Kimberly A. Selzman, MD, MPH

• Assistant Professor of Medicine
• Director of Electrophysiology
• George E. Wahlen Department of Veterans Affairs Medical Center
• Salt Lake City, Utah

The law states that if the volume and mass of a gas remain constant allergy forecast kalamazoo buy discount benadryl 25 mg on-line, the absolute temperature of the gas is directly proportional to the pressure of the gas allergy shots charlotte nc purchase benadryl from india. Or allergy testing johns hopkins order generic benadryl on line, stated another way kenalog allergy shots side effects order benadryl toronto, if the volume and mass stay the same as the temperature increases allergy symptoms hair dye safe benadryl 25mg, the pressure increases allergy forecast long island order benadryl 25 mg line, and vice versa. The easiest practical example of this is that if a can of soda is heated it may explode. As the temperature rises, the pressure inside the can increases until the can is no longer able to contain it. These laws can be combined into the combined gas law and used to compare the same gas under two sets of conditions. The equation for the combined gas law is: where: P1 = Initial pressure V1 = Initial volume T1 = Initial temperature P2 = Final pressure V2 = Final volume T2 = Final temperature the laws discussed up to this point allow for calculations involving varying pressure, volume, and temperature with a constant mass of gas. The inclusion and quantification of other variables, such as mass, expands the application of these laws. The molecular weight of carbon dioxide is 44 g/mol, and 1 g/mol of carbon dioxide has a mass of 44. This law allows for the calculation of four independent properties of a gas-pressure, volume, mass, and temperature- under any conditions. The ideal gas law states that the condition of an amount of gas is determined by its pressure, volume, and temperature. The first step in quantifying how much oxygen crosses the membrane is calculating the concentration gradient, which is expressed as the partial pressure of inspired oxygen in the alveolus and the partial pressure of oxygen in the capillary blood. Because water vapor is added to the gas being inspired, the partial pressure of the water vapor must be deducted from the atmospheric pressure. As the inspired oxygen moves deeper into the respiratory tract, it becomes diluted with the air already in the lungs and further reduced by oxygen diffusing out of the lungs into the capillaries. The difference between the partial pressure of oxygen and carbon dioxide in the alveolus and the partial pressure of oxygen and carbon dioxide in the pulmonary capillaries is called the diffusion gradient. As it moves into the lungs, the air is humidified and warmed and mixes with gases in the tracheobronchial tree. At the alveolar level, the oxygen level is 100 mm Hg and the carbon dioxide level is 40 mm Hg. The difference in oxygen pressures in the alveolus (100 mm Hg) and the pulmonary capillaries (40 mm Hg) is the diffusion gradient. Oxygen moves from an area of higher concentration in the alveolus to an area of lower concentration in the blood. The higher levels of carbon dioxide in the pulmonary capillaries (45 mm Hg) move to areas of lower concentration in the alveolus (40 mm Hg). Description the Alveolar Gas Equation Note that the calculation just outlined denotes the partial pressure of oxygen in the alveoli under ideal normal conditions. Because it is not possible to collect gases directly from the alveoli, the alveolar gas equation is used to calculate the alveolar oxygen partial pressure from parameters that are measurable. This equation includes the ratio of the amount of carbon dioxide diffusion into the alveoli from the capillaries to the amount of oxygen diffusion out of the alveoli into the capillaries. Because mixed venous blood moves through the pulmonary capillary system at a speed of 0. In a healthy lung, this decrease in potential diffusion time does not impact the transfer of these gases. In addition, the increased speed of the blood moving through the pulmonary capillary system means that more blood is passing through the system in a shorter period of time, resulting in a greater uptake of oxygen into the additional amount of blood, as well as an increased release of carbon dioxide into the alveoli. The increased cardiac output also results in the recruitment of nonperfused capillaries, thereby providing even more surface area for the diffusion of oxygen into the blood and carbon dioxide into the alveolus to occur. Normal, healthy lungs are able to compensate for this increased blood velocity and complete the diffusing process. Other lung diseases, such as emphysema, are associated with a decrease in the surface areas of the alveolus. The inhalation of nitrous oxide (N2O) can be used to demonstrate perfusion-limited gas flow and measure pulmonary blood flow. Inhaled N2O diffuses quickly into the pulmonary capillary blood, and the blood quickly reaches its capacity to absorb this gas. Pulmonary function laboratories utilize exercise testing with an N2O rebreathing method to assess perfusion-limited gas flow and measure recirculation time, cardiac output, and pulmonary blood flow. Summary Knowledge of the gas laws is necessary to understand the interactions of respiratory gases. Among the most important principles to remember is that gases always move from a level of low concentration to a level of high concentration until they reach equilibrium. Case Study A 46-year-old male is seen in the respiratory clinic for a preoperative diagnostic workup. Heart sounds S1 and S2 were heard upon auscultation in all four cardiac areas with normal rhythm. His abdomen is soft and symmetrical with hypoactive bowel sounds present in all four quadrants. What additional testing or calculation will be needed to complete this calculation The movement of molecules, atoms, or particles from an area of high concentration to an area of low concentration is known as: a. Which law states that the rate of diffusion across a permeable membrane is directly proportional to the concentration gradient on either side of the membrane Identify the components and locations of the ventilation control centers of the brain. Describe the physiology supporting ventilation as both an involuntary and a voluntary process. Discuss the locations and functions of the central chemoreceptors, the peripheral chemoreceptors, and the lung receptors. The body responds to physiologic changes by altering the ventilatory pattern without the individual being aware of the need for these changes. When an individual voluntarily takes a deep breath or holds their breath, he or she consciously directs his or her body to do so. Should the individual stop breathing or attempt to hold their breath for a prolonged period of time, neural control mechanisms will take over and reinitiate ventilation. Three primary components are involved in the neurologic control of ventilation: the receptors, the control centers of the brain, and the effectors. Disruptions or alterations in the function of these three components can stop or alter ventilation. Description Ventilation Control Centers of the Brain the normal periodic in-and-out rhythm of ventilation originates in two portions of the brain stem: the medulla oblongata and the pons. The medulla oblongata is located in the lower portion of the brain stem, and the pons is located in the upper part of the brain stem. Description the Medulla Oblongata Inside the medulla oblongata are three groups of neurons that play a role in regulating ventilation. This area of the medulla oblongata acts as a processing center for information from the body. This results in progressively stronger contractions of the muscles and a smooth uniform inspiratory effort. Approximately 2 seconds from the onset of inspiration, the inhibitory impulses overtake the impulses of the inspiratory ramp signal. During the early portion of exhalation, the inspiratory impulses fire at a low rate to slow exhalation and create a smooth expiratory pattern. The nucleus ambiguus innervates the muscles of the soft palate, pharynx, larynx, and upper esophagus via the glossopharyngeal, vagus, and spinal accessory nerves. The nucleus retroambigualis contains inspiratory neurons that innervate the diaphragm via the phrenic nerve and the intercostal nerves that stimulate the intercostal muscles. The muscle actions from these impulses are active only during exercise or in instances of rapid or stressed breathing. The nucleus retroambigualis also contains expiratory neurons that transmit impulses to the internal intercostal muscles and the abdominal muscles via the intercostal nerves to assist in exhalation. The Pons Located in the upper portion of the brain stem, the pons also has two ventilation control centers called the pontine centers. The apneustic center is located in the lower portion of the pons immediately above the medulla oblongata. These signals are regulated by the pneumotaxic center, which is located in the upper portion of the pons. The pneumotaxic center regulates the stopping phase of the inspiratory ramp and is believed to "fine-tune" the ventilatory rhythm by its ability to shorten the inspiratory cycle. If the pneumotaxic center sends a strong signal, the inspiratory time is shortened, the tidal volume decreases, and the respiratory rate increases. If the pneumotaxic center sends a weak signal, the inspiratory time is lengthened, the tidal volume increases, and the respiratory rate decreases. If an injury to the pneumotaxic center occurs, the apneustic center takes over and regulates the ventilatory cycle. When this occurs, the impulse from the pneumotaxic center to slow and then halt the inspiratory ramp is lacking, resulting in a condition called apneustic breathing or apneusis. This ventilation pattern is characterized as a prolonged inspiration followed by a shortened exhalation. Several clinical conditions are associated with apneustic breathing, including stroke, cerebral edema, poliomyelitis, and medications that affect the neuronal signaling, resulting in drug-induced respiratory depression. If an injury occurs to both the pneumotaxic and the apneustic centers, the respiratory rate will become irregular. Table 10-1 provides a summary of breathing patterns that may be seen in the clinical context. Apneustic breathing Deep gasping inspiration followed by a short exhalation that occurs when both the pneumotaxic center and the apneustic center are injured. Irregular rate and depth of ventilation that may be accompanied by periods of apnea. Ataxic breathing Biot breathing (also known as cluster breathing) Rapid, shallow breathing followed by periods of apnea. Cheyne-Stokes breathing Progressively deeper and faster breathing followed by a gradual decrease in breathing. Kussmaul breathing Deep, rapid breathing in which the rate remains constant and apnea does not occur. The Cerebral Cortex the cerebral cortex is the portion of the brain that can override involuntary ventilation. However, the capability of the cerebral cortex to completely override the brain stem is limited. Voluntary hyperventilation, as well as hypoventilation, is possible; however, the brain stem will override these impulses if physiologic conditions become life-threatening. For example, when an individual holds his or her breath for an extended time, the partial pressure of dissolved oxygen in the arterial blood drops, causing his or her arterial blood oxygen level (PaO2) to fall and his or her arterial blood carbon dioxide level (PacO2) to rise. Via other pathways in the brain, the inspiratory muscles are stimulated to contract and trigger inspiration. It is the elevation in carbon dioxide levels in the blood that is the primary stimulus for breathing.

The sub-brow dermis is sutured to the superior periosteum of forehead and then the wound is closed in layers allergy shots and xanax buy discount benadryl line. Delayed onset facial paralysis is usually due to edema rather than actual transection allergy medicine in japan purchase benadryl once a day. When facial paralysis is immediate after surgery allergy testing naturopath order benadryl paypal, one has to ensure nerve integrity allergy medicine high blood pressure order cheapest benadryl. Liaising with the chief surgeon about the confidence of nerve continuity is important allergy treatment reviews cheap benadryl 25 mg visa. If the nerve is found to be transected allergy symptoms and treatment cheap benadryl online mastercard, a primary tensionless repair or interpositional graft should be executed without delay. Although a short course of oral steroids does not carry significant side-effects, it has been shown to have no additional benefits regarding the rate and extent of facial nerve recovery. The potential for spontaneous recovery must be weighed against the risk of having a poor outcome after a long period of denervation. Traditionally, reinnervation procedures are indicated when there is no spontaneous recovery by 1 year. Thus, it is important to identify early the group of patients who will likely fail the watchful-waiting policy of 1 year. The endoscopic approach has the advantage of hiding the scar in the hairline and direct endoscopic visualization of the neurovascular bundles. However, it is not applicable to patients with frontal bossing and a receding hairline, nor in patients requiring a large amount of brow elevation. Incisions of 2 cm are made at the midline or paramedian, lateral, and temporal areas. Supraorbital and supratrochlear neurovascular bundles are identified and preserved under endoscopic guidance. Forehead scalp with eyebrows is lifted and secured onto the cranium with the Bonebridge device or Endotines. Midface When the muscle is no longer salvageable, muscle transfer is the only option for smile restoration. A onestage free latissimus dorsi transfer is possible in a certain group of patients. However, patients have to undergo an intensive postoperative physiotherapy program to achieve volitional smiling. A simultaneous sling with the tensor fascia lata can be done to better achieve resting symmetry. Eyelids Lagophthalmos can be corrected by placing a weight or a spring onto the upper eyelid. With the higher density, platinum is preferred over gold, with less prominence and lower extrusion rate. For patients who would prefer a more synchronized blinking, a palpebral spring is an alternative. However, placing a palpebral spring requires more experience and the surgical revision rate is high. For lower lid laxity or ectropion, lateral tarsal strip procedure with or without medial canthal plication is usually adequate. In addition, dermatochalasis is not uncommon in a patient with facial paralysis, especially in the older population. A prospective, randomized trial for use of prednisolone in patients with facial nerve paralysis after parotidectomy. Predictors and timing of recovery in patients with immediate facial nerve dysfunction after parotidectomy. Facial nerve grading instruments: systematic review of the literature and suggestion for uniformity. Emerging vs timetested methods of facial grading among patients with facial paralysis. Effect of postoperative brachytherapy and external beam radiotherapy on functional outcomes of immediate facial nerve repair after radical parotidectomy. Effect of axonal load on the functional and aesthetic outcomes of the cross-facial nerve graft procedure for facial reanimation. Correlation between facial nerve axonal load and age and its relevance to facial reanimation. Cross-facial nerve grafting for facial reanimation: effect on normal hemiface motion. The motor nerve to the masseter muscle: an anatomic and histomorphometric study to facilitate its use in facial reanimation. The subzygomatic triangle: rapid, minimally invasive identification of the masseteric nerve for facial reanimation. Management of Synkinesis Synkinesis is the abnormal contraction of muscle during volitional movement of another muscle. It is believed to be due to an aberrant regeneration of axon during recovery or hyperexcitability of facial nucleus. Switching to another isoform may help and permanent myectomy or selective neurectomy is necessary. Spontaneity of smile after facial paralysis rehabilitation when using a non-facial donor nerve. Functional and anatomical basis for brain plasticity in facial palsy rehabilitation using the masseteric nerve. Irreversible muscle contracture after functioning free muscle transplantation using the ipsilateral facial nerve for reinnervation. A comprehensive approach to longstanding facial paralysis based on lengthening temporalis myoplasty. Temporalis muscle tendon unit transfer for smile restoration after facial paralysis. A model for early prediction of facial nerve recovery after vestibular schwannoma surgery. Fifteen-year survey of onestage latissimus dorsi muscle transfer for treatment of longstanding facial paralysis. Botulinum toxin injection of both sides of the face to treat post-paralytic facial synkinesis. About 80% of salivary gland lymphomas occur in the parotid glands, and about 20% are found in the submandibular and minor salivary glands. Bone marrow biopsy, echocardiogram, and endoscopy of the other extranodal sites are performed in selected cases. Treatment options include surgery, radiotherapy, chemotherapy, and immunotherapy, as single modality or in combination. For low-grade lymphoma, radiotherapy is usually given with biopsy alone, or positive margin after excision, and has been shown to improve disease-free survival. Other rare subtypes (below 5%) include small lymphocytic lymphoma and Hodgkin lymphoma. There is no pathognomonic imaging finding of lymphomas affecting the salivary glands. Once the diagnosis of lymphoma is made, patients should be referred to oncologists for staging work-up and further management. Primary mucosaassociated lymphoid tissue lymphoma of the salivary glands: a multicenter rare cancer network study. Primary salivary gland lymphoma among Japanese: a clinicopathological study of 30 cases. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue of the salivary glands: a population-based study from 1994 to 2009. Hypoechoic mass with cystic spaces, which could be found in other salivary gland tumors, such as Warthin tumor. Radiation sterilizes areas of residual microscopic disease, areas of tumor spillage, and areas of peripheral nerve involvement (named or unnamed) while sparing the patient the additional morbidity and disfigurement of a more comprehensive surgical resection. Radiotherapy in the Recurrent Setting for Malignant and Benign Tumors the overall prognosis of recurrent salivary gland cancer is poor due to the fact that salvage options may be limited because of the infiltrative pattern of disease and the proximity to critical structures. Long-term toxicities were uncommon, and included soft tissue necrosis, which seemed correlated with cumulative dose. In addition, patients who develop local recurrences even after salvage surgery are at a significantly higher risk of experiencing additional recurrences. Of course, these patients may have the option of undergoing additional surgical resection, but this may not be sufficient to control disease. Chemotherapy and Chemoradiation the efficacy of chemotherapy either alone or with radiation is not well understood. Chemotherapy alone may be employed in the treatment of unresectable, recurrent, or metastatic disease. Despite the lack of response, chemotherapy alone has demonstrated improvement of tumor-associated symptoms and may have a role in palliation. At present, the study is closed to accrual and the anticipated primary completion is 2023. The unique physical properties of particles allow for very a favorable dose distribution, specifically in regards to exit dose, dose to adjacent structures, and conformality. Proton Therapy Proton therapy is the most frequently used particle therapy in the United States. The advantage of protons, as with all other forms of particle therapy, is the deposition of maximal dose near the end of its range in tissue forming a Bragg peak. Beyond the Bragg peak, there is no further dose deposited in the case of protons, which eliminates excess dose to normal tissue distal to the target. The proximity of major salivary glands to critical structures, such as the mandible, base of skull, temporal lobe, auditory canal optic structures, and cochlea make protons an appealing choice. The barriers to treatment with protons include markedly higher costs of construction, maintenance, and treatment compared with Photon Therapy Versus Particle Therapy Photons remain the mainstay of radiation treatment for the majority of salivary gland tumors and are readily available in most academic and community centers. Protons can be used in conjunction with photons to aid in boosting areas that would otherwise be limited due to normal tissue dose constraints. As with protons, the cost of constructing, maintaining, and treating patients along with a lack of clinical evidence demonstrating a true advantage relative to photons, has hampered widespread adoption. There is some evidence that suggests neutron therapy may be superior for controlling slow-growing tumors such as salivary gland tumors, soft tissue sarcomas, and prostate adenocarcinomas. Neutron therapy remains an experimental form of treatment confined to large academic medical centers at this time. Therefore, its ability to kill malignant cells is less dependent upon oxygen concentration. Like other forms of particle therapy, it is quite costly, with only a small number of centers offering treatment worldwide. Surgeons should be encouraged to place clips to help identify the resection cavity. The Role of Elective Nodal Radiation Retrospective data suggest that nodal failure rates depend on the size of the primary tumor and/or differentiation or discovery of intraparotid nodal metastasis. Major salivary glands are well lateralized and therefore ipsilateral neck treatment is appropriate. Nodal failure rates overall for well-lateralized tumors (2 cm from midline) is ~2%. Broadly, the involvement of a named nerve should be treated to the base of the skull, especially for all adenoid cystic carcinomas. Carcinoma of the major salivary glands treated by surgery or surgery plus postoperative radiotherapy. Treatment results of major salivary gland cancer by surgery with or without postoperative radiation therapy. The role of postoperative radiation therapy in carcinoma ex-pleomorphic adenoma of the parotid gland. A matched-pair analysis of the role of combined surgery and postoperative radiotherapy. Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Role for postoperative radiation therapy in adenoid cystic carcinoma of the head and neck. The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation. Long-term outcome of patients treated by radiation therapy alone for salivary gland carcinomas. Recurrent salivary gland carcinomas treated by surgery with or without intraoperative radiation therapy. Fractionated stereotactic radiotherapy as reirradiation for locally recurrent head and neck cancer. An analysis of the treatment of 114 patients with recurrent pleomorphic adenomas of the parotid gland. Systemic therapy in the management of metastatic or advanced salivary gland cancers. Postoperative radiation therapy for salivary gland malignancies: risk stratification for the impact of concurrent chemotherapy. Proton beam or photon-based intensity-modulated radiation therapy in treating patients with salivary gland cancer, skin cancer, or melanoma. Stereotactic or hypofractionated radiation therapy in treating patients with recurrent or metastatic head and neck cancer.

They also have a reduced excretion of urinary citrate (also due to the more severe metabolic acidosis) mould allergy treatment uk generic benadryl 25 mg otc, which predisposes them to nephrolithiasis and nephrocalcinosis allergy treatment vitamin c purchase benadryl toronto. Treatment is aimed at correcting the serum K + first allergy desensitization generic benadryl 25 mg with visa, then the metabolic acidosis allergy zapper safe benadryl 25 mg. Correction of the metabolic acidosis also controls the nephrocalcinosis in most patients allergy testing anchorage cheap benadryl on line. In some patients hypokalemia is very severe requiring large dose of potassium replacement therapy allergy symptoms from tree pollen purchase benadryl now. It occurs when collecting duct K+ secretion is impaired by either a tubular defect itself, or hypoaldosteronism, which may be secondary to aldosterone deficiency or resistance to its actions. Aldosterone resistance may result from drugs like triamterene, amiloride, aldosterone receptor antagonists (spironolactone and eplerenone), trimethoprim, and pentamidine, as well as tubulointerstitial nephritis, distal chloride shunt and pseudohypoaldosteronism. Dietary modifications may be sufficient, but occasionally chronic use of Kayexalate (sodium polystyrene sulfonate) is needed. Sometimes, administration of mineralocorticoid replacement (in patients with hypoaldosteronism) such as fludrocortisone 0. Close monitoring of such patients is recommended to avoid development of volume expansion and worsening of hypertension. Its pathogenesis involves both the generation of metabolic alkalosis and the maintenance of metabolic alkalosis. The generation of bicarbonate results from the loss of hydrogen ions and/or the addition of new bicarbonate. Impaired renal capacity to secrete excess bicarbonate or enhanced kidneys reclamation of bicarbonate are important factors to maintain metabolic alkalosis. Gastrointestinal losses as in vomiting, nasogastric suctioning, and loss of intestinal secretions, which may occur in villous adenoma and laxative abuse with factitious diarrhea. Renal losses result from the combined effect of increased distal sodium delivery to the distal nephron and increased mineralocorticoid activity because of volume contraction, This, in turn, leads to enhanced sodium reabsorption by the sodium channels in the principle cells and creation of more electronegative charge in the lumen of the collecting duct, which facilitates the secretion of both hydrogen ions and potassium into the lumen. Primary mineralocorticoid hyperactivity as in primary hyperaldosteronism: the primary increase in mineralocorticoids leads to both increased sodium reabsorption in the sodium channels and increased distal sodium delivery to the distal tubules because of volume expansion. A similar mechanism is present in Liddle syndrome, which results from a gain of function of the sodium channel in the collecting duct. Intracellular shifts of hydrogen ions: this usually occurs in patients with hypokalemia. In this condition, as potassium moves out of the cells to replete the extracellular stores, hydrogen ions move into the cells to maintain electroneutrality. Posthypercapnic alkalosis: the compensatory response in respiratory acidosis is the increase in plasma bicarbonate to mitigate the decrease in blood pH. Rapid correction of chronic respiratory acidosis as in mechanical ventilation leads to the development of metabolic alkalosis. Alkali administration: Administration of alkali that exceeds the ability of the kidneys to excrete excess bicarbonate leads to the development of metabolic alkalosis. The excess of both bicarbonate and bicarbonate equivalents like lactate, acetate, and B-hydroxybutyrate (which are metabolized to bicarbonate) may lead to the development of metabolic alkalosis. Contraction alkalosis: the loss of large volume of bicarbonate-poor fluid leads to volume depletion. The plasma bicarbonate concentration increases as the relatively unchanged extracellular bicarbonate is present in a less fluid volume. Milk alkali syndrome and hypercalcemia: Metabolic alkalosis results from the increase in alkaline load and hypercalcemia, which leads to increased bicarbonate reabsorption by the kidneys. Congenital chloridorrhea: Metabolic alkalosis results from the increased secretion of chloride with the diarrhea and reabsorption of bicarbonate. To simplify differential diagnosis of metabolic alkalosis, its causes can be divided into chloride responsive and chloride resistant metabolic acidosis. Gastrointestinal loss- vomiting, nasogastric suctioning, villous adenoma, and congenital chloridorrhea. Hypomagnesemia Hypercalcemia Increased delivery of unabsorbable anions to the distal nephron (nafcillin and penicillin) metabolic alkalosis, not responsive to other therapies and when rapid correction is necessary. Treatment Treatment of metabolic alkalosis includes correction of the etiologic factor and varies according to its type. In chloride responsive metabolic alkalosis, correction of volume depletion with normal saline results in bicarbonate excretion by the kidneys. In patients with chloride responsive metabolic alkalosis and volume overload as in cirrhosis and congestive heart failure the use of acetazolamide, which inhibits proximal tubular bicarbonate reabsorption is recommended. In either case, correction of the underlying electrolyte abnormalities like hypokalemia and hypomagnesemia is of paramount importance in management of metabolic alkalosis. In chloride resistant metabolic alkalosis correcting or mitigating of the underlying etiology is the major factor in management. In patients with primary hyperaldosteronism, surgical removal of adrenal adenoma and the use of aldosterone receptor blockers (spironolactone and eplerenone) and potassium sparing agents (amiloride and triamterene) improves hypokalemia and metabolic alkalosis. In patients with Liddle syndrome, the use of potassium sparing agents but not aldosterone receptor blockers corrects metabolic alkalosis. In glucocorticoid remediable hyperaldosteronism, the use of dexamethasone suppresses both cortisol and aldosterone production and improves the alkalosis. The use of isotonic hydrochloric acid, which buffers excess bicarbonate is effective in patients with severe Clinical Approach to Acid Base Disorders Evaluation of acid-base disorder should start with blood pH to determine the primary disorder. It is important to remember that acidemia and alkalemia refer to changes in the blood pH, while acidosis and alkalosis refer to processes that tend to lower or raise the pH. Here it is important to remember that the compensatory response always goes in the same direction as the primary abnormality and a normal pH in the presence of acid-base disorder is usually secondary to a mixed disorder. Next knowing the anion gap is very important to differentiate between gap and non gap acidosis. A 30-year-old female presents to the emergency room with mental status changes and with smell of alcohol in her breath. Development (Generation) of metabolic alkalosis Extrarenal Mechanisms Persistent vomiting (pyloric stenosis, gastritis) Nasogastic suction (postsurgery, ileus) Excessive intake of bicarbonate or citrate/ acetate mixture for metabolic acidosis Milk-bicarbonate (Milk-Alkali Syndrome) Renal Mechanisms Diuretic therapy Primary or secondary hyperaldosteronism Corticosteroid therapy Metabolic alkalosis (metabolic alkalemia) might have the most common acid-base disorder among the hospitalized patients in the past. Metabolic alkalosis is frequently accompanied by severe hypokalemia and less often cardiac arrhythmias which warrant hospital admission. In arterial blood gas analysis from Loma Linda University, California, simple metabolic alkalosis was found in 36 percent of patients with abnormal acid-base status. Metabolic alkalosis can be simple; it is often associated with chronic respiratory acidosis or mixed with respiratory alkalosis. Although simple metabolic alkalosis may be more common than other acid-base disorders in large metropolitan or university hospitals population, mixed respiratory acidosis and metabolic alkalosis is apparently more common in the veterans hospitals and community hospitals population. In the outpatient setting or in office practice, diuretic therapy is the most common cause of metabolic alkalosis. However, severe metabolic alkalosis as seen in surgical floor of a hospital generally makes patient symptomatic such as tetany or convulsion warranting intensive therapy. Poorly absorbable/ nonabsorbable anions, including carbenicillin, penicillin Congenital chloride diarrhea Hypercalcemia not associated with hyperparathyroidism Overshoot alkalosis The development of hyperbicarbonatemia is not very critical, since bicarbonate is rapidly excreted by kidneys. Therefore maintenance of metabolic alkalosis is more critical than its development. Mechanism of Maintenance of Metabolic Alkalosis Maintenance of metabolic alkalosis is essentially a function of the kidneys. In this context, it is important to have some understanding of bicarbonate handling by the kidneys. The hydrogen ion secretion by the renal tubules operates in such a manner that when the plasma bicarbonate is below a threshold level, reabsorption of bicarbonate is complete, and no bicarbonate appears in the urine. However, as the plasma bicarbonate concentration is increased above this threshold level, reabsorption does not increase proportionately and excretion of bicarbonate into the urine begins. The increase in salt and water reabsorption Metabolic Alkalosis: Pathophysiology and Management 83 Table 2. In renal failure, the ability to excrete bicarbonate by the kidneys remains active. However, excessive bicarbonate loads in the presence of renal failure can produce alkalosis with or without edema. The various chloride responsive and chloride resistant states are shown in Table 6. If no cause for metabolic alkalosis is evident, a thorough physical examination can be a helpful guide to identify the cause of metabolic alkalosis. If the patient has persistent vomiting, or requires nasogastic suction, ranitidine (150 mg) can be given intravenously twice daily. If urinary K + loss is very high (200 to 300 mEq/day), K + sparing agent can be added to the regimen. Amiloride While spironolactone (Aldactone) is preferable in cases with primary hyperaldosteronism, triamterene and amiloride can be used irrespective of aldosterone level. Spironolactone is also very effective in correcting hypokalemia in congestive heart failure and cirrhosis of liver. Side effects of indomethacin include bleeding peptic ulcer, sodium retention and edema, elevation of blood pressure, and rarely acute interstitial nephritis with heavy proteinuria and renal failure. Spironolactone is a slow acting drug, whereas triamterene and amiloride are fast acting drugs. Side effects are common and include bilateral, painful breast and decreased libido in females; gynecomastia and impotence in males, hyperkalemia. Side effects are uncommon, but include hyperkalemia, megaloblastic anemia and renal stones. Side effects are uncommon, but include hyperchloremic metabolic acidosis and hyperkalemia. For more details about potassium sparing agents, see Chapter on Hypokalemia and Hyperkalemia. Management of Metabolic Alkalosis with Volume Overload but Low Urinary Chloride the following agents should be considered: 1. Monitor: Arterial blood gas every four hours to control progress and continuity of administration. Metabolic Alkalosis with Volume Overload Moderate to severe renal failure (serum creatinine 3. Prompt recognition and effective treatment of severe metabolic alkalosis is essential. Delay in the initiation of treatment could result in high morbidity and mortality. Shifting of O2 dissociation curve to the left interfering with O2 release to tissue. Alkalemia associated with renal failure: correction by haemodialysis with lowbicarbonate dialysate. Hypokalemic metabolic alkalosis caused by surreptitious vomiting: report of four cases. The maintenance of metabolic alkalosis: factors which decrease bicarbonate excretion. Correction of postoperative metabolic alkalosis and renal failure by hemodialysis. Intravenous hydrochloric acid in patients with metabolic alkalosis and hypercapnia. Polyuria is not to be confused with the frequency of urination caused by genitourinary tract infections such as urethritis, cystitis, and prostatism. This is accompanied by dysuria, a small volume of concentrated urine, and sometimes abnormal-appearing urine; the urinalysis is almost always abnormal. In contrast, polyuria caused by diabetes insipidus, diabetes mellitus, chronic renal disease, or compulsive water drinking is accompanied by polydipsia, elimination of very dilute urine, sleeplessness, and tiredness; generally the urinalysis is normal. A thorough patient history, complete physical examination, and laboratory testing should establish the cause of polyuria in a given patient and help in formulating an appropriate plan for management. The causes can be determined provided the mechanism of urinary concentration is well understood. Expansion of the extracellular fluid volume can occur as a result of excessive intake of free water or other types of fluids. Typical examples of excessive fluid intake include that by compulsive water drinkers and heavy beer drinkers. Excessive Solute Load An excessive solute load, such as glucose, sodium chloride, and urea, can give rise to polyuria and increased urinary frequency, as occurs in association with diabetes mellitus and chronic renal failure with impaired sodium conservation and enhanced urea excretion. Medullary Interstitial Osmolality Osmotic diuresis caused by excessive sodium and urea excretion may be associated with nephrostomy drainage, bladder decompression with a catheter in acute urinary retention, and the early stage of hypernatremia (before volume depletion occurs from natriuresis and water diuresis). Therefore, if the medullary interstitium is not adequately hypertonic, as may occur through renal parenchymal damage, the urine will not be fully concentrated regardless of the plasma vasopressin levels. Thus, polyuria, with elimination of dilute urine, may occur in acute and chronic tubulointerstitial nephritis as well as in other types of chronic renal Polyuria and Diabetes Insipidus Table 1. Causes of polyuria Causes Expanded extracellular volume by free water intake Excessive urinary solute load 87 Examples Compulsive water drinking; Heavy beer drinking Glucose load: diabetes mellitus; Mannitol load: mannitol infusion; Sodium load: excessive ingestion The hypertonic medullary interstitium may be diluted by chronic water loading as in compulsive water drinkers. Dilution may also occur by inhibition of sodium and chloride transport in the ascending thick limb of loop of Henle, which may account for the inability to concentrate urine in the water-deprived state induced by loop diuretics. This destruction can be idiopathic or can be caused by a variety of acquired or genetic diseases. Nephrogenic diabetes insipidus is also caused by a variety of drugs, including demeclocycline and lithium. Genetic the only clearly defined genetic form of neurohypophyseal diabetes insipidus is transmitted in a completely penetrant autosomal dominant mode. Along with increased urine flow, fluid intake increases to balance urine output, and dehydration is prevented. At this stage of response, the deficiency state can be classified as partial diabetes insipidus. Patients with neurohypophyseal diabetes insipidus continue to exhibit usual diurnal variation in urine output.

Proximal muscle weakness characterized by difficulty in combing or setting hair allergy medicine 906 order benadryl 25mg with amex, climbing stairs and rising from a chair is common in all forms of renal osteodystrophy allergy report houston discount 25mg benadryl with amex. However allergy medicine raise blood pressure buy cheap benadryl on line, the pathogenesis is not well elucidated and it is often difficult to differentiate among disuse atrophy quitting allergy shots benadryl 25mg with amex, specific muscle lesions and malnutrition allergy symptoms 1 week before period generic 25mg benadryl amex. Before the closure of the growth plate in children allergy control products discount benadryl 25mg on line, growth retardation is common and epiphyseal slipping is sometimes reported. Skeletal deformity can occur in adults with severe osteomalacia due to aluminum toxicity. In such a situation, vertebral and rib fractures have been known to result in deformity of the thoracic spine and pelvis. Pruritus is often seen in the azotemic patient and has been attributed to the deposition of calcium and phosphorus under the skin. It has been associated with high serum phosphorus levels and is common in all forms of renal osteodystrophy. The mental changes include loss of enthusiasm, inability to concentrate and depression. Dialysis dementia appears to be unique to severe aluminum toxicity and in addition to the dementia, other signs include stuttering and stammering speech or even total inability to speak, hallucinations, paranoid ideation, twitching, myoclonic jerks and seizures. Calciphylaxis is due to tissue ischemia from systemic medial calcification of the small to medium sized arteries. It is now more common in obese patients as the calcified blood vessels in these patients fail to provide sufficient blood supply, predisposing to tissue ischemia. Ischemic necrosis of the dermis, subcutaneous fat and sometimes muscle are manifestations of the disease. A more proximal form of this disease in obese dialysis patients has been reported in which ischemic necrosis is in the abdominal fat, breast and buttock. Other treatment options include lowering the phosphorus levels with the use of noncalcium containing phosphate binders and more recently, the use of sodium thiosulfate. Thiosulfate increases the solubility of calcium and phosphorus deposits and there have been many case reports showing that thiosulfate is effective in improving and even resolving the manifestations of calciphylaxis. Thiosulfate is given intravenously after hemodialysis sessions in doses ranging from 5 to 25 grams. The major side effect has been an increased anion gap metabolic acidosis which probably originates from sulfate retention. Beta 2 amyloidosis-Carpal tunnel syndrome is the most frequent presentation in beta 2 amyloidosis. Amyloid deposition often produces a scapulohumeral periarthritis and a painful spondyloarthropathy of the lower cervical spine due to narrowing of the disk space with an associated radiculopathy. Bone cysts Renal Osteodystrophy 261 occur mostly in the ends of long bones and carpal bones and may be associated with pathologic fracture. The Allegro assay was a sandwich assay that used antibodies directed against both carboxy-terminal and amino-terminal sites. The amino-terminal epitopes recognized by this assay were after the first six amino acids. Serum Chemistries Serum calcium and phosphorus levels by themselves are not particularly helpful for the diagnosis of various bone diseases. The hypercalcemia develops because of the low capacity for bone to buffer a calcium load. However, hypercalcemia can also develop in patients with severe osteitis fibrosa, even in the absence of calcitriol treatment, because of the marked hyperparathyroidism. Diagnosis of Aluminum Bone Disease Measurement of serum aluminum is the first step in the diagnosis of aluminum bone disease. Aluminum bone disease is now rarely seen in dialysis patients in the developed world. However, it may still be seen in areas in which water purification methods are not adequate. Osteomalacia is also sometimes seen in geographic areas in which the aluminum concentration of the domestic water supply is not high, but periodic spikes in the aluminum concentration occur because aluminum sulfate (alum) is added to the domestic water supply after heavy rains to precipitate flocculent material present. However, X-rays may be used as an adjunct to help make the diagnosis of renal osteodystrophy. Osteitis Fibrosa Subperiosteal, intracortical and endosteal surface erosion of the cortical bone is the hallmark of bone resorption. The presence of subperiosteal erosions on the radial surface of the middle phalanges of second and third digits of the dominant hand have been stated to be the earliest X-ray change. Osteomalacia and Adynamic Bone There are not well-defined radiolographic criteria for the diagnosis of adynamic bone but there are some relatively specific findings for diagnosis of osteomalacia. Looser zones are sometimes present in acute phase of osteomalacia; in more chronic disease, osteopenia is often present, but specific diagnostic criteria are lacking. Moreover, osteomalacia may be misdiagnosed as osteitis fibrosa because old resorption cavities are filled with osteoid. Beta 2 Amyloidosis the presence of bone cysts without subperiosteal erosion is highly suggestive of amyloid related bone disease. Scintigraphic studies with imaging of beta 2 microglobulin deposits by injection of either I-131 labeled beta 2 microglobulin or I-123 labeled serum amyloid P component have been used for the diagnosis of beta 2 amyloidosis. In these studies, beta 2 amyloid deposits were often detected before the development of clinical signs and symptoms and X-ray changes. Bone Biopsy Bone biopsies are now performed infrequently and the processing and interpretation of bone biopsies are done 4. Serum Markers for Bone Formation the most sensitive and reliable diagnostic bone marker for bone formation has been reported to be bone specific alkaline phosphatase. Total alkaline phosphatase is also helpful in the diagnosis of the different forms of bone disease provided that other sources of alkaline phosphatase such as intestine and liver have been excluded. Beta 2 Amyloidosis Blood levels of beta 2 microglobulin are not a useful marker for the diagnosis of dialysis related amyloidosis. Tissue from synovial biopsies or joint aspirations is needed for a definite diagnosis. Beta 2 microglobulin amyloid is congo red positive and under polarized light, shows an apple green birefringence. Under electron microscopy, nodules are composed of short, thick Renal Osteodystrophy 263 at a limited number of specialized centers. Nevertheless, bone biopsy may be required to make a definitive diagnosis of renal osteodystrophy. Turnover may be abnormally low to very high, and is measured by tetracycline labeling. Mineralization is measured by osteoid maturation time or by mineralization lag time. The classic disease with an abnormality in mineralization is osteomalacia, in which the bone-formation rate is low and the osteoid volume is high. Bone volume on the other hand, represents the balance between bone formation and resorption. Normal or increased bone volume might suggest a decreased fracture risk, but the quality of bone, as reflected by bone turnover and adequacy of mineralization are also important determinants of bone histomorphometry. The goal of treatment in these patients is to protect the bone against progression of hyperparathyroidism and to prevent parathyroid gland hyperplasia. There is little question that once hyperphosphatemia develops, phosphate binders must be started. Several studies in predialysis patients have shown that hypocalcemia is associated with an increased osteoid seam width. In addition to restricting or binding phosphorus and maintaining a normal serum calcium, progressive hyperparathyroidism can also be controlled by the use of vitamin D metabolites. It has been shown in prospective studies that a low dose of calcitriol or active analogues can successfully control or retard the progression of hyperparathyroidism. Studies have also shown that calcitriol does not produce any deterioration in renal function provided that hypercalcemia is prevented. However, calcitriol treatment may increase serum creatinine values because calcitriol inhibits renal tubular creatinine secretion. Dialysis Patient In the dialysis patient, the treatment goal is slightly different than in the predialysis patient. It is essential that hyperphosphatemia be controlled and 264 Textbook of Nephrology normal serum calcium should be maintained. Treatments for hyperparathyroidism in the dialysis patient are shown in Table 3 and discussed below. However, even dietary phosphorus restriction is insufficient to adequately control serum phosphorus because each hemodialysis session only removes approximately 800 mg or 2400 mg/week. Thus, even in the patient rigidly adhering to a phosphorus restricted diet (800 mg daily), the weekly dietary phosphorus intake is 5600 mg exceeding the capacity of dialysis to remove phosphate. The currently available phosphate binders include calcium-containing phosphate binders such as calcium acetate, sevelamer and lanthanum. Ethanol or calcitriol injection of hyperplastic parathyroid glands magnesium containing phosphate binders are no longer used because of their toxicity. Calcium containing phosphate binders lower serum phosphorus by binding phosphorus in the gut. Calcium acetate is the most widely used calcium containing phosphate binder because it has a similar phosphorus binding capacity as calcium carbonate but contains a lesser calcium burden. By weight calcium carbonate contains 40 percent, while calcium acetate contains 21 percent calcium. The better binding of calcium acetate may be due to its better solubility and it also is less dependent on gastric acidity to be dissolved and activated. The maximal dose of elemental calcium given as a phosphate binder should be limited to 1500 mg daily. In the United States, the commercially available calcium acetate contains 169 mg of elemental calcium. Sevelamer hydrochloride and sevelamer carbonate are nonabsorbable agents that do not contain calcium and are cationic polymers which bind phosphorus through ion exchange. Sevelamer carbonate is the buffered form of sevelamer hydrochloride and does not cause metabolic acidosis. In patients not taking a phosphate binder, the initial dose of sevelamer hydrochloride or carbonate is 800 to 1600 mg three times daily with meals. Although the data are inconclusive, there may be less progression of vascular calcification with sevelamer versus calcium containing phosphate binders. Lanthanum, a rare earth element has also been shown to be an effective phosphorus binding agent. Lanthanum is associated with a lower incidence of hypercalcemia than calcium-containing phosphate binders. Crushing the tablets and mixing the crushed tablets in apple sauce might also be acceptable. As shown in a systematic review, there is no difference in the phosphorus binding capacity of the different binders. However an approach that is solely based on calcium based binders often leads to the development of hypercalcemia. Due to the increased cost, use of Renal Osteodystrophy 265 sevelamer and lanthanum are often restricted to patients with hypercalcemia, or as an adjunct to a regimen supplying a maximum dose of 1500 mg of elemental calcium from calcium based binders. In summary, the dialysate calcium concentration must be individualized for the needs of the patient. Furthermore, the response to calcitriol is likely to be better in hypocalcemic patients due to the correction of hypocalcemia with calcitriol. The autocrine effects of vitamin D include control of local inflammation and cell cycle regulation. Also, deficiency of vitamin D has been associated with increased cardiovascular disease and mortality in the general population. Vitamin D deficiency may be corrected by the use of either cholecalciferol or ergocalciferol. Because calcitriol increases the gut absorption of calcium and phosphorus, it should not be started if a patient has hypercalcemia (serum calcium >10. There have been several studies which have evaluated the route of administration (oral vs intravenous) and the frequency of dosing (daily vs intermittent bolus). While intermittent dosing has not been shown to be better than daily dosing, the advantage of intermittent dosing is better compliance because the dose (oral or intravenous) can be administered at each dialysis session. Failure to control serum phosphorus is associated with a decreased response to calcitriol. Dosing of calcitriol depends on the magnitude of hyperparathyroidism and the serum calcium and phosphorus levels. At this stage, hypercalcemia often develops if the initial dose of calcitriol is maintained. This is sometimes difficult because calcitriol enhances intestinal phosphorus absorption and may be associated with decreased bone buffering. Often it is necessary to discontinue or reduce the calcitriol dose because of the failure to control serum phosphorus. To prevent the development of hypercalcemia during calcitriol treatment, it is customary to reduce the dialysate calcium to 2. If hypercalcemia develops during calcitriol treatment, discontinuation of calcitriol is required until serum calcium returns to an acceptable value. An important consideration with calcitriol therapy is the marked difference in the response to calcitriol.

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