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Renin, Angiotensin Aldosterone & Acid-Base Balance

Renal Control of Electrolyte Balance

The kidneys play a crucial role in maintaining electrolyte balance by matching the excretion of various electrolytes (including sodium Na+, potassium K+, chloride Cl−, bicarbonate, and phosphate) to their ingestion. The control of sodium levels is particularly important because it directly impacts blood pressure and blood volume. Furthermore, potassium levels must be regulated for proper skeletal and cardiac muscle function. Aldosterone, a steroid hormone produced in the adrenal cortex, is a key player in the balance of sodium and potassium.

Role of Aldosterone in Sodium and Potassium Balance

Approximately 90% of filtered sodium and potassium is reabsorbed early in the nephron without hormonal regulation. The body assesses its needs, and aldosterone adjusts the reabsorption of sodium and the secretion of potassium, primarily at the distal tubule and collecting duct. This hormonal control is vital for maintaining homeostasis in electrolyte levels.

Potassium Secretion Mechanisms

Potassium secretion occurs in the collecting duct through two mechanisms. The aldosterone-independent response is triggered by an increase in blood potassium levels, which enhances the expression of potassium channels in the cortical collecting duct. Conversely, when potassium levels decline, these channels are removed. The aldosterone-dependent response involves increased potassium levels stimulating the adrenal cortex to produce aldosterone, which subsequently increases potassium secretion in the distal tubule and collecting duct.

Inverse Relationship Between Sodium and Potassium

There is a notable inverse relationship between sodium absorption and potassium secretion. Increases in sodium reabsorption lead to enhanced potassium secretion due to several factors: (1) the potential difference created by sodium reabsorption drives potassium through potassium channels; (2) the presence of water and sodium in the filtrate stimulates aldosterone production, promoting potassium secretion; and (3) increased flow rates in the distal tubule activate potassium channels by bending cilia on renal tubular cells.

Control of Aldosterone Production

Aldosterone production is regulated by two mechanisms: (1) a direct increase in blood potassium levels stimulates aldosterone secretion from the adrenal cortex; (2) a decrease in blood sodium levels indirectly stimulates aldosterone production via the renin-angiotensin-aldosterone system, which is a physiological pathway that also responds to low blood pressure.

Juxtaglomerular Apparatus and Renin Secretion

The juxtaglomerular apparatus, located where the afferent arteriole contacts the distal tubule, plays a significant role in renin secretion. Low salt levels diminish blood volume by inhibiting the secretion of antidiuretic hormone (ADH), leading to more urinary excretion of water. The granular cells in the juxtaglomerular apparatus, acting as baroreceptors, detect reduced blood volume and secrete renin. Additionally, these cells receive sympathetic innervation during baroreceptor reflex activation.

Renin-Angiotensin-Aldosterone System (RAAS)

Upon secretion, renin acts on angiotensinogen, converting it to angiotensin I, which is subsequently transformed into angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II has multiple significant effects: it prompts the adrenal cortex to increase aldosterone production, enhancing sodium reabsorption, potassium secretion, and thereby raising blood volume and blood pressure.

Negative Feedback Mechanism

In response to increased sodium and water in the filtrate, a feedback signal is sent to inhibit renin production from the granular cells, allowing for more sodium to be excreted as a means to lower sodium levels in the blood and regulate volume.

Atrial Natriuretic Peptide (ANP)

When blood volume rises, the atria of the heart release atrial natriuretic peptide (ANP). This hormone promotes sodium excretion, thus leading to increasing water excretion, which results in decreased blood volume and pressure. Brain natriuretic peptide (BNP), produced by the heart ventricles, has similar effects on blood volume regulation.

Acid-Base Balance by the Kidneys

The kidneys also play a crucial role in maintaining acid-base balance. They regulate blood pH by reabsorbing bicarbonate and secreting hydrogen ions (H+), leading to acidic urine. The proximal tubule utilizes sodium/hydrogen (Na+/H+) pumps for this exchange, where some of the H+ is utilized for bicarbonate reabsorption through antiport mechanisms.

Bicarbonate Reabsorption

Bicarbonate cannot freely cross the inner tubule membrane and must first be converted to carbon dioxide (CO2) and water (H2O) using carbonic anhydrase. The reaction sequence is as follows:

  1. Bicarbonate + H+ → carbonic acid
  2. Carbonic acid (catalyzed by carbonic anhydrase) → H2O + CO2
  3. CO2 enters tubule cells and is converted back to bicarbonate, which then diffuses into the interstitial space.

Distal Tubule and pH Regulation

In addition to proximal tubular action, the distal tubule also increases hydrogen secretion through H+ ATPase pumps. This is essential particularly in compensating for pH disturbances in states of alkalosis (where urine bicarbonate is secreted) and acidosis (where additional bicarbonate is generated to counterbalance acidosis).

Urinary Buffers and Kidney Function

The kidneys cannot produce urine with a pH below 4.5, necessitating buffering for H+ secretion. Phosphates and ammonia serve as buffers, with phosphates entering via filtration and ammonia produced from amino acid deamination. Thus, the kidneys utilize these mechanisms to buffer urine effectively, maintaining acid-base homeostasis.

Summary of Relationship Between Electrolytes

  1. Sodium reabsorption stimulates the secretion of other cations, such as potassium (K+) and hydrogen (H+), which compete for secretion.
  2. Acidosis induces H+ secretion and inhibits K+ secretion, potentially leading to hyperkalemia, while alkalosis promotes K+ loss.
  3. Conversely, conditions of hyperkalemia can suppress hydrogen secretion leading to acidosis.

Through these intricate systems and hormonal controls, the kidneys adeptly maintain homeostasis of electrolytes and acid-base balance in the body.