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By K. Nerusul. Frostburg State University.
Ammonia metabolism is a major function of The liver is efficient in producing ketone bodies purchase sinemet 110mg with visa. The liver has an ammonia level 10 times higher mans 125mg sinemet sale, it can produce half of its equivalent weight of ketone than the plasma ammonia level discount sinemet 110 mg with amex. However buy sinemet 300mg, it lacks the ability to metabolize levels are highly neurotoxic, and a deficiency in hepatic the ketone bodies formed because it lacks the necessary en- function can lead to several distinct neurological disorders, zyme ketoacid-CoA transferase. The level of ketone bodies circulating in the blood is The liver synthesizes most of the urea in the body. The usually low, but during prolonged starvation and in dia- enzymes involved in the urea cycle are regulated by protein betes mellitus it is highly elevated, a condition known as intake. In patients with diabetes, large amounts of -hy- droxybutyric acid can make the blood pH acidic, a state called ketoacidosis. Liver cholesterol is derived from both de novo synthesis and the lipoproteins taken up by the liver. Hepatic cholesterol can be used in the formation of bile acids, biliary cholesterol secretion, the synthesis of VLDLs, and the synthesis of liver membranes. Because the absorption of biliary cholesterol and bile acids by the GI tract is incom- plete, this method of eliminating cholesterol from the body is essential and efficient. However, patients with high plasma cholesterol levels might be given additional drugs, such as statins, to lower their plasma cholesterol levels. Statins act by inhibiting enzymes that play an essential role in cholesterol synthesis. VLDLs secreted by the liver provide cholesterol to organs that need it for the synthesis of steroid hormones (e. PROTEIN AND AMINO ACID METABOLISM IN THE LIVER The liver is one of the major organs involved in synthesiz- ing nonessential amino acids from the essential amino acids. The body can synthesize all but nine of the amino The regulation of protein and amino acid FIGURE 28. CHAPTER 28 The Physiology of the Liver 521 The Liver Plays an Important Role in the Amino Synthesis and Interconversion of Amino Acids Retinyl acid ester The essential amino acids (see Table 27. The liver can form nonessential amino acids from the essential amino acids. For instance, tyrosine Rough ER can be synthesized from phenylalanine and cysteine can be Retinol synthesized from methionine. Glutamic acid and glutamine play an important role in Retinol- the biosynthesis of certain amino acids in the liver. Glu- Hydrolysis binding protein tamic acid is derived from the amination of -ketoglutarate (RBP) Retinyl by ammonia. This reaction is important because ammonia ester is used directly in the formation of the -amino group and constitutes a mechanism for shunting nitrogen from waste- ful urea-forming products. Glutamic acid can be used in the amination of other -keto acids to form the corresponding Retinol/RBP amino acids. It can also be converted to glutamine by cou- complex Chylomicron remnant pling with ammonia, a reaction catalyzed by glutamine containing retinyl ester synthetase. After urea, glutamine is the second most im- Chylo- portant metabolite of ammonia in the liver. It plays an im- micron Lipoprotein lipase portant role in the storage and transport of ammonia in the blood. Through the action of various transaminases, gluta- The metabolism of vitamin A (retinol) by mine can be used to aminate various keto acids to their cor- FIGURE 28. It also acts as an important oxida- tive substrate, and in the small intestine it is the primary substrate for providing energy. Retinol (an alcohol) is transported in chylomicrons mainly as an ester of long-chain fatty acids (see Chapter 27). When chylomicrons enter the circula- THE LIVER AS A STORAGE ORGAN tion, the triglyceride is rapidly acted on by lipoprotein li- pase; the triglyceride content of the particles is signifi- Another important role of the liver is the storage and me- cantly reduced, while the retinyl ester content remains tabolism of fat-soluble vitamins and iron.
It has also been shown that at I I very short lengths discount 300mg sinemet with mastercard, the effectiveness of some of the steps in A A A the excitation-contraction coupling process is reduced buy discount sinemet 110 mg. These include reduced calcium binding to troponin and some loss of action potential conduction in the T tubule system sinemet 110mg lowest price. Some of the consequences for the muscle as a whole are apparent when the mechanical behavior of mus- Most overlap cle is examined in more detail (see Chapter 9) cheap sinemet 300 mg on line. The overall shortening is the sum of Events of the Crossbridge Cycle the shortening of the individual sarcomeres. Drive Muscle Contraction The process of contraction involves a cyclic interaction be- tween the thick and thin filaments. The steps that comprise amount of force that can be produced, since a shorter the crossbridge cycle are attachment of thick-filament length of thin filaments interdigitates with A band thick fil- crossbridges to sites along the thin filaments, production of aments and fewer crossbridges can be attached. Thus, over a mechanical movement, crossbridge detachment from the this region of lengths, force is directly proportional to the thin filaments, and subsequent reattachment of the cross- degree of overlap. At lengths near the normal resting bridges at different sites along the thin filaments (Fig. Most of our knowledge of this process comes from studies on skeletal muscle, but the same basic steps are followed in all muscle types. Initially, the crossbridges extend at right angles from each thick filament, but they rapidly undergo a 1. An ATP molecule bound to each crossbridge supplies the energy for this step. The myosin head to which the ATP is bound is called “charged myosin” (M*ADP*Pi in step 1). When charged myosin interacts with actin, the association is represented as A*M*ADP*Pi (step 2). The force a muscle can produce depends sociated with the final hydrolysis of the bound ATP and re- on the amount of overlap between the thick and thin filaments lease of the hydrolysis products (step 3), an inorganic phos- because this determines how many crossbridges can interact ef- phate ion (P ) and ADP. An impor- tant series of these steps, called excitation-contraction coupling, takes place deep within a muscle fiber. This is the Hydrolysis subject of the remainder of this chapter; the very early Product events (communication between nerve and muscle) and the A M*ADP release and very late events (actual mechanical activity) are discussed Detachment power in Chapter 9. The SR controls the internal concentration of these ions, and changes in the internal calcium ion concentration have The events of the crossbridge cycle in profound effects on the actions of the contractile proteins FIGURE 8. Undesired contraction is prevented by a spe- new ATP molecule binds to the myosin head and is ⑦ subse- quently hydrolyzed. These cyclic reactions can continue as long cific inhibition of the interaction between actin and as the ATP supply remains and activation (via Ca2 ) is main- myosin. The long tropomyosin molecules, lying in the grooves of the en- twined actin filaments, interfere with the myosin binding tion pulls the actin filaments past the myosin filaments, a sites on the actin molecules. Following this tions increase, the ions bind to the Tn-C subunit associated movement (which results in a relative filament displace- with each tropomyosin molecule. Through the action of ment of around 10 nm), the actin-myosin binding is still Tn-I and Tn-T, calcium binding causes the tropomyosin strong and the crossbridge cannot detach; at this point in molecule to change its position slightly, uncovering the the cycle, it is termed a rigor crossbridge (A*M, step 5). The myosin detachment to occur, a new molecule of ATP must bind to (already “charged” with ATP) is allowed to interact with the myosin head (M*ATP, step 6) and undergo partial hy- actin, and the events of the crossbridge cycle take place un- drolysis to M*ADP*Pi (step 7). Once this new ATP binds, the newly recharged myosin head, momentarily not attached to the actin fila- The Switching Action of Calcium. An effective switching ment (step 1), can begin the cycle of attachment, rota- function requires the transition between the “off” and “on” tion, and detachment again. This can go on as long as the states to be rapid and to respond to relatively small changes muscle is activated, a sufficient supply of ATP is avail- in the controlling element. The calcium switch in skeletal able, and the physiological limit to shortening has not muscle satisfies these requirements well (Fig. If cellular energy stores are depleted, as curve describing the relationship between the relative force happens after death, the crossbridges cannot detach be- developed and the calcium concentration in the region of cause of the lack of ATP, and the cycle stops in an at- the myofilaments is very steep. This produces an overall stiffness 8 of 1 10 M, the interaction between actin and myosin of the muscle, which is observed as the rigor mortis that is negligible, while an increase in the calcium concentration sets in shortly after death. The crossbridge cycle obviously must be subject to con- This process is saturable, so that further increases in cal- trol by the body to produce useful and coordinated muscu- cium concentration lead to little increase in force. This control involves several cellular tal muscle, an excess of calcium ions is usually present dur- processes that differ among the various types of muscle.
The ovaries atrophy and are characterized by the presence of few discount sinemet 300 mg on line, if any 110mg sinemet mastercard, healthy follicles trusted 110 mg sinemet. One of five women in the United States will be affected by The decline in ovarian function is associated with a de- infertility cheap sinemet 300mg. A thorough understanding of female endocrinol- crease in estrogen secretion and a concomitant increase in ogy, anatomy, and physiology are critical to gaining in- LH and FSH, which is characteristic of menopausal women sights into solving this major health problem. Environmental factors, disor- LH stimulates ovarian stroma cells to continue producing ders of the central nervous system, hypothalamic disease, androstenedione. Estrone, derived almost entirely from the pituitary disorders, and ovarian abnormalities can interfere peripheral conversion of adrenal and ovarian androstene- with follicular development and/or ovulation. Be- ovulation occurs, structural, pathological, and/or endocrine cause the ratio of estrogens to androgens decreases, some problems associated with the oviduct and/or uterus can pre- women exhibit hirsutism, which results from androgen ex- vent fertilization, impede the transport or implantation of cess. The lack of estrogen causes atrophic changes in the the embryo, and, ultimately, interfere with the establish- breasts and reproductive tract, accompanied by vaginal ment or maintenance of pregnancy. Similar changes in the urinary tract may give rise to urinary distur- Amenorrhea Is Caused by Endocrine Disruption bances. Menstrual cycle disorders can be divided into two cate- Hot flashes, as a result of the loss of vasomotor tone, os- gories: amenorrhea, the absence of menstruation, and teoporosis, and an increased risk of cardiovascular disease are oligomenorrhea, infrequent or irregular menstruation. Hot flashes are associated with episodic in- mary amenorrhea is a condition in which menstruation has creases in upper body and skin temperature, peripheral va- never occurred. They occur concurrently with LH called gonadal dysgenesis, a congenital abnormality caused pulses but are not caused by the gonadotropins because they by a nondisjunction of one of the X chromosomes, resulting are evident in hypophysectomized women. Because the two X chro- sisting of episodes of sudden warmth and sweating, reflect mosomes are necessary for normal ovarian development, temporary disturbances in the hypothalamic thermoregula- women with this condition have rudimentary gonads and do tory centers, which are somehow linked to the GnRH pulse not have a normal puberty. Estrogen an- Other abnormalities include short stature, a webbed neck, a tagonizes the effects of PTH on bone but enhances its ef- coarctation of the aorta, and renal disorders. Another congenital form of primary amenorrhea is hy- Estrogen also promotes the intestinal absorption of calcium pogonadotropism with anosmia, similar to Kallmann’s syn- TABLE 38. Patients do not progress ies reveal that exogenous TRH increases the secretion of through normal puberty and have low and nonpulsatile LH PRL. However, they can have normal stature, press ovulation is not entirely clear. The disorder is caused by a that PRL may inhibit GnRH release, reduce LH secretion in failure of olfactory lobe development and GnRH defi- response to GnRH stimulation, and act directly at the level ciency. Primary amenorrhea can also be caused by a con- of the ovary by inhibiting the action of LH and FSH on fol- genital malformation of reproductive tract structures origi- licle development. Secondary amenorrhea is the cessation of menstrua- Anorexia nervosa, a severe behavioral disorder associated tion for longer than 6 months. Pregnancy, lactation, and with the lack of food intake, is characterized by extreme menopause are common physiological causes of second- malnutrition and endocrine changes secondary to psycho- ary amenorrhea. Other causes are premature ovarian fail- logical and nutritional disturbances. About 30% of patients ure, polycystic ovarian syndrome, hyperprolactinemia, develop amenorrhea that is not alleviated by weight gain. Strenuous exercise, especially by competitive athletes and Premature ovarian failure is characterized by amenor- dancers, frequently causes menstrual irregularities. Two rhea, low estrogen levels, and high gonadotropin (LH and main factors are thought to be responsible: a low level of FSH) levels before age 40. The symptoms are similar to body fat, and the effect of stress itself through endorphins those of menopause, including hot flashes and an in- that are known to inhibit the secretion of LH. The etiology is variable, in- of stress, such as relocation, college examinations, general cluding chromosomal abnormalities; lesions resulting illness, and job-related pressures, have been known to in- from irradiation, chemotherapy, or viral infections; and duce some forms of oligomenorrhea. Polycystic ovarian syndrome, also called Stein-Leven- Female Infertility Is Caused by thal syndrome, is a heterogeneous group of disorders char- Endocrine Malfunction and Abnormalities acterized by amenorrhea or anovulatory bleeding, an ele- vated LH/FSH ratio, high androgen levels, hirsutism, and in the Reproductive Tract obesity. Although the etiology is unknown, the syndrome The diagnosis and treatment of amenorrhea present a chal- may be initiated by excessive adrenal androgen production, lenging problem.
Almost fully dissociated generic sinemet 300mg online, lactic acid causes stimulating the respiratory center and feedback modulation metabolic acidosis 125 mg sinemet amex. During exercise sinemet 300 mg otc, healthy lungs re- from the lung discount sinemet 110mg otc, respiratory muscles, chest wall mechanore- spond to lactic acidosis by further increasing ventilation, ceptors, and carotid body chemoreceptors. Through a range of exercise Unchanged by Training levels, the pH effects of lactic acid are fully compensated The effects of training on the pulmonary system are mini- by the respiratory system; however, eventually in the mal. Lung diffusing capacity, lung mechanics, and even hardest work—near-exhaustion—ventilatory compensa- lung volumes change little, if at all, with training. The wide- tion becomes only partial, and both pH and arterial PCO2 spread assumption that training improves vital capacity is may fall well below resting values (see Table 30. Tidal false; even exercise designed specifically to increase inspi- volume continues to increase until pulmonary stretch re- ratory muscle strength elevates vital capacity by only 3%. The demands placed on respiratory muscles increase their Frequency increases at high tidal volume produce the re- endurance, an adaptation that may reduce the sensation of mainder of the ventilatory volume increases. Nonetheless, the primary respiratory Hyperventilation relative to carbon dioxide produc- changes with training are secondary to lower lactate pro- tion in heavy exercise helps maintain arterial oxygena- duction that reduces ventilatory demands at previously tion. The blood returned to the lungs during exercise is heavy absolute work levels. Because the pulmonary arterial PO2 is re- In Lung Disease, Respiratory Limitations May Be duced in exercise, blood shunted past ventilated areas can Evidenced by Shortness of Breath or Decreased profoundly depress systemic arterial oxygen content. Oxygen Content of Arterial Blood Other than having a diminished oxygen content, pul- monary arterial blood flow (cardiac output) rises during Any compromise of lung or chest wall function is much exercise. In compensation, ventilation rises faster than more apparent during exercise than at rest. One hallmark of cardiac output: The ventilation-perfusion ratio of the lung disease is dyspnea (difficult or labored breathing) dur- lung rises from near 1 at rest to greater than 4 with stren- ing exertion, when this exertion previously was unprob- uous exercise (see Table 30. Restrictive lung diseases limit tidal volume, reduc- nearly constant arterial PO2 with acute exercise, although ing the ventilatory reserve volumes and exercise capacity. This in- Obstructive lung diseases increase the work of breathing, crease shows that, despite the increase in the ventilation- exaggerating dyspnea and limiting work output. Lung dis- perfusion ratio, areas of relative pulmonary underventila- eases that compromise oxygen diffusion from alveolus to tion and, possibly, some mild diffusion limitation exist blood exaggerate exercise-induced widening of the alveo- even in highly trained, healthy individuals. Second, Normally, the respiratory system does not limit exercise their primary complaint is usually shortness of breath, or tolerance. In fact, patients with chronic obstructive pul- tion with oxygen, which averages 98% at rest, is main- monary disease often first seek medical evaluation be- tained at or near 98% in even the most strenuous dy- cause of dyspnea experienced during such routine activi- namic or isometric exercise. In healthy people, includes the ability to augment ventilation more than car- exhaustion is rarely associated solely with dyspnea. In em- diac output; the resulting rise in the ventilation-perfusion physematous patients, exercise-induced dyspnea results, ratio counterbalances the falling oxygen content of in part, from respiratory muscle fatigue exacerbated by di- mixed venous blood. Third, in emphysematous patients, arterial oxygen exercise occur long before ceilings are imposed by either saturation will characteristically fall steeply and progres- skeletal muscle oxidative capacity or by the ability of the sively with increasing exercise, sometimes reaching dan- cardiovascular system to deliver oxygen to exercising gerously low levels. These limitations are manifest during a stress test oxygenate blood at rest is compounded during exercise by on the basis of three primary measurements. First, patients increased pulmonary blood flow, and by increased exer- with ventilatory limitations typically cease exercise at rela- cise oxygen extraction that more fully desaturates blood tively low heart rate, indicating that exhaustion is due to returning to the lungs. The signs and symptoms of a respiratory limitation to Although strenuous exercise can reduce intramuscular pH exercise include exercise cessation with low maximal heart to values as low as 6. The best correlate prospects of training-based rehabilitation are modest, al- of fatigue in healthy individuals is ADP accumulation in the though locomotor muscle-based adaptations can reduce face of normal or slightly reduced ATP, such that the lactate production and ventilatory demands in exercise. Because the complete oxida- Specific training of respiratory muscles to increase their tion of glucose, glycogen, or free fatty acids to carbon diox- strength and endurance is of minimal benefit to patients ide and water is the major source of energy in prolonged with compromised lung function. In healthy individuals, cate- of disorders exemplified by the various muscular dystro- cholamine release from the adrenal medulla and sympa- phies. In these illnesses, the loss of active muscle mass as a thetic nerves dilates the airways during exercise.
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