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Renal Pathphysiology II Regulation of Plasma Composition. Nancy Long Sieber November 28, 2011. Normal Plasma Values. Normal Plasma Values, Continued. Normal Plasma Values, Continued. Urine Composition. Osmolarity. Plasma Osmolarity.
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Renal Pathphysiology IIRegulation of Plasma Composition Nancy Long Sieber November 28, 2011
Plasma Osmolarity Posm = 2 x [Na+(mEq/L)]p + [glucose(mg/dl)]/18 + [urea (mg/dl)]/2.8 • The difference between measured and calculated plasma osmolarity is the result of unmeasured osmoles. • These include potassium, chloride and proteins, but they account for very little of the total osmolarity.
Plasma Osmolarity Values: • Posm = 2 x [Na+(mEq/L)]p + [glucose(mg/dl)]/18 + [urea (mg/dl)]/2.8 • Posm = 2 x [140 mEq/L)]p + [90 (mg/dl)]/18 + [14 (mg/dl)]/2.8 • 280 + 5 + 5 = about 290 mOsm/kg • Sodium is responsible for about 97% of plasma osmolarity.
Conditions in which plasma Na+ is low, but osmolarity is normal • Usually there is another solute present. • Body responds to increase osmolarity by increasing ADH release, and water retention. This dilutes the sodium. • Eg: High glucose in diabetic patient • Eg: Ethylene glycol poisoning
True hypoosmolarity(low sodium and low osmolarity) • Could be due to : • Problems with ability to sense osmolarity, or to changes in set point for osmolarity • Alterations in thirst mechanism • Problems with ADH release • Problems with renal response to ADH • Drinking too much water before or during exercise
To consider the possible causes of hypoosmolarity, consider the components of the negative feedback loop for osmoregulation. • Sensor: osmoreceptors • Set point: normal value = about 295 mOsm/L • Responses: • Thirst (decreased in response to hypoosmolarity) • ADH release (decreased in response to hypoosmolarity)
Hypo-osmolarity Example: PregnancyLower setpoint for osmolarity - ADH release and thirst occur at a lower than normal osmolarity. ADH release progesterone 280 290 300 310 320 Plasma osmolarity (sOsm/L)
Hypo-osmolarity example: Psychogenic Polydipsia Vasopressin = ADH
Hypo-osmolarity example: Loss of plasma volume ADH release is triggered by decrease in plasma volume rather than an increase in osmolarity. Note that ADH is an effector for regulating two different regulated variables.
Hypo-osmolarity Example:Fluid loss to interstitium • Example: Cirrhosis of the liver • Damage to liver interferes with protein production • Fluid leaks out of capillaries due to shift in Starling forces • Fluid accumulates in abdomen – ascites • Also: portal hypertension increases hydrostatic pressure, injury and inflammation increases permeability to proteins, exacerbating the condition.
Hyperosmolarity of plasma due to high sodium conc. • Can be caused by: • Administration of sodium salts • Loss of hypotonic fluids (vomiting diarrhea, sweating) • Extrarenal fluid loss (eg: increased ventilation as occurs in fever) • Excessive renal water loss (inability to secrete or respond to ADH)
Example: Diabetes insipidus • Can be due to lack of ADH production, or in the case of nephrogenic diabetes insipidus, lack of ability to generate an osmotic gradient for water reabsorption • Results in loss of large volume of hypotonic urine
Potassium Regulation • Most (55%) of the filtered potassium is reabsorbed in the proximal tubule, another 30% is absorbed in the loop of Henle. • Depending on diet, potassium may be reabsorbed or secreted in the distal convoluted tubule and the cortical collecting duct.
Regulation of potassium secretion • Na+/K+/ATPase A high K+ diet enhances update of K+ into the principal cells (the ones that line the tubule) • Aldosterone increases K+ uptake into the principal cells (via Na+/K+/ATPase), and makes the luminal membrane more permeable to K+ • K+ secretion is flow dependent – high urine production can lead to K+ deficiency.
Hyperkalemia in diabetes mellitus K+ insulin adrenalin aldosterone K+ Na+ K+ Na+ acidosis increased osmolarity cell injury K+
Aldosterone alters the expression of this enzyme
From: Physiology of the Kidney and Body Fluids” by R.F. Pitts.
From: Physiology of the Kidney and Body Fluids” by R.F. Pitts.
Increased urine volume in diabetes mellitus ↑plasma glucose ↑filtered glucose Tm exceeded glucose remains in tubules H2O retained osmotically increased urine volume if not replaced by drinking, blood volume decreases
Increased urine volume in diabetes mellitus Example: Untreated diabetes mellitus (assuming no renal damage) Increased plasma glucose i Increase filtered glucose i Tm exceeded i Glucose remains in tubules i Water retained in tubules osmotically i Increased urine volume i Blood volume decreases (if not replaced by drinking) i Decreased blood pressure (by Frank-Starling mechanism)
Alterations in plasma H+ concentrations can be potentially life-threatening Condition [H+] pH Significance (nmol/L) Acidosis >100 <7.0 life-threatening 50-80 7.1-7.3 clinically signif. Normal 40+2 7.4+0.02 normal Alkalosis 25-30 7.4-7.6 clinically signif. <20 >7.7 life-threatening from Clinical Detective Stories, Halperin and Rolleston. Portland Press 1993.)
Alterations in plasma H+ concentration can influence potassium balance • Acidosis (excessive H+) causes K+ to move out of cells • Alkalosis (insufficient H+) causes K+ to move into cells. • Mechanisms of these interactions is not clear. • Diabetics are at risk for hyperkalemia (plasma K+ levels too high) since they tend to develop acidosis as a result of the production of ketoacids.
Hydrogen Ion Balance • We gain hydrogen ion through diet and metabolism • Meat eaters tend to produce more acid • Dietary hydrogen ion is consumed through metabolism, and lost through the expiration of CO2, and excreted in the urine. • Meat eaters produce a more acidic urine
Hydrogen Ion Balance is Maintained by Buffers • Most important is Bicarbonate (HCO3-) • Also: • Proteins • Phosphate • NH4+
How does hydrogen ion concentration get out of balance? • There are two basic kinds of problems • Acidosis • Alkalosis • There are two basic causes of these problems: • Metabolic • Respiratory • In addition, there are metabolic and respiratory compensations for imbalances in either system.
Acid-Base Imbalances Involve Shifts in This Equation: CO2 + H2O H2CO3 HCO3- + H+ Normal Values: H+ = 0.00004 mmol/L HCO3- = 24 mmol/L
Acidosis • Metabolic – results from excess acid production or loss of alkaline fluid • High lactic acid production during exercise • Prolonged diarrhea • Respiratory – results from hypoventilation • Injury that makes ventilation painful • Lung disease
Compensation for Acidosis • Metabolic Acidosis • Increased ventilation • Respiratory or Metabolic Acidosis • Increased excretion of H + (requires a phosphate group, which is in limited supply • Increased NH4+ production
Alkalosis • Metabolic – results from prolonged vomiting, which causes the loss of an acid-containing fluid, or from the ingestion of alkali fluid • Respiratory – results from hyperventilation
Compensation for Alkalosis • Metabolic Alkalosis • Sometimes results in decreased ventilation, but this is a relatively small response • Respiratory or Metabolic Alkalosis • Increased renal excretion of bicarbonate • NH4+ production and excretion are inhibited