The kidneys control acid-base balance by secreting hydrogen ions into the urine and reabsorbing bicarbonate from filtered blood. About 4400 mEq of hydrogen ions must be secreted daily to reabsorb filtered bicarbonate and remove metabolic acids. The kidneys also generate new bicarbonate ions through secretion of hydrogen ions or ammonium ions in urine. Renal tubular acidosis can occur if the kidneys are unable to properly secrete hydrogen ions or reabsorb bicarbonate. Metabolic acidosis may result from conditions like diarrhea, diabetes, or kidney failure that produce or prevent removal of excess acids.
The kidneys control acid-base balance by secreting hydrogen ions into the urine and reabsorbing bicarbonate from filtered blood. About 4400 mEq of hydrogen ions must be secreted daily to reabsorb filtered bicarbonate and remove metabolic acids. The kidneys also generate new bicarbonate ions through secretion of hydrogen ions or ammonium ions in urine. Renal tubular acidosis can occur if the kidneys are unable to properly secrete hydrogen ions or reabsorb bicarbonate. Metabolic acidosis may result from conditions like diarrhea, diabetes, or kidney failure that produce or prevent removal of excess acids.
The kidneys control acid-base balance by secreting hydrogen ions into the urine and reabsorbing bicarbonate from filtered blood. About 4400 mEq of hydrogen ions must be secreted daily to reabsorb filtered bicarbonate and remove metabolic acids. The kidneys also generate new bicarbonate ions through secretion of hydrogen ions or ammonium ions in urine. Renal tubular acidosis can occur if the kidneys are unable to properly secrete hydrogen ions or reabsorb bicarbonate. Metabolic acidosis may result from conditions like diarrhea, diabetes, or kidney failure that produce or prevent removal of excess acids.
The kidneys control acid-base balance by secreting hydrogen ions into the urine and reabsorbing bicarbonate from filtered blood. About 4400 mEq of hydrogen ions must be secreted daily to reabsorb filtered bicarbonate and remove metabolic acids. The kidneys also generate new bicarbonate ions through secretion of hydrogen ions or ammonium ions in urine. Renal tubular acidosis can occur if the kidneys are unable to properly secrete hydrogen ions or reabsorb bicarbonate. Metabolic acidosis may result from conditions like diarrhea, diabetes, or kidney failure that produce or prevent removal of excess acids.
Lecture 3 CHEM-1121 BS 4th Renal control of Acid-base Balance • The kidneys control acid-base balance by excreting either acidic or basic urine. Excreting acidic urine reduces the amount of acid in extracellular fluid, whereas excreting basic urine removes base from the extracellular fluid. • The overall mechanism by which the kidneys excrete acidic or basic urine is as follows: • Large numbers of HCO3- are filtered continuously into the tubules, and if they are excreted into the urine, this removes base from the blood. • Large numbers of H+ are also secreted into the tubular lumen by the tubular epithelial cells, thus removing acid from the blood. • If more H+ is secreted than HCO3- is filtered, there will be a net loss of acid from the extracellular fluid. • So, if more HCO3- is filtered than H+ is secreted, there will be a net loss of base. • The lungs can dispose of the volatile acid (carbonic acid) in the form of CO2. • Kidneys remove the metabolic acids generated by cellular metabolism: Such as phosphoric acid, uric acid, lactic acids, and ketone bodies. About 80mM metabolic acids/day. Each day the kidneys filter about 4320 mEq of HCO3- (180 L/day × 24 mEq/L); under normal conditions, almost all this is reabsorbed from the tubules, thereby conserving the primary buffer system of the extracellular fluid
Hydrogen ion secretion and HCO3- reabsorption occur
in virtually all parts of the tubules except the descending and ascending thin limbs of the loop of Henle • Both the reabsorption of HCO3- and the excretion of H+ are accomplished through the process of H+ secretion by the tubular cells. • Filtered HCO3- must react with a secreted H+ to form H2CO3 before it can be reabsorbed. • 4320 mEq of H+ must be secreted each day just to reabsorb the filtered HCO3-. • an additional 80 mEq of H+ must be secreted to rid the body of the nonvolatile acids produced each day, for a total of 4400 mEq of H+ secreted into the tubular fluid each day. • The reduction in the extracellular fluid H+ concentration (alkalosis), the kidneys secrete less H+ and fail to reabsorb all the filtered HCO3-, thereby increasing the excretion of HCO3-. • Normally HCO3- buffers H+ in the extracellular fluid, this loss of HCO3- is the same as adding an H+ to the extracellular fluid. • The removal of HCO3- raises the extracellular fluid H+ concentration back toward normal. Renal mechanism kidneys regulate extracellular fluid H+ concentration through three fundamental mechanisms: 1. secretion of H+ 2. reabsorption of filtered HCO3- 3. production of new HCO3-.
Important to note that for each HCO3- reabsorbed, a H+ must be secreted in the luminal fluid. • The secretory process begins when CO2 either diffuses into the tubular cells or is formed by metabolism in the tubular epithelial cells. • CO2, under the influence of the enzyme carbonic anhydrase, combines with H2O to form H2CO3, which dissociates into HCO3- and H+. • The H+ is secreted from the cell into the tubular lumen by sodium-hydrogen anti-transport. • When Na+ moves from the lumen of the tubule to the interior of the cell, it first combines with a carrier protein in the luminal border of the cell membrane; at the same time, a H+ in the interior of the cells combines with the carrier protein in the luminal border of the cell membrane. • Simultaneously, H+ in the interior of the cells combines with the carrier protein. . Reabsorption of Bicarbs • The HCO3- generated in the cell (when H+ dissociates from H2CO3) then moves downhill across the basolateral membrane into the renal interstitial fluid and the peritubular capillary blood. • The net result is that for every H+ secreted into the tubular lumen, an HCO3- enters the blood Filtered HCO3- is reabsorbed by interaction with H+ in the tubules
• This reabsorption of HCO3- is initiated by a reaction in the tubules between
HCO3- filtered at the glomerulus and H+ secreted by the tubular cells. The H2CO3 then dissociates into CO2 and H2O. • The CO2 can easily cross the tubular membrane, where it recombines with H2O, under the influence of carbonic anhydrase, to generate a new H2CO3 molecule. • This H2CO3 in turn dissociates to form HCO3- and H+; the HCO3- then diffuses through the basolateral membrane into the blood. • The transport of HCO3- across the basolateral membrane is facilitated by two mechanisms: (1) Na+-----HCO3- Co-transport in the proximal tubules (2) Cl-----HCO3- exchange in the late segments of the proximal tubule, the thick ascending loop of Henle, and the collecting tubules and ducts. Cellular mechanisms (1) active secretion of H+ into the renal tubule (2) tubular reabsorption of HCO3- by combination with H+ to form carbonic acid, which dissociates to form carbon dioxide and water. (3) sodium ion reabsorption in exchange for H+ secreted.
About 95 % of the bicarbonate is reabsorbed in this manner, requiring about 4000 mM of
H+ to be secreted each day by the tubules. Renal Control of Acid-base balance • Each time a H+ is formed in the tubular epithelial cells, a HCO3- is also formed and released back into the blood. • The net effect of these reactions is “reabsorption” of HCO3- from the tubules. • The reabsorption of filtered HCO3- does not result in net secretion of H+ because the secreted H+ combines with the filtered HCO3- and is therefore not excreted. (become the part of water molecule). Generating New Bicarbonate Ions
• Two renal mechanisms carried out by cells of the PCT and collecting ducts generate new HCO3─ that can be enter the plasma. • Both mechanisms involve renal excretion of acid, via secretion and excretion of either H+ or ammonium ions in urine. • once the filtered HCO3 ─ is “used up” (usually by the time the filtrate reaches the collecting ducts), any additional H+ secreted is excreted in urine. • A normal diet/metabolism introduces new H+ in the body, and this additional H+ must be balanced by the generation of new HCO3─. • The excreted H+ also must bind with buffers in the filtrate. A H+ secretion ceases when urine pH falls to 4.5. • The most important urine buffer is the phosphate buffer system, specifically its weak base monohydrogen phosphate (HPO42─). • The secreted H+ combines with HPO42-, forming H2PO4- which then flows out in urine. when H+ is being excreted, entirely new bicarbonate ions are entered into the blood • in response to acidosis, the kidneys generate new HCO3- and add it to the blood (alkalinizing the blood) while adding an equal amount of H+ to the filtrate (acidifying the urine). Excretion of H +
• Via NH4+ Excretion: The second and more important mechanism for excreting acid uses the ammonium ion produced by glutamine metabolism in the PCT cells. • Ammonium ions are weak acids that donate few H at physiological pH. As for each glutamine metabolized (deaminated, oxidized, and acidified by combination with H), two NH4 and two HCO3- result. The HCO3- moves through the basolateral membrane into the blood. • The NH4, in turn, is excreted and lost in urine). As with the phosphate buffer system, this buffering mechanism replenishes the alkaline reserve of the blood, because the newly made HCO3- enters the blood as NH4 is secreted. Abnormalities of Acid-Base Balance
Metabolic Acidosis The term metabolic acidosis refers to all other types of acidosis besides those caused by excess CO2 in the body fluids.
Metabolic acidosis can result from several general causes:
(1) failure of the kidneys to excrete metabolic acids normally formed in the body, (2) Formation of excess quantities of metabolic acids in the body, (3) Addition of metabolic acids to the body by ingestion or infusion of acids, (4) Loss of base from the body fluids, which has the same effect as adding an acid to the body fluids. Renal Tubular Acidosis
• Renal tubular acidosis results from a defect in renal secretion of H+ or in
reabsorption of HCO3-, or both. • These disorders are generally of two types: (1) Impairment of renal tubular HCO3- reabsorption, causing loss of HCO3- in the urine, (2) Inability of the renal tubular H+ secretory mechanism to establish normal acidic urine, causing the excretion of alkaline urine. There is net accumulation of acid in the body fluids. Some causes of renal tubular acidosis include chronic renal failure, insufficient aldosterone secretion (Addison’s disease), and several hereditary and acquired disorders that impair tubular function, such as Fanconi’s syndrome Metabolic Acidosis • Diarrhea. Severe diarrhea is probably the most frequent cause of metabolic acidosis. • The cause of this acidosis is the loss of large amounts of sodium bicarbonate into the feces. • The gastrointestinal secretions normally contain large amounts of bicarbonate, and diarrhea results in the loss of HCO3- from the body, which has the same effect as losing large amounts of bicarbonate in the urine. • This form of metabolic acidosis can be particularly serious and can cause death, especially in young children. Diabetes Mellitus • In the absence of insulin/insulin resistance, the normal use of glucose for metabolism is prevented. • the fats are metabolized into ketone bodies (acetoacetic acid), and this acid is metabolized by the tissues for energy in place of glucose. • With severe diabetes mellitus, blood acetoacetic acid levels can rise very high, causing severe metabolic acidosis. Hyperventilation vs hypoventilation • During hyperventilation, [CO2] decreases in the lungs and arterial blood, reducing [H+] and increasing pH above the normal 7.4 value. Hyperventilation removes H+, raising the pH of blood. • Dissolving more CO2 in the blood increases [H+] in blood and ECF lowering pH.
• In hypoventilation, [CO2] increases in the lungs and arterial blood, driving the equilibrium to the right, raising [H+] and lowering pH.
