Block 6 Renal Physiology BRS W Expl Prt 2

Glucose is extensively reabsorbed in the early proximal tubule by the Na+–glucose cotransporter. The glucose concentration in tubular fluid is highest in Bowman's space before any reabsorption has occurred.

By sweating and then replacing all volume by drinking H20, the woman has a net loss of NaCl without a net loss of H20. Therefore, her extracellular and plasma osmolarity will be decreased, and as a result, water will flow from extracellular fluid (ECF) to intracellular fluid (ICF). The intracellular osmolarity will also be decreased after
the shift of water. Total body water (TBW) will be unchanged because the woman replaced all volume lost in sweat by drinking water. Hematocrit will be increased because of the shift of water from ECF to ICF and the shift of water into the red blood cells (RBCs), which causes their volume to increase.

Para-aminohippuric acid (PAH) is an organic acid that is filtered and subsequently secreted by the proximal tubule. The secretion process adds PAH to the tubular fluid; therefore, the amount that is present at the end of the proximal tubule is greater than the amount that was present in Bowman's space.

K+ is the major intracellular cation.

Para-aminohippuric acid (PAH) has the greatest clearance of all of the substances because it is both filtered and secreted. Inulin is only filtered. The other sub stances are filtered and subsequently reabsorbed; therefore, they will have clearances that are lower than the inulin clearance.

Alanine, like glucose, is avidly reabsorbed in the early proximal tubule by a Na+–amino acid cotransporter. Thus, the percentage of the filtered load of alanine remaining in the tubular fluid declines rapidly along the proximal tubule as alanine is reabsorbed into the blood.

The history strongly suggests chronic obstructive pulmonary disease (COPD) as a cause of respiratory acidosis. Because of the COPD, the ventilation rate is decreased and CO2 is retained. The [H+] and [HCO3] are increased by mass action. The [HCO3-] is further increased by renal compensation for respiratory acidosis (increased HCO3- reabsorption by the kidney facilitated by the high Pc02).

The tubular fluid inulin concentration depends on the amount of water present. As water reabsorption occurs along the nephron, the inulin concentration progressively increases. Thus, the tubular fluid inulin concentration is lowest in Bowman's space, prior to any water reabsorption.

The history of vomiting (in the absence of any other information) indicates loss of gastric H+ and, as a result, metabolic alkalosis (with respiratory compensation).

The blood values in respiratory alkalosis show decreased Pco2 (the cause) and decreased [H+] and [HCO3] by mass action. The [HCO3-] is further decreased by renal compensation for chronic respiratory alkalosis (decreased HCO 3- reabsorption).

Once inulin is filtered, it is neither reabsorbed nor secreted. Thus, 100% of the filtered inulin remains in tubular fluid at each nephron site and in the final urine.

Both individuals will have hyperosmotic urine, a negative free-water clearance (- CH20), a normal corticopapillary gradient, and high circulating levels of antidiuretic hormone (ADH) The person with water deprivation will have a high plasma osmolarity, and the person with syndrome of inappropriate antidiuretic hormone (SIADH) will have a low plasma osmolarity (because of dilution by the inappropriate water reabsorption).

This patient's plasma and urine osmolarity, taken together, are consistent with water deprivation. The plasma osmolarity is on the high side of normal, stimulating the posterior pituitary to secrete antidiuretic hormone (ADH). Secretion of ADH, in turn, acts on the collecting ducts to increase water reabsorption and produce hyperosmotic urine. Syndrome of inappropriate antidiuretic hormone (SIADH) would also produce hyperosmotic urine, but the plasma osmolarity would be lower than normal because of the excessive water retention. Central and nephrogenic diabetes insipidus and excessive water intake would all result in hyposmotic urine.

Effective renal plasma flow (RPF) is calculated from the clearance of para-aminohippuric acid (PAH) [CpAH = UpAH X V/PpAH = 600 ml/min]. Renal blood flow (RBF) = RPF/1 - hematocrit = 1091 ml/min.

A person who is deprived of water will have high circulating levels of antidiuretic hormone (ADH). The tubular fluid/plasma (TF/P) osmolarity is 1.0 throughout the proximal tubule, regardless of ADH status. In antidiuresis, TF/P osmolarity > 1.0 at site C because of equilibration of the tubular fluid with the large corticopapillary osmotic gradient. At site E, TF/P osmolarity > 1.0 because of water reabsorption out of the collecting ducts and equilibration with the corticopapillary gradient. At site D, the tubular fluid is diluted because NaC1 is reabsorbed in the thick ascending limb without water, making TF/P osmolarity

K+ is secreted by the late distal tubule and collecting ducts. Because this secretion is affected by dietary K + , a person who is on a high-K + diet can secrete more K+ into the urine than was originally filtered. At all of the other nephron sites, the amount of K+ in the tubular fluid is either equal to the amount filtered (site A) or less than the amount filtered (because K+ is reabsorbed in the proximal tubule and the loop of Henle).

Because inulin, once filtered, is neither reabsorbed nor secreted, its concentration in tubular fluid reflects the amount of water remaining in the tubule. In antidiuresis, water is reabsorbed throughout the nephron (except in the thick ascending limb and cortical diluting segment). Thus, inulin concentration in the tubular fluid progressively rises along the nephron as water is reabsorbed, and will be highest in the final urine

Untreated diabetes mellitus results in the production of ketoacids, which are fixed acids that cause metabolic acidosis. Urinary excretion of NH4+ is increased in this patient because an adaptive increase in renal NH 3 synthesis has occurred in response to the metabolic acidosis.

Exercise causes a shift of K+ from cells into blood. The result is hyperkalemia. Hyposmolarity, insulin, fl-agonists, and alkalosis cause a shift of K + from blood into cells. The result is hypokalemia.

Hypertension, hypokalemia, metabolic alkalosis, elevated serum aldosterone, and decreased plasma renin activity are all consistent with a primary hyperaldosteronism (e.g., Conn's syndrome). High levels of aldosterone cause increased Na + reabsorption (leading to increased blood pressure), increased K+ secretion (leading to hypokalemia), and increased H+ secretion (leading to metabolic alkalosis). In Conn's syndrome, the increased blood pressure causes an increase in renal perfusion pressure, which inhibits renin secretion. Neither Cushing's syndrome nor Cushing's disease is a possible cause of this patient's hypertension
because serum cortisol and adrenocorticotropic hormone (ACTH) levels are normal. Renal artery stenosis causes hypertension that is characterized by increased plasma renin activity. Pheochromocytoma is ruled out by the normal urinary excretion of vanillylmandelic acid (VMA).

Acause of metabolic alkalosis is hyperaldosteronism; increased aldosterone levels cause increased H+ secretion by the distal tubule and increased reabsorption of "new" HCO3-. Diarrhea causes loss of HCO3- from the gastrointestinal (GI) tract and acetazolamide causes loss of HCO3- in the urine, both resulting in hyperchloremic metabolic acidosis with normal anion gap. Ingestion of ethylene glycol and salicylate poisoning lead to metabolic acidosis with increased anion gap.

Parathyroid hormone (PTH) acts on the renal tubule by stimulating adenyl cyclase and generating cyclic adenosine monophosphate (cAMP). The major actions of the hormone are inhibition of phosphate reabsorption in the proximal tubule, stimulation of Ca2+ reabsorption in the distal tubule, and stimulation of 1,25-dihydroxycholecalciferol production. PTH does not alter the renal handling of K+.

In patients who have chronic renal failure and ingest normal amounts of protein, fixed acids will be produced from the catabolism of protein. Because the failing kidney does not produce enough NH4+ to excrete all of the fixed acid, metabolic acidosis (with respiratory compensation) results.

Thiazide diuretics have a unique effect on the distal tubule; they increase Ca2+ reabsorption, thereby decreasing Ca2+ excretion and clearance. Because parathyroid hormone (PTH) increases Ca2+ reabsorption, the lack of PTH will cause an increase in Ca 2+ clearance. Furosemide inhibits Na + reabsorption in the thick ascending limb, and extracellular fluid (ECF) volume expansion inhibits Na+ reabsorption in the proximal tubule. At these sites, Ca2+ reabsorption is linked to Na + reabsorption, and Ca2+ clearance would be increased. Because Mg2+ competes with Ca2+ for reabsorption in the thick ascending limb, hypermagnesemia will cause increased Ca2+ clearance

First, the acid-base disorder must be diagnosed. Alkaline pH, low PCO2, and low HCO3 are consistent with respiratory alkalosis. In respiratory alkalosis, the [H+] is decreased and less H+ is bound to negatively charged sites on plasma proteins. As a result, more Ca2+ is bound to proteins and, therefore, the ionized [Ca2+] decreases. There is no respiratory compensation for primary respiratory disorders. The patient is hyperventilating, which is the cause of the respiratory alkalosis. Appropriate renal compensation would be decreased reabsorption of HCO3-, which would cause his arterial [HCO3-] to decrease and his blood pH to decrease (become more normal).

First, the acid-base disorder must be diagnosed. Alkaline pH, with increased HCO3- and increased PCO2, is consistent with metabolic alkalosis with respiratory compensation. The low blood pressure and decreased turgor suggest extracellular fluid (ECF) volume contraction. The reduced [H+] in blood will cause intracellular H+ to leave cells in exchange for extracellular K. The appropriate respiratory compensation is hypoventilation, which is responsible for the elevated PCO2 . excretion in urine will be decreased, so less titratable acid will be excreted. K+ secretion by the distal tubules will be increased because aldosterone levels will be increased secondary to ECF volume contraction.