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Unformatted text preview: Renal Physiology Lecture 5 Potassium regulation Hydrogen ion regulation-1 Potassium regulation
Potassium (K) is the most abundant intracellular ion. 98% Intracellular fluid 2% Extracellular fluid The K concentration in the extracellular fluid is extremely important for the function of excitable tissues (nerve and muscle). Reason: the resting membrane potentials of these tissues are directly related to the relative intracellular and extracellular K concentrations. Potassium regulation
Hyperkalemia: high concentration of K in the extracellular fluid (>5 mEq/L) Hypokalemia: low concentration of K in the extracellular fluid (<3.5 mEq/L) Both cause abnormal rhythms of the heart and abnormalities of skeletal muscle contraction. Potassium balance is maintained by the kidney
Dietary intake 90% Excreted into urine 10% Excreted into feces/sweat Renal regulation of potassium
K is freely filtered at glomerulus.
same as Na+ Normally, the tubules reabsorb most of this filtered K so that very little of the filtered K appear in the urine. similar to Na+ and water However, unlike sodium or water, K can be secreted at the cortical collecting ducts. difference between regulation of Na+
how regulation of K+ happens and water Changes in K excretion are due mainly to changes in K secretion in the CCD (some in the DCT). same location of reabsorption of Na+ K+ can be secreted back into the tubule depending net reabsorption varies dramaticallyeat on how much you 15%-99% (normally ~86%)
net reabsorption will become much smaller if you eat alot of K+ basolateral membrane in the cell the K+ concentration is high, allowing for diffusion along the gradient into the lumen of the tubule Secretion of K+ in the CCD is coupled with Na+ reabsorption. Regulation of potassium secretion
Potassium secretion is regulated by 1. 2. Dietary intake of potassium Aldosterone Regulation of K+ secretion by dietary intake and aldosterone Figure 14.26 K+ secretion can occur when reninaldosterone system is activated by other causes
volume depletion can also stimulate aldosterone - can inadvertently increase potassium secretion Hyperaldosteronism
• The conditions in which the adrenal hormone the status of the aldosterone is released in excess. regardless of(volume of plasma,body and metabolism ion
concentration etc.) • The most common cause: adenoma of the adrenal gland that produces aldosterone autonomously. active tumor that makes aldosterone regardless of plasma volume • Increased fluid volume, hypertension, hypokalemia. Renin is suppressed. Metabolic alkalosis is often seen. Hydrogen ion regulation
Metabolic reactions are highly sensitive to the hydrogen ion concentration of the environment.
all enzyme mediated chemical reactions are dependent on pH Thus, the hydrogen ion concentration of the extracellular fluid is tightly regulated. pH: ~7.4 ([H+]: ~40 nmol/L) Important mass action
Carbonic anhydrase CO2 + H2O H2CO3 HCO3- + H+ When bicarbonate ion is lost from the body, it is the same as if the body had gained a hydrogen ion. Conversely, when the body gains a bicarbonate ion, it is the same as if the body had lost a hydrogen iron.
- losing bicarbonate is the equivalent of gaining protons in the body - the kidneys maintain the pH status of the body by mainly regulating bicarbonate concentration (although H+ regulation also happens) Table 14.07
= volatile acid, it is a gas very acidic, no bicarbonate #4 #2 #3 (loss of CO2) corresponds to gain #1 - they cancel out generally Nonvolatile acids
Phosphoric acid Sulfuric acid Lactic acid
constantly in our body - contribute to the production of H+ Average net production: 40-80 mmol of H+ per day
the average concentration of H+ in the plasma is about 40 nmol, so there must be a buffering system to reversibly bind protons and maintain plasma pH Buffer of hydrogen ion
Any substance that can reversibly bind hydrogen ions is called a buffer. Most hydrogen ions are buffered by extracellular and intracellular buffers. pH = -log [H+] Normal ECF pH 7.4 corresponds to 40 nanomoles/L of H+. Without buffering, hydrogen ion concentrations changes a lot. Buffer of hydrogen ion
Buffer - + H+ Hbuffer Major extracellular buffer is the CO2/HCO3- system. Major intracellular buffers are phosphates and proteins. Buffering does not eliminate hydrogen ions from the body. It only keeps them “locked up”.
they are buffered reversibly Ultimate balance of hydrogen ion
is controlled by Respiratory system (by controlling CO2) Kidneys (by controlling HCO3-) Both systems work together to minimize the change of hydrogen ion concentration (pH). Renal mechanisms of hydrogen ion control: via control of HCO3Low H+ concentration----> Kidneys excrete HCO3(high pH: alkalosis) High H+ concentration----> Kidneys produce new (low pH: acidosis) HCO3- and add to the plasma Renal mechanisms of hydrogen ion control: via control of HCO3Henderson-Hasselbalch equation: pH = 6.1 + log10 [HCO3-] [CO2]
(concentrations are in mmol/L) pH = -logKa + log10 [HCO3-](mmol/L) 0.03[CO2](mmHg) Ka: dissociation constant for CO2/HCO3- system 0.03 is solubility of CO2 at 37OC Renal handling of HCO3small, freely filtered HCO3- excretion = HCO3- filtered (+ HCO3- secreted) - HCO3- reabsorbed
Normally, the kidneys reabsorb all filtered HCO3-. Exception: alkalosis
the kidneys try to eliminate bicarbonate, the pH of urine will rise (it is normally about 6) in a normal person, bicarbonate is completely reabsorbed on the lumenal side of the proximal tubular cells there is a brush structure that is rich in CA proximal tubule cells are rich in CA Also mediated by H+/K+-ATPase Na+/H+ antiporter HCO3- reabsorption
predominantly in the proximal tubule ...
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- Winter '08