medullary washout dogsromain 12 2 explication
A wide USG range is possible in healthy euhydrated animals. Figure 8-6 illustrates the essential features of this process. gas washout methods (Birtch et al., 1967). Measurements of GFR or serum biochemical analytes of GFR was not done in these dogs (Rudinsky et al 2019). Polyuria and polydipsia. The physical examination may provide clues about the cause of increased thirst and urination. In a patient with hypokalemia, the H+/K+-ATPase activity in the MCD is increased. After passing the hairpin turn of the loop, the vasa recta climb back toward the renal cortex. This is calculated by multiplying the last two digits of the USG by 36. Loss of this osmotic gradient in, for example, cases of hypoadrenocorticism with chronic sodium wasting, results in inadequate urine concentration, despite the presence of adequate amounts of circulating ADH. Hyposthenuric (SG < 1.005) urine is indicative of diabetes insipidus (either central or nephrogenic) or primary polydipsia, but importantly, imparts knowledge about the normality of the kidneys, i.e., it indicates that the renal tubules are able to actively dilute the glomerular filtrate and are thus functioning appropriately. Osmolality can be measured by freezing point depression (the technique used at the Clinical Pathology Laboratory of the Animal Health Diagnostic Center at Cornell University) and changes in vapor pressure. In metabolic acidosis, the appropriate renal response is to increase net acid excretion. A hereditary predisposition for the development of reactive amyloidosis (AA) has been found in Abyssinian cats, and a familial tendency is suspected in Siamese cats. Now they encounter a medullary interstitium of progressively decreasing osmolality so that water enters the vessels and solutes are removed. USG is influenced by the number of molecules in urine, as well as their molecular weight and size, therefore it only approximates solute concentration. Hence, precipitation of calcium carbonate may provide a nidus for the precipitation of calcium phosphate. The most common screening tests are acomplete blood count(CBC), aserum biochemistry profile, and aurinalysis. In this proposed scheme, it is currently unclear whether the apatite crystals would form in the hypertonic interstitial fluid in the renal medulla, or in the lumen of the descending limb and then migrate into the interstitium. We use cookies to help provide and enhance our service and tailor content and ads. Stephen P. DiBartola, in Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice (Fourth Edition), 2012. RhBG is localized to the basolateral membrane, whereas RhCG is found in both the apical and basolateral membranes. Evan proposed that apatite deposits formed in the basement membrane of the thin loops of Henle extend into the interstitial space where they form plaques. The dog with polydipsia and polyuria. Thus in response to acidosis, both NH4+ production and excretion are stimulated. : Even with aquaporins in place in the collectingtubular cells, water will not be reabsorbed if the medulla is not hypertonic. E.J. From here on the clinician should perform the test that he/she thinks will yield the most information for the "diagnostic dollar" that the client provides. 5. Factors affecting USG other than concentrating ability. To assess NH4 production, and especially the amount of NH4 excreted, the urinary net charge, or urine anion gap, can be calculated by measuring the urinary concentrations of Na+, K+, and Cl: The concept of urine anion gap during a metabolic acidosis assumes that the major cations in the urine are Na+, K+, and NH4 and that the major anion is Cl (with urine pH less than 6.5, virtually no HCO3 is present). Webmedullary washout dogs PDF - Introduction The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. Textbook of Veterinary Internal Medicine. Further pointers during the clinical examination could include peripheral lymphadenopathy (i.e., cases of multicentric lymphoma) or the presence of a bradycardia that could indicate hypoadrenocorticism or hypercalcaemia. Erosion of a relatively soft surface, such as a roadbed, by a sudden gush of water, as from a downpour or floods. As previously mentioned, this segment is also permeable to urea, and some interstitial urea enters the tubule lumen by diffusion down its concentration gradient. (2) Structural lesions need not be In a primary renal azotemia, the kidney cannot concentrate or dilute urine, so there is often a fixed (constant) isosthenuric USG, i.e. Over time, their water intake will normalize. Over time, their water intake will normalize. d. From: Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003, Kamel S. Kamel MD, FRCPC, Mitchell L. Halperin MD, FRCPC, in Fluid, Electrolyte and Acid-Base Physiology (Fifth Edition), 2017. Web1. However, normally, the kidneys excrete NH4+ in the urine and thereby produce new HCO3. Cysts can range in size from 1 mm to more than 2 cm. WebMedullary washout occurs in small animal patients for two common reasons: 1 Washout results from large amounts of urine passing through the tubules. Medullary washout may occur. This situation occurs as a result of generalized dysfunction of the distal tubule and collecting duct with impaired H+, NH4, and K+ secretion. Over time, their water intake will normalize. Renal medullary washout (370493008) Recent clinical studies. WebMedullary washout is not serious and is reversible once the increased thirst and urination have improved. The reasons underlying this apparent insensitivity of the medullary circulation to angiotensin II are unclear but in vitro studies have established that the peptide has both vasoconstrictor effects, mediated via angiotensin type 1 (AT1) receptors and vasodilator effects, mediated via AT2 receptors and NO, at this location (Evans etal., 2010). In the distal tubule and collecting duct, where the tubular fluid contains little or no HCO3 because of upstream reabsorption, H+ secreted into the tubular fluid combines with a urinary buffer. If the water removed from the medullary collecting duct in the presence of ADH were allowed to remain in the medullary interstitium, the hyperosmotic gradient would dissipate rapidly. Because of this process, NH4+ excretion is critically involved in the formation of new HCO3. There is the production of extracellular nucleotides such as adenosine, which may be vasodilator or vasoconstrictor depending on their sites of action. In addition, urinary constituents (erythrocytes, leukocytes and casts) can lyse in dilute urine (USG < 1.008), affecting interpretation of the urine sediment results. Diabetes insipidus is entirely different from diabetes mellitus; the term 'mellitus' refers to the sweetness of the urine in sugar diabetes, and the term 'insipidus' refers to the watery nature of the urine in diabetes insipidus. NH4+ is then secreted into the tubular fluid of the collecting duct. A physical examinationinvolves looking at all parts of the body, listening to the heart and lungs with a stethoscope, and palpatingthe abdomen (gently squeezing or prodding the abdomen with the fingertips to detect abnormalities of the internal organs). WebMedullary washout occurs in small animal patients for two common reasons: 1 Washout results from large amounts of urine passing through the tubules. Bartges JW. The main causes of increased water intake that are tied to underlying disease are diabetes, kidney failure, and Cushings disease. Urine osmolality is directly related to the number of particles in solution and is unaffected by molecular weight and size. In this condition, the brain fails to produce proper levels of ADH. The modified water deprivation test protocol attempts to eliminate this problem by recommending mild water restriction for a number of days before the test. Both autosomal dominant and autosomal recessive forms of distal RTA have been identified. By continuing you agree to the use of cookies. In a pet with increased thirst and urination, some of the changes seen on a urinalysis may include: Various additional tests might be recommended depending on the results of history, physical exam, and screening tests. If NH4+ is not excreted in the urine but enters the systemic circulation instead, it is converted into urea by the liver. If collecting duct H+ secretion is inhibited, the NH4+ reabsorbed by the thick ascending limb of Henles loop is not excreted in the urine. The presence of constantly isosthenuric urine (SG 1.0051.012) is highly suggestive of chronic renal failure. In this way, the HCO3 lost each day in the buffering of nonvolatile acid is replenished by the extra HCO3 ingested in the diet. WebGenerally, the normal intake of water in dogs is 1 ounce (30ml) of water per pound of body weight in 24 hours, explains veterinarian Dr. Dave. Some dogs just start drinking water because they enjoy it, which can lead to a kidney condition known as medullary washout, which causes them to keep drinking lots of water. Intracellular signaling pathways through cyclic adenosine monophosphate regulate the insertion of these channels. This segment of the nephron is impermeable to NaCl and urea, thus the osmolality of luminal fluid in the most distal portion of the loop approaches that of the interstitium. This is a subjective value, making a definitive diagnosis of partial CDI very difficult. As already noted, cortisol levels increase during acidosis and cortisol stimulates ammoniagenesis (i.e., NH4+ production from glutamine). Urinalysis is a simple test that analyses urine's physical and chemical composition. d. When excess water is in the body, ADH levels fall, and the kidney allows excess water to flow into the urine. Electrolyte abnormalities are consistent with hypoadrenocorticism. Finally, an autosomal dominant form of proximal RTA has been identified. Increased renal gluconeogenesis as a compensation of insufficient hepatic gluconeogenesis may cause the kidneys to enlarge.52 In addition, increased systemic circulating growth factor concentrations released from the pancreas may play a role in this increased volume.53 Normally, these growth factors act only in the liver, as they do not reach the systemic circulation in high concentrations. Prostaglandins produced by the renal medullary interstitial cells are vasoconstrictor while there is a range of other arachidonic acid metabolites that are also vasoactive, for example, the epoxyeicosatrienoic acids and hydroxyeicosatetraenoic acids (Imig, 2005). Normal urine production is approximately 20-40 ml/kg/day or, put differently, 1-2 ml/kg/hour. Medullary amyloidosis is usually asymptomatic unless it obstructs blood flow and causes papillary necrosis. Mechanisms to explain how this could occur have been proposed [287]. The detection of cataracts during ophthalmoscopic examination could point to diabetes mellitus, whereas thin, alopecic, non-elastic abdominal skin could be suggestive of hyperadrenocorticism. Remember that primary NDI is a very rare diagnosis. RTA can be caused by a defect in H+ secretion in the proximal tubule (proximal RTA) or distal tubule (distal RTA) or by inadequate production and excretion of NH4. The thick ascending limb is the primary site of this NH4+ reabsorption, with NH4+ substituting for K+ on the Na+-K+-2Cl symporter. There are two primary forms of increased thirst and urination. In addition to providing information regarding the possible cause of your pet's symptoms, these screening tests may uncover other conditions that need to be addressed or treated. Trace amounts of interstitial plaque are detectable in all kidneys [283], but large amounts are only found in Ca ox SFs. A significant portion of the NH4+ secreted by the proximal tubule is reabsorbed by the loop of Henle. (1) Long-standing PU/PD of any cause can result in loss of medullary solutes (e.g., NaCl, urea) necessary for normal urinary concentrating ability. Because this response involves the synthesis of new enzymes, it requires several days for complete adaptation. As a result, distal tubule and collecting duct function is impaired. Hypokalemia decreases the sensitivity of cyclic adenosine monophosphate to arginine-vasopressin, which results in decreased insertion of aquaporin-2 channels into the cell membrane.50 This leads to nephrogenic diabetes insipidus and PU. This conversion process generates H+, which is then buffered by HCO3. Van Vonderen IK. Hyposthenuria indicates that the kidney can dilute the urine but is unable to concentrate, i.e. If you enjoy the site, please support our mission and consider a small gift to help us keep pace with its rapid growth. Much less frequently, polydipsia is primary with a compensatory polyuria to excrete the excess water load. Distal RTA also occurs in a number of hereditary and acquired conditions (e.g., medullary sponge kidney, certain drugs such as amphotericin B, and conditions secondary to urinary obstruction). These dogs are then mistakenly diagnosed as suffering from NDI. Some urea also is reabsorbed into the interstitium. An accurate history is very informative and enables the clinician to distinguish in the first instance between polyuria and urinary incontinence, nocturia or pollakiuria. Together, this points to a very complex interaction of factors within the medulla which means that it is difficult to precisely define the role and functions of each of these autocrine and paracrine factors. For routine clinical purposes, USG is determined using a refractometer (refractive index generally correlates well with USG). It measures how well the kidneys are working, identifies inflammation and infection in the urinary system, and helps detect diabetes and other metabolic disturbances. Richard E. Goldstein DVM, DACVIM, DECVIM-CA, in Small Animal Critical Care Medicine (Second Edition), 2015. renal tubular disease, loop diuretics). NH4+ is produced in the kidneys through the metabolism of glutamine. An autosomal dominant form results from mutations in the gene coding for the Cl-HCO3 antiporter (anion exchanger-1) in the basolateral membrane of the acid-secreting intercalated cell. Defects in any of these can cause decreased urine concentrating ability. Because this transporter also is expressed in the eye, these patients also have ocular abnormalities. That the vasa recta can effectively remove water and recycle solute may be appreciated by considering the different flow rates in the vasa recta and medullary collecting duct. Web-Renal blood flow distribution was measured in control dogs and dogs in endotoxic shock by utilizing a modification of 85Kr washout. 1998. History is very important and can provide clues about the cause of increased thirst and urination. c. Renal medullary washout of solute. Urine specific gravity (USG) and osmolality are measures of the solute concentration in urine and are used to assess tubular function, i.e. 4. Liver failure, for example, results in decreased production of urea (thus causing decreased renal medullary hypertonicity) and increased levels of corticosteroids that inhibit the release of ADH (thus causing a degree of central diabetes insipidus). c. Renal medullary washout of solute. 43.1. Primary polyuria is either due to osmotic (solute) diuresis, ADH deficiency or renal insensitivity to ADH. Johan P. Schoeman, BVSc, MMedVet (Med), PhD, DSAM, DECVIM-CA Polyuria is defined as a daily urine output of greater than 50 ml/kg per day, while polydipsia is defined as a fluid intake of more than 100 ml/kg/day. Web1. An exception to this occurs in cats, in which glomerular disease (and azotemia) can precede loss of concentrating ability. This effect occurs with the antifungal drug amphotericin B, the administration of which leads to the development of distal RTA. It is also unclear how the plaques relate to interstitial nephrocalcinosis seen in inherited defects and infants with phosphate depletion (see Section 5.1). Ensure, once again, that all the other causes of secondary NDI have been properly eliminated before confidently making the diagnosis. This underlines the importance of establishing or excluding a diagnosis of hyperadrenocorticism in dogs before administering this test. 2004. To maintain acid-base balance, the kidneys must replace this lost HCO3 with new HCO3. If the acidosis that results from any of these forms of RTA is severe, individuals must ingest alkali (e.g., baking soda or a solution containing citrate) to maintain acid-base balance. The amount of plaque increased with higher 24h urinary Ca2+ excretion and lower 24h urine volume [284,285]. Another autosomal recessive form of proximal RTA occurs in persons who lack carbonic anhydrase (CA-II). Web-Renal blood flow distribution was measured in control dogs and dogs in endotoxic shock by utilizing a modification of 85Kr washout. This process is illustrated in Figure 8-5. Pathophysiology of Disorders of Water Balance. In this study, the sonographic appearance of the outer renal medulla in dogs without evidence of renal disease is described. This effect explains why dogs with hypoadrenocorticism often have impaired urinary concentrating ability at presentation despite having structurally normal kidneys. In this study, the sonographic appearance of the outer renal medulla in dogs without evidence of renal disease is described. Increased white blood cells may indicate pyometra in an intact female or hyperadrenocorticism. Increased medullary blood flow in vasa recta: This flushes out the solutes accumulating and creating hypertonicity in the medulla. This situation, in turn, decreases RNAE, with the subsequent development of acidosis. The patient should be closely monitored (i.e., bodyweight, hydration status, serum urea and creatinine) and the test should be stopped if the patient appears dehydrated or has lost 5% of its bodyweight. Jill W. Verlander, in Cunningham's Textbook of Veterinary Physiology (Sixth Edition), 2020. Most disorders of water balance are due to the inability of the kidney to conserve water - thus primary polyuria. Partial CDI, or a relative lack of vasopressin, can be very hard to diagnose, because a rise in urine specific gravity will be induced by dehydration. The medullary interstitium is a complex milieu of factors all of which impinge on the pericytes of the DVR to determine their tone. WebCalcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma. When the liver receives little portal venous blood, an insufficient amount of substrate (i.e., ammonia) is available for hepatic urea production. Webwhy is washington a good place to live; brass cedar chest; opry entertainment group careers; guinea pig lethargic but eating; youngest player to win world cup Knowledge of urinary solute concentration is essential for proper interpretation of urea and creatinine, which are indicators of glomerular filtration rate. It is therefore important to note that this test is contraindicated in animals with renal failure. Dogs with hyperadrenocorticism may appear to have CDI or partial CDI per a water deprivation test, leading to a misdiagnosis. In these cases polydipsia represents a compensatory mechanism to maintain total body fluids within normal limits. (1) Long-standing PU/PD of any cause can result in loss of medullary solutes (e.g., NaCl, urea) necessary for normal urinary concentrating ability. The opposite would occur during hypokalemia. Other factors can alter renal NH4+ excretion. d. and the low blood flow in the medullary vessels is critical for efficient function ofthe countercurrent mechanism. However, autosomal recessive and autosomal dominant forms of proximal RTA have been identified. WebHealthy dogs generally consume between 50-60 ml/kg/day depending on the moisture content of their diets, the ambient temperature and humidity and their level of activity. Renal medullary washout (370493008) Recent clinical studies. Proteinuria, especially in the presence of dilute urine, indicates significant protein loss and is suggestive of glomerulonephritis. Melanie A. Breshears, Anthony W. Confer, in Pathologic Basis of Veterinary Disease (Sixth Edition), 2017. If a pet cannot concentrate urine when deprived of water but can concentrate urine when given ADH, a diagnosis ofcentral diabetes insipiduscan be made. Testing For Increased Thirst And Urination, Kidney disorders (e.g., kidney failure, kidney infection), Pyometra (uterine infection in intact females), Hormone disorders, including hyperadrenocorticism (overactive adrenal glandsCushings disease), hypoadrenocorticism (adrenal gland failureAddisons disease), hyperthyroidism (overactive thyroid gland), diabetes mellitus (sugar diabetes), and diabetes insipidus (see below), Rarely, a behavioral problem calledprimary polydipsia or psychogenic thirst. For the kidney to make concentrated urine, ADH must be produced, the renal collecting tubules must respond to ADH, and the renal medullary interstitium must be hypertonic. These factors contribute to the effective removal of water from the medullary interstitium and prevent dissipation of the osmotic gradient in this region of the kidneys. In a pet with increased thirst and urination, the serum biochemistry panel could show some of the following changes: Urinalysisis a simple test that analyses urine's physical and chemical composition. In this study, the sonographic appearance of the outer renal medulla in dogs without evidence of renal disease is described. As a result, the urine anion gap yields a negative value when adequate amounts of NH4 are being excreted and thereby reflects the amount of NH4 excreted in the urine. Glucosuria significantly narrows the list of differential diagnoses. A portion of the new HCO3 is produced when urinary buffers (primarily Pi) are excreted as titratable acid. WebAldosterone deficiency in hypoadrenocorticism impairs NaCl reabsorption in the collecting ducts and contributes to medullary washout of solute. Isosthenuric urine has an osmolality similar to plasma, approximately 300 to 320 mOsm/kg. For this reason, osmolality is superior to specific gravity, which is affected by particle weight and size. Of these mechanisms for NH4+ secretion, quantitatively the most important is nonionic diffusion and diffusion trapping. As discussed previously, reabsorption of the filtered HCO3 is important for maximizing RNAE. Affiliate of Mars Inc. 2023 | Copyright VCA Animal Hospitals all rights reserved. WebIntroduction. Accordingly, little or no HCO3 appears in the urine, the urine is acidic, and NH4 excretion is increased. Therefore, the transport of two mmol of Na+ ions requires the hydrolysis of two thirds of a molecule of ATP, whereas the transport of one mmol of Na+ ions requires the hydrolysis of only one third of a molecule of ATP. This measures the kidneys ability to concentrate urine when ADH is administered directly to the pet. Healthy dogs generally consume between 5060 ml/kg/day, depending on the moisture content of their diets, the ambient temperature and humidity and their level of activity. ACTH-hypersecretion can be explained by the production of false neurotransmitters (e.g., octopamine), whose effect is about one-fiftieth that of dopamine on the dopamine receptors.35, Central diabetes insipidus also contributes to PU in dogs with HE. Polyuria is defined as a daily urine output of greater than 50 ml/kg per day, while polydipsia is defined as a fluid intake of more than 100 ml/kg/day. The kidneys could be enlarged in conditions such as pyelonephritis or renal neoplasia and small and misshapen in chronic interstitial nephritis or congenital renal dysplasia. As previously described, H+ secretion by the intercalated cells of the collecting duct acidifies the luminal fluid (a luminal fluid pH as low as 4.0 to 4.5 can be achieved). Polyuria and polydipsia are frequent presenting complaints in small animal practice. BSAVA Manual of Endocrinology, 2nd edition. WebHealthy dogs generally consume between 50-60 ml/kg/day depending on the moisture content of their diets, the ambient temperature and humidity and their level of activity. 5th ed, 2000:8588. Hypokalemia and -Renal blood flow distribution was measured in control dogs and dogs in endotoxic shock by utilizing a modification of 85Kr washout. The assessment of a random plasma osmolality could aid the differentiation between psychogenic polydipsia (which should have a serum osmolality below 280 mOsm/kg) and CDI or NDI (which should have serum osmolalities above 305 mOsm/kg). Looking for a convenient way to access your pets health records, refill prescriptions, view upcoming appointments and more? WebGenerally, the normal intake of water in dogs is 1 ounce (30ml) of water per pound of body weight in 24 hours, explains veterinarian Dr. Dave. However, clearance of nitrogenous waste products sufficient to prevent azotemia, persists until roughly three-quarters of functional nephrons are lost. The external genitalia should be examined for discharge (i.e., open cervix pyometra) or testicular atrophy (cases of Cushing's disease). However, as noted, increased excretion of Pi does occur with acidosis and therefore contributes to the kidneys response to the acidosis. Therefore, if azotemia is due to loss of nephron mass (> three-quarters loss, i.e., renal failure), ability to concentrate urine will have already been lost (i.e. He concluded that the stones were growing from the plaques and exposed to the calyceal urine. Their response should be more dramatic, though, than in dogs with psychogenic polydipsia. Some dogs just start drinking water because they enjoy it, which can lead to a kidney condition known as medullary washout, which causes them to keep drinking lots of water. Although glomeruli are the most common renal sites for deposition of amyloid in most domestic animal species, deposition can occur in the medullary interstitium (see the section on Amyloidosis). An additional rise in urine specific gravity should occur after desmopressin is given. High blood sugar (glucose)level is a sign of diabetes mellitus. As such, dogs with diabetes insipidus or primary polydipsia are generally bright and alert, whereas dogs with Addison's disease or pyometra are generally unwell. Typically ADH works by opening up water channels, specifically aquaporin-2 (aquapore = water pore) in the collecting ducts (. Water is reabsorbed down its concentration gradient from the thin descending limb of the loop of Henle (Figure 3.2-1, E) as a consequence of medullary hypertonicity. Several mechanisms contribute to the development of PU/PD in portosystemic shunting. The basic elements of this system are illustrated in Fig. This rise, though, will be of inappropriately low magnitude and a very subjective value, and these dogs can be misdiagnosed as having psychogenic polydipsia. Just click, Approach to the Dog with Polyuria and Polydipsia, World Small Animal Veterinary Association World Congress Proceedings, 2011, Johan P. Schoeman, BVSc, MMedVet(Med), PhD, DSAM, DECVIM-CA, Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa, 4d2c0952-b8de-4840-b5f7-91d5b3c15ba5.1677993812, VINcyclopedia of Diseases (Formerly Associate), Books & VINcyclopedia of Diseases (Formerly Associate), Glucocorticoids in Neurology/Neurosurgery, Canine Mammary Tumors: Prognostic Factors, Johan P. Schoeman, BVSc, MMedVet (Med), PhD, DSAM, DECVIM-CA. Hypokalemia and hypercalcemia can both cause this effect. Medullary amyloidosis may predispose the dog to various aspects of end-stage renal disease, including interstitial fibrosis, lymphoplasmacytic infiltration, tubular atrophy, tubular dilation, mineralization, deposition of oxalate crystals, glomerular atrophy, and glomerulosclerosis. Both RhBG and RhCG are expressed to a greater degree in intercalated cells versus principal cells. However animals that are dehydrated, hypovolemic or have decreased effective blood circulating volume should be conserving water (and trying to reconstitute effective blood volume), therefore concentrating their urine. Dogs >100 ml/kg/day Normal water consumption is larger in dogs 4 kg 1 kg dog ->132 ml/kg/day is normal Cats >45 ml/kg/day. The mineral in the plaques was always CaP (mainly carbapatite, but with some amorphous CaP [286]) and osteopontin and heavy chain 3 (H3) of the interalpha-trypsin molecule were identified protein components. Cornell University uses a temperature-compensated Reichert refractometer or digital refractometers for USG measurements in animals. In addition, NH3 can diffuse out of the cell across the plasma membrane into the tubular fluid, where it is protonated to NH4+.
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