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Acid-Base Balance

The pH of the blood is tightly regulated within the range 7.35–7.45 to ensure proper physiologic functions. Large amounts of acid are generated each day through normal processes (aerobic/anaerobic respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy and dietary intake), and these are efficiently managed and eliminated by buffers in the blood, the respiratory system, and the renal system. When these regulatory systems are disturbed, acid–base balance disorders occur, including respiratory acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis, respiratory alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis, metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis, and metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis.

Last updated: Jul 20, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

pH Overview

pH is the quantitative measurement of the acidity or basicity of a solution.

  • pH = –log10[H+]:
    • [H+] = concentration of hydrogen ions (i.e., protons) in solution
    • Logarithmic scale Scale Dermatologic Examination from 1 to 14 
      • 1 = maximally acidic, 14 = maximally basic
      • 7 = neutral point: equal concentrations of H+ and OH 
  • Normal arterial blood pH is approximately 7.40. 
  • The normal range is tightly regulated to stay between 7.35 and 7.45.
  • “-emia” vs. “-osis”
Relation between blood ph and concentration of hydrogen ions

Relation between blood pH and concentration of hydrogen ions

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Table: Examples of pH values of various fluids
Compartment pH
Gastric secretions Gastric secretions Gastrointestinal Secretions (under conditions of maximal acidity) 0.7
Lysosome 5.5
Chromaffin granule 5.5
Neutral H2 at 37°C 6.81
Cytosol Cytosol A cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement. The Cell: Cytosol and Cytoskeleton of a typical cell 6.0–7.4
CSF 7.3
Arterial blood plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products 7.35–7.45
Mitochondrial inner matrix 7.5
Pancreatic secretions Pancreatic Secretions Gastrointestinal Secretions 8.1

Acids, Bases, and Buffers

The relative concentrations of acids and bases in the blood determine its pH. Buffers provide a short-term solution for disturbances in this balance before the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy can act definitively to restore balance. 

Acids

Acids are compounds that can donate protons (H+)  or accept electrons.

  • H+ are released when acids dissociate in solution → ↓ pH
  • Classified by strength and volatility:
    • Strong acids: 
      • Fully ionize in water 
      • More H+ released into water → greater effect on pH
      • Example: hydrochloric acid Hydrochloric acid A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. Caustic Ingestion (Cleaning Products) ( HCl HCL Hairy cell leukemia (HCL) is a rare, chronic, B-cell leukemia characterized by the accumulation of small mature B lymphocytes that have “hair-like projections” visible on microscopy. The abnormal cells accumulate in the peripheral blood, bone marrow (causing fibrosis), and red pulp of the spleen, leading to cytopenias. Hairy Cell Leukemia)
    • Weak acids:
      • Partially ionize in water 
      • Less H+ released into water → relatively less effect on pH
      • Example: carbonic acid (H2CO3)
    • Volatile acids:
      • Can change phase into a gas → removable through the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
      • Primary example: CO2
      • The body produces approximately 15,000 mmol of volatile acid per day through aerobic metabolism.
    • Nonvolatile (fixed) acids:
      • Cannot change phase into a gas → not removable through the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
      • Removed by the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
      • The body produces approximately 70 mmol of fixed acids per day through anaerobic metabolism and the GI tract.
      • Examples: lactic acid, uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis, sulfuric acid Sulfuric acid Inorganic and organic derivatives of sulfuric acid (h2so4). The salts and esters of sulfuric acid are known as sulfates and sulfuric acid esters respectively. Caustic Ingestion (Cleaning Products), phosphoric acid Phosphoric Acid Caustic Ingestion (Cleaning Products)

Bases

Bases are compounds that can accept protons (H+) or donate electrons.

  • Hydroxide ions (OH) are released when bases dissociate into solution:
    • OH combine with free H+ to form H2O.
    • Net result is less [H+] → ↑ pH (becomes more basic)
  • Classified by strength:
    • Strong bases:
      • Fully ionize in water
      • More OH released into water → greater effect on pH
      • Example: sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia hydroxide (NaOH)
    • Weak bases:
      • Partially ionize in water
      • Less OH released into water → relatively less effect on pH 
      • Examples: bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes (HCO3), ammonia (NH3)

Buffers

Buffers are substances that consume or releases hydrogen ions (H+) to stabilize the pH.

  • Buffer power refers to the quantity of H+ that can be added or removed.
  • Categorized as bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes and nonbicarbonate buffers:
    • Bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes (HCO3):
      • Most physiologically important buffer
      • HCO3 + H+ ⇆ H2CO3 ⇆ CO2 + H2O
    • Nonbicarbonate buffers:
      • Less physiologically important
      • Examples: proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (e.g., albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests, hemoglobin), phosphates
  • pK: pH of a buffer when it is 50% ionized
    • Example: bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes
      • HCO3 + H+ ⇆ H2CO3 
      • 50% HCO3 and 50% H2CO3 occurs at pH 6.1.
      • pK of bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes = 6.1
    • Defines the optimal pH range for buffering capability of a particular buffer
    • Buffers work best when pK is near the pH of the fluid they are buffering.
  • Henderson–Hasselbalch equation:
    • Formula used to determine the pH of blood
    • The pH of the blood depends primarily on the ratio between the amounts of HCO3 (base) and CO2 (acid) in the blood.
    • Equation: pH = 6.1 + log ([HCO3]/[0.03 × PCO2])
      • 6.1 = pK of HCO3 (dominant buffer in the blood)
      • [HCO3] = concentration of bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes in the blood measured in mEq/L 
      • PCO2 = partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of CO2 in the blood measured in mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
      • 0.03 = solubility factor for CO2
    • Used to generate titration curves
Table: Henderson–Hasselbalch examples
Normal ABG Acidic ABG Alkalotic ABG
HCO3 24 mEq/L 26 mEq/L 22 mEq/L
PaCO2 40 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg 60 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg 20 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
pH 7.40 7.26 7.66
ABG: arterial blood gas Arterial blood gas Respiratory Alkalosis
HCO3: bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes
PaCO2: partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of CO2 in arterial blood
Titration curve for bicarbonate in the blood

Titration curve for bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes in the blood

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Acid Handling in the Lungs

The body produces approximately 15,000 mmol of volatile and 70 mmol of nonvolatile acids daily. The lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy work in concert to eliminate this daily acid load, which prevents the buffering capability of the blood from being overwhelmed and allows it to maintain a normal pH.

  • The primary acid load produced by the body is in the form of CO2 (a volatile acid) produced via aerobic metabolism.
  • CO2 is eliminated through the respiratory tract.
  • ↑ CO2 → ↑ respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy
Acid handling in the lungs

Factors involved in daily acid–base balance

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Acid Handling in the Kidneys

The kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy are primarily responsible for elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy of the fixed (nonvolatile) acids, approximately 70 mmol daily. They prevent excretion of bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes, and also pair acid excretion with new bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes generation so that the bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes buffering system is always available at full capacity.

Bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes reabsorption

Bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes is freely filtered at the glomerulus, and 100% of it is then reabsorbed (80% in the proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System) through the following process:

  1. Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia–hydrogen ion exchanger 3 ( NHE3 NHE3 A sodium-hydrogen antiporter expressed primarily by epithelial cells in the kidneys, it localizes to the apical membrane of the proximal kidney tubule, where it functions in sodium and water reabsorption and possibly calcium homeostasis. It also is expressed in heart, brain, and lung tissues and is resistant to amiloride inhibition. Carbonic Anhydrase Inhibitors) absorbs Na+ and secretes H+.
  2. Secreted H+ combine with the filtered HCO3 to form H2CO3 in the tubular lumen.
  3. H2CO3 is converted into H2O and CO2 by apical carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors IV. 
  4. CO2 diffuses freely across the apical membrane back into the cell.
  5. Intracellular carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors II converts CO2 + H2O back into H2CO3.
  6. H2CO3 then can dissociate into H+ and HCO3:
    • H+ are recycled through the process through NHE3 NHE3 A sodium-hydrogen antiporter expressed primarily by epithelial cells in the kidneys, it localizes to the apical membrane of the proximal kidney tubule, where it functions in sodium and water reabsorption and possibly calcium homeostasis. It also is expressed in heart, brain, and lung tissues and is resistant to amiloride inhibition. Carbonic Anhydrase Inhibitors.
    • HCO3 is absorbed through the basolateral membrane via:
      • Na+-HCO3 cotransporter 
      • HCO3-Cl exchanger 
  7. Net effects of the entire process:
    • Excretion of H+
    • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of HCO3– 
  8. Note: Bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes is not freely permeable across the apical membrane because it is a charged molecule.
  9. Locations of HCO3 reabsorption:
    • Proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System: 80%
    • Thick ascending limb Thick ascending limb Renal Sodium and Water Regulation: 10%
    • Distal convoluted tubule Distal convoluted tubule The portion of renal tubule that begins from the enlarged segment of the ascending limb of the loop of henle. It reenters the kidney cortex and forms the convoluted segments of the distal tubule. Gitelman Syndrome: 6%
    • Collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma: 4%
Bicarbonate reabsorption in the proximal tubule

Bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes reabsorption in the proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System

CA-IV: carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors IV
CA-II: carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors II

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Ammonia (NH3)

NH3 is able to help excrete fixed acids. 

  • Accounts for 60% of fixed acid excretion
  • Occurs primarily in the proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System
  • NH3 can bind BIND Hyperbilirubinemia of the Newborn H+, which is then eliminated in the urine:
    • Within the tubule, NH3 can bind BIND Hyperbilirubinemia of the Newborn to H+ → becomes NH4+, which remains in the urine and is excreted 
    • NH4+ can be generated within the proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System cell and excreted into the tubular fluid.
  • NH4+ (ammonium) and HCO3 are generated from the metabolism of glutamine Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. Synthesis of Nonessential Amino Acids in the mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles
    • Glutamine Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. Synthesis of Nonessential Amino Acids dehydrogenase: glutamine Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. Synthesis of Nonessential Amino Acids glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids + NH4+, then
    • Glutamate dehydrogenase Glutamate dehydrogenase An enzyme that catalyzes the conversion of l-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. Synthesis of Nonessential Amino Acids: glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids →  𝛼-ketoglutarate + NH4+, then
    •  𝛼-ketoglutarate enters the Krebs cycle Krebs cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle → 2 molecules of HCO3 generated
  • NH4+ is secreted into tubular fluid via 2 mechanisms:
    • NHE3 NHE3 A sodium-hydrogen antiporter expressed primarily by epithelial cells in the kidneys, it localizes to the apical membrane of the proximal kidney tubule, where it functions in sodium and water reabsorption and possibly calcium homeostasis. It also is expressed in heart, brain, and lung tissues and is resistant to amiloride inhibition. Carbonic Anhydrase Inhibitors directly exchanges Na+ for NH4+.
    • NH3 is membrane-permeable:
      • Crosses freely from inside cell into tubular lumen
      • Combines with free H+ to form NH4+
  • HCO3 produced in the Krebs cycle Krebs cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle is reabsorbed across the basolateral membrane into the bloodstream.
  • This process is highly adaptable: upregulates in chronic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis.
Nh3 and nh4+ transport to the lumen for excretion

NH3 and NH4+ transport to the lumen for excretion

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Titratable acids

  • Accounts for 40% of fixed acid excretion
  • Occurs in the proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System, distal convoluted tubule Distal convoluted tubule The portion of renal tubule that begins from the enlarged segment of the ascending limb of the loop of henle. It reenters the kidney cortex and forms the convoluted segments of the distal tubule. Gitelman Syndrome, and collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma
  • Titratable acids buffer a H+ and then are eliminated in the urine:
    • Intracellular H2CO3 dissociates into H+ and HCO3.
    • H+ ions are secreted into the tubular lumen by:
      • V-type H+-ATPase 
      • NHE3 NHE3 A sodium-hydrogen antiporter expressed primarily by epithelial cells in the kidneys, it localizes to the apical membrane of the proximal kidney tubule, where it functions in sodium and water reabsorption and possibly calcium homeostasis. It also is expressed in heart, brain, and lung tissues and is resistant to amiloride inhibition. Carbonic Anhydrase Inhibitors 
    • Titratable acid binds H+.
    • Bound compound is excreted in the urine.
    • HCO3 (from first step) is left over inside the cell and is considered “regenerated.”
  • Examples of titratable acids:
    • pK is closest to the pH of normal urine → most useful for binding H+ under normal conditions:
    • pK further away from normal urine pH → less useful:
      • Urate (pK 5.8)
      • Creatinine (pK 5.0)
    • pK less than the minimum possible urine pH (approximately 4.4) → not useful:
      • Lactate (pK 3.9)
      • Pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis (pK 2.5)
  • This system does not upregulate in chronic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis (unlike the ammonia system).

Clinical Relevance

When a disease process overwhelms the normal capability to regulate pH, the primary acid–base disorders listed below occur. Compensatory mechanisms also occur, which help to offset the change in pH.

  • Metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis: processes that result in the accumulation of H+ and generally cause acidemia Acidemia Respiratory Acidosis (i.e., the lowering of blood pH): This process can be the result of either excessive loss of buffers (e.g., diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea) or increased production of acids (e.g., ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis and lactic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis).
  • Metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis: processes that result in the accumulation of HCO3 and generally cause alkalemia Alkalemia Respiratory Alkalosis (i.e., the rise of blood pH): This process can be the result of excessive supply of buffers or increased excretion of hydrogen ions. Common causes are vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia and calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes–alkali syndrome.
  • Respiratory acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis: processes that result in the accumulation of arterial CO2 and generally cause acidemia Acidemia Respiratory Acidosis (i.e., the lowering of blood pH): This process can be the result of deficient clearance of CO2 by the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy. Common causes are chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) and asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma.
  • Respiratory alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis: processes that result in the decrease of arterial CO2 and generally cause alkalemia Alkalemia Respiratory Alkalosis (i.e., the rise of blood pH): This process can be the result of excessive clearance of CO2 from the blood by increased ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing. Common causes include pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, and aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) overdose.

References

  1. Emmett, M., Palmer B.F. (2020). Simple and mixed acid–base disorders. UpToDate. Retrieved April 1, 2021, from https://www.uptodate.com/contents/simple-and-mixed-acid-base-disorders 
  2. Theodore, A. C. (2020). Arterial blood gases. UpToDate. Retrieved April 1, 2021, from https://www.uptodate.com/contents/arterial-blood-gases

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