Module 5: Renal Physiology (Acid-Base Balance and Buffering)

What is the kidney's response to alkalosis?

- Decreased H+ secretion - Decreased HCO3- reabsorption - Loss of HCO3- in urine

How can you conclude if acidosis if respiratory or metabolic in nature?

Acidosis: ph < 7.4 If elevated pCO2, likely respiratory is the source of abberrancy If decreased HCO3, likely metabolic source of aberrancy

For bicarb to be reabsorbed, what ion must be secreted?

H+ ion For each HCO3 reabsorbed, there must be a H+ secreted.

Buffering system reaction of Bicarbonate:

H2O + CO2 ↔ H2CO3 ↔ (H+) + (HCO3-) Most important ECF buffer Reaction can be reversed in the lungs, reading from the left, so that CO2 can be exhaled

How do the kidneys regulate Acid-Base balance?

Kidneys conserve HCO3- and excrete acidic or basic urine depending on the body needs

What quantities of of bicarb and H+ are reabsorbed and excreted by the kidneys to maintain pH?

Kidneys filter out and then reabsorb a large quantity of bicarb per day, with only a small amount being secreted. A small amount of new bicarb is synthesized Bicarb: - filtered = 4320 mmol/day - reabsorbed = 4219 mmol/day - excreted = 1 mmol/day - production = 80 mmol/day Meanwhile, Hydrogen is secreted and excreted in significant quantities daily H+: - secretion = 4400 mmol/day

Describe the bicarbonate buffer system

Kidneys work in concert with the Lungs to maintain H+ concentration in ideal pH range (7.2-7.4) Lungs —> rapidly eliminate CO2: increased H+ triggers increased ventilation which increases CO2 loss Kidneys —> slow, powerful, eliminates non-volatile acids: - secretes H+ - reabsorbs HCO3- - generates new HCO3-

What are the effects of metabolic acidosis on pCO2, serum bicarb and pH? How do the lungs attempt to compensate?

Metabolic acidosis: decreased pH, decreased CO2, decreased HCO3- Lungs increase RR to decrease CO2 Kidneys respond by reabsorbing bicarb from tubules using buffer systems and make more bicarb Compensation: increased ventilation, increased renal HCO3 production

What are the effects of metabolic alkalosis on pCOs, serum bicarb, and pH? How do the kidneys/lungs attempt to compensate?

Metabolic alkalosis: increased pH, increased CO2, Increased HCO3 Kidneys decrease reabsorption of HCO3- and increase its excreting, while decreasing H+ excretion to bring pH back down Lungs decrease ventilation to hold on to CO2 Compensation: decreased ventilation, increased renal HCO3 excretion

Where is most of the bicarb reabsorption taking place?

Proximal tubule (85%) Most of the bicarb is recovered almost immediately after it is filtered out of the glomerulus

Where does the mechanism of HCO3 reabsorption and H+ removal in exchange for Na+ occur?

Proximal tubule and the thick loop of Henle

What are the effects of respiratory acidosis on pCO2, serum bicarb, and pH? How do the kidneys attempt to compensate?

Respiratory acidosis: decreased pH, increased CO2, increased HCO3- Bicarb is maintained but is insufficient to completely offset the acidosis In response, kidneys excrete more H+, reabsorb more bicarb, increase other buffering systems, and produce new bicarb = which will usually attenuate the decreased pH Compensation: increased renal HCO3 production

What are the effects of respiratory alkalosis on pCO2, serum bicarb, and pH? How do the kidneys attempt to compensate?

Respiratory alkalosis: increased pH, decreased CO2, decreased HCO3- Kidneys increase secretion of HCO3- to bring pH back down Compensation: increased renal HCO3 excretion

Where is the buffering of H+ ion secretion by Ammonia occurring?

The collecting tubules

What is the lowest that the urine can concentrate H+ ions

To a minimal pH of 4.5

Buffering system reaction of Proteins:

(H+) + Hb ↔ HHb Important intracellular buffer (hydrogen combines with hemoglobin)

Buffering system reaction of Phosphate:

(HPO4-) + (H+) ↔ (H2PO4-) Important renal tubular buffer

What are the 4 predominant buffering systems?

- Bicarbonate - Proteins - Ammonia - Phosphate (Rapid but temporary)

What is the kidney's response to acidosis?

- Increase H+ secretion - Increase HCO3- reabsorption - Production of new HCO3-

Describe the mechanism of H+ secretion and HCO3- reabsorption taking place in the intercalated cells

1. CO2 enters tubular cells, combines with H2O, and is converted by Carbonic Anhydrase into Carbonic Acid (H2CO3) 2. Carbonic Acid (H2CO3) is divided into H+ and Bicarb (HCO3-) 3. Bicarb is retained in the kidney, H+ is excreted in the urine via ATP transport

Describe the mechanism of H+ secretion via phosphate (NaHPO4-), and generation of "new" bicarb

1. CO2 enters tubular cells, combines with H2O, and is converted to Carbonic Acid (H2CO3) by Carbonic Anhydrase 2. Carbonic Acid (H2CO3) is broken down into "new" bicarb and H+. Bicarb enters into the interstitial fluid 3. H+ is exchanged with Na+ into the tubular lumen, and is buffered with sodium phosphate (NaHPO4-) to become sodium dihidyrophnosphate (NaH2PO4), which is excreted in the urine

Describe the mechanism of H+ secretion by ammonia

1. H+ ions are actively secreted in ATP dependent transport into the tubular lumen 2. H+ is buffered with Ammonia (NH3) in the filtrate to become Ammonium (NH4+), and is excreted in the urine

Describe the mechanism HCO3 reabsorption and H+ removal in exchange for Na+

1. H+ is exchanged for Na+ in the tubular membrane out into the tubular filtrate 2. H+ is buffered with Bicarbonate to form Carbonic Acid in the tubular lumen (H + HCO3 = H2CO3) 3. Carbonic acid redivides into CO2 and H2O; the water is excreted with the filtrate 4. CO2 re-enters the tubular cell and combines with H2O again via Carbonic Anhydrase to form Carbonic Acid (H2CO3) 5. Carbonic Acid (H2CO3) is broken down again into bicarb (HCO3) and H+ ions. 6. Bicarb is reabsorbed into the circulatory system, the H+ is Resecreted in exchange for Na+ 7. Go back to step 1, and the process starts again

What are some conditions that cause the increased secretion of H+? (3)

1. Increased pCO2 (respiratory acidosis) 2. Increased extracellular H+ (metabolic or respiratory acidosis) 3. Increased tubular fluid buffers (metabolic or respiratory acidosis)

Describe the mechanism of new bicarb synthesis and NH4+ secretion by the proximal, thick loop of Henle, and distal tubules.

1. New bicarb is synthesized by the breakdown of the amino acid Glutamine into ammonium and bicarbonate ions. 2. Ammonium combines with Cl- for excretion 3. Bicarb is reabsorbed into the blood

If not for the buffering system, how much urine would have to excreted in 24 hours to remove non-volatile acids?

2000 L/day Minimal urine pH = 4. 5, which equals about 3x10^5 moles/L Maximal H+ concentration is 0.03 mmol/L Kidneys must excrete at least 60 mmol non-volatile acids each day. To excrete this as free H+ would require: 60 mmol/0.03 mmol/L = 2000 L/day The rest of H+ not excreted freely into the 1L/day that we excrete, must be handled through the buffering system

How can you conclude if alkalosis is respiratory or metabolic in nature?

Alkalosis: pH > 7.4 If decreased pCO2, likely respiratory is the cause (hyperventilation s/t anxiety) If elevated HCO3-, likely metabolic in origin

When Ammonia is used as a buffer in the tubule, what compound is produced?

Ammonium (NH4+)

What is the effect of high levels of aldosterone on pH?

Can increase pH and cause metabolic alkalosis As Aldosterone levels are increased by the renin-angiotensin system, it causes increased renal retention of Na+ in exchange for increased excretion of K+ K+ excretion is followed by increased H+ secretion and excretion, which causes increased pH

Where is the previous processes occurring?

In the intercalated cells of the late distal and collecting tubules

How do the kidneys respond to metabolic acidosis

Increase secretion of H+

How do the kidneys respond to respiratory acidosis?

Increase secretion of H+ ions in response to higher blood levels of CO2

Buffering system reaction of Ammonia:

NH3 + (H+) ↔ (NH4+) Important renal tubular buffer (becomes ammonium)

Why does phosphate buffering capacity not change much with acid-base disturbances?

Phosphate is not the major tubular buffer in chronic acidosis Even though, there is a high concentration of phosphate in tubular fluid, it normally only buffers about 30 mmol/day H+, and although 100 mmol/day phosphate is filtered, 70% of it is reabsorbed.

What is H+ precisely regulated at with the bicarb buffering system?

pH 7.2-7.4 (3-5 x 10^-8 moles)