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Does THC excretion increase if urine volume increases?

Does THC excretion increase if urine volume increases?


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In regards to the body metabolizing and excreting THC: if urination is increased as a result of drinking lots of fluids, does that mean that more THC is leaving the body? To rephrase the question, is metabolism required for urination? Or can you simply urinate as a body process without metabolizing toxins from your body?


This question asks about the urinary excretion of THC. Before answering the question I think you're getting at, I'll first note that cannabinoids (of which THC is one) are primarily metabolized by hepatic cytochromes rather than being excreted directly. This article is a classical pharmacokinetic paper on the topic if you're able to access it; this one is a more recent general review accessible on Pubmed Central.

Cannabinoid metabolites are excreted both renally (via kidneys) and in the feces, so I'll understand your question to refer to the renally excreted portion. When considering renal excretion of any substance we think in terms of glomerular filtration rate, which refers to the volume of blood filtered through the glomerular capillaries per unit time, often estimated as creatinine clearance. The question then boils down to:

Does excess hydration increase GFR?

And the basic answer is: no. The kidneys control both volume and osmolality more distally, i.e. after the event of glomerular filtration.1

In the scenario you posit - drinking a lot of dilute fluid - osmoreceptors in the hypothalamus will sense the decreased plasma osmolality and suppress ADH (antidiuretic hormone, a.k.a. arginine vasopressin), the hormone that acts on the distal nephron to control water reabsorption. If ADH is completely suppressed, the kidneys can produce up to 25 L/day of urine with an osmolality as low as 60 mOsm/kg.2,3 This huge volume of urine, however, reflects water homeostasis achieved at the distal tubule rather than increased glomerular filtration. It does not correlate with increased excretion of THC metabolites or anything else at the level of the glomerulus.


Notes and References

1. If this makes no sense to you, you may want to check out this basic introduction to renal physiology that is available online. The referenced textbook in #3 below is more comprehensive but requires a library or purchase for access.

2. "Normal" urine osm ~300-800 mOsm/kg; plasma Osm ~280-290 mOsm/kg.

3. Christopher Lote. (2012). Principles of Renal Physiology. Springer New York.

P.S. If the question you really wanted to ask was, "Will drinking lots of water make my tox screen negative faster?"… I'm not answering that question. For reasons largely unrelated to the discussion here (but see references in paragraph #1), I suggest assuming that THC metabolites will be forever detectable via tox screen. ;-)


Urine: Concentration, Dilution & Formation | Excretory System | Biology

The normal kidney has tremendous capability to vary the relative proportions of solutes and water in the urine. They can excrete urine with an osmolarity as low as 50 mOsm/L, when there is excess water in the body and ECF osmolarity low. They can also excrete urine with a concentration of 1200-1400 mOsm/L, when there is a deficit of water and extracellular fluid osmolarity high.

Obligatory Urine Volume (OUV):

The maximal concentrating ability of the kidney depends on how much urine volume must be excreted each day, to void the body of waste products of metabolism and ions that are ingested. A normal 70 kg human must excrete about 600 mOsm of solute each day.

If maximum urine concentrating ability is 1200 mOsm/L, the minimal volume of urine is OUV can be calculated as:

(600 mOsm/day)/(1200 mOsm/L) = 0.5 L/day

Requirements for Excreting Concentrated Urine:

2. Hyperosmotic renal medulla.

When osmolarity of the body fluids increases above normal the posterior pituitary secretes more ADH.

This increases the permeability of the distal tubule and collecting duct to water. So, more water is reabsorbed and concentrated urine is formed.

When there is excess water and ECF osmolarity is reduced, ADH from posterior pituitary decreases, thereby reducing permeability of distal tubule and collecting duct to water causing dilute urine.

Hyperosmotic Renal Medulla:

Hyperosmotic renal medulla is produced by counter-current mechanism and urea.

The renal medullary interstitium surrounding the collecting duct is very hyperosmotic. So, when ADH levels are high, the water moves through the tubular membrane by osmosis into the renal interstitium, from there into vasa recta back into blood.

The countercurrent mechanism depends on the special anatomical arrangement of the long loops of Henle of juxtamedullary nephrons and the vasa recta, the specialized peritubular capillaries of the renal medulla. Loop of Henle is called as countercurrent multiplier and vasa recta as countercurrent exchanger.

The corrected osmolar activity which accounts for intermolecular attraction and repulsion is about 282 mOsm/L. The osmolarity of renal interstitium is about 1200 to 1400 mOsm/L in the tip of medulla.

The major factors that contribute to high solute concentration into the renal medulla are:

1. Active transport of sodium ions and cotransport of potassium chloride out of the thick ascending limb of LOH into medullary interstitium.

2. Active transport of ions from the collecting ducts into the medullary interstitium.

3. Passive diffusion of large amounts of urea from inner medullary CD into the medullary interstitium.

4. Diffusion of only small amounts of water from tubules into interstitium.

Countercurrent Multiplier System in the Loop of Henle (Fig. 8.24):

Assume the loop of Henle (LOH) is filled with fluid with a concentration of 300 mOsm/L, the same concentration as in proximal tubule.

The active transport of Na + and other ions out of thick ascending limb of LOH reduces the concentra­tion of solute inside tubule but raising in interstitium.

The tubular fluid in the descending limb of LOH and interstitium reaches osmotic equilibrium because of osmosis of water out of descending limb. The osmolarity in interstitium maintained at 400 mOsm/L.

It is additional flow of fluid into LOH from proximal tubule which causes hyperosmotic fluid in descending limb to move into ascending limb.

When fluid is in ascending limb, additional ions are pumped into interstitium with water remaining behind until a 200 mOsm/L osmotic gradient is reached, with interstitium fluid osmolarity raising to 500 mOsm/L.

Once again the fluid in descending limb reaches equilibrium with hyperosmotic interstitial fluid. This fluid moves from descending limb to ascending limb so more solute is pumped out of the tubules and deposited in interstitium. These steps are repeated again and again till interstitium osmolarity reaches 1200-1400 mOsm/L.

Urea Contribution to Hyperosmotic Renal Medullary Interstitium (Fig. 8.25):

Urea contributes about 40% (500 mOsm/L) of osmolarity of the renal medullary interstitium. When there is water deficit and ADH levels in blood are high, large amounts of urea are passively released from inner medullary collecting duct into interstitium which is highly permeable to urea.

Urea can also be re-circulated from collecting duct into interstitium. The thick ascending limb of LOH, distal tubule and cortical collecting duct are imper­meable to urea. A person usually excretes 40-60% of filtered urea.

Excretion depends on two factors:

a. Concentration of urea in plasma.

Countercurrent Exchange in the Vasa Recta Preserves Hyperosmolarity (Fig. 8.26):

The vasa recta are highly permeable to solutes in the blood, except for the plasma proteins. Plasma flowing down the descending limb of vasa recta becomes more hyperosmotic because of diffusion of solutes from interstitial fluid into blood. In the ascending limb LOH, solutes diffuse back into interstitial fluid and water diffuses back into vasa recta.

Osmolar Clearance (Cosm):

It is the volume of plasma cleared of solutes each minute. It is expressed in ml/min.

Uosm is urine osmalarity. V is urine flow rate. Posm is plasma osmolarity.

Free Water Clearance (CH2O):

The rate at which solute-free water is excreted by the kidneys. It is expressed in ml/min.

It is calculated as the difference between urine flow rate and osmolar clearance. When CH2O is positive, excess water is being excreted by kidney. When CH2O is negative excess solutes are being removed from the blood by kidneys.

Disorders of Urine Concentrating Ability:

1. Inappropriate secretion of ADH as in central diabetes insipidus, cause being congenital infections or head injuries.

2. Impairment of countercurrent mechanisms.

3. Inability of DT, CD to respond to ADH. In conditions like nephrogenic diabetes insipidus and in usage of various drugs like lithium and tetracyclines, even if ADH is produced in normal amounts, abnormality of kidneys makes them to fail to respond to ADH.

Formation of Urine—Glomerular Filtration:

The rate at which different subs the urine represents the sum of three renal processes:

2. Tubular reabsorption of substances from the renal tubules into the blood.

3. Tubular secretion of substances from the blood into renal tubules.

Excretion = Filtration – Reabsorption + Secretion

Urine Formation Renal Handling of Substances:

Four classes of substances:

a. Filtered, not reabsorbed (creatinine, inulin, uric acid).

b. Filtered, partly reabsorbed (Na + , CI – , bicarbonate).

c. Filtered, totally reabsorbed (amino acids, glucose).

d. Filtered, totally secreted (organic acids and bases).

Glomerular Filtration (Fig. 8.13):

It is the first step in urine formation.

Glomerular filtrate is produced from blood plasma. It must pass through the glomerular membrane which is relatively impermeable to proteins. So the filtrate is similar to plasma in terms of concentrations of salts and of organic molecules (e.g., glucose, amino acids) except it is essentially protein-free and devoid of cellular elements including red blood cells.

Formation of Urine—Tubular Reabsorption and Tubular Secretion:

Tubular reabsorption and tubular secretion are selective and quantitatively large. It includes both passive and active transport mechanisms. Water and solutes can be transported through all membranes themselves (transcellular route) or through the junctional spaces between the cells (paracellular route). From the cells into interstitial fluid, water and solutes are transported by ultrafiltration (bulk flow) mediated by hydrostatic and colloid osmotic forces.

Potassium ATPase, hydrogen ATPase, hydrogen-potassium ATPase and calcium ATPase are examples of primary active transport. It moves solutes against an electrochemical gradient. The energy is provided by the membrane bound ATPase.

In secondary active co-transport of glucose and amino acids, sodium diffuses down its electrochemical gradient the energy released is used to drive another substance that is glucose/amino acid.

2. Secondary Active Counter Transport:

Sodium hydrogen counters transport. The energy liberated from the downhill of one of the substances (e.g., sodium) enables uphill of a second substance (hydrogen) in the opposite direction.

Reabsorption of proteins occurs by this process. In this, protein gets attached to the brush border of the luminal membrane which invaginates into the interior of the cell until it completely pinches off and a vesicle is formed.

As water moves across the tight junctions by osmosis, it can also carry with it some of the solutes a process called solvent drag.

Transport maximum (Tm) for substances that are actively reabsorbed or secreted. There is a limit to the rate at which the solute can be transported, termed as transport maximum. This is due to the saturation of the specific transport systems involved when the tubular load of solutes exceed the capacity of the carrier proteins involved in the transport process.

There is a relation between tubular load of glucose, Tm for glucose and rate of glucose loss in the urine, when tubular load is 125 mg/min, there is no loss of glucose in urine. When tubular load rises above 180 mg/min, a small amount appears in the urine that is called renal threshold for glucose. This appearance of glucose occurs even before Tm is reached. The reason being not all nephrons have same Tm for glucose.

The ideal curve shown in this diagram (Fig. 8.18) is obtained if the TmG in all the tubules was identical. This is not the case in humans, the actual curve is rounded and deviates from the ideal curve. This deviation is called splay. The magnitude of the splay is inversely proportionate to the avidity with which the transport mechanism binds the substance it transports. Tm for actively secreted substances.

Gradient Time Transport:

It is for passively reabsorbed substances which depend on the electrochemical gradient and the time that the substance is in the tubule which in turn depends on the tubular flow rate.

Regulation of Tubular Reabsorption:

Sympathetic nervous system stimulation decreases.

a. Sodium and water excretion by constricting the renal arterioles.

b. Increase Na reabsorption in proximal tubule and thick ascending limb of LOH.

c. Increases renin and angiotensin II release.

Hormones that regulate tubular reabsorption:

Site of action ― Collecting duct.

Effects ― Increases NaCl, H2O reabsorption increases K + secrection.

Site of action ― Proximal convoluted tubule, thick ascending limb of loop of Henle.

Effects ― Increases Nacl, H2O reabsorption and H + secrection

Site of action ― Distal tubule/Collecting duct

Effects ― Increases H2O reabsorption

Site of action ― Distal tubule/Collecting duct

Effects ― Increases NaCl reabsorption

Site of action ― Proximal tubule, thick ascending limb, distal tubule

Effects ― Decrease PO4 – reabsorption in proximal tubule

Increases Ca ++ release in loop of Henle

Increases Mg + reabsorption in loop of Henle

a. Glomerulotubular balance: Increased GFR increases the tubular load thereby increasing tubular reabsorption.

b. Peritubular capillary and renal interstitial forces. Reabsorption = Kf × Net reabsorption force (NRF).

The NRF represents the sum of hydrostatic and colloid osmotic forces which favor or oppose reabsorption across peritubular capillaries.

These forces are (Fig. 8.19):

a. Peritubular hydrostatic (Pc) pressures oppose RA = 13 mm Hg.

b. Renal interstitial hydrostatic (Pif) favoring RA = 6 mm Hg.

c. Colloid osmotic pressure in peritubular capillaries favors RA (C) = 32 mm Hg.

d. Colloid osmotic pressure in renal interstitium opposes RA (if) = 15 mm Hg.

Proximal Convoluted Tubules:

i. Reabsorbs 65% of glomerular filtrate by active transport.

ii. Reabsorbs Na + , CP, HCO3, K + , Ca + , H2O, glucose, amino acids, vitamins, uric acid and phosphates. Pars recta secretes substances like creatinine, phenolphthalein dyes, PAH, acids, bases, drugs like penicillin, sulphonamides.

Descending thin segment is highly permeable to water. Water moves out of nephron reducing the volume of filtrate and increasing its osmolarity.

Ascending thick segment is not permeable to water but is permeable to solutes. 25% of filtered solutes are reabsorbed.

Distal Tubule (Fig. 8.20):

The very first portion of the distal tubule forms part of JG apparatus. The next early part is highly convoluted and has same re-absorptive characteristics as that of ascending limb of loop of Henle. Na + , Cl – H2O, HCO3, Ca + and K + are reabsorbed but impermeable to water and urea. This is also known as diluting segment because it dilutes the tubular fluid.

The second part of the distal tubule is the late distal tubule continues as cortical collecting tubule having principal cells and intercalated cells. The tubular membranes are impermeable to urea is concerned with Na + , CI – reabsorption, HCO3 secretion, HCO3 reabsorption, secretion of K + and H + secretion. The permeability of the tubules to water is controlled by antidiuretic hormone (ADH) (Fig. 8.21).

Medullary Collecting Duct:

They are the final site for processing urine. The permeability to water depends on presence of ADH. They are permeable to urea and secrete H + against a large concentration gradient. 15% of solutes are reabsorbed in distal tubule and collecting duct.

Sodium and Chloride Reabsorption:

Na + is reabsorbed in PCT, thick segment of LOH and distal nephron except in thin segment.

Unidirectional Na Transport:

Movement of Na + against concentration gradient-glucose, amino acids and phosphate are transported with it.

Na + — H + exchange (antiport)

In thick ascending limb-25%:

1 Na + — 1 K + — 2 CI – symporter.

Unidirectional Na + transport but under the influence of aldosterone.

Glucose and Amino Acid Reabsorption:

ii. Na + cotransport mechanism.

Sodium dependent glucose transporter (SGLT) on luminal (apical) membrane and glucose transporter on the basolateral membrane (GLUT).

Passive transport by osmosis (couples to Na re­absorption).

Solvent drag through paracellular route—water takes Na + , CI – , K + , Ca + , Mg + along with it. As the substances are absorbed proportionally, the fluid remains isotonic at the end of PCT. This passive reabsorption of water is called obligatory type of reabsorption.

ADH introduces water channels called aquaporins which allows water absorption. Water is absorbed from collecting duct only in the presence of ADH. This is called facultative type of reabsorption.

Potassium and Reabsorption Secretion (Fig. 8.21):

In PCT- Solvent drag through paracellular route causes K + reabsorption.

Minimal secretion of K + occurs through the luminal membrane.

In Thick Ascending Limb:

1 Na + — 1 K + 2 Cl – co-transporter causes reabsorption.

In late distal tubule and collecting duct, P cells, reabsorb Na + and secrete K + . I cells reabsorb K + and HCO3, secretes H + ions.


Antidiuretic hormone (ADH)

ADH, a 9-amino acid peptide released by the posterior pituitary – in brain, works to do the exact opposite. It promotes the recovery of water, decreases urine volume, and maintains plasma osmolarity and blood pressure. It does so by stimulating the movement of aquaporin proteins into the apical cell membrane of principal cells of the collecting ducts to form water channels.

A proper water balance in the body is important to avoid dehydration or over-hydration. The water concentration of the body is monitored by osmoreceptors in the hypothalamus, which detect the concentration of electrolytes in the extracellular fluid. The concentration of electrolytes in the blood rises when there is water loss caused by excessive perspiration, inadequate water intake, or low blood volume due to blood loss. An increase in blood electrolyte levels results in a neuronal signal being sent from the osmoreceptors in hypothalamus.

The hypothalamus produces a polypeptide hormone known as antidiuretic hormone (ADH), which is transported to and released from the posterior pituitary gland. The principal action of ADH is to regulate the amount of water excreted by the kidneys. As ADH (which is also known as vasopressin) causes direct water reabsorption from the kidney tubules, salts and wastes are concentrated in what will eventually be excreted as urine. The hypothalamus controls the mechanisms of ADH secretion, either by regulating blood volume or the concentration of water in the blood. Dehydration or physiological stress can cause an increase of osmolarity above 300 mOsm/L, which in turn, raises ADH secretion and water will be retained, causing an increase in blood pressure. ADH travels in the bloodstream to the kidneys. Once at the kidneys, ADH changes the kidneys to become more permeable to water by temporarily inserting water channels, aquaporins, into the kidney tubules and collecting ducts. . Water moves out of the kidney tubules through the aquaporins, reducing urine volume. The water is reabsorbed into the capillaries lowering blood osmolarity back toward normal. As blood osmolarity decreases, a negative feedback mechanism reduces osmoreceptor activity in the hypothalamus, and ADH secretion is reduced. ADH release can be reduced by certain substances, including alcohol, which can cause increased urine production and dehydration.

Diabetes insipidus (DI)

Diabetes insipidus (DI) is a rare disease that causes frequent urination. Chronic underproduction of ADH or a mutation in the ADH receptor results in diabetes insipidus. If the posterior pituitary does not release enough ADH, water cannot be retained by the kidneys and is lost as urine. To make up for lost water, a person with diabetes insipidus may feel the need to drink large amounts and is likely to urinate frequently, even at night, which can disrupt sleep and, on occasion, cause bedwetting. Because of the excretion of abnormally large volumes of dilute urine, people with diabetes insipidus may quickly become dehydrated if they do not drink enough water. If the condition is not severe, dehydration may not occur, but severe cases can lead to electrolyte imbalances due to dehydration.

Diabetes insipidus should not be confused with diabetes mellitus (DM), which results from insulin deficiency or resistance leading to high blood glucose, also called blood sugar. Diabetes mellitus has two main forms, type 1diabetes and type 2 diabetes. Diabetes insipidus is a different form of illness altogether.


ADH, also known as arginine vasopressin, is formed in the hypothalamus and stored in the posterior pituitary via a pituitary stalk. The main function of ADH is osmoregulation. However, a severe reduction in effective blood volume shifts the function of ADH to volume regulation, even at the expense of effective plasma osmolality or tonicity. "Plasma osmolality" should be differentiated from "effective plasma osmolality" or "plasma tonicity," as the latter is determined by effective osmoles in the extracellular fluid  (ECF) such as sodium (which is not freely permeable across cell membranes), the main component of the ECF. Glucose and urea also increase the plasma osmolality, but these are ineffective osmoles as they are freely permeable across the cell membranes and do not take part in maintaining plasma tonicity.  

The most important and primary function of ADH is to maintain the plasma tonicity, primarily by an alteration in water balance. Osmoreceptors detect the change in effective plasma osmolality in the hypothalamus. A decrease in tonicity prevents ADH release and prevents water retention. An increase in tonicity causes ADH release, which acts on V2 receptors on the luminal surface of cortical and medullary collecting tubular cells. Under the influence of ADH, uniqueਊquaporin-2 water channels are formed by the fusion of pre-formed cytoplasmic vesicles in the tubular cells, and water is absorbed down the concentration gradient. Once the water is absorbed, these channels are removed by endocytosis and returned to the cytoplasm. The osmoreceptors are extremely sensitive, responding to alterations in the plasma tonicity of as little as 1%.[6] The osmotic threshold for ADH release in humans is about 280 to 290 mOsmol/kg. There is little circulatingꂭH below this level, and the urine should be maximally diluted with an osmolality below 100 mOsmol/kg. Above the osmotic threshold, there is a relatively linear rise in ADH secretion. This system is so efficient that the plasma osmolality does not typically vary by more than 1% to 2%, despite wide water intake fluctuations.[7]

In patients with SIADH, levels of ADH are high even in the presence of decreased plasma osmolality and/or hyponatremia. Excess water absorption keeps the blood volume high or normal. 

An acute drop in blood pressure as sensed by " volume receptors" rather than "osmoreceptors" causes ADH release (along with other hormones like rennin and epinephrine), which generates free water absorption from the kidneys. This can potentially lead to hyponatremia and a decrease in effective ECF osmolality. So, the main focus in rapid and/or substantial decrease in blood volume is "volume regulation," even at the cost of osmolality. This effect is more prominent in patients with liver disease or cardiac disease, and hyponatremia in such patients is the direct predictor of a worse prognosis.[8]


Results

Demographics

A total of 31 healthy women and men were enrolled in the study. Five subjects were excluded due to: abnormal blood samples (1), 24-h BP above 130/80 mmHg (1), non-compliance (1) and withdrawal of informed consent (2). Thus, 26 persons completed the study. Three were not able to void satisfactorily during clearance experiments and were excluded from analysis. One was not able to void in two post intervention periods after 3% NaCl and was excluded in channel analysis only.

The remaining 23 males (n = 9) and women (n = 14) had a median age of 26 years (range 18–42) and a mean BMI of 24.4 ± 2.3 kg/m 2 . Mean ambulatory blood pressure was 119/70 ± 8/4 mmHg. Screening blood values were b-haemoglobin 8.5 ± 0.7 mmol/L, p-sodium 139 ± 2, p-potassium 3.9 ± 0.4 mmol/L, p-creatinine 74 ± 9 μmol/L, p-albumin 42 ± 3 g/L, p-glucose 5.1 ± 0.6 mmol/L, p-alanine transaminase 25 ± 9 U/L and p-cholesterol 4.5 ± 0.5 mmol/L.

Twenty-four-hour urine collection

Table 1 shows the results of the 24-h urine collection in 23 healthy subjects after 4 days of standardized diet. Mean u-AQP2, u-ENaCγ, urinary sodium, urine osmolarity, CH2O and urine volume were the same in all three examination days indicating that the subjects had kept their supplied diets and fluid intake.

Water excretion, u-AQP2, u-osm

Table 2 shows the absolute values of UO, CH2O, u-AQP2CR, u-AQP2 excretion rate and u-osm during the baseline period, the infusion period and the post infusion period.

UO increased significantly after 0.9% NaCl and glucose. The 3% NaCl infusion induced a significantly and sustained decrease in UO. The relative changes in UO were significantly different between the three interventions.

CH2O increased during the infusion with 0.9% NaCl, and decreased slightly, although significant in the postinfusion period. At the end of the examination-day CH2O increased towards baseline levels with an over all relative change of -10%. There was a pronounced increase in CH2O after glucose, whereas CH2O decreased after 3% NaCl and changed from positive values at baseline to negative values after infusion. Thus, indicating a change from free water excretion to water reabsorption (Table 2).

U-AQP2CR increased by 27% (p < 0.001) in response to 0.9% and by 26% (p < 0.0001) after 3% NaCl and reached maximum at 240 min after baseline. During glucose infusion (90–150 min) there was a primary increase in u-AQP2CR after which u-AQP2CR decreased and reached a minimum of - 16% (p < 0.0001) at 210–240 min (Figure 1A). The excretion of u-AQP2 divided by gender, showed that u-AQP2CR tended to be higher in women than in men, but there was no statistical significant difference. This was due to a lower creatinine concentration in women’s urine (data not shown). U-AQP2 excretion rate followed the same pattern (Table 2). The relative changes in u-AQP2 did not differ between 3% NaCl and 0.9% NaCl, but both were significantly different from the relative change in u-AQP2 after glucose infusion.

Effects of isotonic 0.9% saline (■), hypertonic 3% saline () and isotonic glucose () on urinary excretion of A) u-AQP2 and B) u-ENaCγ adjusted to creatinine, C) plasma concentration of vasopressin (AVP) and D) plasma osmolality in 23 healthy subjects. Values are means ± SEM. Paired t-test was used for comparison of post infusion period 210–240 min vs. baseline. * p < 0.01 ** p < 0.001 *** p < 0.0001.

U-Osm decreased during 0.9% NaCl infusion with minimum after infusion ended at 150 minutes, after which u-osm increased, coherent with the changes seen in CH2O. U-osm increased significantly in response to 3% NaCl and lasted throughout the experiment. During glucose infusion u-osm remained constant for 60 minutes until glucose infusion was completed, after which u-osm declined and reached minimum at 210–240 min (Table 3).

Sodium excretion, u-ENaCγ, u-Na, FENa, u-K and FEK

Table 3 shows the absolute values of u-Na, FENa, u-K, FEK, u-ENaCγCR and u-ENaCγ excretion rate during the baseline period, the infusion period and the post infusion period.

Infusion with 0.9% NaCl and 3% NaCl were accompanied by a significant and similar increase in u-Na and FENa that lasted throughout the experiment. There were no significant differences between 0.9% NaCl and 3% NaCl infusions. In contrast, U-Na and FENa decreased after glucose infusion. The relative changes in u-Na and FENa were significant lower after glucose compared to both saline infusions.

U-K and FEK decreased significantly after all three infusions, but with the greatest extend after glucose infusion. In the post infusion period (150–240 min) the excretion of potassium in urine increased slightly more after 3.0% NaCl than 0.9% NaCl, but did not reach baseline levels.

U-ENaCγCR decreased slightly, but non-significantly during 0.9% NaCl and glucose infusions. A significant increase was seen in u-ENaCγCR in response to 3% NaCl (p < 0.01) (Figure 1B) and the relative increase in u-ENaCγCR were significantly higher in response to 3% NaCl compared to 0.9% NaCl and glucose. Divided by gender the differences in u-ENaCγCR showed no statistical significant difference, although u-ENaCγCR tended to be higher in women due to the lower urine creatinine (data not shown). U-ENaCγ excretion rate followed the same pattern with regard to saline infusions, whereas a significantly lower u-ENaCγ excretion rate occurred after glucose infusion (Table 3).

Vasoactive hormones

PRC, Ang II and Aldo were suppressed to the same extent in all three parameters in response to 0.9% NaCl and 3% NaCl with no significant difference between interventions. There was a primary decrease during glucose infusion (90–150 min), but when infusion ceased values returned to baseline levels with no overall significant change (Figure 2).

Effects of isotonic 0.9% saline (■), hypertonic 3% saline () and isotonic glucose () on plasma renin (A), plasma angiontensin II (B) and plasma aldosterone (C) concentrations. Values are expressed as mean ± SEM. General linear model (GLM) with repeated measures within subjects was significant for all three variables. Paired t-test was used for comparison within treatment groups at postinfusion 240 min vs. basal. * p < 0.0001.

AVP did not change in response to 0.9% NaCl and glucose, but increased significantly after 3% NaCl with a maximum at 150 minutes and a steady fall during the post infusion period (Figure 1C).

Blood pressure, pulse rate, GFR, p-Na, p-alb and p-osm

Table 4 shows the absolute values of systolic and diastolic blood pressure, pulse rate, GFR, plasma sodium and plasma albumin during the baseline period, the infusion period and the post infusion period.

Systolic BP was the same after all three infusions. There was a small difference in diastolic BP pattern during the examination day, but the changes were very small and might be by chance. During the examination day pulse rate increased slightly in response to 0.9% NaCl and 3% NaCl, while the heart rate increased to a higher extent in response to the glucose infusion (Table 4). The increase in pulse rate did not differ between 0.9% saline and 3% saline, but there was a difference in the relative increase in pulse rate between saline and glucose infusion (p < 0.01).

GFR increased slightly, although significantly, on the examination day. However the changes were very small (Table 4).

P-Na increased in response to both 0.9% NaCl and 3% NaCl with maximum after 150 minutes. In response to glucose p-Na decreased markedly after 150 minutes to a mean of 128.7 mmol/l (Table 4). The increase was higher after 3% NaCl compared to 0.9% NaCl and accordingly the changes after glucose were lower compared to saline.

P-alb decreased significantly in response to 0.9%, 3% NaCl and glucose infusions. The decline was significantly lower and sustained after both saline infusions compared to glucose, which is related to an expected increase in extracellular fluid.

P-osm increased slightly during 0.9% NaCl infusion, but remained unchanged at the end of the examination day. P-osm increased significantly in response to 3% NaCl, with a maximum of 293 mosm/kg and decreased significantly after glucose to 280 mosm/kg at 150 min. The changes in p-osm indicated that isotonic, hypertonic and hypotonic conditions were established (Figure 1D).

Fluid, sodium balance and body weight during the examination days

The average fluid administered intravenous was 1749 ml of 0.9% NaCl (SD 270), 555 ml of 3% NaCl (SD 90) and 1736 ml of glucose (SD 282). The cumulative water input was 3674 ml (SD 270), 2480 ml (SD 90) and 3661 ml (SD 282) respectively, as participants drank an additional 1925 ml of tap water each examination day. During the examination days the average total urine output was 1858 ml (SD 246) in subjects who received 0.9% NaCl, 984 ml (SD 202) in subjects who received 3% NaCl and 2682 ml (SD 351) in subjects who received glucose. The fraction of water excreted after 240 min was 51% when 0.9% NaCl was infused, 40% when 3% NaCl was infused and 73% when glucose was infused. The total amount of sodium infused was 269 mmol (SD 42) of 0.9% NaCl and 285 mmol (SD 46) of 3.0% NaCl. The cumulative sodium output at 240 min was 50 mmol (SD 16) after 0.9% NaCl, 54 mmol (SD 21) after 3% NaCl and 21 mmol (SD 9) after glucose. The fraction of sodium excreted after 240 min was 19% after both 0.9% and 3% NaCl infusions. This was accompanied by a significant increased bodyweight in response to 0.9% NaCl from 73.2 kg (SD 11.3) at baseline to 74.3 kg (SD 11.4) at the end of the study day [+1.1 kg (SD 0.39) p < 0.0001], in response to 3% NaCl from 73.3 kg (SD 11.6) at baseline to 74.1 kg (SD 11.7) at the end of the study day [+0.8 kg (SD 0.39) p < 0.0001] and to a smaller extent in response to glucose from 72.8 kg (SD 11.8) at baseline to 73.1 kg (SD12.0) at the end of the study day [+0.3 kg (SD 0.5) p <0.05].


How Long Does Weed Stay in Your System

Unfortunately, it is impossible to say EXACTLY how long weed stays in your system. We can only calculate the approximate length of time. What we do know is that the half life of THC metabolites in the human body ranges between 1 and 10 days.

Every case is different, though, and too many factors influence THC half life, so we can only approximate how long marijuana stays in the human body.

The length of time depends on such factors as the age and weight of the individual, personal metabolism, physical activity, and amount and potency of the weed. Infrequent users eliminate THC faster, while it will usually stay in the system of frequent users for a longer period of time.

Frequency of use The time THC stays in urine
Single use 2–3 days
Occasional use 4–7 days
Regular use 7–30 days

If you smoke marijuana occasionally, you have a good chance to pass a urine drug test in less than a week.

A person’s weight is also very important. THC accumulates in fat cells, so thin people have less space to store it. They also usually have faster metabolism. These two factors make it easier for them to beat a drug test.

Home Urine Test for Marijuana


Stop smoking weed, and test your urine in the morning every day until you see negative results. This is your personal detection time, but even this time can vary, if you change your smoking habits and lifestyle. Don’t trust a friend’s experience! Monitor your own THC levels, because everybody is different.


Hormonal disorders

It is of interest that the serum sodium concentration may be low (by as much as 130 mmol/L) in pregnant women owing to human chorionic gonadotropin-induced release of a hormone (relaxin) that is associated with a downward resetting of serum osmolality. 31

Hyponatremia can occur in the setting of adrenal (primary or secondary) insufficiency and hypothyroidism. 32 , 33 Therefore, serum levels of thyroid-stimulating hormone and random cortisol should be determined in confusing cases of hyponatremia and before a diagnosis of SIADH is made. Glucocorticoid deficiency increases water permeability in the collecting tubules. Elevated ADH levels have also been found in patients with glucocorticoid deficiency. 32 In patients with hypothyroidism, both ADH-mediated and intrarenal mechanisms have been implicated in the pathogenesis of hyponatremia. 33


Methods

This study was approved by the Mayo Clinic Institutional Review Board.

GENOA cohort

The multi-phase Genetic Epidemiology Network of Arteriopathy (GENOA), a member of the Family Blood Pressure Program (FBPP), recruited non-Hispanic white hypertensive sibships from Rochester, Minnesota (MN), for linkage and association studies to investigate the genetic underpinnings of hypertension in phase I (1996–2001) [8]. The Genetic Determinants of Urinary Lithogenicity (GDUL) study (2006–2012) is an ancillary study conducted in Rochester, MN, GENOA cohort members [9]. Participants were invited to collect 24-h urine samples and complete a food frequency questionaire (FFQ, Viocare Technologies, Princeton, NJ, USA) [10]. Participants were excluded from this study if they were in endstage renal failure (stage 5 CKD). All other GENOA subjects were eligible. Of note, recruitment for the original GENOA study and the current GDUL ancillary study was not based on CKD status or on the presence (or absence) of urinary stones.

Study visit

After informed consent, participants completed at least one 24-h urine collection [11, 12] and the FFQ at a CKD and/or GDUL study visit. A total of 299 (42.7 %), 227 (32.0 %), and 183 (25.8 %) participants had a total of one, two, or three urine collections, respectively. For individuals with two or three urine collections, values were averaged for analysis. The mean time between the earliest and latest urine collections was 1.73 years (range = 0.9 to 3.6 years). The average time between the two GDUL collections was 22 days. Intraclass correlation coefficients (ICCs) for urine factors across collections revealed that the majority of urine measures were relatively stable across time. Urine osmolality ICC was 0.59 and urine volume ICC was 0.67. Participants also completed a detailed Kidney Stone Questionnaire (to assess stone forming status). Subjects completed the questionnaires at the time of a study visit, which was in general within 1 to 2 days of the urine collection.

Urine collection

Toluene (30 ml) was added as a preservative [13] to the collection bottle at the start of all 24-h collections.

Twenty-four-hour urine osmolality, volume, sodium, and potassium were measured in the Mayo Clinic Renal Testing Laboratory. Serum creatinine was assessed using a standardized enzymatic assay on a Roche Cobas chemistry analyzer (c311) (Roche Diagnostics Indianapolis, IN, USA) while cystatin C was measured using an immunoturbidimetric assay (Gentian Moss, Norway) that was traceable to an international reference material. Glomerular filtration rate (GFR) was independently estimated using cystatin C (eGFRCys) [14].

Descriptive statistics

Data management and statistical analyses were conducted in SAS version 9.3 (SAS Institute Inc., Cary, NC, USA) [15]. Urine measures appeared to have relatively normal distributions thus, no variable transformations were applied. Values that were ≥4 standard deviations from the mean of any urine or diet measure were removed. The contribution of electrolytes to urine osmole load was estimated as 2 × (urine sodium + urine potassium), while urea contribution was calculated as the difference between the total osmole excretion and electrolyte contribution. Linear mixed effects models (LMM) that included sibship as a random intercept (to properly account for family structure) were used to test whether there were significant differences by sex for the urinary and diet measures.

Association testing

To account for the sibships, a randomly selected, independent subset of the GENOA cohort (one individual per sibship n = 414) was used for stepwise linear regression to determine the variables that were associated with each urinary measure. Variables available for selection included the following: weight, body mass index (BMI), smoking status (current or never smoker), diabetes status (yes/no), fasting blood glucose level, systolic blood pressure (SBP), diastolic blood pressure (DBP), eGFRCys, diuretic loop use (yes/no), diuretic thiazide use (yes/no), and dietary variables from the FFQ including animal protein, sodium, water (including food-derived water), calcium, fructose, oxalate, total protein, and sucrose intakes. The entry criterion was p < 0.05, and the exit criterion was p > 0.10. Age, sex, and serum creatinine were forced into each model.

After model selection, LMM was performed on the full GENOA sample to assess significant predictors of the urinary measures, accounting for the sibship structure in GENOA. Interaction models were also conducted to assess interactions of age, sex, and weight (if weight was included in the model selection as a predictor) with the variables included in the models. Interactions were considered significant at an alpha level of 0.05.

Figures 1, 2, and 3 were created using a scatter plot of the variable of interest (age or urine volume) and an outcome variable (urine osmolality or total mOsm/day) to visualize the relationship between the two variables. Scatter plots were colored by gender, and linear mixed model regression lines were superimposed on the scatter plots controlling for sex and accounting for sibship structure. Lines were plotted by taking the intercept for males and the intercept for females, with the slope from the variable of interest. The beta estimate for sex is reported as the difference in outcome variable for males versus females with corresponding significance.

Effect of age on urine osmolality in males and females (age β = −5.00, p < 0.0001 sex β = 142.6, p < 0.0001)

Relationship between total urine osmole excretion and age in females and males (age β = −12.296, p < 0.0001 sex β = 272.633, p < 0.0001)

Relationship between urine osmolality and volume in females and males (volume β = −0.1597, p < 0.0001 sex β = 135.63, p < 0.0001)


Journal of Sports Medicine and Therapy

Javier Calderón Montero*

Physical and Sports Education, Research Group of the Physiology of Effort Laboratory, Spain

*Address for Correspondence: Javier Calderón Montero, Physical and Sports Education, Research Group of the Physiology of Effort Laboratory, Spain Tel: 512-400-0398 (or) 91-336-40-20 Email: [email protected]

Dates: Submitted: 14 December 2018 Approved: 31 January 2019 Published: 01 February 2019

How to cite this article: Montero JC. Renal function during exercise and recovery. J Sports Med Ther. 2019 4: 008-015. DOI: 10.29328/journal.jsmt.1001037

Copyright: © 2019 Montero JC. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This review paper analyzes the response of renal function during two types of exercise: 1) exercise of increasing intensity and 2) exercise of submaximal intensity and prolonged duration. During an effort of increasing intensity there is a decrease in renal blood flow that, theoretically, could compromise renal function. However, several studies seem to show that the kidney has self-regulatory mechanisms that allow maintaining the filtration fraction. On the other hand, ultra resistance exercises, such as ironman, are becoming more frequent. Knowing the renal response to this type of exercise is essential to apply knowledge to emergency situations such as dehydration or hyponatremia.

Introduction

The function of the kidneys in vertebrates is not limited to the plasma filtration process. Since the final result of renal function, urine, is practically water, electrolytes and waste substances, implies that the kidney plays a major role in the regulation of body fluids. The kidney intervenes with great precision on the extracellular fluid both quantitatively and qualitatively. For this you have two possibilities. First, the kidney is able to concentrate or dilute urine through complex mechanisms. Secondly, the kidney is the “target organ” of hormonal systems that play a decisive role in the formation of a concentrated or diluted urine.

Apart from this transcendental function in the control of hydroelectrolytic homeostasis, this double organ intervenes in the following general functions:

1. control of acid-base balance

2. the control of erythropoiesis, since it is the main organ in secreting erythropoietin, a hormone that stimulates the bone marrow

3. the control of calcium homeostasis, since it transforms 25 hydroxycholecalciferol, that is, into physiologically active vitamin D.

Thus, the magnitude of renal function transcends that corresponding to the formation of urine. However, in this revision work the indicated functions will not be addressed. Despite the importance of the renal function reviewed, it is paradoxical that the treatment given in the exercise physiology books. For example, in two books widely used in the field of exercise physiology [1,2] there are no specific sections related to renal function during exercise. What may be the reasons why this part of physiology has not been addressed, even in an elementary way, in the physiology texts of the exercise of frequent use? The reasons may be the following:

1. The kidney is a “silent” organ during physical exercise that does not intervene in the supply of oxygen and obtaining energy. This may determine that it is not necessary to study kidney function during exercise.

2. The complexity of the study of renal function during exercise, which is limited to the analysis of urine and inferring renal function.

However, these reasons are somewhat weak, since this body is primarily responsible for the quantitative and qualitative control of the extracellular fluid. The study of renal function during physical exercise and prolonged duration is essential to understand the participation of the kidney in the regulation of body fluids and the recovery process after training. Despite the aforementioned, some researchers have shown interest in the kidney-exercise relationship. Mainly, the interest in renal function during exercise can be grouped into two types of questions that, as often happens, allude to physiology and pathology and that are listed in the form of the following questions:

1ª) Does the reduction of FSR affect renal function during exercise? [3-6].

2) How does it participate in the kidney during efforts in which the loss of fluid is considerable? [7-11].

3ª) What is the origin of some of the renal alterations that athletes suffer? Are these alterations transitory or can they harm the athlete’s health in the long term, once he has left the competition? [3-6].

This review paper analyzes in a simple way the renal function in exercise and post-exercise situation based on the research carried out, fundamentally in two types of efforts:

Exercise of increasing intensity and short duration

The release of this acid can compromise the acid-base state. The importance of renal function lies in reversing the state of metabolic acidosis. This is not a simple process and requires time after the end of the exercise. Unfortunately, there are few articles that address the role of the kidney during recovery. An elementary search in medline (renal function AND post-exercise AND recovery in title / abstract) shows 3 articles, two of which [12,13] study renal function in resistance efforts.

In a simple way, table 1 shows the situation of imbalance that has occurred as a result of a high intensity exercise during a limited period of time. The analysis of the table allows us to ask the following questions:

Table 1: Some parameters of the acid-base state after intense exercise.
Reposo 25 % 50 % 75 % 100 %
PH 7,42 7,40 7,35 7,30 7,00
Exceso de bases (mEq/L) 0 193,3
Bicarbonato (mEq/L) 24 24 24 22 18

1ª) given the need to restore the acid base state to the resting situation, to what extent does renal function intervene? The situation of metabolic acidosis triggered by the release of acids into the bloodstream during intense exercise must be compensated in an elementary manner with the replacement of the “spent base” as a result of the plasma buffer.

2nd) inevitably, the restitution of spent bicarbonate determines the elimination of acids by urine. This elimination is done in a controlled manner by the kidney, mainly through the elimination of an acid, the ammonium ion (NH4 +)

2) Renal function during an exercise of submaximal intensity and prolonged duration.

Unlike the efforts of high intensity and short duration, in the efforts of resistance or ultra-resistance, the renal function aims to maintain the hydro-electrolytic balance, since there is loss of water and electrolytes by the main mechanism of heat removal, sweating. Table 2 shows the fluid losses during the exercise of high intensity and prolonged duration. The analysis of the data in this table suggests two relevant considerations:

Table 2: Approximate loss of fluid at rest and exercise.
REPOSO EJERCICIO
Riñón 1400 ml 500 ml
Piel (transpiración) 350 ml 350 ml
Pulmón 350 ml 650 ml
Heces 200 ml 200 ml
Piel (sudoración) 100 ml 4000 ml

1ª) Reduction of urine volume (oliguria). Logically, it is an “intelligent” adaptation of the organism, because it preserves it from a loss of fluid that would lead to dehydration in a short time, due to loss of water and electrolytes due to sweating. Now, how is oliguria related to renal function?

2nd) the loss of fluid requires the immediate restitution of the quantitative and qualitative levels of the two corporal compartments, in order to return to homeostasis: what type of water and electrolyte replacement should be done?

Next, renal function is approached in these two forms of exercise in a simple way based on the understanding of the functional unit of the kidney: the nephron. Of the general, in the different studies that have approached the renal function during the exercise there are two ways: 1st) according to the different parts of the nephron, you can study the glomerular and tubular functions in relation to the exercise and 2nd) depending on the functions of renal function (filtration, reabsorption, excretion and elimination).

The renal function during the rising intensity exercise

In regulated efforts such as those carried out during conventional stress tests or in those performed at intervals and intensities above the value corresponding to the maximum oxygen consumption, the anaerobic energy yield increases, with the consequent production of a strong acid (pK = 3.86, [14]). The acid-base state during the exercise has been deeply studied from an elementary level to relatively deep physical-chemical explanations, so this section will be limited to explain the variations of the acid-base state from the renal perspective.

Lactic acid concentration / intensity ratio: It is amply demonstrated that the concentration of lactic acid in plasma increases as the intensity increases, experiencing an exponential increase from a certain load. Up to this value, known as the lactic threshold, the muscle is an excellent “buffer” of the acid load following the dissolution of the acid in water (LH + H2O = L- + H3O +), since it has a high difference of strong ions (SID). ) and a high concentration of anions (A-) [15]. However, when the production of lactic acid could exceed the capacity “cushioning” of the muscle, through a complex mechanism linked to transporters of monocarboxylic acids (MCT) [16], the “elimination” of the acid to the blood. Again, the cushioning capacity of this “liquid” fabric is remarkable. On the one hand, the erythrocytes have a high buffer capacity (high SID) and the fundamental function of hemoglobin. In addition, the high concentration of bases, mainly of sodium bicarbonate (LH + NaHCO3 = LNa + H2CO3), make the plasma an extraordinary buffer solution: 1) it transforms a strong acid into its corresponding salt and 2º) a weak acid is formed, which can be “managed” through an open system, the respiratory system.

However, from the lactic threshold the buffer capacity of the plasma is overcome by the production and elimination of lactic acid by the muscle. The consequence is the accumulation of lactic acid and consequently of H + (in fact of H3O +). Although the abandonment of an exercise of the aforementioned characteristics is multifactorial, when the activity of glycolysis is very high, the organism enters in a situation of acute metabolic acidosis, partially compensated with respiratory alkalosis. That is, it has ended with a situation of acid-base imbalance as indicated in table 1.

Role of the kidney during exercise and recovery: Renal function during exercise of increasing intensity and limited duration is double. On the one hand, the renal circulation is one of the circulatory zones where there is a restriction of the blood flow, allowing a derivation of the renal flow towards the active territories. On the other hand, it intervenes in the recovery of the triggered metabolic acidosis state (see above). Next, the current knowledge of these two functions is reviewed, with more information on the role of the kidney during exercise than in recovery.

Repercussion of renal flow bypass. Several authors [6,7], argue that during exercise there is a decrease in renal blood flow (RBF), renal plasma flow (RPF), glomerular filtration rate (GFR) and filtration fraction (FF). This reduction is an “intelligent” response to the mechanisms of cardiac output regulation. Indeed, not only with the increase in cardiac output is sufficient to supply the muscles during the exercise of increasing intensity. Redistribution of the largest volume of blood expelled in one minute is necessary. Considering that resting FSR is 20% of cardiac output (6 L / min) = 1200 ml / min), different authors have found decreases in FSR that vary considerably (15 to 60%). This is due to the study techniques, characteristics of the exercise and animal species studied. However, a reduction of 3% in cardiac output in maximal exercise (25 L / min) = 750 ml / min), would imply a reduction of 40% in relation to resting values. The reduction of FSR during intense physical exercise suggests that nephrons may be “damaged”.

The reduction of the FSR naturally implies a decrease in the RPF. However, the important thing and what has awakened the curiosity of the researchers is to know whether, despite this reduction, the glomerular filtration (FG) value is maintained. If this were to happen, it would necessarily imply an increase in the filtration fraction (FG / FPR). Again, the results are controversial, as some researchers have not observed variation in the FG, while others have recorded declines even of 50%. Therefore, the FF can be increased or maintained at the same value as at rest. In any case, how does the kidney regulate FG during exercise?

Mechanisms that could explain the variations of the FPR, FG and FF. Two mechanisms have been proposed to explain the response of the FG during the exercise Fallo F (1993), Johansson BL et al. 1987, McKelvie RS et al. 1989, Poortmans JR 1977: [6,10,17,18] Self-regulation and nervous regulation. The net effect of the mechanism of self-regulation would be a vasoconstriction of the efferent arteriole, which would make it possible to keep the GFR relatively constant despite the vasoconstriction of the afferent arteriole. Since the blood is “stagnant” in the glomerulus, glomerular patency would increase, favoring glomerular filtration. However, this may also be the reason for the appearance of pathological renal manifestations, such as the appearance of proteins, blood cells or both in urine, which is relatively frequent in background athletes. On the other hand, the action of the sympathetic vegetative nervous system, which causes a generalized vasoconstriction, would allow the derivation of the blood flow to the active territories and the modulation of the mechanism of self-regulation. Based on these two mechanisms, it is postulated that the combined effect of both is the maintenance of the filtration pressure and consequently of the glomerular filtration.

Intervention of renal function in restoring the acid-base balance. From a performance point of view, the post-exercise recovery process is essential to be able to “assimilate” training loads. However, documentation is scarce [9,19]. Therefore, the role of the kidney after intense exercise with a high production of lactic acid is here subjected to a more theoretical analysis than the result of contracted research.

After an exercise of the aforementioned characteristics, a state of metabolic acidosis has occurred (Table 1 and Figure 1). This imbalance of the acid-base state has an important renal compensation. The tubular function will increase to the purpose of: 1) reabsorb filtered bicarbonate (18 mM / L in table 2) formation of spent bicarbonate (go from 18 mM / L to 24 mM / L) and eliminate the acid produced by the urine. In a simple way these two functions are exposed and the reader is referred to the texts of human physiology for more information.

Figure 1:Resorption of fi ltered bicarbonate.

Resorption of filtered bicarbonate. At rest, this is a complex phenomenon in which most of the bicarbonate of the filtered bicarbonate is reabsorbed in the first part of the nephron (80%) and the rest in the last part of the nephron (20%). It seems coherent to think that after exercise the activity of the nephron is equivalent to the rest situation, so that the 18 mM / L that have remained as a consequence of the buffering of the lactic acid are completely reabsorbed. Naturally, it is unknown whether the proportions of reabsorption of the bicarbonate in the different parts of the nephron are maintained.

Formation of spent bicarbonate. With the reabsorption of the filtered bicarbonate becoming important, the formation of “new bicarbonate” (6 mM / L) is of paramount importance. Although the kidney is capable of forming new bicarbonate by means of two buffer systems, dibasic phosphate / monobasic phosphate (HPO42- / H2PO4-) and ammonia / ammonium ion (NH3 / NH4 +), the latter is the most important, since it is responsible for forming the 60% “new bicarbonate”. In an elementary way, the tubular cells have a high metabolic activity with glutamic acid, so that they release ammonium ion and keto-glutarate. The ammonium ion is released into the tubular fluid and consequently into the urine. Thus, 60% of the acid load, which would be released in the form of H + through the urine (pH urine), is released in the form of ammonium ion, avoiding a very high acid load in urine. The amount of acid that is not buffered by one of the two systems (HPO42- / H2PO4- or NH3 / NH4 +) are released as free protons and are measured through the pH of the urine.

Therefore, taking as an example the data shown in table 1, the tubular function:

1º) reabsorbs the 18 mM / L that have remained after the buffering of the lactic acid produced during the exercise.

2nd) formation of 6 mM / L in order to restore the normal concentration of bicarbonate (24 mM / l). As a result, a greater amount of titratable acidity (NH4 + and H2PO4-) and free protons in urine is eliminated by urine, that is, the pH of the urine decreases. The pH of the urine can decrease from 1 to 2 units with respect to the resting values ​​(around 6.0).

The renal function during the exercise of constant intensity and prolonged duration

Unlike exercise of increasing intensity and limited duration, during an exercise of relatively constant intensity and prolonged duration, the kidney participates in hydroelectrolytic conservation. Using logical reasoning it is feasible to think that kidney function has the purpose of counteracting the losses that are produced by other ways of eliminating the heat generated during this type of exercise. The most important form of heat removal in homothermal animals is sweating or equivalent forms of water loss by evaporation. As shown in table 2, the loss of water through sweating can reach 70% of the losses. Thus, during an exercise such as the ultra-marathon can produce oliguria (15 to 50%), although there may even be an increase in diuresis, due to multiple causes such as intensity, previous hydration, temperature, etc. Next, the role of renal function in this type of exercise is briefly discussed.

Unlike the role of the kidney during recovery, information regarding hydration and prolonged exercise is very abundant and, indirectly, renal function is deduced during this type of exercise. Thus, for example, doing an elementary search with the following terms “hydration AND exercise” in PubMed shows 1106 records and adding to the indicated search the term “renal function” the search is reduced to 53 records, when the search terms are found anywhere in the text. Therefore, then, I will rely not so much on the existing literature, but on common sense on the basis of physiology.

Functional sense of the tubular function for hydroelectrolytic control: The urine, in addition to decreasing its volume, would increase its osmolarity, when the mechanism of ADH-thirst is set in motion. However, the osmolarity of the urine during a physical effort can vary due to, among other reasons, to the state of previous hydration, to the rehydration during the same and to the environmental conditions (humidity and temperature). It has been found that the concentration of ADH in plasma increases at a certain intensity of effort, facilitating the reabsorption of water and salt. This seems an obvious effect, since, although the sweat is hypotonic with respect to the plasma, the “sodium loss” through the skin should not increase through the kidney. The stimulus for ADH secretion may be the result of a variation in osmolarity, total blood volume, or both. The increase in salt reabsorption contributes to the increase in aldosterone secretion and has a response similar to that of ADH. The mechanism by which aldosterone secretion is stimulated during physical exercise is not sufficiently clarified and could intervene: concentrations of other hormones, renin levels and potassium concentration in plasma.

However, a simple calculation determines that the oliguria does not have a purpose of water replacement. If we consider a reduction in urine volume of 1.5 ml / min by half (0.75 ml / min), it seems to be an important water saving. Now, if we value the clearance of free water, the question is not so clear. Under normal conditions this value is frequently negative. In this way, oliguria does not represent a great saving of water. For this reason, several authors [10,11,17,20-24], have proposed that more than in a quantitative sense, oliguria represents a qualitative “saving”, to be able to intervene in the cooling of the skin, evaporation and maintaining the flow to the muscles.

Figure 2 shows the results of a study [25] concerning osmolar clearance and free water in two circumstances: with or without water intake. The values ​​of osmolar clearance and free water before and after exercise have a very similar behavior, which suggests that voluntary ingestion does not seem to be effective in reducing the decrease in the ability to concentrate urine under the indicated experimental conditions.

Figure 2: Moment of determination.

Mechanism of regulation: Stress oliguria necessarily suggests an increase in the reabsorption of water and osmotically active electrolytes [6,17,23,24,26-28]. An increase in sodium reabsorption has been indicated. The increase in sympathetic activity, the increase in FF, the increase in the concentration of hormones whose target organ is the kidney (natriuretic factor, angiotensin, aldosterone and ADH) could intervene in the increase of salt reabsorption and, therefore, in the decrease in its elimination by urine. Studies in animals seem to indicate that, during exercise, sympathetic activity is the main determinant of the increase in salt reabsorption. The renin-angiotensin-aldosterone system increases its activity during exercise with direct effects of some of the components of the system on tubular salt reabsorption.

Practical applications: Given the information that the athletes have, alterations in the hydroelectrolytic state have also been recorded [11], such as: 1) positive free water clearance. This implies that a greater amount of water is eliminated than solutes, 2) hyponatremia. This alarming state is due to an exaggerated loss of sodium by sweating, accompanied or not by a difficulty in eliminating hypotonic urine and 3) difficulty in rehydration. These alterations are caused by renal impairment (decreased tubular sensitivity to hormones) or extra renal causes difficult to elucidate.

Another interesting aspect, related to the homeostasis of body fluids, is to know what type of drink is the most appropriate to ingest. A priori, to know the composition of the liquid necessary to balance the losses, it would be enough to know precisely the content of the sweat losses. In an unpublished study, commercial beverages with different mineral waters were compared, in relation to: mineral concentration, carbohydrate content and price. An important conclusion of the mentioned work, was that according to the indicated characteristics, the replacement was more economical and equally effective, by ingesting mineral water with a slight preparation. It follows, then, that any mineral water offers the same advantages as all the products that are currently marketed. Moreover, certain mineral waters offer other advantages from the point of view of health, which do not have those marketed.


Disorders of Mineral and Bone Metabolism in Chronic Kidney Disease

Keith A. Hruska , . Kameswaran Surendran , in Chronic Renal Disease , 2015

FGF23

FGF23 is the original phosphatonin ( phosphate excretion regulating hormone) discovered in studies of autosomal dominant hypophosphatemic rickets and oncogenic osteomalacia. 61,62 The principal hormonal functions identified for FGF23 are regulation of proximal tubular phosphate reabsorption, inhibition of CYP27B1, the 1α-hydroxylase synthesizing calcitriol in the proximal tubule, and stimulating the 25-hydroxyvitamin D3 24R-hydroxylase, 24-(OH) hydroxylase, CYP24A1. FGF23 levels are stimulated by mild renal injury 23,63 and progressively rise during the course of CKD due to increased secretion by osteocytes and decreased catabolism by the diseased kidney. FGF23 contributes to maintainance of phosphate homeostasis during early CKD and causes vitamin D deficiency through increased catabolism. Hormonal FGF23 is produced by osteocytes and osteoblasts, although it is expressed elsewhere in disease. 12

FGF23 levels strongly associate with clinical outcomes of CKD, 64 especially with the intermediate surrogate, left ventricular hypertrophy. 65 Extremely high FGF23 levels in CKD cause cardiac myocyte hypertrophy independent of klotho co-receptor function. 66 FGF23 represents direct bone–kidney, bone–parathyroid and bone–heart connections in the systems biology involved in the CKD-MBD.



Comments:

  1. Rutledge

    seeing what character of work

  2. Kenrick

    Very wonderful topic

  3. Deorsa

    do something



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