Question

Why do you think that the ammonia content of both urine and renal venous blood fell markedly so that ammoniogenesis was depressed by 60% or more within 60 minutes after the onset of infusion?

Excerpt:

Infusion of ketone bodies to ammonium chloride-loaded acidotic dogs was found to induce significant reduction in urinary excretion of ammonia. This effect could not be attributed to urinary pH variations. Total ammonia production by the left kidney was measured in 25 animals infused during 90 min with the sodium salt of D,L-β-hydroxybutyric acid adjusted to pH 6.0 or 4.2. Ketonemia averaged 4.5 mM/liter. In all experiments the ammonia content of both urine and renal venous blood fell markedly so that ammoniogenesis was depressed by 60% or more within 60 min after the onset of infusion. Administration of equimolar quantities of sodium acetoacetate adjusted to pH 6.0 resulted in a 50% decrease in renal ammonia production. Infusion of ketone bodies adjusted to pH 6.0 is usually accompanied by a small increase in extracellular bicarbonate (3.7 mM/liter). However infusion of D,L-sodium lactate or sodium bicarbonate in amounts sufficient to induce a similar rise in plasma bicarbonate resulted in only a slight decrement in ammonia production (15%). The continuous infusion of 5% mannitol alone during 90-150 min failed to influence renal ammoniogenesis.

Infusion of pure sodium-free β-hydroxybutyric acid prepared by ion exchange (pH 2.2) resulted in a 50% decrease in renal ammoniogenesis in spite of the fact that both urinary pH and plasma bicarbonate fell significantly. During all experiments where ketones were infused, the renal extraction of glutamine became negligible as the renal glutamine arteriovenous difference was abolished. Renal hemodynamics did not vary significantly. Infusion of β-hydroxybutyrate into the left renal artery resulted in a rapid decrease in ammoniogenesis by the perfused kidney. The present study indicates that ketone bodies exert their inhibitory influence within the renal tubular cell. Since their effect is independent of urinary or systemic acid-base changes, it is suggested that they depress renal ammoniogenesis by preventing the transformation of glutamine and glutamate into α-ketoglutarate in the mitochondria of the renal tubular cell.

Answer 1

To understand the process clearly, we need to first understand the definition of Infusion.

INFUSION: It is the process of injecting (mostly intravenously) a particular drug or fluid as a therapeutic process.

Ammonia content of both urine and renal venous blood fell markedly so that ammoniogenesis was depressed on infusion with ketone bodies:

KETONE BODIES: Produced in the body during prolonged starvation by the breakdown of fatty acids.

It is proven that ketone bodies infusion decrease renal ammonogenesis (process of producing ammonia by the nephrons in the kidneys).

It is said that 90% of ammonia is produced from the amino acid Glutamine and this glutamine is metabolised in the body by two different ways. That is Glutamine can either be broken down to ammonia or it can be converted to Alpha-Ketoglutarate that enters the Tricarboxylic Acid Cycle (TCA) to be broken down to Carbon di-oxide and water.

Sometimes, The Alpha-Ketoglutarate enters the cytosol to be converted to glucose. The process of Gluconeogenesis (producing glucose) plays an important role in the control of ammonia production.

Research has proved that infusing a person with ketone bodies has shown to decrease renal ammonogenesis as it is known to increase the intracellular Alpha-Ketoglutarate level.

Ketone bodies are oxidized to Acetyl CoA that then enters the TCA cycle. This is later converted to citrate, citrate is then converted to Alpha-Ketoglutarate. This increased levels of Alpha-Ketoglutarate will prevent the transport of glutamine and thus its deamidation by the renal mitochondria. Thus, there is a decrease in the level of ammonia produced.

Gluconeogenesis is linked to ammoniagenesis as both are stimulated by acidosis. I-Glutamine is a gluconeogenic precursor and is a substrate for ammoniagenesis. It is believed that the ketone bodies inhibit the I-Glutamine there by decreasing the process of gluconeogenesis which in turn decreases ammoniogenesis.