SECTION VI THE KIDNEY Myocardial Infarctian and Renal Functica A 65-year-old man had a myocardial infarction 4 months ago,and now he complains of easy fatigability.shortness of breath,and swelling of his ankles.On physical exanination he is found to have distended neck veins and pitting edema of the ankles. His breathing is rapid (20 respirations/min),and rales are heard bilaterally at the bases of the lungs.He is afebrile,his pulse rate is 90 beats/min.and his blood pressure is 110/70.Since his myocardial infarction,he has been taking a cardiac glycoside and a thiazide diuretic.A blood sample is obtained,and the following abnormalities are poted: 1.Is the extracellular fluid (ECF)volune in this man above or below mormal? What evidence in the physical examination supports your conclusion? 2.Is the effective circulating volure (ECV)in this man above or below normal? What laboratory test could you perform to support your coeclusion? 3.Bow would you characterize renal Na+handling in this man?What evidence in the physical exanination supports this conclusion? 4.What is the mechanisn for the develogeent of hyponatrenia in this man? 5.What is the mechanisn for the developeent of hypokalenia in this man? 6.What type of acid-base disturbance does this man have?What is the mechanisn for the developrent of this disorder? 7.What is the significance of the elevated serum [creatinine]? 8.The physician treating this man prescribes a loop diuretic in addition to the thiazide diuretic to further reduce his Na+retention and edems.What effect will this treatneat have on the man's ECV?What is the potential effect of this treatment on the man's serum Na+.K,HC03-,and creatinine concentrations? ANSVER
SECTION VI THE KIDNEY Myocardial Infarction and Renal Function A 65-year-old man had a myocardial infarction 4 months ago, and now he complains of easy fatigability, shortness of breath, and swelling of his ankles. On physical examination he is found to have distended neck veins and pitting edema of the ankles. His breathing is rapid (20 respirations/min), and rales are heard bilaterally at the bases of the lungs. He is afebrile, his pulse rate is 90 beats/min, and his blood pressure is 110/70. Since his myocardial infarction, he has been taking a cardiac glycoside and a thiazide diuretic. A blood sample is obtained, and the following abnormalities are noted: 1. Is the extracellular fluid (ECF) volume in this man above or below normal? What evidence in the physical examination supports your conclusion? 2. Is the effective circulating volume (ECV) in this man above or below normal? What laboratory test could you perform to support your conclusion? 3. How would you characterize renal Na+ handling in this man? What evidence in the physical examination supports this conclusion? 4. What is the mechanism for the development of hyponatremia in this man? 5. What is the mechanism for the development of hypokalemia in this man? 6. What type of acid-base disturbance does this man have? What is the mechanism for the development of this disorder? 7. What is the significance of the elevated serum [creatinine]? 8. The physician treating this man prescribes a loop diuretic in addition to the thiazide diuretic to further reduce his Na+retention and edema. What effect will this treatment have on the man's ECV? What is the potential effect of this treatment on the man's serum Na+, K+, HCO3-, and creatinine concentrations? ANSWER
1.The ECF volune of this man is increased above normal.The presence of edema, distension of the neck veins,and rales (sounds caused by rluid)in the lungs are evidence of this increased volume.Additional evidence could be obtained by measuring weight gain,because accumulation of each liter of extracellular fluid would increase body weight by I kg. 2.The ECV in this man would be decreased below normal.With damage to the myocardiun.cardiac output and therefore tissue perfusion would he reduced:this would be semsed by the body as a decrease in the ECV.The ECV canmot be measured directly.Therefore to deternine if the ECV is reduced.measurements would have to be nade of parameters that change in response to alterations in the ECV.For exanple, the kidneys redace Na+excretion in response to a decrease in the ECV.Measurement of fractional Na texcretion could confirm the existence of a reduced effective circulating volure (fraction Nat excretion 18).Bwever,in this man fractional excretion may not be very low because a thiazide diuretic was used.Alternatively. measurements would be made of plasma renin activity because this would be stimulated by the decreased ECV. 3.The kidneys would be avidly retaining Nat.With a decrease in the effective circulating volume,semsors in the low-pressure (cardiac atria and pulromary vasculature)and high-pressure (juxtaglonerular apparatus.aortic arch.and carotid sinus)sides of the circulation would be activated.and the signals would be sent to the kidneys to retain Nat. Sympathetic nerves that innervate the afferent and efferent arterioles of the glomeruli would cause vasocoestriction.The net result would be to reduce the GFR: this in turm would reduce the filtered load of Na+. Syupathetic innervation of the proximal tubule and the thick ascending linb of Henle's loop will also increase Nat reabsorption at these sites
1. The ECF volume of this man is increased above normal. The presence of edema, distension of the neck veins, and rales (sounds caused by fluid) in the lungs are evidence of this increased volume. Additional evidence could be obtained by measuring weight gain, because accumulation of each liter of extracellular fluid would increase body weight by 1 kg. 2. The ECV in this man would be decreased below normal. With damage to the myocardium, cardiac output and therefore tissue perfusion would be reduced; this would be sensed by the body as a decrease in the ECV. The ECV cannot be measured directly. Therefore to determine if the ECV is reduced, measurements would have to be made of parameters that change in response to alterations in the ECV. For example, the kidneys reduce Na+ excretion in response to a decrease in the ECV. Measurement of fractional Na +excretion could confirm the existence of a reduced effective circulating volume (fraction Na+ excretion < 1%). However, in this man fractional excretion may not be very low because a thiazide diuretic was used. Alternatively, measurements would be made of plasma renin activity because this would be stimulated by the decreased ECV. 3. The kidneys would be avidly retaining Na+. With a decrease in the effective circulating volume, sensors in the low-pressure (cardiac atria and pulmonary vasculature) and high-pressure (juxtaglomerular apparatus, aortic arch, and carotid sinus) sides of the circulation would be activated, and the signals would be sent to the kidneys to retain Na+. Sympathetic nerves that innervate the afferent and efferent arterioles of the glomeruli would cause vasoconstriction. The net result would be to reduce the GFR; this in turn would reduce the filtered load of Na+. Sympathetic innervation of the proximal tubule and the thick ascending limb of Henle's loop will also increase Na+ reabsorption at these sites
Increased sympathetic nerve activity,together with decreased perfusion pressure at the afferent arteriole,will result in the secretion of renin.This activation of the renin-angiotensin-aldosterone system will further stimulate Na+ reabsorption,hecause angiotensin II stimulates proximal tubule Nat reabsorption, and aldosterone stimulates Nat reabsorption in the distal tubule and collecting duct. With the increase in the ECV,atrial natriuretic peptide (ANP)levels will be elevated.Bowever,the effect of ANP (inhibition of renin secretion and natriuresis) appears to he blunted by the effect of the other factors.all of which act to reduce Na+excretion. The net effect of these respoases is retention of Nat by the kidneys.As a result of this Na+retention (positive Na halance).the ECF volune will increase and lead to the formation of edema,as seen in the physical examination of this man. 4.The developnent of hyponatremia indicates that this man is in positive water halance.In this case the ingestion of water has exceeded the capacity of the kidneys to excrete solute-free water.Solute-free water excretion is impaired in this man for several reasons: ADH secretion is stimalated because of the decreased ECV.As a comsequence, solute-free water is reabsorbed by the collecting duct. The filtered load of solute (NaCl)and water is reduced,and fractiooal reabsorption by the proximal tubule is enhanced.As a result,delivery of solute and water to the thick asceeding limb (the primary site where solute-free water is generated)is decreased. The thiazide diuretie inhibits Naclreabsorption in the distal tubule.This portion of the nephron also participates in the generation of solute-free water. With impaired NaCl reabsorption less solute-free vater can be generated
Increased sympathetic nerve activity, together with decreased perfusion pressure at the afferent arteriole, will result in the secretion of renin. This activation of the renin-angiotensin-aldosterone system will further stimulate Na+ reabsorption, because angiotensin II stimulates proximal tubule Na+ reabsorption, and aldosterone stimulates Na+ reabsorption in the distal tubule and collecting duct. With the increase in the ECV, atrial natriuretic peptide (ANP) levels will be elevated. However, the effect of ANP (inhibition of renin secretion and natriuresis) appears to be blunted by the effect of the other factors, all of which act to reduce Na+ excretion. The net effect of these responses is retention of Na+ by the kidneys. As a result of this Na+ retention (positive Na+ balance), the ECF volume will increase and lead to the formation of edema, as seen in the physical examination of this man. 4.The development of hyponatremia indicates that this man is in positive water balance. In this case the ingestion of water has exceeded the capacity of the kidneys to excrete solute-free water. Solute-free water excretion is impaired in this man for several reasons: ADH secretion is stimulated because of the decreased ECV. As a consequence, solute-free water is reabsorbed by the collecting duct. The filtered load of solute (NaCl) and water is reduced, and fractional reabsorption by the proximal tubule is enhanced. As a result, delivery of solute and water to the thick ascending limb (the primary site where solute-free water is generated) is decreased. The thiazide diuretic inhibits NaClreabsorption in the distal tubule. This portion of the nephron also participates in the generation of solute-free water. With impaired NaCl reabsorption less solute-free water can be generated
5.Hypokalemia in this ran is the result of increased renal K+excretion.Two factors contribute to stimulating Ktexcretion.The first is related to the adninistration of the thiazide diuretic.Thiazide diuretics act on the early portion of the distal tubule to inhibit NaCI reabsorption.Inhibition of Nacl reabsorption in the distal tubule results in the delivery of increased quantities of Na+and fluid to the portion of the nephrom responsible for Ktsecretion (cortical portion of the collecting duct).This increased delivery stimulates Ke secretion by the principal cells in this part of the nephron.Second,the ECV is decreased in this man,which in turn stimulates the renin-angiotensin-aldosterone systen.Aldosterone then acts on the collecting duct to stimlate K+secretion.The enhanced secretion of K+by the collecting duct will result in inereased K+excretion and the developrent of hypokalenia.Extrarenal factors will also comtribute to the development of hypokaleaia because both alkalosis and aldosteroce cause K+to nove into cells. 6.Although an arterial blood sample was not obtained.the plasms [HC03-]is elevated,suggesting the presence of a netabolic alkalosis.The developoent of a metabolic alkalosis could reflect enhanced renal H003-reabsorption and excretion.HC03-reabsorption by the proximal tubule would he stimulated because proximal tubule reabsorption is enhanced when the ECV is decreased (see the answer to question 3).Virtually all of the filtered load of HC03-vill be reabsorbed by the time the tubular fluid reaches the distal tubule and collecting duct.H+secretion at these sites will titrate urinary buffers and lead to the generation of 'nev B03-"Because of the decreased ECV.aldosterone levels are elevated.Because aldosterone stimulates H+secretion in the distal tubule and collecting duct,"new HC03-"generation will be increased,and metabolic alkalosis will develop. 7.Creatinine is excreted from the body mainly by glomerular filtration (10% is excreted as a result of secretion by the proximal tubule).Therefore the anount of creatinine excreted is determined mainly by its filtered load.Nith a reduction in the ECV,the glooerular filtration rate is reduced (see the answer to question
5.Hypokalemia in this man is the result of increased renal K+ excretion. Two factors contribute to stimulating K+excretion. The first is related to the administration of the thiazide diuretic. Thiazide diuretics act on the early portion of the distal tubule to inhibit NaCI reabsorption. Inhibition of NaCl reabsorption in the distal tubule results in the delivery of increased quantities of Na+ and fluid to the portion of the nephron responsible for K+secretion (cortical portion of the collecting duct). This increased delivery stimulates K+ secretion by the principal cells in this part of the nephron. Second, the ECV is decreased in this man, which in turn stimulates the renin-angiotensin-aldosterone system. Aldosterone then acts on the collecting duct to stimulate K+ secretion. The enhanced secretion of K+ by the collecting duct will result in increased K+ excretion and the development of hypokalemia. Extrarenal factors will also contribute to the development of hypokalemia because both alkalosis and aldosterone cause K+ to move into cells. 6. Although an arterial blood sample was not obtained, the plasma [HCO3-] is elevated, suggesting the presence of a metabolic alkalosis. The development of a metabolic alkalosis could reflect enhanced renal HCO3- reabsorption and H+ excretion. HCO3- reabsorption by the proximal tubule would be stimulated because proximal tubule reabsorption is enhanced when the ECV is decreased (see the answer to question 3). Virtually all of the filtered load of HCO3- will be reabsorbed by the time the tubular fluid reaches the distal tubule and collecting duct. H+ secretion at these sites will titrate urinary buffers and lead to the generation of "new HCO3-" Because of the decreased ECV, aldosterone levels are elevated. Because aldosterone stimulates H+ secretion in the distal tubule and collecting duct, "new HCO3-" generation will be increased, and metabolic alkalosis will develop. 7. Creatinine is excreted from the body mainly by glomerular filtration (10% is excreted as a result of secretion by the proximal tubule). Therefore the amount of creatinine excreted is determined mainly by its filtered load. With a reduction in the ECV, the glomerular filtration rate is reduced (see the answer to question
3).The reduced filtration rate vill decrease the filtered load of creatimine,and thus its excretion.As a result,the serun [ereatinine]will increase.The serum [creatinine]should return to normal when the ECV is restored to its normal value. 8.A loop diuretic will act on the thick ascending linb of Henle's loop to inhibit NaCI reabsorption and increase Natexcretion.This enhanced excretion of Nat will further decrease the ECV.The loop diuretic can further redace the serum Na+and Kt concentrations.make the netabolic alkalosis worse.and further increase the serun [creatinine]. The thick ascending limb of Benle's loop is the primary site where tubular fluid is diluted.The loop diuretic will inhibit the separation of solute (NaCl)and water at this site and further impair the generation of solute-free water (see the answer to question 4).If water ingestion is not reduced.hyponatremia could becone nore severe. The thick ascending linb of Henle's loop reabsorbs approximately 20%of the filtered load of K+.This process is inhibited by loop diuretics.Also,the loop diuretic will cause increased delivery of Nat and fluid to the K+secretory site. Together,these effects will further enhance K+secretion and thus renal K+excretion,leading to a worsening of the hypokalenia. Because the loop diuretic leads to a further reduction in the ECV,the stirli for enhancing both proximal tubule BC03-reabsorption and distal tubule and collecting duct l secretion will be increased.As a result,the metabolic alkalosis my beccoe more severe. With the added decrement in the ECY caused by the loop diuretic,the glorerular filtration rate vill fall further and thereby cause the serun [creatinine]to increase
3). The reduced filtration rate will decrease the filtered load of creatinine, and thus its excretion. As a result, the serum [creatinine] will increase. The serum [creatinine] should return to normal when the ECV is restored to its normal value. 8. A loop diuretic will act on the thick ascending limb of Henle's loop to inhibit NaCI reabsorption and increase Na+excretion. This enhanced excretion of Na+ will further decrease the ECV. The loop diuretic can further reduce the serum Na+ and K+ concentrations, make the metabolic alkalosis worse, and further increase the serum [creatinine]. The thick ascending limb of Henle's loop is the primary site where tubular fluid is diluted. The loop diuretic will inhibit the separation of solute (NaCl) and water at this site and further impair the generation of solute-free water (see the answer to question 4). If water ingestion is not reduced, hyponatremia could become more severe. The thick ascending limb of Henle's loop reabsorbs approximately 20% of the filtered load of K+. This process is inhibited by loop diuretics. Also, the loop diuretic will cause increased delivery of Na+ and fluid to the K+secretory site. Together, these effects will further enhance K+ secretion and thus renal K+ excretion, leading to a worsening of the hypokalemia. Because the loop diuretic leads to a further reduction in the ECV, the stimuli for enhancing both proximal tubule HCO3- reabsorption and distal tubule and collecting duct H+ secretion will be increased. As a result, the metabolic alkalosis may become more severe. With the added decrement in the ECV caused by the loop diuretic, the glomerular filtration rate will fall further and thereby cause the serum [creatinine] to increase
The abnormalities in serum electrolytes seen in this man are caused nainly by the decreased ECV,which was a result of his myocardial infarction.The diuretic therapy is directed at preventing the kidneys from responding to the decreased ECV. Although the diuretics reduce Nat retention by the kidneys and help alleviate edema formtion,they decrease further the ECV and thus my prodoce the water.Nat.K+and acid-base abnormalities seen in this patient
The abnormalities in serum electrolytes seen in this man are caused mainly by the decreased ECV, which was a result of his myocardial infarction. The diuretic therapy is directed at preventing the kidneys from responding to the decreased ECV. Although the diuretics reduce Na+ retention by the kidneys and help alleviate edema formation, they decrease further the ECV and thus may produce the water, Na+, K+ and acid-base abnormalities seen in this patient