Info

🌱來自: Pathogenesis: Generation and Maintenance of Metabolic Alkalosis A Brief Pathophysiologic Review

Normal HCO3− Reclamation, Regeneration, and Generation

Nonvolatile acids are generated by metabolism of ingested foods and oxidation of endogenous substrates. A typical Western European/American diet generates 80–100 meq/d of nonvolatile strong acids (mainly sulfuric, phosphoric, and hydrochloric). These acids release H+ that mainly reacts with HCO3− to form H2CO3, which rapidly dehydrates to CO2 and H2O. Thus, serum [HCO3−] falls and is “replaced” by the anions of the generated strong acids, i.e., Cl−, SO4−2, HPO4−2, etc. Acid-base homeostasis is restored by the kidney, which filters and secretes the acid anions mainly with Na+, then the tubules reabsorb the Na+ in exchange for H+, and finally the anions are excreted together with an equal quantity of H+, in the form of titratable acid (largely H2PO4−) and NH4+. In this way, 80–100 meq of H+ are “buffered” and excreted in the urine and 80–100 meq of HCO3− are regenerated and added back to the body fluids.

However, before the kidney can secrete/excrete the daily required load of acid and thereby regenerate the decomposed HCO3−, all the filtered HCO3− must first be reclaimed and returned to the body. About 85%–90% of the normal filtered HCO3− load (4000–4500 meq/d) is reclaimed by the proximal tubules via H+ secretion. A large fraction of proximal Na+ reabsorption occurs via the Na-H exchanger 3 (NHE3) in the luminal membrane. This exchange is energized by basolateral membrane Na-K ATPase, which reduces intracellular Na+ and generates a negative intracellular charge. This creates a strong inward (lumen into cell) electrochemical Na+ gradient. Additionally, ATP-energized H+ pumps in the lumenal membrane contribute a smaller fraction (about 30%) of proximal H+ secretion. Each secreted H+ generates a HCO3− molecule that is added to the ECF and causes the disappearance of an HCO3− molecule from the lumen. Major aspects of proximal tubule Na+ reabsorption/H+ secretion are shown in Figure 3. The 10%–15% of HCO3− that escapes proximal reclamation is reclaimed in the distal tubules/collecting ducts, as shown in Figure 4.

After HCO3− has largely disappeared from the distal tubules/collecting ducts, continued H+ secretion regenerates decomposed ECF HCO3−. If dietary and metabolic acids have produced 80–100 meq/d of nonvolatile acids, then 80–100 meq/d of H+ must be excreted by the kidneys. This regenerates the HCO3− that reacted with H+derived from nonvolatile acids and thereby decomposed or “disappeared.” Also, any HCO3− lost in stool must be regerated. As HCO3− disappears from the tubular fluid, the fluid pH falls. The minimum achievable urine pH is about 4.5, which represents only 0.03 meq/L of free [H+]. Therefore, virtually the entire excreted H+ load must be bound to urine buffers: HPO4−2 (titrated to H2PO4−) represents most of the titratable acid, and NH3 binds to H+ to form NH4+. These buffered H+ charges are electrically balanced by acid anions such as SO4− and Cl− in the urine.

Figure 4 shows the major distal kidney transport mechanisms for HCO3− reclamation, regeneration, and generation (all linked to H+ secretion) and also HCO3− secretion (by type B intercalated cells).

Explain by ChatGPT

• Acid-base homeostasis : Acid-base homeostasis is the regulation of the pH of the blood and extracellular fluid. The body maintains the pH within a narrow range, despite changes in diet or metabolism.

• Normal HCO3− reclamation, regeneration, and generation : The kidney filters and secretes the acid anions mainly with Na+, then the tubules reabsorb the Na+ in exchange for H+, and finally the anions are excreted together with an equal quantity of H+, in the form of titratable acid (largely H2PO4−) and NH4+. In this way, 80–100 meq of H+ are “buffered” and excreted in the urine and 80–100 meq of HCO3− are regenerated and added back to the body fluids.

• Proximal tubule Na+ reabsorption/H+ secretion : A large fraction of proximal Na+ reabsorption occurs via the Na-H exchanger 3 (NHE3) in the luminal membrane. This exchange is energized by basolateral membrane Na-K ATPase, which reduces intracellular Na+ and generates a negative intracellular charge. This creates a strong inward (lumen into cell) electrochemical Na+ gradient. Additionally, ATP-energized H+ pumps in the lumenal membrane contribute a smaller fraction (about 30%) of proximal H+ secretion. Each secreted H+ generates a HCO3− molecule that is added to the ECF and causes the disappearance of an HCO3− molecule from the lumen.

• Distal tubules/collecting ducts : The 10%–15% of HCO3− that escapes proximal reclamation is reclaimed in the distal tubules/collecting ducts, as shown in Figure 4. After HCO3− has largely disappeared from the distal tubules/collecting ducts, continued H+ secretion regenerates decomposed ECF HCO3−.

• HCO3− secretion : HCO3− is secreted by type B intercalated cells in the distal tubules/collecting ducts. This is linked to H+ secretion and is a mechanism for HCO3− regeneration.

窩的英文不太好，只好請估🐶

• 酸鹼穩態：酸鹼穩態是血液和細胞外液 pH 值的調節。儘管飲食或新陳代謝發生變化，但身體會將 pH 值維持在一個狹窄的範圍內。

• 正常HCO3−的回收、再生和生成 : 腎臟主要以Na+過濾分泌酸陰離子，然後腎小管重吸收Na+換取H+，最後陰離子與等量的H+，以可滴定酸（主要是 H2PO4-）和 NH4+ 的形式存在。通過這種方式，80-100 meq 的 H+ 被“緩衝”並在尿液中排出，80-100 meq 的 HCO3− 被再生並加回到體液中。

• 近端小管 Na+ 重吸收/H+ 分泌：大部分近端 Na+ 重吸收通過管腔膜中的 Na-H 交換器 3 (NHE3) 發生。這種交換由基底外側膜 Na-K ATP 酶激活，減少細胞內 Na+ 並產生細胞內負電荷。這會產生強烈的向內（細胞腔內）電化學 Na+ 梯度。此外，管腔膜中 ATP 激活的 H+ 泵貢獻了一小部分（約 30%）的近端 H+ 分泌。每個分泌的 H+ 都會產生一個 HCO3- 分子，該分子被添加到 ECF 中並導致 HCO3- 分子從管腔中消失。

• 遠端小管/集合管：逃避近端回收的 10%–15% HCO3− 被回收到遠端小管/集合管中，如圖 4 所示。在 HCO3− 大部分從遠端小管中消失後/收集管，持續的 H+ 分泌再生分解的 ECF HCO3−。

• HCO3− 分泌：HCO3− 由遠曲小管/集合管中的 B 型嵌入細胞分泌。這與 H+ 分泌有關，是 HCO3− 再生的一種機制。