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Guyton and Hall Medical Physiology (13th Ed)
Acid-Base Regulation
H+ concentration of the body fluids normally is kept at a low level hydrogen ion is a single free proton ACIDS are containing hydrogen atoms that can release hydrogen ions in solutions. Ex. HCl (strong acid), H2CO3 (weak acid) (carbonic acid=ionizes in water to form H+ and bicarbonate) BASE is an ion or a molecule that can accept an H+. Ex. HCO3, HPO terms base and alkali are often used synonymously the term alkalosis refers to excess removal of H+ from the body fluids, in contrast to the excess addition of H+ , which is referred to as acidosis
DEFENDING AGAINST CHANGES IN H+ CONCENTRATION: BUFFERS, LUNGS, AND KIDNEYS
primary systems regulate the H+ concentration to prevent acidosis or alkalosis: (1) the chemical acid- base buffer systems of the body fluids, which immediately combine with an acid or a base to prevent excessive changes in H+ concentration; (2) the respiratory center, which regulates the removal of CO2 (and, therefore, H2CO3) from the extracellular fluid; and (3) the kidneys, which can excrete either acid or alkaline urine, thereby readjusting the extracellular fluid H+ concentration toward normal during acidosis or alkalosis Buffer systems do not eliminate H+ from or add H+ to the body but only keep them tied up until balance can be re-established. Respiratory system acts within a few minutes to eliminate CO2 and, therefore, H2CO3 from the body third line of defense, the kidney are relatively slow to respond over a period of hours to several days, they are by far the most powerful of the acid-base regulatory systems
RENAL CONTROL OF ACID-BASE BALANCE
kidneys excrete either acidic or basic urine MECHANISM: Large numbers of HCO3 − are filtered continuously into the tubules, and if they are excreted into the urine, this removes base from the blood. Large numbers of H+ are also secreted into the tubular lumen by the tubular epithelial cells,
thus removing acid from the blood. If more H+ is secreted than HCO3 − is filtered, there will be a net loss of acid. Conversely, if more HCO3 − is filtered than H+ is secreted, there will be a net loss of base. kidneys must also prevent the loss of bicarbonate in the urine, a task that is quantitatively more important than the excretion of nonvolatile acid , the kidneys regulate extracellular fluid H+ concentration through three fundamental mechanisms: (1) secretion of H+ , (2) reabsorption of filtered HCO3 − , and (3) production of new HCO
RENAL CORRECTION OF ACIDOSIS—INCREASED EXCRETION OF H+ AND ADDITION OF HCO3 − TO THE EXTRACELLULAR FLUID
If this ratio decreases because of a fall in HCO3, the acidosis is referred to as metabolic acidosis. If the pH falls because of an increase in PCO2, the acidosis is referred to as respiratory acidosis. Note that in respiratory acidosis , there is a reduction in pH, an increase in extracellular fluid H+ concentration, and an increase in PCO2, which is the initial cause of the acidosis : Compensatory response is an increase in plasma HCO3 − , caused by the addition of new HCO3 − to the extracellular fluid by the kidneys Metabolic acidosis , there is also a decrease in pH and a rise in extracellular fluid H+ concentration. However, in this case, the primary abnormality is a decrease in plasma HCO3 : Primary compensations include increased ventilation rate, which reduces PCO2, and renal compensation, which, by adding new HCO3 − to the extracellular fluid, helps minimize the initial fall in extracellular HCO3 − concentration
RENAL CORRECTION OF ALKALOSIS—DECREASED TUBULAR SECRETION OF H+ AND INCREASED EXCRETION OF HCO3 –
Respiratory alkalosis , there is an increase in extracellular fluid pH and a decrease in H+ concentration. The cause of the alkalosis is decreased plasma PCO2, caused by hyperventilation : compensatory response to a primary reduction in PCO2 in respiratory alkalosis is a reduction in plasma HCO3 − concentration, caused by increased renal excretion of HCO3 −.
Metabolic alkalosis , there is also decreased plasma H+ concentration and increased pH. The cause of metabolic alkalosis, however, is a rise in the extracellular fluid HCO3 – concentration causing hypoventilation The excess HCO3 in the tubular fluid fails to be reabsorbed because there is no H+ to react with , and it is excreted in the urine : primary compensations are decreased ventilation, which raises PCO2, and increased renal HCO3 − excretion, which helps compensate for the initial rise in extracellular fluid HCO3 – concentration
Nelson Textbook (Chap68.7)
ACID-BASE PHYSIOLOGY
Control of acid-base balance depends on the kidneys, the lungs, and intracellular and extracellular buffers. NORMAL PH = 7.35 to 7. NORMAL PCO2 = 35-45 mmHg An acid is a substance that releases (“donates”) a hydrogen ion (H+). A base is a substance that accepts a hydrogen ion Buffers are substances that attenuate the change in pH that occurs when acids or bases are added to the body The best physiologic buffers have a pKa close to 7.40. The concentration of a buffer and its pKa determine the buffer’s effectiveness buffer works best when it is (weak acid, weak base) 50% dissociated (half HA and half A−) bicarbonate buffer system is routinely monitored clinically and is based on the relationship between carbon dioxide and bicarbonate Henderson-Hasselbalch equation expresses the relationship among pH, pKa, and the concentrations of an acid and its conjugate base. 3 VARIABLE = pH, bicarbonate concentration, carbon dioxide concentration nonbicarbonate buffers include proteins (albumin=extratracellular, haemoglobin=intracellular), phosphate , and bone. Proteins are effective buffers , largely because of the presence of the amino acid histidine Bone is an important buffer. Bone is basic composed sodium bicarbonate and calcium
carbonate and thus dissolution of bone releases base Clinically, we measure the extracellular pH, but it is the intracellular pH that affects cell function Carbon dioxide generated during normal metabolism is a weak acid 3 principal sources of H+ (acid production):
- dietary protein metabolism 2. incomplete metabolism of carbohydrates and fat producing lactic acid & keto acid
- stool losses of bicarbonate (1 loss = 1 H+ gain) The kidneys regenerate this bicarbonate by secreting H+. The lungs cannot regenerate bicarbonate During a metabolic acidosis, hyperventilation can lower [CO2], decrease [H+ ], and thus increase pH During a respiratory acidosis, increased renal generation of bicarbonate can decrease [H+ ] and increase pH, but cannot repair the respiratory acidosis only the lungs can regulate [CO2], and only the kidneys can regulate [HCO3 − ]
2 Step process of HCO3 regulation
First, the renal tubules resorb the bicarbonate that is filtered at the glomerulus. Second, there is tubular secretion of H+ kidneys regulate the serum bicarbonate concentration by modifying acid excretion in the urine The proximal tubule is the site where most filtered bicarbonate is reclaimed , even though other sites along the nephron, especially the thick ascending limb of the loop of Henle, resorb some of the filtered bicarbonate. The collecting duct is the principal location for the hydrogen ion secretion that acidifies the urine. The proximal tubule generates the ammonia that serves as a urinary buffer in the collecting duct
volume, but also leads to increased urinary losses of potassium, exacerbating the hypokalemia. 4 forms of renal tubular acidosis (RTA): distal (typeI), proximal (typeII), mixed (typeIII) and hyperkalemic (typeIV) Proximal RTA is part of Fanconi syndrome , a generalized dysfunction of the proximal tubule. The dysfunction leads to glycosuria, aminoaciduria, and excessive urinary losses of phosphate and uric acid Hyperkalemic RTA, the renal excretion of acid and potassium is impaired. It is the result of hyperkalemia, absence of aldosterone, or inability of the kidney to respond to aldosterone Lactic acidosis typically occurs when inadequate oxygen delivery to the tissues leads to anaerobic metabolism and excess production of lactic acid Lactic acidosis may be secondary to shock, severe anemia, or hypoxemia In insulin-dependent diabetes mellitus , inadequate insulin leads to hyperglycemia and DKA. Insulin corrects the underlying metabolic problem and permits conversion of acetoacetate and β- hydroxybutyrate into bicarbonate starvation ketoacidosis the lack of glucose leads to keto-acid production, which in turn can produce a metabolic acidosis In alcoholic ketoacidosis usually follows a combination of an alcoholic binge with vomiting and poor intake of food Renal failure causes a metabolic acidosis because of the need for the kidneys to excrete the acid produced by normal metabolism Salicylate intoxication causes metabolic acidosis Ethylene glycol , a component of antifreeze, is converted in the liver to glyoxylic and oxalic acids, causing a severe metabolic acidosis toxicity of methanol ingestion also depends on liver metabolism; formic acid is the toxic end product that causes the metabolic acidosis Toluene inhalation and paraldehyde ingestion are other potential causes of a metabolic acidosis Inborn errors of metabolism cause a metabolic acidosis
CLINICAL MANIFESTATIONS
At a serum pH <7.2 (acidosis), there may be impaired cardiac contractility and an increased risk of arrhythmias (hyperkalemia) ONRMAL RESPONSE TO MET ACIDOSIS = HYPERVENTILATION Acute metabolic effects of acidemia include insulin resistance , increased protein degradation , and reduced ATP synthesis Chronic metabolic acidosis causes failure to thrive in children
DIAGNOSIS
measurements of BUN, serum creatinine, serum glucose, urinalysis, and serum electrolytes DKA = Metabolic acidosis, hyperglycemia, glycosuria, and ketonuria metabolic acidosis causes potassium to move from the ICS to the ECS = HYPERKALEMIA With diarrhea, there are high stool losses of K+ and, often, secondary renal losses of K = HYPOKALEMIA aldosterone deficiency = metabolic acidosis, hyperkalemia, and hyponatremia
TREATMENT
DKA = give insulin Lactic acidosis/shock = IV fluids Renal insufficiency = hemodialysis/peritoneal dialysis salicylate poisoning = alkali administration severe acute lactic acidosis/ severe DKA = bicarbonate therapy Bicarbonate therapy increases the generation of CO2 , which can accumulate in patients with respiratory failure chronic metabolic acidosis = oral base therapy (Na bicarbonate) metabolic acidosis + respiratpry acidosis = tromethamine (THAM) methanol or ethylene glycol intoxication = hemodialysis
METABOLIC ALKALOSIS
most often secondary to emesis or diuretic use serum bicarbonate concentration is increased with a metabolic alkalosis, although a respiratory acidosis also leads to a compensation mechanism
Etiology and Pathophysiology
2 responses of kidneys 1. the generation of the metabolic alkalosis, which requires the addition of base to the body, and 2. the maintenance of the metabolic alkalosis, which requires impairment in the kidney’s ability to excrete base alkalosis in patients with a low urinary chloride = correction by volume repletion alkalosis in a patient with an elevated urinary chloride = unresponsive to volume repletion “ Cl- resistant metabolic alkalosis ” generation phase of the metabolic alkalosis = releasing bicarbonate by gastric mucosa maintenance phase of the metabolic alkalosis = caused by volume depletion, hypokalemia (decreases bicarbonate loss) loop or thiazide diuretics = increases angiotensin II, aldosterone, and adrenergic stimulation of the kidney = alkalosis/hypokalemia cystic fibrosis = excessive NaCl losses
CLINICAL MANIFESTATIONS
Cl− -responsive causes = thirst, letargy Cl− -unresponsive causes = hypertension, cushing, congenital adrenal hyperplasia Hypokalcemia due to alkalosis tetany (carpopedal spasm) Arrhythmias are a potential complication of a metabolic alkalosis HYPOVENTILATION seen in severe metabolic alkalosis can cause hypoxia
DIAGNOSIS
Measurement of the urine [Cl−] Diuretics and gastric losses = metabolic alkalosis Cystic fibrosis = Metabolic alkalosis with hypokalemia Adrenal adenomas = Aldosterone is high and renin is low Cushing syndrome = Renin and aldosterone are low
TREATMENT
necessary in children with moderate or severe metabolic alkalosis most effective approach is to address the underlying etiology eliminate or reduce dose of diuretics
potassium-sparing diuretic is also helpful in a child with a metabolic alkalosis from diuretics Arginine HCl may also be used to treat chloride- responsive metabolic acidosis and causes increase in serum potassium acetazolamide decreases resorption of bicarbonate in the proximal tubule, causing significant bicarbonate and potassium loss in the urine
RESPIRATORY ACIDOSIS
inappropriate increase in blood carbon dioxide tension (PCO2) Decreased effectiveness of CO2 removal by the lungs respiratory acidosis is secondary to either pulmonary disease, such as severe bronchiolitis, or non-pulmonary disease, such as a narcotic overdose impairment of alveolar ventilation, the rate of body production of CO2 may affect the severity of the respiratory acidosis increase of serum [HCO3 −] during a chronic respiratory acidosis is associated with a decrease in body chloride
Etiology and Pathophysiology
causes are either pulmonary or nonpulmonary CNS disorder = reduce ventilator drive = acidosis Respiratory muscle failure = inadequate ventilation Airway obstruction = decrease ventilation High levels of exercise, fever, hyperthyroidism, excess caloric intake = increase in CO
CLINICAL MANIFESTATIONS
often tachypneic in an effort to correct the inadequate ventilation HYPERCARBIA hypoxia is always present if a respiratory acidosis is present anxiety, dizziness, headache, confusion, asterixis, myoclonic jerks, hallucinations, psychosis, coma, and seizures ACIDEMIA ALWAYS AFFECTS CARDIO SYSTEM ex. arrhythmias Hypercapnia causes vasodilation = cerebral vasculature Hypercapnia produces vasoconstriction = pulmonary circulation
