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Horizontal bars represent the range of red/green (R/G) mixture polychromatic plates 800 mg viagra gold for sale. Distinction between deutan and settings that each subject m atched to the standard yel ov/ light 800mg viagra gold mastercard. Depending upon the mistakes made discount viagra gold 800mg overnight delivery, a standardized score is calculated and recorded on a special chart cheap viagra gold 800mg fast delivery. The human retina contains two classes of photoreceptor Characteristic patterns for protans, deutans, and tritans are cells, rods and cones. Rods are responsible for vision in dim obtained but differentiation between protanomaly and light, while cones arc responsible for vision in bright light protanopia is difficult. Human color vision is due to the A nom aloscopy has been used widely and is based on absorption of light by three classes of cone photoreceptors: color matching. The observer views a pure yellow or red) cones, which have overlapping sensitivity curves light (589-590 nm) on one half of a screen while the other with maxima at -560, -530, and -420 nm, respectively12,1* half of the screen projects a mixture of red (650 nm ) and (Fig. The ratio the yellow light as well as the proportion of the green and of the quantal catches, which varies with wavelength of light red lights are adjusted by the subject until both hemi- (Fig. Since three classes of photoreceptors are used, frequently used instrument is the Nagel Anomaloscope. There are approximately twice as many accepted matches of mixtures of green and red light red as green cones in the human retina, with considerable against yellow is recorded, as is the mid-point of such variation in this ratio among individuals. The various opsins subtle variation in the width of the Rayleigh match range share varying degrees of homology. The red and green has also been observed among individuals classified as opsins are far more closely related to each other (96% having normal color vision. Studies during the past few amino acid identity) than to the blue and the rod pigment years have focused on correlating the genotype at the red/ rhodopsin (40-45% identity). A characteristic structural green gene locus with the color vision phenotype (see motif of this family of photopigmcnts is the heptahelical below). Despite having an identical Wavelength (nm) chromophore, these pigments have very different absorp­ tion spectra. Ihercfore, differences in spectral characteristics Я Ш of the photopigments are dictated by the interaction of figure 302 Absorption spectra of the four human photoreceptors. This is referred to as spectral tuning of the chromophore the green Normal photopigment in the Caucasian population. In addition, approximately 15% of males had Ser instead of Ala in some I 1 1 1 1 1 I > D eutan of their green pigment genes. The pigment, we hypothesized that this polymorphism may number of green pigment genes that follow the single red pigment gene account for some of the variations observed in both normal vanes (1 -6 ) in the population. Eech gene is about 15 kb in length, and these genes are separated by 25 Kb of intergenic regions. Fifty Caucasian males with (locus control region) is essential for expression of both the red and normal color vision were tested for the hypothesis that the green pigment genes in the array. The diagram includes six exons two major groups in the distribution of color matching (squares). The red and green pigment genes {including introns) and the could be explained by the above Ser/Ala polymorphism. The gene duplication event that gave rise to the red and green pigment genes of the New World primates must have w occurred after separation of the New and Old World lin­ «> я eages. It is interesting to note that despite the presence of £ only the blue and red-green pigment genes in the New ф -О World primates, a limited degree of trichromatic color E vision has been observed in females who arc heterozygotes for two alleles of the single X-chromosome-linked pig­ ment gene that encode pigments of different absorption maxima. O f great interest was the finding that one genus of New Word monkeys (Alouatta, the howler monkey) has 0. Defective colour vision Subtle variation in color perception in the red-green region associated with a m issen se mutation in the human green visual pigment of the spectrum has been observed among individuals gene. Later, duced into the population a variety of chimeric pigments Sanocki and colleagues*1,85 showed that the Ser/Ala poly­ with different absorption maxima, depending on the point morphism at position 180 of the red pigment genc underlies of fusion between the red and green pigment genes. This is somewhat analogous to pigment genes, but more importantly will convert a red pig­ the situation in the New World monkeys, who have only a ment into a green-like pigment and vice versa. The struc­ single X-chromosome-encodcd pigment genc with sev­ ture of hybrid genes observed among color-deficient eral alleles, where females heterozygous for two alleles of individuals and the absorption maxima of the encoded pig­ this genc achieve trichromacy, while males and homozy­ ments are shown in Figure 30. Note that recom­ mined the absorption spectra of recombinant human red binations in intron 5 would not result in a hybrid encoding pigments that differed in sequence by having only Scr or a new pigment, since the exon 6 of the red and green pig­ Ala at position 180. The significance of hybrid genes in Defects determining the color vision phenotype will be discussed the relatively common (8% of Caucasian males) red-green below in conjunction with expression of red and green color vision defects in which the red or the green cones arc pigment genes in the retina. These defects arc associated with loss of function of either the red or the green photopigmcnts, or with the formation of red- 8 S - <4 N green hybrid pigments with shifted absorption maxima. СЛ > t- Unequal homologous recombination, to which this locus is highly predisposed, is the driving force behind both the N orm als loss of pigment genes and the formation of hybrid pigment genes. The X-linked mode of inheritance, the lack of selec­ tion against individuals with defective color vision, and the high frequency of unequal recombination between the red and green pigment genes arc believed to be responsible 1 I I 1 I I j > for the high frequency of these defects among males. Deletion of green pigment genes results from unequal recombination or crossing-over events that occur within ngure 30. The three amino acid residues that make a major contribution to residues that contribute to the majority of the difference the spectral difference between the red and green pigment genes are (30 nm) in absorption maxima between the red and green indicated. G4-R5 represents a hybrid gene with the first four exons being G reen-S eries green and last two exons being 20 red. Deuteranopic individuals have no functional green- spectral sensitivity of the photopigments. Considerable variation in the 5 of the red opsin gene was predicted, since it contains two severity of anomalous trichromacy has been observed.

In myelinated axon discount viagra gold 800 mg amex, the speed membrane cheap 800mg viagra gold fast delivery, positive charges flow away from the site of and mode of propagation of action potential is different action potential generic viagra gold 800mg online, whereas outside the membrane discount viagra gold 800mg otc, posi- from that in unmyelinated axon. The speed of conduction of the impulse depends on This circular pattern of current flow tries to restore the two factors: resting potential of the membrane where the action 1. Myelination: Conduction velocity is more in myeli- potential was previously generated. Diameter of the axon: Conduction velocity is propor- tionate to the diameter of the fiber. In Unmyelinated Axon At the site of genesis of an action potential, large influx of positive charges into the membrane occurs, which is known as current sink. Myelin acts as an insulator and does not allow free In myelinated axon, the velocity of conduction is faster. Since positive charges flow from the site of action potential + the ionic flux occurs only at the nodes of Ranvier, the total to the adjacent area, large Na influx (as occurs dur- membrane area across which ionic balance has to be ing an action potential) does not occur in the myeli- restored is much less compared to the unmyelinated axon. The local current (the positive charges) travels like a Direction of Propagation of Action Potential graded potential and dies away 37% of its maximal In the motor neuron, the action potential is conducted strength over a distance of about 3 mm. This is called anterograde conduction of impulse: decreases its membrane potential. The axon contains a large number of voltage gated the voltage gated Na channels are present in large + Na channels that promotes in quick generation of an numbers at the nodes of Ranvier. Therefore, as soon action potential in the axonal membrane next to the as the nodal membrane gets depolarized to threshold trigger zone. Thus, in the myelinated axon, the action potential is back toward the trigger zone. Because the action potential rapidly proceeds from action potential was produced becomes refractory. Therefore, though local currents from the site of regenerated, the mode of propagation of action next action potential tend to bring the membrane toward threshold value, the membrane does not fire an action potential, as the sodium channels remain inactivated. Hence, the action potential can be conducted only in the direction away from the site of previous action potential. The action potential can spread from the point of sti- mulus in both directions along the axon, if it is initiated between trigger zone and axon terminal. Differences between Graded Potential and Action Potential From the above discussions, we note that many differ- ences exist between graded potentials and action poten- Fig. Amplitude Amplitude is proportional to the strength of the Once threshold potential is reached, amplitude remains same stimulus; small amplitude irrespective of the strength of the stimulus; large amplitude 2. Conduction Travels in a decremental fashion; amplitude gradually Conducted in an all-or-none manner; appears with the same decreases with time and distance amplitude and shape all along the axon 3. Nature Can be a depolarizing or hyperpolarizing potential Always a large depolarizing potential 5. Mechanism Due to opening of ligand-gated or leaky ion channels Due to opening of voltage-gated ion channels 6. Electrotonic potentials are local, non-propagated potentials of small magnitude, in response to a depolarizing or hyperpolarizing stimulus of lesser strength. Threshold stimulus is the lowest strength of stimulus that elicits an action potential. The stimuli less in strength than the threshold are known as subthreshold stimuli and the stimuli higher in strength than the threshold are known as suprathreshold stimuli. Chronaxie is the time required for a stimulus of double the rheobase strength to produce an action potential. In an action potential, depolarization is due to influx of sodium and repolarization is due to efflux of potassium. The speed of conduction of impulse in myelinated neuron is much faster due to presence of large number of Na+ channels at nodes of Ranvier that makes the conduction saltatory in nature. Electrotonic potentials, Local response, Strength-duration curve, Labeled diagram and ionic basis of action potential, All or none law, Refractory period, Propagation of action potential along the axon, and Saltatory conduction, are usual Short Questions in exams. Describe the degenerative (Wallerian degeneration) and regenerative changes following nerve injury. Strength and duration of the stimulus Important properties of the nerve fibers are as follows: ++ 2. Excitability Conductivity Excitability is the property by virtue of which cells or On stimulation, action potential is generated in the nerve tissues respond to changes in the external or internal fiber, which is propagated along its entire length to the environments. It is due to the disturbances in the ionic axon terminal (described in detail in the previous chapter). They respond Orthodromic and Antidromic to various forms of stimuli—mechanical, thermal, chemical Conduction or electrical. In experiment set‑up, ‘electrical’ stimulus is usually employed, because its strength and frequency An axon can conduct in either direction. If the stimulus is can be accurately controlled, nerves respond well to applied in the middle junction of axon, the action potential chemical and thermal stimuli. The production of a wave initiated in the middle of it can travel in both directions, of depolarization, and (excitation or activation) impulse due to set‑up of electronic depolarization on either side of demonstrates that a nerve has been excited. Impulses normally pass from synaptic junction to Scientists contributed the axon terminal, which is called orhtodromic con- duction. Conduction in the opposite direction is called antidro- mic conduction, seen in sensory nerve supplying the blood vessels. Summation Application of a subthreshold stimulus does not evoke an Joseph Erlanger Herbert S. However, if subthreshold stimuli are applied (1874–1965) (1888–1963) in rapid succession, they are summated and they produce the Nobel Prize in Physiology or Medicine for the year 1944 was an action potential. They worked extensively Application of continuous stimuli may decrease the excit‑ on nerve fiber types and the classification of nerve fibers is named after them ‘Erlanger-Gasser classification’). This decreases the transmission of impulse across Erlanger-Gasser Classification the neurons. If a nerve is submitted to the passage of constant strength based on their diameter and conduction velocities. Broadly of current, the site of stimulation shows decrease in fibers are classified into three categories: A, B and C. The accommodation consists of a rise in threshold of the membrane during stimulation Type A Nerve Fibers 2. Thus, nerve fiber accommodates while the nerve end‑ velocity ranging from 70 to 120 m/sec. Aα fibers supply extrafusal fibers in skeletal muscles and also carry proprioception. They have a diameter of less than 3 µm and conduc‑ are classified as myelinated and unmyelinated. Fiber types Fiber diameter (µm) Conduction velocity (m/s) Function Aα 12–20 70–120 Somatic motor and proprioception Ab 5–12 30–70 Touch-pressure Ag 3–6 15–30 Motor to muscle spindle Ad 2–5 12–30 Pain, cold and touch B < 3 3–15 Autonomic preganglionic fibers C-dorsal root fiber 0. Classification by Susceptibility Scientist contributed to Various Agents (Hypoxia, Pressure and Augustus Volney Waller showed the relation of nerve fibers to nerve cells, by describing pe- Local Anesthetics) ripheral degeneration of nerve fibers after sec- tioning the main trunk of the nerve, the central Hypoxia: Type B fibers are most susceptible to hypoxia. He is widely known for his description of Local anesthetics: Type C fibers are most susceptible to changes in neurons following injury, which is popularly known as Wallerian degeneration. First-degree injury is transient loss of function that occurs due to a mild pressure on the nerve. The tempo‑ In multiple sclerosis, patchy loss of axonal myelin occurs at rary loss of function is mainly caused by local ischemia several areas in the nervous system, resulting in decreased following obstruction to the blood flow. Second-degree injury includes nerve damage with intact cerebellar tracts, medial longitudinal fasciculus, optic endoneural tube. Third-degree injury is the severe damage to the nerve weakness, fatigue, spasticity, optic neuritis, diplopia fiber that interrupts endoneural tube. Fourth-degree injury refers to a severe damage to the nerve associated with disorganization of nerve fasciculi. In demyelinating form of Guillain‑Barre syndrome, loss of myelin causes abnormal conductions. The degenerative changes occurring in the distal segment Types Origin Fiber types of the axon are called Wallerian degeneration, named Ia Primary spindle afferent from annulospi- Aα after its discoverer August Waller. If the axon is myelinated, round Chapter 24: Properties, Classifcation and Applied Aspects of Nerve Fibers 239 fatty enlargements form all over the myelin sheath Changes in Target Structure that looks like a series of beads (Fig. The myelin Following degeneration of the nerve, the neurotransmit‑ sheath breaks down but the myelinating cells remain ter release at axonal terminal decreases. The debris created by the disintegration of the upregulation of the receptors in the target structure. Effect of stimulation: On stimulation, the distal axon can conduct an action potential upto 3 days; this ability is impaired from 3rd to 5th day, and action potential cannot be initiated after the 5th day. Changes in soma and the stump: Following injury, degenerative changes are seen in the soma and, to A some extent in the proximal stump. Endoplasmic reticulum instead of being closer to the nucleus reassembles around the periphery of the cell body. The Nissl granules gradually disintegrate and are stained weakly with basic dyes; this is known as chromatolysis (Fig. Regenerative Changes the soma tries to repair the axon by synthesizing new struc‑ tural proteins that fills up and distends the cisterns of the rough endoplasmic reticulum. Chromatolysis is reversible, if the neuron survives and re‑establishes its contact with the appropriate target. The Schwann cells that had survived the degeneration multiply and form rows along the pathway previously taken by the disintegrated distal axon. Out of the many sprouting branches, one branch finds the way through the Schwann cells and finally reinner- vates the original target structure. The Schwann cells then lay down their bilayered mem‑ diate change depicting swelling of soma, swelling of nucleus, brane to form the myelin sheath around the newly which is eccentrically placed, swelling of axon distal to the section; formed axon. The number of Nissl granules axon; (D) Regenerative changes with reduction in soma swelling, slowly reappears.

The repetitive process of tearing and healing of the musculotendinous units of the extensor tendons sets up an inflammatory process that ultimately results in pain and functional disability cheap viagra gold 800mg with visa. If not properly treated generic viagra gold 800 mg online, complete rupture of the tendinous insertion of these extensor muscles can occur (Fig cheap 800 mg viagra gold fast delivery. It has been postulated that the poor blood supply of the extensor tendons combines with the significant concentric and eccentric stresses placed on these tendons to be responsible for the evolution of this common pain syndrome cheap viagra gold 800 mg line. Subtle osseous irregularity (curved arrow) is noted at the humeral attachment of the common extensor tendon. Longitudinal ultrasound image demonstrating the classic tendinosis of the common extensor tendon observed in tennis elbow. If tennis elbow remains untreated, complete rupture of the extensor tendons can occur. Activities that require increased grip pressure and high torque twisting of the wrist have been implicated in the evolution of tennis elbow. The biomechanics responsible for the development of tennis elbow in players of racquet sports include (1) the use of an increased grip strength to support a racquet that is too long or too heavy for the player and (2) making backhand shots with a leading shoulder and elbow rather than keeping the shoulder and elbow parallel to the net. The signs and symptoms frequently observed in patients suffering from tennis elbow include pain that is localized to the lateral epicondyle with maximal point tenderness at the site of the insertion of the musculotendinous units of the extensor carpi radialis brevis and extensor carpi ulnaris muscles. The pain is constant in nature with the patient experiencing an acute exacerbation of pain with any activity that requires gripping with the hand, extending the wrist, or supinating the forearm. The patient suffering from tennis elbow may complain of significant sleep disturbance with awakening when the patient rolls over onto the affected elbow. On physical examination, there is exquisite point tenderness to palpation 379 at or just below the lateral epicondyle. Careful palpation of the area may reveal a band-like thickening of the extensor tendons and color may be noted. Grip strength is often diminished and patients will exhibit a positive tennis elbow test. The tennis elbow test is performed by stabilizing the patient’s forearm and then having the patient clench his or her fist and actively extend the wrist (Fig. The tennis elbow test is performed by stabilizing the patient’s forearm and then having the patient clench his or her fist and actively extend the wrist. Tennis elbow can be confused with radial tunnel syndrome as well as a C6–C7 radiculopathy. Tennis elbow can be distinguished from radial tunnel syndrome by determining the site of maximal tenderness to palpation. Patients suffering from tennis elbow will experience maximal tenderness to palpation over the lateral epicondyle, whereas patients suffering from radial tunnel syndrome will experience maximal tenderness to palpation distal to the lateral epicondyle over the radial nerve. Furthermore, it should be remembered that cervical radiculopathy and ulnar nerve entrapment may coexist as the so-called double crush syndrome. The double crush syndrome is seen most commonly with median nerve entrapment at the wrist or with carpal tunnel syndrome, but has been reported with the radial nerve. Electromyography and nerve conduction velocity testing are useful in helping in the differentiation of tennis elbow from cervical radiculopathy and radial tunnel syndrome. Plain radiographs, ultrasound imaging, and magnetic resonance imaging are indicated in all patients who are thought to be suffering from tennis elbow in order to confirm the diagnosis as well as to rule out occult bony pathology involving the lateral epicondyle and elbow joint and to identify occult fractures, masses, tumors or other occult pathology that may be responsible for the patient’s symptomatology (Fig 43. Based on the patient’s clinical presentation, additional testing may be indicated, including complete blood count, uric acid, sedimentation rate, and antinuclear antibody testing. The ultrasound-guided injection technique described below serves as both a diagnostic and therapeutic maneuver as ultrasound imaging can clearly delineate pathology of the extensor musculotendinous units at their insertion on the lateral epicondyle. Coronal T2-weighted fat-suppressed magnetic resonance imaging of a patient suffering from tennis 380 elbow. The solid straight arrow indicates partial tearing of the extensor tendons, and the curved arrow indicates tissue edema. With the patient in the above position, the lateral epicondyle is identified and the point of maximal tenderness is then isolated by careful palpation. A high-frequency linear ultrasound transducer is then placed in a longitudinal over the lateral epicondyle at the point of maximal tenderness (Fig. The gentle hyperechoic slope of the lateral epicondyle and the overlying common extensor tendon insertions attaching to the lateral epicondyle are then identified. The radial head will be seen distally as a hyperechoic hill-shaped structure (Fig. The area of extensor tendinous insertions on the lateral epicondyle are identified and evaluated for tendinosis which will appear as hyperechoic areas within the substance of the tendon (Figs. Careful evaluation for intrasubstance tears, spurs, calcifications, abnormal masses, and crystal deposition is also carried out (Figs. Color Doppler may help identify tendon pathology by demonstrating neovascularization of the tendinous insertion (Fig. The radial collateral ligament is then imaged to identify tears and other pathology (Figs. Dynamic scanning with valgus and varus stress on the elbow may help identify subtle abnormalities of the radial collateral ligament. Proper longitudinal position for the linear high-frequency ultrasound transducer to perform ultrasound evaluation of the elbow. Longitudinal ultrasound image demonstrating the gentle slope of the lateral epicondyle, the river-like appearing extensor tendons inserting into the lateral epicondyle, and the hill-shaped radial head. Sonogram longitudinal to the common extensor tendons show small tear of the common extensor tendon. Note enthophyte of the lateral epicondyle which is a classic finding of tennis elbow. Longitudinal ultrasound image of the common extensor tendon and its insertion into the lateral epicondyle. Note the area of hyperechoic irregularity of the insertion, which is a classic finding of tennis elbow. Longitudinal ultrasound image demonstrating tearing of the common extensor tendon with tendinopathy as evidenced by edematous tendon fibers. Transverse ultrasound image demonstrating tendinosis and tearing of the common extensor tendon in a patient presenting clinically with tennis elbow. Longitudinal scan demonstrates punctate calcifications within the origin of the common extensor tendon from the lateral epicondyle. Longitudinal ultrasound image of the lateral epicondyle demonstrating multiple calcification of the insertion of the common extensor tendon in a patient with severe tennis elbow. Transverse ultrasound image of epicondyle in a patient with tennis elbow demonstrating tearing of the common extensor tendon with significant calcification. Longitudinal scan demonstrates elongated excrudescence contiguous with the lateral epicondyle. Longitudinal ultrasound image of the elbow joint, lateral joint margin view, of patient suffering from rheumatoid arthritis demonstrating large cyst impinging on the common extensor tendon. Longitudinal ultrasound image demonstrating tearing of the common extensor tendinous insertion. Transverse ultrasound image demonstrating calcification and complex tearing of the common extensor tendon in a patient with longstanding tennis elbow. Note the anechoic tears and tendinopathy as indicated by the decreased echogenicity of the tendon. Color Doppler ultrasound of the common extensor origin in the longitudinal plane showing multiple vessels (white arrowheads) graded as 4. Lateral elbow tendinopathy: correlation of ultrasound findings with pain and functional disability. Ultrasound of the common extensor origin in the longitudinal plane showing discontinuity between the deep echogenic band of tendon fibers consistent with a lateral collateral ligament tear (arrows). Lateral elbow tendinopathy: correlation of ultrasound findings with pain and functional disability. Long-axis ultrasound image shows a high-grade partial tear of the radial collateral ligament (black arrows), associated with lateral epicondylitis, seen as a thickened and hypoechoic common extensor tendon (round- ended white arrow) with an epicondylar enthesophyte (straight white arrow). Dynamic scanning with flexion, extension, and valgus and varus stress views will be helpful in further elucidating the cause of the patient’s functional disability and pain. It should be remembered that tennis elbow and abnormalities of the radial collateral ligament can coexist with other abnormalities of the elbow. Recent advances in the ultrasound diagnosis of tennis elbow and other musculoskeletal abnormalities include the use of sonoelastography (Figs. Surgical denervation of the posterior cutaneous nerve of the forearm, which provides sensory innervation to the lateral epicondyle, as well as the ultrasound-guided injection of platelet-rich plasma have shown promise in the treatment of recalcitrant tennis elbow (Fig. Longitudinal (A) and transverse (B) grayscale ultrasound and sonoelastographic images of an asymptomatic elbow with a normal common extensor tendon in a 45-year-old patient. The ultrasound images (left) show the normal structure of the common extensor tendon (asterisks), and the sonoelastograms (right) show sonoelastographic score 4 (hard) with the red elastic spectrum. Diagnostic confidence of sonoelastography as adjunct to grayscale ultrasonography in lateral elbow tendinopathy. Longitudinal (A) and transverse (B) grayscale ultrasound and sonoelastographic images showing tendinosis of the common extensor tendon in a 48-year-old woman. The ultrasound images (left) depict areas of softening (asterisks; sonoelastographic score 2 [mostly soft]); note the green-to-yellow contrast to the surrounding red area in the sonoelastograms (right) consistent with tendinopathy. Diagnostic confidence of sonoelastography as adjunct to grayscale ultrasonography in lateral elbow tendinopathy. Longitudinal (A) and transverse (B) grayscale ultrasound and sonoelastographic images of a partial- thickness tear of the common extensor tendon in a 38-year-old female violinist. The ultrasound images (left) depict areas of softening (asterisks; sonoelastographic score 1 [soft]). Note the purple-to-green contrast to the surrounding red area in the sonoelastograms (right). Diagnostic confidence of sonoelastography as adjunct to grayscale ultrasonography in lateral elbow tendinopathy. Ultrasound-guided needle placement in a 31-year-old man with lateral epicondylitis.

Estrogen secreted from the granulosa cells help in the mining region of the Y) which is located on the distal female development quality 800 mg viagra gold. These are glycopro- system develops generic 800 mg viagra gold, and in the absence of any hormonal tein antigens present on the surface of all male cells buy generic viagra gold 800mg online. Both these antigens are involved in rejection of male the development of brain is also linked to the phenotypic tissue by the female recipients purchase viagra gold 800mg. Virilization of the genital duct and external genitalia ducts develop which gives rise to epididymis, vas defer- requires the presence of an androgen hormone recep- ens, seminal vesicles, and ejaculatory ducts. Therefore, X chromosomal gene ance of Leydig cells in the testis that secrete testoster- also contributes to the development of maleness. Note, in male, Müllerian duct degenerates, and in female, Wolffian duct degenerates. Chapter 65: Sex Diferentiation and Development, Puberty and Menopause 581 Flowchart 65. Wolffian ducts on each side, the Müllerian ducts arise, which develops into fallopian tubes and uterus. This differentiation is com- genitalia in the early part of life, which is influenced by exposures to androgens. It is proposed that the pattern of hypothalamic control of pleted by 18–20 weeks of gestation. The concentration then declines gradually to a low level the common chromosomal abnormalities are Turner’s during puberty and a lower concentration of about syndrome, Klinefelter’s syndrome, testicular feminization 2–5 ng/mL is maintained through rest of life. Note the small breast, webbed neck and short stature in a female with this syndrome; (B) Klinefelter syndrome. Thus, the syndrome usually presents with primary hypogonadism and infertility in male. It is characterized by diminished sexual development, dwarfism, and webbing of the neck in patients with no Superfemales gonadal tissue or rudimentary gonads (Fig. It results from nondisjunction of one of the X chromo- analysis for some other causes. At puberty though breasts develop normally, the growth of pubic and Klinefelter’s Syndrome axillary hairs is scanty. Though the external genitalia are of female type, there the syndrome is otherwise called seminiferous tubule is no development of uterus. The gonads are testis, with immature seminiferous nine features in an apparent male with small testes tubules. The patient is genetically female, but the presence of Though testes are present, spermatogenesis does not an extra Y chromosome causes development of the occur. They have male genitalia and at puberty male charac- This is a rare condition in which both testes and ovaries teristics develop due to adequate testosterone. But, seminiferous tubules are not properly developed the testis on the opposite side. Male external genital development occurs in genetic females exposed to androgen during 8th to 13th week of gestation. Source of androgen is usually congenital virilizing adre- Though other chromosomal abnormalities are not com- nal hyperplasia of fetus or virilizing ovarian tumor of mon, they do occur. Sometimes it may be iatrogenically-induced following Transposition of a part of one chromosome to other chro- treatment of mother with androgens or progestational mosome is possible. In a typical female pseudohermaphrodite, the indivi- of their father’s Y chromosome into the father’s X chromo- dual possesses ovaries, oviducts, but there is varying some during meiosis. They receive X chromosome from their degrees of masculine differentiation of external geni- mother and transpositioned X chromosome from father. Nondisjunction of Chromosome Nondisjunction of chromosome 21 (an autosome) is not 2. This is called trisomy 21, which is associated prevents development of female gonads, in defective with Down’s syndrome or mongolism. It is not an aberra- testicular development the internal genitalia are also tion of sex chromosome, rather an autosomal abnormality. Male pseudohermaphroditism could also be due Developmental Abnormalities to androgen resistance that usually occurs in defi- the developmental abnormalities are mainly hormonal ciency of 5α-reductase, the enzyme that forms dehy- disorders. However, nonhormonal abnormalities are also droepiandrosterone or due to defects in androgen encountered. In complete androgen resistance syndrome (testicular male patterns) and enzyme deficiencies. A pseudohermaphrodite is an individual with genetic Enzyme Deficiencies constitution and gonad of one sex, but the external geni- talia of the other sex. There are male and female pseudo- Congenital 17α-hydroxylase deficiency causes male hermaphroditisms. This also occurs in congenital normal gonadal development in accordance with their adrenal hyperplasia in which enzyme defects block the chromosomal sex, but afterward they develop heterosex- formation of pregnenolone (for details, refer to Chapter 59, ual characteristics due to opposite hormonal excess. Both these antigens are involved in rejection of male tissue by the female recipients. Virilization of the genital duct and external genitalia requires the presence of an androgen hormone receptor. Hence, instead of male gonads ovaries develop when both the sex chromosomes are X. In Viva, examiner may ask… How the genetic sex is determined in males and females, How the gonadal sex is determined in males and females, How the phenotypic (genital) sex is determined in males and females, What is called a genetic male and a genetic female? Appreciate the physiological basis of causation of precocious puberty and delayed puberty. Describe the mechanism of onset of puberty, and physiological basis of changes at puberty. Puberty is the physiological phenomenon of attainment Age and Initiating Stimulus of sexual maturity. In females, Age of Onset of Puberty reproducibility totally stops at menopause, whereas in the age of onset of puberty varies depending on various fac- males reproducibility continues. In advanced nations, it occurs between the age of 8–13 in girls Definition and 9–14 in boys. In developing nations, the age of onset of puberty is 11–16 years in girls and 13–18 years in boys. The period of transition from the non-reproductive state to the state of reproductive functions that allows Initiating Stimulus procreation is defined as puberty. During this period, the the increased secretion of adrenal androgen, called hypothalamic-pituitary-gonadal axis is activated to bring adrenarche, occurs about 1 to 2 years before the onset the gametogenic functions of the gonads to their thres- of puberty. Normally, gonads of both genders remain quiescent late the production of gonadal hormones that cause until the onset of puberty. Chapter 66: Physiology of Puberty and Menopause 585 Stages of Puberty Stage 3 Breast enlarges with enlargement of areola. Stage 4 Breast further enlarges with areola and papillae projecting Stage 1 out of it. Pubic hair becomes adult type, but covers smaller This is the preadolescent stage. Menstrual cycle starts (menarche), but irregular at of external genitalia (penis, scrotum and testes). Scrotum and testes are further some role in the determination of the time of onset of enlarged. This theory is sup- ported by the fact that experimental pulsatile injection Full adult pattern of sexual features develops. The pubertal development in females also described in five stages (by Tanner method, modified). It has been observed that body weight increases to a criti- cal level before the onset of puberty, especially in females. Stage 1 It is also observed that the onset of puberty is delayed in This is the preadolescent stage. Leptin, the hormone secreted from adipose tissue cell adrenal androgen is increased (adrenarche). This is supported by the experimental evidence that Breast development starts (thelarche). Breast paillae is injection of leptin in female mice results in precocious elevated and the diameter of areola is increased. But, the exact role of leptin in the control of puberty is hairs appear along the labia majora. Puberty may be delayed in spite of presence of normal gonads, which is called eunuchoidism in males and Abnormalities of puberty can be broadly classified into primary amenorrhea in girls. In females, ovaries become unresponsive to the puberty and precocious pseudopuberty. The functions of gonads slowly decrease finally resulting in complete cessation of menstrual cycle. Early development of secondary sexual characteristics, may be associated with premature development of Mechanism and Features gonads is known as true precocious puberty. This occurs due Mechanism of Menopause to early pubertal pattern of secretion of gonadotropin the mechanism and purpose of menopause are not clear. The female gonads progressively become unresponsive True precocious puberty occurs due to following to gonadotropins with advancing age. Hypothalamic precocity: Usually occurs due to tumor Ovaries stop secreting progesterone and estrogen in or infection of hypothalamus that causes premature appreciable amount. The uterus and vagina become gametogenesis without increase in gonadotropin atrophic. In males, though there is some decline in reproductive capacity from 5th decade of life, climacteric does not the development of secondary sexual characteristics with- occur. Testicular functions and potency persist till 8th out gametogenesis is called as precocious pseudopuberty. Thus, in males, there is no andropause (male This occurs due to exposure of immature males to abnor- menopause).

Saline with or without preservative can be used cheap 800 mg viagra gold visa, although there is some evidence that saline with benzyl alcohol is associated with reduced pain on injection [20] 800 mg viagra gold mastercard. The graduations on the syringe should be clearly visible requires extremely small injection aliquots and a more during injection diluted solution may increase spread and diffusion of the toxin following injection order viagra gold 800 mg. For injection purchase 800mg viagra gold amex, the author to draw up the solution or several syringes should be prefers a 0. Anesthesia is not required for product remains in the “dead space” of the 30-gauge botulinum toxin injections using 30-gauge needles and needle hub and cannot be used. As ball ready to gently compress the injection point 10 Botulinum Toxins 113 a b Fig. This reduces the is rare if the muscle is injected carefully with conser- incidence of ecchymosis. The thin fbers of the lateral corrugator sues can also be wiped along the extent of the muscle are easily denervated, and excessive doses will also using 2–3 gentle strokes. This maneuver allows a con- denervate frontalis in this area and may create medial trolled spread of toxin within the chosen parts of the brow heaviness. It muscle, or across a broad sheet of muscle such as fron- is useful to “visualize” the anatomy under the skin and talis. Various general techniques are used to hold the gently wipe the skin with the cotton ball from the syringe during injection (Fig. The patient is asked to frown to determine the strength of the muscles and identify the 10. These muscles are brow depressors so Horizontal forehead lines vary in prominence from their treatment usually produces a subtle brow eleva- subtle fne lines to deep furrows depending on the tion. If the patient with deep lines an injection is made perpendicularly into the belly of actively contracts the muscle during speech and ani- the muscle. Dysport 12–14 U is usually suffcient in a mation, look for dermatochalasis and consider sparing female patient, but up to 20 U may be required in a frontalis to avoid brow ptosis and hooding. To inject the medial part of corrugator, elderly patients with excess skin under the brow should the thumb or fnger is placed along the orbital rim to be treated conservatively [21]. The author directs the small 4–5 U aliquots of Dysport across the superior needle along the long axis of the muscle, depositing aspect of frontalis are suffcient to smooth lines com- 8–10 U Dysport in the medial part in a female patient. This is usu- the muscle fbers extend more superiorly toward the ally at least 1 cm from the orbital margin, but the site hairline, two rows of injections can be placed of injection is determined by the muscle itself and (Fig. Over the lateral frontalis, even less toxin should not be dictated by bony landmarks here. This injection is made perpendicularly just above the cerus is gently pinched and a perpendicular injection is made periosteum and deep to frontalis. Just 1 U the lateral frontalis is treated with low doses high in the fore- Dysport is placed close to the lateral brow to prevent frontalis head. W hen the forehead is treated, the glabella is always treated activity creating creases or “peaking” here. Diagram brow lift, a further injection is made in fbers of orbicularis oculi shows units of Dysport at each injection point at the temporal crest line near the tail of the brow depends on the morphology and strength of the muscle in this region. In patients with a very weak frontalis and almost no movement over the lateral brow, the lat- eral forehead can be avoided completely. By treating the medial frontalis only, resting tone in fbers of the lateral part increases, creating a slight lateral brow lift. W hen contraction of frontalis produces bunching of skin immediately above the lateral brow, minute doses should be placed in the area of maximal wrinkling to soften the lines and prevent “peaking” above the brow (Fig. Although brow ptosis is less likely when extremely small doses are placed immediately above Fig. A small dose of the brow, an additional injection of 3 U should be made botulinum toxin should be placed within the area marked by the in fbers of orbicularis oculi near the tail of the brow to circle to soften these lines. If no injections the X to prevent lateral brow ptosis are placed in a lateral frontalis that is strong, the “M ephisto” or “Spock” appearance is likely (Fig. The injection in the Dysport 2 U placed superiorly near the hairline and 1 U depressor part of orbicularis oculi serves two purposes. This should be corrected with a small dose lateral brow, presumably to avoid the risk of lateral brow ptosis. Secondly, its action-halo affects patients usually beneft from two rows of injections, fbers of frontalis just above the lateral brow, thus soft- with 6 U aliquots of Dysport typically required. Before ening the “peaking” or wrinkle above the tail of the treatment, asymmetries in the brow and muscle activ- brow that commonly occurs when frontalis is spared. A loss of resistance should be felt as the should raise minimally but be pulled down strongly at needle tip traverses the dermal-subcutaneous junction. The pattern of injections in the male If the needle tip remains in the dermis, excessive resis- patient differs, with more aggressive chemodenerva- tance is felt and the solution may leak onto the surface tion over lateral frontalis to maintain an aesthetically of the skin. M icrodroplets of botulinum toxin injected intrader- mally in the cheeks may improve cheek lines, but the risk of mouth asymmetry still exists [22]. Although rare, lateral injections should be made at least 1 cm from the bony orbital margin to prevent spread into the globe, resulting in extraocular muscle weakness and diplopia [23]. The fnger is placed on the rim as injec- tions are made superfcially, either in the dermis or subcutaneous plane between the visible blood vessels (Fig. As a general rule, 3–4 injections can be made, keeping the inferior injection lateral to an imag- inary line dropped vertically from the lateral canthus (Fig. Infraorbital injections can be made in the pretarsal portion of orbicularis oculi, however, to reduce lid bulging (Fig. Before treating the lower eyelid, example, 114 U Dysport is used for treatment of the frown and the snap test should be performed. Higher doses may be required, particularly in the gla- gazing forwards, gently retract the lower eyelid inferi- bellar muscles orly away from the eye. If it returns sluggishly, avoid Every effort should be made to avoid the visible veins treating this area to prevent complications. Bleeding should be stemmed immediately with external pressure for 90s to avoid ecchymosis. The brow elevates when the depressors are treated and the elevators, or parts of them, are pre- the crow’s feet or lateral orbital rhytids are commonly served. Subtle elevation of the lateral brow is treated with 3–4 injections of botulinum toxin achiev- achieved by denervating the lateral orbicularis oculi ing excellent periorbital rejuvenation (Fig. Further lat- patient should understand prior to treatment that the eral brow elevation occurs when the medial frontalis aim is to soften lateral lines, and that some “smile is treated and fbers of lateral frontalis are preserved lines” at the upper cheek will remain. Prendergast avoid unopposed action of the depressor muscles to denervate inferior most fbers of procerus that act to pull the brow inferiorly. Rarely, dilator naris is injected with 4 U under treat lateral frontalis and allow the brow to lift, Dysport to reduce the faring associated with wide rather than over treat, with a risk of brow ptosis. The tip of the nose can also be made to ele- abnormally elevated lateral brow can easily be vate in patients with active depressor septi muscles. If the tip of the nose tugs inferiorly with movement of the mouth, injecting depressor septi is appropriate. This may also elongate the of the nose, the compressor naris portion of nasalis is upper lip and should be avoided in older patients where targeted with about 6 U Dysport injected under the the upper lip is already lengthened. In these patients, skin on either side of the nose where there is maximal the injection can be made at the insertion point of the wrinkling. Frontalis over the left lateral brow is spared since Patient contracting frontalis. The muscle is relatively strong, frontalis does not produce any furrows in this area. The inferiorly placed toxin spread into the lateral lip elevators where they originate over the zygoma Fig. Pretarsal orbicularis oculi is treated by placing the needle tangential to the lid and inserting it superfcially in the mid-pupillary line. A second injection can be placed more later- ally in the lid, but medial injections close to the lacrimal appara- tus should be avoided 10. The perioral lines and folds, botulinum toxin is appropriate orbital rim is palpated with the index fnger. Chemodenervation of distribution of lines, 3–6 injections are placed, avoiding superf- muscles that act on the mouth must be precise, with cial vessels where possible small doses to avoid excessive weakness or asymme- tries. To treat “smokers’ lines,” four injections into orbicularis oris are made 5 mm above the vermilion border. Using Dysport, 2 U are placed just under the dermis, two on either side with two further injections in the lower lip if required (Fig. The patient should be warned that even with conservative doses a transient subjective feeling of weakness lasting about 1 week can occur. Additional injections can be made after at least 2 weeks if no improvement is observed and the patient reports no weakness. The most inferior injection should not be over the zygoma, where denervation of maximally (Fig. The injections should be placed the lip elevators can occur at the same depth bilaterally to avoid asymmetry. A hypertrophic pretarsal orbicularis the mid-pupillary line just below the eyelash line. By preserving fbers of lateral frontalis, and/or treating the lateral brow depressor, the brow elevates the “peachpit” chin, or cobblestone appearance muscle where it inserts into the periosteum at the bor- results from activity of dermal insertions of mentalis der of the mandible. Softening the chin is achieved with two contract when the patient is asked to pull the mouth injections into each head of the muscle. Each injection corners downward, if in doubt, place the injection more (8–10 U Dysport) is placed deeply into the body of the laterally to avoid inadvertent chemodenervation of muscle (Fig.

It has been observed that body weight increases to a criti- cal level before the onset of puberty buy generic viagra gold 800mg on-line, especially in females buy viagra gold 800 mg otc. Stage 1 It is also observed that the onset of puberty is delayed in This is the preadolescent stage cheap viagra gold 800 mg on line. Leptin generic viagra gold 800mg visa, the hormone secreted from adipose tissue cell adrenal androgen is increased (adrenarche). This is supported by the experimental evidence that Breast development starts (thelarche). Breast paillae is injection of leptin in female mice results in precocious elevated and the diameter of areola is increased. But, the exact role of leptin in the control of puberty is hairs appear along the labia majora. Puberty may be delayed in spite of presence of normal gonads, which is called eunuchoidism in males and Abnormalities of puberty can be broadly classified into primary amenorrhea in girls. In females, ovaries become unresponsive to the puberty and precocious pseudopuberty. The functions of gonads slowly decrease finally resulting in complete cessation of menstrual cycle. Early development of secondary sexual characteristics, may be associated with premature development of Mechanism and Features gonads is known as true precocious puberty. This occurs due Mechanism of Menopause to early pubertal pattern of secretion of gonadotropin the mechanism and purpose of menopause are not clear. The female gonads progressively become unresponsive True precocious puberty occurs due to following to gonadotropins with advancing age. Hypothalamic precocity: Usually occurs due to tumor Ovaries stop secreting progesterone and estrogen in or infection of hypothalamus that causes premature appreciable amount. The uterus and vagina become gametogenesis without increase in gonadotropin atrophic. In males, though there is some decline in reproductive capacity from 5th decade of life, climacteric does not the development of secondary sexual characteristics with- occur. Testicular functions and potency persist till 8th out gametogenesis is called as precocious pseudopuberty. Thus, in males, there is no andropause (male This occurs due to exposure of immature males to abnor- menopause). Features of Menopause Precocious pseudopuberty occurs due to following causes: Hot flushes (sensation of warmth spreading from trunk 1. Adrenal causes: Congenital virilizing adrenal hyper- to the face) occur frequently. Gonadal causes: Leydig cell tumor of testis in male increased, which occurs in episodes of 30–60 minutes. It occurs usually due to panhypopituitarism that Management of Menopause causes failure of maturation of gonads. It needs proper care, counseling and assurance of hormonal supplementation of estrogen is usually the spouse to make her understand and adjust to this helpful. In some cases, hot flushes and psychological symp- gen should be kept in mind while continuing estrogen toms become more problematic. Increased secretion of adrenal androgens (adrenarche) sensitizes hypothalamo-pituitary-gonadal axis for pubertal changes. Reproducibility totally stops at menopause, whereas in males reproducibility continues. Precocious puberty, Stages of puberty in boys and girls, Mechanism of onset of puberty, Mechanism, features and management of menopause may be asked as Short Questions in exam. In Viva, examiner may ask… Define puberty, What is the age of onset of puberty in boys and girls, What are the stages of puberty in boys, What are the stages of puberty in girls, Explain the mechanism of onset of puberty, What is true precocious puberty and what are its causes, What is precocious pseudopuberty and what are its causes, What is delayed puberty, What is menopause, What is the mechanism of menopause, What is the age of menopause, What are the features of menopause, How menopause can be managed. Name the different parts of male reproductive system, and give the functions of each. Name the steps of spermatogenesis and describe the mechanism and regulation of spermatogenesis. Describe the regulation of testicular functions and hypothalamo-pituitary-gonadal axis in males. The primary objective of the male reproductive system is the epididymis from where they pass into the vas deferens to produce healthy sperms capable of fertilizing the ovum. Epididymis and proximal part of vas deferens the main specialty of male reproduction is that the male store sperms. At the time of ejaculation, sperms enter into gametes are produced in millions and after puberty the the urethra in the body of prostate through the ejaculatory process of production is a continuous phenomenon. Scientist contributed the Testes Enrico Sertoli (1842–1910) an Italian physiologist and histologist was a professor of anatomy and physiology In human beings, testes are located in scrotum. During intra- at the Royal School of veterinary medicine in Milan, uterine life, testes are placed in the abdominal cavity beneath and after 1907, he worked only as a professor of phys- the posterior abdominal wall. In Milan, he founded the laboratory of to the inguinal canal during mid-pregnancy. He is remembered for his 1865 months before term, they descend further through the discovery of the eponymous Sertoli cell that provide Enrico Sertoli inguinal canal into the scrotum (Application Box 67. In female, the male reproductive system consists of testes, epididymis, the gonads (ovaries) are well preserved in the abdominal cavity. Scrotum is the sac, which keeps testis at about 2– 3°C below the mation of spermatozoa) and steroidogenesis (synthesis core body temperature and this cooler environment is highly favorable for spermatogenesis. Spermatozoa produced by testes enter Chapter 67: Male Reproductive System 589 Fig. The scrotal temperature is cooler than core body temper- ature for following reasons: 1. Anatomical location: Scrotum forms sacs that are like outpouching from the body, which has less direct transmission of the inner body temperature into it. Pampiniform plexus of the blood vessels: These plex- uses of blood vessels serve as counter-current exchanger between warm arterial blood entering the testes and cooler venous blood leaving the testes (Fig. Role of cremasteric & dartos muscles: Cremaster mus- cle is a small band of skeletal muscle present in the spermatic cord that contracts or relaxes in response to change in environmental temperature. This increases wrinkling Kulkarni, 2016; Jaypee Brothers Medical Publishers (P) Ltd. Each testis is made up of seminif- cles prevent temporary sterility in extreme weathers. Hundreds of tubules are tightly packed to Weight of each testis is about 10–15 grams, length 5 cm from a mass of coiled loops (Fig. Each loop begins and ends in a single duct called tubu- the spermatic arteries that originate directly from the aorta. Seminiferous Tubule Each seminiferous tubule has a basement membrane that separates it from the surrounding Leydig cells, the peritu- bular cells (myoid cells) and the connective tissue. Spermatogonia and Sertoli cells are located in the wall of the tubule just beneath the basement membrane (Fig. There are two principal cell types in seminiferous tubules: somatic cells (Sertoli cells) and germ cells (Fig. Sertoli Cells Sertoli cells are the sustentacular cells in seminiferous tubules, which form the major cell mass in them. Structure of Sertoli cells They are irregularly shaped cells that are extended from the basement membrane into the lumen of seminiferous Fig. Sperms are attached to the apical membrane of (1) and spermatoginia (2) lie in the periphery of the tubules, and sperms in different stages of development in the middle of the tubule (3 to 6). The interstitial cells of Leydig are present between the seminiferous tubules (7). Tubules are arranged in lobules separated by septa formed by extensions of tunica albuginea. Myoid cells are present surrounding the basal lamina of the seminiferous tubules and interstitial cells of Leydig are present in the space between the seminif- erous tubules (Fig. Thus, testis consists of seminiferous tubules and inter- stitium that mainly contains Leydig cells, connective tissues and capillaries, and few myoid cells and fibro- Fig. The proposed explanation is that when spermatocytes attempt to penetrate the barrier, the tight junction in front of them dislocate and give way for them, and immediately after the spermatocytes pass through the tight junctions the new tight junctions are concomi- tantly formed behind them. Antigenic elements are produced by germ cells dur- ing their growth and multiplication, which are capable of inducing immunological reactions in the body. Tight junctions divide Functions of Sertoli Cells tubules into two compartments: basal compartment and Sertoli cells have multiple functions. Germ cell development: Sertoli cells are critical to the basal compartment is the outer compartment that germ cell development. Sertoli cells are rich in culating substances as the capillaries are in close contact glycoproteins that nourish the germ cells. Phagocytosis: Sertoli cells phagocytose residual bod- Adluminal Compartment ies and damaged germ cells from the seminiferous Adluminal compartment is the inner compartment that tubules. Residual bodies are cytoplasmic fragments consists of primary and secondary spermatocytes and formed by excess cytoplasm resulting from transfor- spermatids. Sertoli cells synthe- Blood-Testis Barrier size transferrin, an iron-transport protein that helps in Because, the tight junctions between Sertoli cells are development of sperms. Formation of tubular fluid: They secrete fluid into the interstitial space and blood to pass through them except lumen of seminiferous tubule. Support spermiation: This is the process of detach- Leydig Cells ment of mature sperms from Sertoli cells into the Leydig cells are primary cells of steroidogenesis. Sertoli cells produce plasminogen activator that causes for- Scientist contributed mation of plasmin. During puberty, Franz Leydig receptors for these hormones on Sertoli cell increase.