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This compensation takes tory acidosis 100mg januvia with mastercard diabetic log, such chemical buffering processes in the body several days to fully develop discount 100mg januvia visa diabetes mellitus type 2 impaired skin integrity. Bicar- creases, on average, by 4 mEq/L for each 10 mm Hg rise in bonate is not a buffer for H2CO3 because the reaction PCO2 (see Table 25. This rise exceeds that seen with acute respiratory acidosis because of the renal addition of H2CO3 HCO3 HCO3 H2CO3 (28) HCO3 to the blood. One would expect a person with is simply an exchange reaction and does not affect the pH. Basic Concepts and duces a rise in PCO2 and a fall in pH and is often associated Clinical Management. These changes stimulate breathing (see a Empirically determined average changes measured in people with Chapter 22) and diminish the severity of the acidosis. CHAPTER 25 Acid-Base Balance 441 With chronic respiratory acidosis, time for renal com- chronic hyperventilation and a PCO2 of 20 mm Hg, the pensation is allowed, so blood pH (in this example, 7. The difference between the two situ- Respiratory alkalosis is most easily understood as the ations is largely a result of renal compensation. Metabolic Acidosis Results From a Gain of Alveolar hyperventilation causes respiratory alkalosis. Noncarbonic Acid or a Loss of Bicarbonate Metabolically produced CO2 is flushed out of the alveo- lar spaces more rapidly than it is added by the pul- Metabolic acidosis is an abnormal process characterized monary capillary blood. This situation causes alveolar by a gain of acid (other than H2CO3) or a loss of HCO3. Hyperventilation and respira- Either causes plasma [HCO3 ] and pH to fall. If a strong 2 tory alkalosis can be caused by voluntary effort, anxiety, acid is added to the body, the reactions direct stimulation of the medullary respiratory center by H HCO H CO H O CO (35) some abnormality (e. This increase occurs only tran- ing respiratory alkalosis more than 95% of chemical siently, however, because the body is an open system, buffering occurs within cells. PCO2 actually falls below normal because an acidic blood pH stimulates phosphates liberate H ions, which are added to the ventilation (see Fig. Many conditions can produce metabolic acidosis, in- cluding renal failure, uncontrolled diabetes mellitus, lac- With acute respiratory alkalosis, plasma [HCO3 ] falls by about 2 mEq/L for each 10 mm Hg drop in PCO2 (see tic acidosis, the ingestion of acidifying agents such as Table 25. For example, if PCO drops from 40 to 20 mm 2 NH4Cl, abnormal renal excretion of HCO3 , and diar- Hg ([CO2(d)] 0. In renal failure, the kidneys cannot excrete H fast mEq/L, and the pH will be 7. Ingested NH4Cl is converted into urea and a strong acid, HCl, in the liver. Diarrhea causes a If plasma [HCO3 ] had not changed, the pH would loss of alkaline intestinal fluids. Excess acid is chemically buffered in extracellular and intracellular fluids and bone. Although hyperventilation acidosis, roughly half the buffering occurs in cells and causes respiratory alkalosis, hyperventilation also causes bone. This action lowers blood [H2CO3] and tends to alkalinize the blood, Renal Compensation. Metabolic acidosis is ac- ratory alkalosis by excreting HCO3 in the urine, thereby, companied on average by a l. A reduced PCO2 reduces H secretion l mEq/L drop in plasma [HCO3 ] (see Table 25. As a result, some of the fil- for example, the infusion of a strong acid causes the plasma tered HCO3 is not reabsorbed. If there was no res- more alkaline, titratable acid excretion vanishes and little piratory compensation and the PCO2 did not change from its ammonia is excreted. The enhanced output of HCO3 normal value of 40 mm Hg, the pH would be 7. Chronic respiratory alkalosis is accompanied by a 4 mEq/L fall in plasma [HCO3 ] for each l0 mm Hg drop in pH 6. The consequent reduction in 2 Diabetes mellitus is a common disorder characterized by blood [H2CO3] acts to move the blood pH back toward nor- an insufficient secretion of insulin or insulin-resistance by mal.

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Answer C: The L4-L5 interspace is commonly used for a lum- in the anterior paracentral gyrus (somatomotor) and in the poste- bar puncture buy 100mg januvia with mastercard diabetes mellitus in older dogs. Because the caudal end of the spinal cord (the tains the motor representation for the face (lateral part) and the conus medullaris) may be as low as L2 in some individuals buy januvia 100 mg mastercard diabetes prevention lesson plans, levels trunk and hip (medial part). The postcentral gyrus is part of the T12-L1 to L2-L3 are not used, as this would most likely result in somatosensory cortex. The S1-S2 vertebrae are fused so there is no intervertebral space through which a needle can pass. Answer D: The M4 segments of the middle cerebral artery serve thermore, the dural sac ends at about S2. Answer B: The oculomotor nerve (III) exits from the medial as- sels that serve the pre- and postcentral gyri (hemorrhage into ap- pect of the midbrain into the interpeduncular fossa/cistern. It tra- proximately the lower two-thirds of these gyri explain the motor verses this space, courses through the lateral wall of the cavernous and sensory deficits) are the precentral branches (prerolandic), sinus to eventually enter (along with the trochlear [IV] and ab- central branches (Rolandic branches), and anterior parietal ducens [VI] nerves) the superior orbital fissure. The M2 segment serves the insular cortex, and the M3 VI, and V (the ophthalmic portion of the trigeminal nerve), along segment serves the inner surface of the frontal, parietal, and tem- 1 poral opercula. The A1 segment serves hypothalamic structures, with III, pass through the cavernous sinus. Answer D: A lesion in area 44 (the pars opercularis) that spreads will affect the lower portions of the precentral gyrus in which the 26. Answer E: The uncus is a small elevation at the rostral and me- face is represented. This will result in weakness of facial muscles, dial aspect of the parahippocampal gyrus adjacent to the crus cere- accompanied by other cranial nerve deficits. In addition to the catastrophic effect of de- hearing and vision are far separated from area 44. Also, a lesion in cerebration, herniation of the uncus may also affect corticospinal the primary auditory cortex will not result in a hearing loss in one and corticonuclear (corticobulbar) fibers in the crus cerebri and ear. The hand area of the sensory cortex and the upper extremity the root of the oculomotor nerve. None of the other areas of the area of the motor cortex are not adjacent to Brodmann area 44. Answer D: The superficial middle cerebral vein is located on the sist of the parieto-occipital and calcarine branches; the latter being surface of the cerebral hemisphere in the immediate vicinity of the located in the calcarine sulcus and a primary blood supply to the lateral sulcus and, of the choices, is the most likely candidate. M3 and M4 segments of the middle cerebral deep middle cerebral vein is located on the surface of the insular are located, respectively, on the inner aspect of the frontal, pari- lobe. The inferior sagittal sinus primarily drains the medial aspect etal, and temporal opercula and on the lateral aspect of the cere- 260 Q & A’s: A Sampling of Study and Review Questions with Explained Answers bral hemisphere. Answer E: Cerebrospinal fluid in the ventricles, and throughout located just distal to the posterior communicating–posterior cere- the subarachnoid space, appears very white in T2-weighted MRI bral intersection and gives rise to medial and lateral posterior images. Structures located in, or traversing the subarachnoid choroidal and to thalamogeniculate arteries. The A1 segment is lo- space (such as vessels or cranial nerve roots, including the oculo- cated between the internal carotid and anterior communicating motor nerve) appear grey to black against a white background. Answer B: The glomus choroideum is found in the atrium of the T1-weighted MRI images. This part of the choroid plexus is rostrally contin- obvious parts of the subarachnoid space, appear black. Changes in uous with that in the body of the lateral ventricle and continuous ventricular shape (i. The roof of the sulci, or even subarachnoid space, most likely represent a poten- third ventricle has a small portion of choroid plexus that is contin- tially serious clinical issue. Answer E: Patients who experience rupture of an intracranial aneurysm frequently complain of an intense, sudden headache 29. Answer E: Trauma is the most common cause of subarachnoid (“the most horrible headache I have ever had”). The most common cause of spontaneous (also subarachnoid space will appear white to very white on CT.

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Although both sympathetic and parasympathetic release lysyl-bradykinin 100mg januvia free shipping metabolic disease due to absolute or relative deficiency of insulin is, which causes dilation of the blood stimulation increases salivary secretion safe januvia 100mg metabolic disease risk, the responses pro- vessels supplying the salivary glands (Fig. Mineralocorticoids act mainly on the striated stimulation also increases blood flow to the salivary glands and excretory ducts. Arginine vasopressin (AVP) reduces directly, apparently via the release of the neurotransmitter the Na concentration in saliva by increasing Na reab- vasoactive intestinal peptide (VIP). Sympathetic fibers arise in the upper evoke salivary secretory responses. Postganglionic fibers leave the superior cervical ganglion and innervate the acini, ducts, GASTRIC SECRETION The major function of the stomach is storage, but it also ab- sorbs water-soluble and lipid-soluble substances (e. An important function of the stomach is to prepare the chyme for digestion in the small intestine. Chyme is the semi-fluid material produced by the gastric digestion of food. Chyme results partly from the conver- sion of large solid particles into smaller particles via the combined peristaltic movements of the stomach and con- traction of the pyloric sphincter. The propulsive, grinding, and retropulsive movements associated with antral peristal- sis are discussed in Chapter 26. A combination of the squirting of antral content into the duodenum, the grinding action of the antrum, and retropulsion provides much of the mechanical action necessary for the emulsification of di- etary fat, which plays an important role in fat digestion. Numerous Cell Types in the Stomach Contribute to Gastric Secretions The fundus of the stomach is relatively thin-walled and can be expanded with ingested food (see Fig. The main body (corpus) of the empty stomach is composed of many longitudinal folds called rugae gastricae. The stomach’s mu- The effect of parasympathetic innervation cosal lining, the glandular gastric mucosa, contains three FIGURE 27. Baltimore: glands contain mucous cells that secrete mucus and HCO3 University Park Press, 1982. The cardiac glands are located in a small area ad- jacent to the esophagus and are lined by mucus-producing columnar cells. The pyloric glands are located in a larger area adjacent to the duodenum. They contain cells similar to mu- cous neck cells but differ from cardiac and oxyntic glands in having many gastrin-producing cells called G cells. The oxyntic glands, the most abundant glands in the stomach, a) are found in the fundus and the corpus. The oxyntic glands contain parietal (oxyntic) cells, chief cells, mucous neck cells, and some endocrine cells (Fig. Surface mucous cells occupy the gastric pit (foveola); in the gland, most mucous cells are located in the neck region. The base of the oxyntic gland contains mostly chief cells, along with some parietal and endocrine cells. Mucous neck cells secrete mucus, parietal cells principally secrete hydrochloric acid (HCl) and intrinsic factor, and chief cells secrete pepsinogen. The structure of resting parietal cells is unique in that they have intracellular canaliculi as well as an abundance of mitochondria (Fig. This network consists of clefts and canals that are continuous with the lumen of the oxyn- tic gland. There is also an extensive smooth ER referred to as the tubulovesicular membranes. Hydrochloric acid is se- creted across the parietal cell microvillar membrane and FIGURE 27. In: Johnson entire surface of the gastric mucosa and the openings of the LR, Christensen J, Jackson MJ, et al. A, A nonsecret- the most striking difference is the abundance of long microvilli and ing parietal cell. The cytoplasm is filled with the paucity of the tubulovesicular system, making the mitochondria tubulovesicular membranes, and the intracellular canaliculi have be- appear more numerous. The H /K -ATPase is inhibited by characteristic of a surface mucous cell is the presence of nu- omeprazole. Omeprazole, an acid-activated prodrug that is merous mucus granules at its apex.

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Neurophysin is important in the pro- HORMONES OF THE ANTERIOR PITUITARY cessing and secretion of AVP januvia 100 mg online diabetes mellitus medications, and mutations in the neuro- The anterior pituitary secretes six protein hormones purchase januvia 100 mg mastercard diabetes insipidus nursing, all of physin portion of the AVP gene are associated with central which are small, ranging in molecular size from 4. During the passage of the glands; they are called tropic (Greek meaning “to turn to”) or granules from the Golgi apparatus to axon terminals, pro- trophic (“to nourish”) hormones. For example, ACTH main- hormones are cleaved by proteolytic enzymes to produce tains the size of certain cells in the adrenal cortex and stim- AVP or oxytocin and their associated neurophysins. Similarly, TSH AVP or oxytocin secretion, action potentials are gener- maintains the size of the cells of the thyroid follicles and ated in these cells, triggering the release of AVP or oxy- stimulates these cells to produce and secrete the thyroid tocin and neurophysin from the axon terminals. The 4 3 substances diffuse into nearby capillaries and then enter two other tropic hormones, FSH and LH, are called go- the systemic circulation. FSH stimulates the development of follicles in the ovaries and regulates the process of spermatogenesis in the testes. AVP Increases the Reabsorption of LH causes ovulation and luteinization of the ovulated Water by the Kidneys graafian follicle in the ovary of the human female and stim- Two physiological signals, a rise in the osmolality of the ulates the production of the female sex hormones estrogen blood and a decrease in blood volume, generate the CNS and progesterone by the ovary. Chemical mediators of AVP re- the Leydig cells of the testis to produce and secrete the lease include catecholamines, angiotensin II, and atrial na- male sex hormone, testosterone. The main physiological action of The two remaining anterior pituitary hormones, GH AVP is to increase water reabsorption by the collecting and PRL, are not usually thought of as tropic hormones be- ducts of the kidneys. The result is decreased water excre- cause their main target organs are not human endocrine CHAPTER 32 The Hypothalamus and the Pituitary Gland 585 TABLE 32. As discussed later, however, these two hormones zymes involved in steroidogenesis. It also maintains the have certain effects that can be regarded as “tropic. Regulation of the secretion of the gonadotropins and PRL, and descriptions of their actions, are given in greater The Structure and Synthesis of ACTH. ACTH Regulates the Function of the ACTH is synthesized in corticotrophs as part of a larger 30- kDa prohormone called proopiomelanocortin (POMC). Adrenal Cortex Enzymatic cleavage of POMC in the anterior pituitary re- The adrenal cortex produces the glucocorticoid hormones, sults in ACTH, an amino terminal protein, and -lipotropin cortisol and corticosterone, in the cells of its two inner (Fig. These its physiological function in humans has not been estab- cells also synthesize androgens or male sex hormones, with the main androgen being dehydroepiandrosterone. Glucocorticoids act on many processes, mainly by alter- ing gene transcription and, thereby, changing the protein composition of their target cells. Glucocorticoids permit metabolic adaptations during fasting, which prevent the development of hypoglycemia or low blood glucose level. They also play an essential role in the body’s response to physical and emotional stress. Other actions of glucocorti- coids include their inhibitory effect on inflammation, their ability to suppress the immune system, and their regulation of vascular responsiveness to norepinephrine. Aldosterone, the other physiologically important hor- mone made by the adrenal cortex, is produced by the cells of the outer zone of the cortex, the zona glomerulosa. Adrenocorticotropic hormone (ACTH) is the physio- logical regulator of the synthesis and secretion of gluco- corticoids by the zona fasciculata and zona reticularis. Although POMC can be cleaved into other peptides, Corticotroph such as -endorphin, only ACTH and -lipotropin are pro- duced from POMC in the human corticotroph. Proteolytic processing of POMC occurs after it is packaged into secre- tory granules. Therefore, when the corticotroph receives a signal to secrete, ACTH and -lipotropin are released into the bloodstream in a 1:1 molar ratio. POMC is also synthesized by cells of the intermediate lobe of the pituitary gland and neurons in the hypothala- mus. In the intermediate lobe, the ACTH sequence of POMC mRNA POMC is cleaved to release a small peptide, -melanocyte- cAMP PKA P proteins stimulating hormone ( -MSH), and, therefore, very little ATP ACTH is produced. As noted Gs earlier, the adult human has only a vestigial intermediate CRH POMC lobe and does not produce and secrete significant amounts of -MSH or other hormones derived from POMC.

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The avid renal reabsorption of Na observed in states of volume depletion is accompanied by a factor influencing the secretion and januvia 100 mg free shipping blood sugar goes up overnight, therefore purchase januvia 100mg without a prescription diabetes medication levemir, the excretion parallel rise in urinary H excretion. An increase in PCO increases the [K ] influence the renal excretion of H. A fall in plasma 2 2 [K ] favors the movement of K from body cells into in- formation of H from H2CO3, leading to enhanced renal terstitial fluid (or blood plasma) and a reciprocal move- H secretion and excretion—a useful compensation for any condition in which the blood contains too much H CO. In the kidney tubule cells, these 2 3 (This will be discussed later, when we consider respiratory movements lower intracellular pH and increase H se- acidosis. K depletion also stimulates ammonia synthesis 2 and, consequently, less complete reabsorption of filtered by the kidneys. The result is the complete reabsorption HCO and a loss of base in the urine (a useful compensa- of filtered HCO3 and the enhanced generation of new 3 tion for respiratory alkalosis, also discussed later). Consequently, hypokalemia (or a decrease in body K stores) leads to increased plasma [HCO3 ] Carbonic Anhydrase Activity. Hyperkalemia (or excess K in the hydrase catalyzes two key reactions in urinary acidification: body) results in the opposite changes: an increase in in- tracellular pH, decreased H secretion, incomplete reab- sorption of filtered HCO3 , and a fall in plasma [HCO3 ] (metabolic acidosis). Aldosterone stimulates the collecting ducts to secrete H by three actions: + 1) It directly stimulates the H -ATPase in collecting Increased H plasma H+-ATPase duct -intercalated cells. This response leads to hy- Na+ reabsorption Decreased pokalemia, which increases renal H secretion. K+ K+ Hyperaldosteronism results in enhanced renal H ex- cretion and an alkaline blood pH; the opposite occurs with H+ - HCO - hypoaldosteronism. The secretion of H by the kidney tubules 2 2 2 3 Increased CA and collecting ducts is gradient-limited. The collecting Carbonic anhydrase PCO2 ducts cannot lower the urine pH below 4. If more buffer base (NH3, 2– HPO4 ) is available in the urine, more H can be secreted Factors leading to increased H secretion before the limiting gradient is reached. As a consequence, the plasma [HCO ] 3 3 ders characterized by chronic metabolic acidosis, a normal falls and chronic metabolic acidosis ensues. The steady state, the tubules are able to reabsorb the filtered kidneys show inadequate H secretion by the distal HCO load more completely because the filtered load is 3 nephron, excessive excretion of HCO , or reduced excre- reduced. In type 2 RTA, the ad- 4 3 In classic type 1 (distal) RTA, the ability of the col- ministration of an NH4Cl challenge results in a urine pH be- lecting ducts to lower urine pH is impaired. This disorder may be inherited, may be associated can be caused by inadequate secretion of H (defective with several acquired conditions that result in a general- H -ATPase or H /K -ATPase) or abnormal leakiness of ized disorder of proximal tubule transport, or may result the collecting duct epithelium so that secreted H ions from the inhibition of proximal tubule carbonic anhydrase diffuse back from lumen to blood. Treatment requires the inappropriately high, titratable acid excretion is dimin- daily administration of large amounts of alkali because ished and trapping of ammonia in the urine (as NH ) is when the plasma [HCO ] is raised, excessive urinary ex- 4 3 decreased. Type 1 RTA may be the result of an inherited cretion of filtered HCO occurs. A diagnosis of this form of RTA is es- both K and H is reduced, explaining the hyperkalemia tablished by challenging the subject with a standard oral and metabolic acidosis. Hyperkalemia reduces renal am- dose of NH4Cl and measuring the urine pH for the next monia synthesis, resulting in reduced net acid excretion several hours. The underlying dis- RTA involves daily administration of modest amounts of order is a result of inadequate production of aldosterone or alkali (HCO , citrate) sufficient to cover daily metabolic impaired aldosterone action. Metabolism If H ions were passively distributed across plasma + H membranes, intracellular pH would be lower than what is - + seen in most body cells. In skeletal muscle cells, for exam- CO2 CO2 ple, we can calculate from the Nernst equation (see Chap- ter 2) and a membrane potential of 90 mV that cytosolic H+ pH should be 5. From this discrepancy, two conclusions are clear: H ions are not at equilibrium across the plasma membrane, and the cell must use active mecha- H+ nisms to extrude H. H is extruded by Na /H exchangers, which are present in nearly all body + Na cells. Five different isoforms of these exchangers (desig- nated NHE1, NHE2, etc. The cell is one H for one Na and, therefore, function in an electri- acidified by the production of H from metabolism and the in- cally neutral fashion. Active extrusion of H keeps the in- flux of H from the ECF (favored by the inside negative plasma ternal pH within narrow limits. To maintain a stable intracellular pH, the The activity of the Na /H exchanger is regulated by cell must extrude hydrogen ions at a rate matching their input. Not surprisingly, an increase in intracellu- picted), which defend against excess acid or base.

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