the kidneys and acid-base Flashcards

1
Q

once the lungs get rid of volatile acid, what happens to the non-volatile acids

A

they cannot be exhaled and secreted by the kidney
- H+ is bound to filtered buffers (phosphate or ammonia)
- must reabsorb virtually all filtered HCO3 as loss of it is the same as adding H+ to the plasma

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2
Q

integrate the roles of the kidney and respiratory systems in the control of plasma pH

A
  • lungs remove CO2 (volatile) by alveolar ventilation
  • liver metabolises amino acids from protein catabolism to glucose or triglycerides and NH4+ released
  • urea synthesis in liver (from NH4 and CO2) produces H+ (and HCO3 is titrated)
  • kidneys excrete NH4 and there is a net gain of HCO3 and net loss of H+
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3
Q

explain how bicarbonate is reclamed and acid is secreted in the cells of the proximal convoluted tubule

A
  • HCO3 is freely filtered, it combines with H+ under influence of brush borders carbonic anhydrase
  • the resulting CO2 diffuses into cell, dissociates and is reabsorbed into the blood via the Na3HCO3 co transported
  • kidney aslo has ability to excrete H+ as ammonium
  • adds flexibility to renal acid base regulation
  • ammonium is ionised - fat insoluble and trapped
  • more used = more made
  • new HCO3 generated

Proximal tubule bicarbonate reclamation
The Na+/K+ ATPase (not shown in the diagram) pumps Na into capillary, maintains low intracellular Na+ drives H+ against conc gradient and ultimately maintains a negative intracellular potential
Filtered HCO3- cannot cross the apical membrane of the PCT cell. Instead it combines with the secreted H+ (under the influence of brush border carbonic anhydrase) to produce CO2 and H2O. The CO2 is lipid soluble and easily crosses into the cytoplasm of the PCT cell. In the cell, it combines with OH- to produce bicarbonate. The HCO3- crosses the basolateral membrane via a Na+-HCO3- symporter. This symporter is electrogenic as it transfers three HCO3- for every one Na+. In comparison, the Na+-H+ antiporter in the apical membrane is not electrogenic because an equal amount of charge is transferred in both directions.

Although not shown on the diagram, energy for the process is provided by basolateral Na+K ATPase

Important things to note:
Secretion of H+ by Na+ H+ exchanger – an antiporter in the luminal membrane
The HCO3- formed in the cell is returned to the circulation
90% is reabsorbed in the proximal tubule – first 1-2mm (rest in intercalated cells in DCT)
Carbonic anhydrase - very important allows continued H+ secretion and bicarbonate reabsorption
Bicarbonate reabsorption stops H2CO3 accumulating in the lumen

Acid secretion
Ammonium (NH4+) is produced predominantly within the PCT. The major source is from glutamine which enters the cell from the peritubular capillaries (80%) and the filtrate (20%). Ammonium is produced from glutamine by the action of the enzyme glutaminase. Further ammonium is produced when the glutamate is metabolised to produce alpha-ketoglutarate. This molecule contains 2 negatively-charged carboxylate groups so further metabolism of it in the cell results in the production of 2 HCO3- anions. This occurs if it is oxidised to CO2 or if it is metabolised to glucose.
The pKa for ammonium is so high (about 9.2) that both at extracellular and at intracellular pH, it is present entirely in the acid form NH4+. The previous idea that lipid soluble NH3 is produced in the tubular cell, diffuses into the tubular fluid where it is converted to water soluble NH4+ which is now trapped in the tubule fluid is incorrect.
The subsequent situation with ammonium is complex. Most of the ammonium is involved in cycling within the medulla. About 75% of the proximally produced ammonium is removed from the tubular fluid in the medulla so that the amount of ammonium entering the distal tubule is small. The thick ascending limb of the loop of Henle is the important segment for removing ammonium. Some of the interstitial ammonium returns to the late proximal tubule and enters the medulla again (ie recycling occurs).

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4
Q

what are the 4 major factors which control bicarbonate reabsorption

A
  • luminal HCO3 concentration
  • luminal flow rate
  • arterial pCO2
  • angiotensin 2

an increase in any of these 4 factors causes an increase in bicarbonate reabsorption. parathyroid hormone aslo has an effect: an increase in hormone level increases cAMP and decreases bicarbonate reabsorption

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5
Q

how does acidification occur in the distal tubule

A
  • uses different mechanism than PCT
  • H+ is secreted in cortical and medullary collectig tubules by active secretion H+ ATPase
  • H+ combine with phosphate buffers and net acid excretion occurs

Na+/H+ antiporter would not be efficient for distal acidification – WHY?
In the early DCT Na+/H+ still mediates most H+ secretion, but more distally in the CD the H+ ATPase performs this role. There are 2 types of cell in the collecting duct cells that are rich in carbonic anhydrase.The type A cells secrete H+ (H+ ATPase and to a lesser extent by the H+K+ ATPase. NB the HCO3- exits via a HCO3-/Cl- anion exchanger. Type B cells are like functionally inverted and secrete HCO3- Their role in acid base control is uncertain.

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6
Q

describe the importance of the generation of ammonium by renal tubular cells

A

Integrated overview of renal ammonia metabolism. Renal ammoniagenesis occurs primarily in the proximal tubule, involving glutamine uptake then glutamine metabolism forming ammonium and bicarbonate, and apical NH4+ secretion involving NHE3 and parallel H+ and NH3 transport.
Ammonia reabsorption in the thick ascending limb, involving apical NKCC2-mediated uptake results in medullary ammonia accumulation. Medullary sulfatides (highlighted in green) reversibly bind NH4+, contributing to medullary accumulation. Ammonia is secreted in the collecting duct via parallel H+ and NH3 secretion. The numbers in blue represent the proportion of total excreted ammonia.
If H+ secretion continues into the medullary CD this would reduce the pH of the luminal fluid even more. A low pH augments transfer of ammonium from the medullary interstitium into the luminal fluid as it passes through the medulla. The lower the urine pH, the higher the ammonium excretion and this ammonium excretion is augmented further if an acidosis is present. This augmentation with acidosis is ‘regulatory’ as the increased ammonium excretion by the kidney tends to increase extracellular pH towards normal.
If the ammonium returns to the blood stream it is metabolised in the liver to urea (Krebs-Henseleit cycle) with net production of one hydrogen ion per ammonium molecule

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7
Q

how is regulation of hydrogen excretion affected when pCO2 is increased

A
  • tubular cells respond directly to an increase in pCO2 of the blood (resp acidosis) by increasing the rate of H+ secretion
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8
Q

how is the regulation of hydrogen excretion effected in the extracellular fluid

A
  • Extracellular fluid volume depletion stimulates sodium reabsorption and increases H+ secretion and HCO3- reabsorption
  • increased angiotensin II levels, which directly stimulate the activity of the Na+-H+ exchanger
  • increased aldosterone levels, stimulate H+ secretion by the cortical collecting tubules
  • tends to cause alkalosis due to excess H+ secretion and HCO3- reabsorption
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9
Q

how does plasma potassium affect the regulation of hydrogen excretion

A
  • Hypokalemia stimulates and hyperkalemia inhibits H+ secretion in the proximal tubule
  • A decreased plasma potassium concentration tends to increase the H+ concentration in the renal tubular cells
  • This, in turn, stimulates H+ secretion and HCO3- reabsorption and leads to alkalosis
  • Hyperkalemia decreases H+ secretion and HCO3- reabsorption and tends to cause acidosis
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10
Q

how does hypochloraemia affect hydrogen excretion

A
  • secretion of HCO3 reabsorption
  • Na must be absorbed in exchange for H+ and K+ secretion
  • paradoxical aciduria
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11
Q

what is the normal pH of arterial blood

A

7.4

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