cell the tubular fluid. This mechanism is important in the acidification of urine (see Na Reabsorption Is the Major Driving Force Chapter 25). Cl may enter the cells by way of a luminal cell membrane Cl -base (formate or oxalate) exchanger. This membrane ATPase pumps three Na out ters the cell from the lumen across the apical cell mem- of the cell and two K into the cell and splits one ATP mol- brane and is pumped out across the basolateral cell mem- ecule for each cycle of the pump. K pumped into the cell diffuses out the basolateral cell membrane mostly through brane by Na /K -ATPase. The Na and accompanying anions and water are then taken up by the blood sur- a K channel. Glucose, amino acids, and phosphate, accu- CHAPTER 23 Kidney Function 393 mulated in the cell because of active transport across the ies was previously filtered in the glomeruli. Because a pro- luminal cell membrane, exit across the basolateral cell tein-free filtrate was filtered out of the glomeruli, the [pro- membrane by way of separate, Na -independent facilitated tein] (hence, colloid osmotic pressure) of blood in the per- diffusion mechanisms. HCO3 exits together with Na by itubular capillaries is high, providing an important driving an electrogenic mechanism; the carrier transports three force for the uptake of reabsorbed fluid. Cl may leave the cell by way of an pressure in the peritubular capillaries (a pressure that op- electrically neutral K-Cl cotransporter. The bal- tablishes an osmotic gradient across the proximal tubule ance of pressures acting across peritubular capillaries favors epithelium that is the driving force for water reabsorption. Some experimental evidence indi- The Proximal Tubule Secretes Organic Ions cates that proximal tubular fluid is slightly hypoosmotic to The proximal tubule, both convoluted and straight por- plasma; since the osmolality difference is so small, it is still tions, secretes a large variety of organic anions and organic proper to consider the fluid as essentially isosmotic to cations (Table 23. Water crosses the proximal tubule epithelium nous compounds, drugs, or toxins. The organic anions are through the cells via water channels (aquaporin-1) in the mainly carboxylates and sulfonates (carboxylic and sulfonic cell membranes and between the cells (tight junctions and acids in their protonated forms). Examples of organic anions actively secreted water is uptake by the peritubular capillaries. Organic nism involves the usual Starling forces that operate across anion transport becomes saturated at high plasma organic capillary walls. Recall that blood in the peritubular capillar- anion concentrations (see Fig. Upward pointing arrows indicate transport metabolism against an electrochemical gradient (energetically uphill trans- aThis list includes only a few of the large variety of organic anions and port) and downward pointing arrows indicate downhill transport. There are two steps in the transcellular secretion of an organic an- ion or organic cation (OC ): the active (uphill) transport step oc- bCreatinine is an unusual compound because it is secreted by both or- ganic anion and cation mechanisms. The creatinine molecule bears curs in the basolateral membrane for PAH and in the luminal (brush border) membrane for the OC. There are actually more negatively charged and positively charged groups at physiological pH (it is a zwitterion), and this property may enable it to interact with transporters for these molecules than are depicted in this figure. This exchange is Descending and Ascending Limbs Differ mediated by an organic anion transporter (OAT) called in Water Permeability OAT1. The cells accumulate -ketoglutarate from metabo- Tubular fluid entering the loop of Henle is isosmotic to lism and because of cell membrane Na -dependent dicar- boxylate transporters. PAH accumulates in the cells at a plasma, but fluid leaving the loop is distinctly hypoos- high concentration and then moves downhill into the tu- motic.

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The biochemical process of visual signal The visual pigments of the photoreceptor cells convert FIGURE 4 order 4 mg aceon amex. This process is best understood as it maintains the ionic balance of a rod cell order aceon 8 mg otc, while Na enters pas- occurs in rod cells purchase aceon 8 mg without prescription. In the dark generic aceon 4mg on-line, the pigment rhodopsin (or sively through channels in the plasma membrane, causing a main- visual purple) consists of a light-trapping chromophore tained depolarization and a dark current under conditions of no called scotopsin that is chemically conjugated with 11-cis- light. Right: The amplifying cascade of reactions (which take retinal, the aldehyde form of vitamin A. When struck by place in the disk membrane of a photoreceptor) allows a single 1 light, rhodopsin undergoes a series of rapid chemical tran- activated rhodopsin molecule to control the hydrolysis of 500,000 cGMP molecules. The end-products of the light-in- and the production of a hyperpolarizing generator potential. The duced transformation are the original scotopsin and an all- release of neurotransmitter decreases during stimulation by light. Un- RH*, activated rhodopsin; TR, transducin; GC, guanylyl cyclase; der conditions of both light and dark, the all-trans form of PDE, phosphodiesterase. A large am- rear of the orbit and pass to the underside of the brain to plification of the light response takes place during the cou- the optic chiasma, where about half the fibers from each pling steps; one activated rhodopsin molecule will activate eye “cross over” to the other side. Fibers from the temporal approximately 500 transducins, each of which activates the side of the retina do not cross the midline, but travel in the hydrolysis of several thousand cGMP molecules. Fibers originating proper conditions, a rod cell can respond to a single pho- from the nasal side of the retina cross the optic chiasma and ton striking the outer segment. The processes in cone cells travel in the optic tract to the opposite side of the brain. The overall sensitivity of the goes through the optic tract to the paired lateral geniculate transduction process is also lower. Specific portions of the process of dark adaptation, which takes about 40 min- each retina are mapped to specific areas of the cortex; the utes to complete, the stores of rhodopsin are gradually built foveal and macular regions have the greatest representa- up, with a consequent increase in sensitivity (by as much as tion, while the peripheral areas have the least. Cone cells adapt more quickly than rods, but in the visual cortex detect and integrate visual information, their final sensitivity is much lower. The reverse process, such as shape, contrast, line, and intensity, into a coherent light adaptation, takes about 5 minutes. Information from the optic nerves is also sent to the Neural Network Layer. Bipolar cells, horizontal cells, suprachiasmatic nucleus of the hypothalamus, where it and amacrine cells comprise the neural network layer. Because the distances be- and pupillary reflexes; and the superior colliculus, which tween neurons here are so small, most cellular communica- tion involves the electrotonic spread of cell potentials, rather than propagated action potentials. Light stimulation of the photoreceptors produces hyperpolarization that is transmitted to the bipolar cells. Some of these cells respond with a depolarization that is excitatory to the ganglion cells, whereas other cells respond with a hyperpolarization that is inhibitory. The horizontal cells also receive input from rod and cone cells but spread information laterally, causing inhibition of the bipolar cells on which they synapse. A strongly stimulated receptor cell can, via lateral inhibitory pathways, inhibit the response of Optic neighboring cells that are less well-illuminated. This has Optic nerve chiasma the effect of increasing the apparent contrast at the edge of an image. Amacrine cells also send information laterally but synapse on ganglion cells. These cells are tonically active, sending action potentials into the optic nerve at an average rate of five per second, even when unstimulated. Input from other cells converging on the ganglion cells modifies this rate up or down. Geniculo- calcarine Many kinds of information regarding color, brightness, tract contrast, and so on are passed along the optic nerve. The output of individual photoreceptor cells is convergent on the ganglion cells.

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