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11.11: Endocrine Regulation of Kidney Function - Biology

11.11: Endocrine Regulation of Kidney Function - Biology



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Learning Objectives

By the end of this section, you will be able to:

  • Describe how each of the following functions in the extrinsic control of GFR: renin–angiotensin mechanism, natriuretic peptides, and sympathetic adrenergic activity
  • Describe how each of the following works to regulate reabsorption and secretion, so as to affect urine volume and composition: renin–angiotensin system, aldosterone, antidiuretic hormone, and natriuretic peptides
  • Name and define the roles of other hormones that regulate kidney control

Several hormones have specific, important roles in regulating kidney function. They act to stimulate or inhibit blood flow. Some of these are endocrine, acting from a distance, whereas others are paracrine, acting locally.

Renin–Angiotensin–Aldosterone

Renin is an enzyme that is produced by the granular cells of the afferent arteriole at the JGA. It enzymatically converts angiotensinogen (made by the liver, freely circulating) into angiotensin I. Its release is stimulated by prostaglandins and NO from the JGA in response to decreased extracellular fluid volume.

ACE is not a hormone but it is functionally important in regulating systemic blood pressure and kidney function. It is produced in the lungs but binds to the surfaces of endothelial cells in the afferent arterioles and glomerulus. It enzymatically converts inactive angiotensin I into active angiotensin II. ACE is important in raising blood pressure. People with high blood pressure are sometimes prescribed ACE inhibitors to lower their blood pressure.

Angiotensin II is a potent vasoconstrictor that plays an immediate role in the regulation of blood pressure. It acts systemically to cause vasoconstriction as well as constriction of both the afferent and efferent arterioles of the glomerulus. In instances of blood loss or dehydration, it reduces both GFR and renal blood flow, thereby limiting fluid loss and preserving blood volume. Its release is usually stimulated by decreases in blood pressure, and so the preservation of adequate blood pressure is its primary role.

Aldosterone, often called the “salt-retaining hormone,” is released from the adrenal cortex in response to angiotensin II or directly in response to increased plasma K+. It promotes Na+ reabsorption by the nephron, promoting the retention of water. It is also important in regulating K+,promoting its excretion. (This dual effect on two minerals and its origin in the adrenal cortex explains its designation as a mineralocorticoid.) As a result, renin has an immediate effect on blood pressure due to angiotensin II–stimulated vasoconstriction and a prolonged effect through Na+ recovery due to aldosterone. At the same time that aldosterone causes increased recovery of Na+, it also causes greater loss of K+. Progesterone is a steroid that is structurally similar to aldosterone. It binds to the aldosterone receptor and weakly stimulates Na+ reabsorption and increased water recovery. This process is unimportant in men due to low levels of circulating progesterone. It may cause increased retention of water during some periods of the menstrual cycle in women when progesterone levels increase.

Antidiuretic Hormone (ADH)

Diuretics are drugs that can increase water loss by interfering with the recapture of solutes and water from the forming urine. They are often prescribed to lower blood pressure. Coffee, tea, and alcoholic beverages are familiar diuretics. ADH, a 9-amino acid peptide released by the posterior pituitary, works to do the exact opposite. It promotes the recovery of water, decreases urine volume, and maintains plasma osmolarity and blood pressure. It does so by stimulating the movement of aquaporin proteins into the apical cell membrane of principal cells of the collecting ducts to form water channels, allowing the transcellular movement of water from the lumen of the collecting duct into the interstitial space in the medulla of the kidney by osmosis. From there, it enters the vasa recta capillaries to return to the circulation. Water is attracted by the high osmotic environment of the deep kidney medulla.

Endothelin

Endothelins, 21-amino acid peptides, are extremely powerful vasoconstrictors. They are produced by endothelial cells of the renal blood vessels, mesangial cells, and cells of the DCT. Hormones stimulating endothelin release include angiotensin II, bradykinin, and epinephrine. They do not typically influence blood pressure in healthy people. On the other hand, in people with diabetic kidney disease, endothelin is chronically elevated, resulting in sodium retention. They also diminish GFR by damaging the podocytes and by potently vasoconstricting both the afferent and efferent arterioles.

Natriuretic Hormones

Natriuretic hormones are peptides that stimulate the kidneys to excrete sodium—an effect opposite that of aldosterone. Natriuretic hormones act by inhibiting aldosterone release and therefore inhibiting Na+ recovery in the collecting ducts. If Na+ remains in the forming urine, its osmotic force will cause a concurrent loss of water. Natriuretic hormones also inhibit ADH release, which of course will result in less water recovery. Therefore, natriuretic peptides inhibit both Na+ and water recovery. One example from this family of hormones is atrial natriuretic hormone (ANH), a 28-amino acid peptide produced by heart atria in response to over-stretching of the atrial wall. The over-stretching occurs in persons with elevated blood pressure or heart failure. It increases GFR through concurrent vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole. These events lead to an increased loss of water and sodium in the forming urine. It also decreases sodium reabsorption in the DCT. There is also B-type natriuretic peptide (BNP) of 32 amino acids produced in the ventricles of the heart. It has a 10-fold lower affinity for its receptor, so its effects are less than those of ANH. Its role may be to provide “fine tuning” for the regulation of blood pressure. BNP’s longer biologic half-life makes it a good diagnostic marker of congestive heart failure.

Parathyroid Hormone

Parathyroid hormone (PTH) is an 84-amino acid peptide produced by the parathyroid glands in response to decreased circulating Ca++ levels. Among its targets is the PCT, where it stimulates the hydroxylation of calcidiol to calcitriol (1,25-hydroxycholecalciferol, the active form of vitamin D). It also blocks reabsorption of phosphate (PO3), causing its loss in the urine. The retention of phosphate would result in the formation of calcium phosphate in the plasma, reducing circulating Ca++ levels. By ridding the blood of phosphate, higher circulating Ca++ levels are permitted.

Table 1. Major Vasoconstrictors That Influence GFR and RFB
HormoneStimulusEffect of GFR[1]Effect on RBF[2]
Symatetic nerves (epinephrine and norepinephrine)↓ ECFV[3]
Angiotensin II↓ ECFV
Endothelin↑ Stretch, bradykinin, angiotensin II, epinephrine
↓ ECFV
Table 2. Major Vasodilators That Influence GFR and RFB
HormoneStimulusEffect of GFREffect on RBF
Prostaglandins (PGE1, PGE2, and PGI2)↓ECFV
↑ shear stress, angiotensin II
No change/ ↑
Nitric oxide (NO)↑ shear stress, acetylcholine, histamine, bradykinin, ATP, adenosine
Bradykinin↓Prostaglandins, ACE[4]
Natriuretic peptides (ANP[5], B-type[6])↑ ECFVNo change

Chapter Review

Endocrine hormones act from a distance and paracrine hormones act locally. The renal enzyme renin converts angiotensinogen into angiotensin I. The lung enzyme, ACE, converts angiotensin I into active angiotensin II. Angiotensin II is an active vasoconstrictor that increases blood pressure. Angiotensin II also stimulates aldosterone release from the adrenal cortex, causing the collecting duct to retain Na+, which promotes water retention and a longer-term rise in blood pressure. ADH promotes water recovery by the collecting ducts by stimulating the insertion of aquaporin water channels into cell membranes. Endothelins are elevated in cases of diabetic kidney disease, increasing Na+ retention and decreasing GFR. Natriuretic hormones, released primarily from the atria of the heart in response to stretching of the atrial walls, stimulate Na+ excretion and thereby decrease blood pressure. PTH stimulates the final step in the formation of active vitamin D3 and reduces phosphate reabsorption, resulting in higher circulating Ca++ levels.

Self Check

Answer the question(s) below to see how well you understand the topics covered in the previous section.

Critical Thinking Questions

  1. What organs produce which hormones or enzymes in the renin–angiotensin system?
  2. PTH affects absorption and reabsorption of what?

[reveal-answer q=”262467″]Show Answers[/reveal-answer]
[hidden-answer a=”262467″]

  1. The liver produces angiotensinogen, the lungs produce ACE, and the kidneys produce renin.
  2. PTH affects absorption and reabsorption of calcium.

[/hidden-answer]

Glossary

endothelins: group of vasoconstrictive, 21-amino acid peptides; produced by endothelial cells of the renal blood vessels, mesangial cells, and cells of the DCT



The RAAS is a signaling pathway involved in blood pressure control. It involves a number of hormones:

  • Angiotensinogen is produced by the liver in response to:
    • Glucocorticoids
    • Thyroid hormones
    • Oestrogens
    • Angiotensin II
    • Various inflammatory proteins

    Renin is a protease produced by the kidneys in response to β1 stimulation or hypotension, and exists to cleave angiotensinogen to angiotensin I

    ACE cleaves angiotensin I to angiotensin II, and also cleaves bradykinin into inactive metabolites

    • Angiotensin II increases blood pressure via a number of mechanisms:
      • Simulates aldosterone release from the adrenal cortex, increasing sodium and water retention
      • Vasoconstriction of efferent greater than the afferent arterioles
        Results in slight decrease in GFR at a lower perfusion pressure, but increases filtration fraction.
        • NB: Different sources quote different changes (increase or decrease) in GFR
          The final effect may vary depending on the contribution of other autoregulatory processes.
        • Aldosterone acts on the distal convoluted tubule to:
          • Increase reabsorption of Na + and water
          • Increase elimination of K + and H +

          Parathyroid Glands

          Parathyroid glands produce parathyroid hormone, which is responsible for specific physiological responses in the body related to calcium.

          Learning Objectives

          Describe how the parathyroid glands regulate calcium levels in the blood

          Key Takeaways

          Key Points

          • Parathyroid glands are responsible for the regulation the body’s calcium and phosphorus levels by producing parathyroid hormone, which helps control calcium release.
          • Oxyphil cells and chief cells are two main types of cells that make up parathyroid tissue chief cells make parathyroid hormone while the role of oxyphil cells remains unknown.
          • Parathyroid hormone is released into the bloodstream where it travels to target cells, binding to a receptor found on the target cells.
          • Parathyroid hormones help regulate calcium levels by increasing blood calcium concentrations when calcium ion levels fall below normal.

          Key Terms

          • parathyroid hormone: a polypeptide hormone that is released by the chief cells of the parathyroid glands and is involved in raising the levels of calcium ions in the blood
          • calcitriol: the active metabolite 1,25-dihydroxycholecalciferol of vitamin D3 that is involved in the absorption of calcium
          • osteoclast: a large multinuclear cell associated with the resorption of bone
          • osteoblast: a mononucleate cell from which bone develops

          Parathyroid Glands

          The parathyroid glands are small endocrine glands that produce parathyroid hormone. Most people have four parathyroid glands however, the number can vary from two to six. These glands are located on the posterior surface of the thyroid gland. Normally, there is a superior gland and an inferior gland associated with each of the thyroid’s two lobes. Each parathyroid gland is covered by connective tissue and contains many secretory cells that are associated with a capillary network. There are two major types of cells that make up parathyroid tissue: oxyphil cells and chief cells, the latter of which actually produce parathyroid hormone. The function of oxyphil cells is unknown.

          Parathyroid glands: The parathyroid glands are located on the posterior of the thyroid gland. The parathyroid glands produce parathyroid hormone (PTH) which increases blood calcium concentrations when calcium ion levels fall below normal.

          One of the parathyroid glands’ most important functions is to regulate the body’s calcium and phosphorus levels. Another function of the parathyroid glands is to secrete parathyroid hormone, which causes the release of the calcium present in bone to extracellular fluid.

          Parathyroid hormone (PTH), also known as parathormone, is released directly into the bloodstream, traveling to its target cells, which are often quite far away. It then binds to a receptor (found either inside or on the surface of the target cells). Receptors bind a specific hormone, resulting in a specific physiologic (normal) response of the body.

          Parathyroid Glands and Calcium Regulation

          PTH opposes the effect of thyrocalcitonin (or calcitonin ), a hormone produced by the thyroid gland that regulates calcium levels. It does this by removing calcium from its storage sites in bones and releasing it into the bloodstream. It also signals the kidneys to reabsorb more of this mineral, transporting it into the blood. PTH can also signal the small intestine to absorb calcium by transporting it from the diet into the blood. Calcium is important for metabolization to occur. Blood cannot clot without sufficient calcium. Skeletal muscles require this mineral in order to contract. A deficiency of PTH can lead to tetany, a condition characterized by muscle weakness due to lack of available calcium in the blood.

          More specifically, PTH increases blood calcium concentrations when calcium ion levels fall below normal. First, PTH enhances reabsorption of calcium by the kidneys it then stimulates osteoclast activity and inhibits osteoblast activity. Finally, PTH stimulates synthesis and secretion of calcitriol by the kidneys, which enhances Ca 2+ absorption by the digestive system. PTH and calcitonin work in opposition to one another to maintain homeostatic calcium levels in body fluids.


          Natriuretic Hormones

          Natriuretic hormones are peptides that stimulate the kidneys to excrete sodium—an effect opposite that of aldosterone. Natriuretic hormones act by inhibiting aldosterone release and therefore inhibiting Na + recovery in the collecting ducts. If Na + remains in the forming urine, its osmotic force will cause a concurrent loss of water. Natriuretic hormones also inhibit ADH release, which of course will result in less water recovery. Therefore, natriuretic peptides inhibit both Na + and water recovery. One example from this family of hormones is atrial natriuretic hormone (ANH), a 28-amino acid peptide produced by heart atria in response to over-stretching of the atrial wall. The over-stretching occurs in persons with elevated blood pressure or heart failure. It increases GFR through concurrent vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole. These events lead to an increased loss of water and sodium in the forming urine. It also decreases sodium reabsorption in the DCT. There is also B-type natriuretic peptide (BNP) of 32 amino acids produced in the ventricles of the heart. It has a 10-fold lower affinity for its receptor, so its effects are less than those of ANH. Its role may be to provide “fine tuning” for the regulation of blood pressure. BNP’s longer biologic half-life makes it a good diagnostic marker of congestive heart failure ([link]).


          Kidney of Human Beings: Regulation and Function

          The functions of the kidney are controlled by antidiuretic hormone (ADH), juxtaglom­erular apparatus (JGA) and Atrial Natriuretic Factor (ANF).

          (i) Control by Antidiuretic Hormone (ADH):

          ADH is secreted by hypothalamus of the brain and released into the blood from the posterior lobe of the pituitary gland. The release of ADH is triggered when osmoreceptors in the hypothalamus detect an increase in the osmolarity of the blood above a set point of 300 mos mL -1 . In this situation the osmoreceptor cells also promote thirst. It increases the reabsorption of water in the distal convoluted tubule and collecting duct.

          (ii) Control by Juxtaglomerular Apparatus (JGA):

          JGA operates a multi hormonal Renin-Angiotensin- Aldosterone System (RAAS). Juxtaglomerular cells secrete an en­zyme, renin into the blood stream. Renin changes plasma protein, called angiotensinogen to a peptide, called angiotensin II, which works as hormone.

          Angiotesin II increases blood pressure by causing arterioles to constrict. It also increases blood volume in two ways: firstly, it induces the proximal convoluted tubules to reabsorb more NaCl and water and secondly it stimulates the adrenal glands to release a hormone, called aldosterone that induces the distal convoluted tubule to absorb more Na + and water.

          (iii) Control by Atrial Natriuretic Factor (ANF):

          There is an another hormone, a peptide called Atrial Natriuretic Factor (ANF) which opposes the regulation by RAAS. The walls of the atria of the heart release ANF in response to an increase in blood volume and pressure.

          ANF inhibits release of renin from the JGA and thereby inhibits NaCl reabsorption by the collecting duct and reduces aldosterone release from the adrenal gland. Thus ADH, RAAS and ANF regulate the functions of kidneys. As a result they control body fluid osmolarity, salt concentration, blood pressure and blood volume.

          The expulsion of urine from the urinary bladder is called micturition. It is a reflex process, but in grown up children and adults, it can be controlled voluntarily to some extent.

          Nerve Supply to urinary bladder and sphincters:

          The urinary bladder and the internal sphincter are supplied by both sympathetic and parasympathetic nervous systems of auto­nomic nervous system whereas, the external sphincter is supplied by the somatic nerve.

          Function of sympathetic nerve:

          The stimulation of nerve causes relaxation of detrusor muscle of the urinary bladder and constriction of the internal sphincter. So, it causes filling of the urinary bladder and the sympathetic nerve is called nerve of filling.

          Function of para sympathetic nerve:

          The stimulation of this nerve causes contraction of detrusor muscle and relaxation of the internal sphincter leading to emptying of the urinary bladder. So the parasympathetic nerve is called the nerve of emptying or nerve of mictu­rition.

          Function of somatic (pudendal) nerve:

          It maintains the tonic contraction of the skel­etal muscle fibres forming external sphincter so that, the external sphincter is constricted always. During micturition, this nerve is inhibited, thus the somatic (pudendal) nerve is responsible for voluntary control of micturition. The urine flows out from the urinary bladder through the urethra.

          Constituents of Urine:

          Urine is a transparent, light yellow liquid with a slightly acid pH (average pH 6.0). The colour of urine is caused by the pigment urochrome, which is a breakdown product of haemoglobin from worn out red blood corpuscles.

          The colour of the urine may be affected by foods. The pH range of urine is normally between 4.5 and 8.2 depending upon the amount of acidic and basic foods in the diet. Fruits increase the acidity and vegetables increase the alkalinity of the urine.

          A high-protein diet also produces an acid urine because of acidic products from amino acid metabolism. A normal adult person secretes about 1.5 litres of urine in 24 hours. Substances that increase the formation of urine are called diuretics.

          Tea, coffee and alcoholic beverages have diuretic effects. The urine is hypertonic (i.e., it has a higher osmotic pressure than the blood plasma). When the urine is allowed to stand for some time it smells strongly of ammonia due to bacterial degradation of urea to ammonia. The specific gravity of urine is usually between 1.015 and 1.025.

          About 95% of the volume of urine is water other substances are only about 5%. Organic substances include nitrogen, urea, creatine, creatinine, ammonia, uric acid, hippuric acid, oxalic acid, amino acids, allantoin, vitamins, hormones and enzymes.

          The inorganic substances include chloride, phosphate, sulphate, potassium, sodium, calcium, magnesium, iodine, arsenic and lead. It is important to note that no glucose is normally found in the urine.

          Abnormal Urine Conditions:

          Presence of albumin in urine is called albuminuria. It usually occurs in nephritis (inflammation of glomeruli). In this condition the size of the filtering slits enlarges.

          Presence of glucose in urine is known as glycosuria. It occurs in Diabetes mellitus.

          Presence of blood or blood cells in urine is called hematuria.

          Presence of abnormally high ketone bodies in urine is termed as ketonuria.

          Presence of haemoglobin in urine is called hemoglobinuria.

          Presence of excess urea in urine is known as uremia.

          The presence of WBCs or pus in the urine is called pyuria.

          Deficiency of ADH causes Diabetes insipidus which is characterised by excessive dilute Urine.

          Functions of Kidney:

          Kidney removes excess of water from the body.

          2. Elimination of Nitrogenous wastes:

          Kidney removes nitrogenous wastes such as urea, and uric acid from the blood.

          Kidney removes excess of acids and alkalies from the blood to maintain proper pH of blood (about 7.4).

          4. Maintenance of Salt contents:

          Kidney maintains proper amount of mineral salts such as sodium, potassium in the body.

          5. Removal of other Substances:

          Kidney eliminates toxic substances, drugs, pig­ments, excess vitamins from the blood.

          6. Maintenance of Blood Pressure:

          Kidney controls the fluid balance in the body, therefore, it maintains blood pressure.

          Because kidney removes various unwanted materials from the blood, it helps in keeping the internal environment of the body constant.

          Kidney secretes an enzyme (which acts as hormone), the renin which changes the plasma, protein, the angiotensinogen (produced by liver) into angio­tensin II. The latter stimulates the adrenal cortex to secrete aldosterone (hormone) which increases the rate of reabsorption of Na + in the nephrons.

          9. Erythropoietin Production:

          The kidney produces erythropoietin (hormone) that stimulates the formation of erythrocytes (RBCs).


          Essay on Kidneys: Functions, Urine Formation and Hormones

          In this article we will discuss about the kidneys:- 1. Introduction to Kidney 2. Functions of Kidney 3. Urine Formation 4. Mechanism of Action of Diuretics 5. Renal Function Tests 6. Congenital Tubular Function Defects 7. Uremia 8. The Artificial Kidney 9. Hormones.

          1. Essay on the Introduction to Kidney
          2. Essay on the Functions of Kidney
          3. Essay on the Urine Formation in Kidney
          4. Essay on the Mechanism of Action of Diuretics
          5. Essay on the Renal Function Tests
          6. Essay on the Congenital Tubular Function Defects in Kidney
          7. Essay on the Uremia –Clinical Kidney Condition
          8. Essay on the Artificial Kidney
          9. Essay on the Hormones of the Kidney

          Essay # 1. Introduction to Kidney:

          A large number of waste products are produced in the body as a result of metabolic activities. The main waste products are carbon dioxide, water, and nitrogenous compounds. The retention of these products produces a harmful effect on the normal health.

          Therefore, the removal of these products from the body is a must. Carbon dioxide is removed mainly through lungs and water as well as nitrog­enous compounds are removed through urogenital system. The kidneys are the most important com­ponent of this system.

          The kidneys are two in number, usually bean shaped, and exist behind the peritoneum on either side of the vertebral column extending from the 12th thoracic to the 3rd lumbar vertebra. Each kid­ney weighs about 120-170 grams and is about 11-13 cms. long, the left being larger than the right one.

          Each kidney is found to consist of two main parts by section. The outer part is called cortex and the inner one is medulla. The cortex consists of a large number of glomeruli and convoluted tubules. The medulla is composed of renal tubules project­ing into a cavity towards the inner region of the kidney called the pelvis, the region where the renal artery and vein enters and leaves the kidney re­spectively.

          Nephron –Basic Unit od Kidney:

          It is a functional basic unit of kid­ney. Each kidney is provided with about one mil­lion nephrons containing the glomerulus and the tubule. The glomerulus is a network of afferent and efferent capillaries.

          Each glomerulus is surrounded by a double-walled epithelial sac known as Bow­man ‘s Capsule which leads to the tubule which is divided into three parts—proximal convoluted tu­bule, loop of Henle, and the distal convoluted tubule.

          The Proximal Convoluted Tubule (PCT) is about 45 mm long and 50 mm in diameter. This lies in the cortex along with glomerulus. Its lumen is continuous with that of the Bowman’s Capsule. It consists of cells with scalloped outline and brush border. The brush border is formed by numerous microvilli which increases the surface enormously for absorption.

          The loop of Henle consists of three parts—the descending limb, a thin segment, and an ascending limb. The proximal convoluted tubule opens into the descending limb which is continued into the thin segment from where the ascending limb arises. The whole loop of Henle is lined by a single layer of flattened epithelial cells.

          The ascending limb of the loop of Henle con­tinues into the distal convoluted tubule (DCT) which finally opens into a collecting tubule or duct which carries the urine to the renal pelvis from where it is carried to the bladder by the ureter.

          The distal convoluted tubule commences near the pole of the glomerulus and establishes a close proxim­ity to the afferent arteriole of its parent glomerulus. The DCT contains cuboidal epithelium.

          Nephrons are mainly of two types—cortical and juxtamedullary. The loop of Henle of the juxtamedullary is long and dips deep into the sub­stance of the medulla. But the loop of Henle of cortical is short and only a very small part of it dips into the medullary tissue and the greater part re­mains embedded in the cortical substances.

          Moreo­ver, the glomeruli of the juxtamedullary lie very close to the medulla while those of cortical lie close to the surface of the kidney. The juxtamedullary nephrons constitute 20 per cent of nephrons, while the cortical nephrons constitute 80 per cent of the total nephrons. These two types of nephrons have the same common function.

          Blood Supply of the Kidneys:

          The short renal artery arising from the abdominal aorta supplies the blood to the kidney. The renal artery after en­tering the kidney divides into a number of arterioles—the afferent arterioles which further branch into capillaries and enter into each glomeru­lus.

          The capillaries then join to form another arteri­ole—the efferent arteriole which opens into another set of capillaries called peritubular capillaries sur­rounding the proximal tubule, the loop of Henle, and the distal tubule. Ultimately, the capillary set opens into a venule which joins with other venules to form the renal vein. The renal vein then opens into the inferior vena cava.

          Blood Flow to Kidney through the Nephron:

          The blood flows through both the kidneys of an adult weigh­ing 70 kg at the rate of about 1200 ml/mt. The portion of the total cardiac output (about 560 ml/ mt.) which passes through the kidneys is called the renal fraction. This is about 560/1200 ml per minute, i.e., about 21 per cent.

          There are two sets of capillaries—the glomeru­lus and the peritubular. These two capillaries are separated from each other by the efferent arteriole which contributes sufficient resistance to blood flow. The glomerular capillary bed provides a high pressure of about 70 mm Hg, while the peritubular bed provides a low pressure about 13 mm Hg.

          The pressures in the artery and vein are 100 mm of Hg. and 8 mm of Hg respectively. The high pressure in the glomerulus exerts the filtering of fluids con­tinually into the Bowman’s Capsule. The low pres­sure in the peritubular capillary system, on the other hand, functions in the same way as the usual ve­nous ends of the tissue capillaries with the fluid being absorbed continually into the capillaries.

          Essay # 2. Functions of Kidney:

          a. Kidney eliminates excess of certain nutri­ents such as sugar and amino acids when their concentration increases in the blood.

          b. It removes certain non-volatile waste prod­ucts such as urea, uric acid, creatinine, and sulphates, etc. from the body.

          c. It eliminates certain foreign or toxic sub­stances such as iodides, pigments, drugs, and bacteria, etc. from the blood.

          d. It regulates hydrogen ion concentration of the blood by removing excess of non­volatile acids and bases.

          e. It maintains the osmotic pressure of the blood by regulating the excretion of wa­ter and inorganic salts and thus preserves the constant volume of the circulating blood.

          f. It regulates the arterial blood pressure by causing the secretion of the hormone renin.

          g. It maintains the erythrocyte production by excreting the secretion of the hormone erythropoietin.

          Essay # 3. Urine Formation in Kidney:

          The regulatory activities of kidneys form urine as a by-product. Urine formation involves three main steps—the glomerular filtration, the tubular reabsorption, and the tubular secretion.

          a. Glomerular Filtration (Ultrafiltration):

          Glomerulus filters out substances of low molecular weight from the blood with the retention of substances of high molecular weight, especially the proteins. Therefore, proteins are retained in the glomeruli and are not normally found in urine. If protein is detected in the urine, it indicates the kidney damage or other disease which ef­fect the glomerular membrane.

          In normal adult, two million nephrons filter one li­tre of blood each minute to give about 1200 ml of glomerular filtrate (primary urine) at Bowman’s Capsule. Therefore, the Glomerular Filtration Rate (GFR) in adult is about 120 ml per minute. The hydrostatic pressure of the blood in the glomerular capillaires (Pg) is the main force for driving the fluid (Water and sol­ute) out of the glomerulus.

          The pressure is opposed by two forces:

          (i) The hydrostatic pressure of the Bow­man’s Capsule fluid (PBC).

          (ii) The osmotic pressure of the plasma proteins (Ppp).

          Therefore, the effective filtration pressure (Pef) is calculated by the following rela­tion:

          . . . Pef = 74 – (30 + 20) mm of Hg

          Thus, by substituting the normal values of the various forces, it has been found that the calculated effective (net) filtra­tion pressure (Pef) is 24 mm Hg.

          A fall in blood pressure may reduce the Pef which results in less amount of urine. When the aortic systolic pressure is re­duced to 70 mm Hg, the hydrostatic pres­sure of the blood in glomerular capillaries is reduced to 50 mm. Hg. This reduces the Pef to Zero [50 – 50] and thus filtration will be ceased. Under such circumstances, urine will not be formed (anuria) until the blood pressure is maintained.

          b. Tubular Reabsorption:

          The rate of forma­tion of the primary urine is 120 ml/minute, while the rate of urine passing to the blad­der under the same condition is 1-2 ml/ minute. Therefore, it indicates that about 99 per cent of the glomerular filtrate is reabsorbed during its passage through the different segments of the renal tubule.

          Al­though, the glomerular filtrate contains nearly the same concentration of glucose as in plasma, the urine contains nil or very little glucose. Hence, glucose is also prac­tically completely reabsorbed in the tu­bules when the blood sugar level is nor­mal. The capacity of reabsorption depends on the renal threshold of that substance.

          The reabsorption of different solids takes place at different sites in the renal tubules. Amino acids, glucose, and small amounts of protein that pass through the glomeru­lus are reabsorbed in the first part of the proximal tubule.

          Sodium, chloride, and bi­carbonate are reabsorbed uniformly along the entire length of the proximal tubule and also in the distal tubule. Potassium is reabsorbed in the proximal and secreted in the distal tubule.

          The glomerular filtrate produces about 170 litres in a day whereas the tubules reabsorb about 168.5 litres of water, 170 gm of glucose, 100 gm of NaCl, 360 gm of NaHCO3, and small amounts of phosphate, sulphate, amino acids, urea, uric acid, etc. and excrete about 60 gm of NaCl, urea and other waste products in about 1.5 li­tres of urine. Most of these solids are reabsorbed by active transport mechanism, while some (e.g., urea) are reabsorbed by passive transport mechanism.

          In diseases, the reabsorption mechanism is altered developing glycosuria, phosphaturia, and amino aciduria.

          Although, most of the substances are reabsorbed by the tubular cells, some substances are actively trans­ported or actively excreted into the tubu­lar lumen. The secreted substance by the tubular epithelium in man are creatinine and potassium. The tubular epithelium also removes a number of foreign sub­stances that are introduced into the body for therapeutic and diagnostic purposes.

          These foreign substances are penicillin, p-Aminosalicylic acid, phenosulphonphthalein (PSP), p-Aminohippuric acid, and diodrast. The hydrogen ions and ammo­nia formed in the distal tubular cells are also actively excreted into tubular lumen and thus pass to urine.

          The function of kidney is regulated by three important hormones. These hormones are aldoster­one (from adrenal cortex), parathormone (from parathyroid), and vasopressin (from hypophyseal posterior lobe).

          Aldosterone restricts the excretion of Na + and stimulates the excretion of K + . Parathormone stimulates excretion of phosphate. Vasopressin, the antidiuretic hormone, is held responsible mainly for the reabsorption of water. In the absence of this hormone, a large amount of very dilute urine is excreted.

          Essay # 4. Mechanism of Action of Diuretics:

          a. Diuretics, the drugs, enhance losses of water and salt via the urine through inter­ference with normal reabsorptive mecha­nisms.

          b. Osmotic diuretics are nonreabsorbable substances which increase tubular osmolarity. The osmotic substances which limit the amount of water. Osmotic diuresis is responsible for the serious dehydration which accompanies diabetic ketoacidosis.

          c. Diamox is the inhibitor of carbonic anhydrase. It blocks both HCO3 − reabsorption in the proximal tubule and regeneration in the distal tubule.

          d. Thiazide diuretics, furosemide, ethacrynic acid and mercurials all inhibit chloride rea­bsorption in the ascending limb.

          Essay # 5. Renal Function Tests:

          Clearance is measured to assess quantitatively the rate of excretion of a given substance by the kid­ney. This is a volume of blood or plasma which contains the amount of the substance which is ex­creted in the urine in one minute.

          A. Inulin Clearance:

          a. Inulin is a polysaccharide which is filtered at the glomerulus but not secreted or reabsorbed by the tubule. Therefore, it is a measure of glomerular filtration rate. Mannitol can also be used for the same purpose.

          b. These clearances vary with the body size. The clearance is calculated on the basis of ml/1.73 m 2 .

          c. To measure inulin clearance it is wise to maintain a constant plasma level of the test substance during the period of urine collections.

          The clearance is measured ac­cording to the following formula:

          where Cin = Clearance of inulin (ml/min)

          U = Urinary inulin (mg/100 ml)

          P = Plasma inulin (mg/100 ml)

          B. Endogenous Creatinine Clearance:

          a. Creatinine is filtered at the glomerulus but not secreted or reabsorbed by the tubule. Its clearance is measured to get the GFR.

          b. This method is convenient for the estima­tion of the GFR because it does not re­quire the intravenous administration of a test substance.

          c. Normal values for creatinine clearance are in males: 130 ± 20 ml/mt and females: 120 ± 15 ml/mt.

          C. The Phenolsulphonephthalein (PSP) Test:

          a. The dye is almost completely eliminated within 2 hours.

          b. If less than 25 per cent of the dye is not excreted in 15 minutes, it is an indication of impairment of renal function.

          D. Other Functional Tests:

          a. Dilution test (water excretion test)

          b. Urine concentration test (specific gravity test)

          d. Urine acidification test

          e. Blood NPN, urea and creatinine

          a. Dilution test:

          (i) After emptying the bladder of the indi­vidual after overnight fast, he is advised to drink 1200 ml water in 30 minutes.

          (ii) During four hours after drinking, the urine is collected at hourly intervals.

          (iii) In normal individuals in cold climates, 1200 ml of urine is excreted in four hours.

          (iv) This test is not applicable to warm climates since the greater part of the ingested water is lost in perspiration during summer.

          (v) In case of impaired renal function, the amount of water eliminated in four hours will be less than 1200 ml depending on the degree of impairment and specific grav­ity of urine is often 1.010 or higher in con­ditions of oliguria.

          b. Urine concentration test (specific gravity test):

          (i) The bladder is emptied on the day of the test at 7 a.m. and the urine is discarded.

          (ii) The urine is collected at 8 a.m. and the specific gravity is measured. If the sp. gr. is 1.022, the test may be rejected.

          (iii) If the sp. gr, is below 1.022, another urine specimen should be collected at 9 a.m. and the sp. gr. is determined.

          (iv) In case, the urine does not have a sp. gr. of 1.022, it is sure that the renal concentrat­ing power is impaired either due to tubu­lar defects or decreased secretion of ADH (diabetes insipidus). If the urine volume is large and the sp. gr. is below 1.022, the ADH test must be carried out. 3.

          c. Vasopressin (ADH) test:

          (i) The individual is not allowed any food or water after 6 p.m. on the night before the test. Vasopressin (5 units) is injected intramuscularly at 7 p.m. in the night.

          (ii) The urine is collected at 7 a.m. and 8 a.m. and the sp. gr. is determined. If the sp. gr. is 1.022, it is quite confident that the indi­vidual suffers from diabetes insipidus and ADH injection is effective in controlling it.

          d. Urine acidification test:

          (i) This test should not be done on individu­als who have acidosis or poor liver func­tion.

          (ii) No dietary or other restrictions are in­volved in carrying out this test. The blad­der is emptied at 8 a.m. Thereafter, hourly specimens of urine are collected until 6 p.m. At 10 a.m., ammonium chloride in a dose of 0.1 gram/kg body weight is given. A portion of each specimen is transferred to stoppered bottles and sent immediately to the laboratory for pH determination.

          (iii) In normal individuals, all urine specimens collected after 2 hours from the time of administration of ammonium chloride should have a pH between 4.6 and 5.0 but in patients with renal tubular acidosis, the pH does not fall below 5.3.

          v. Blood non-protein nitrogen:

          (i) In acute nephritis, the NPN values are in­creased and range from a slight increase (NPN-45 mg, urea N-25 mg, creatinine-2 mg per 100 ml) to very high values (NPN- 200 mg, urea N-160 mg creatinine-25 mg per 100 ml).

          (ii) NPN increase and retention are due to im­paired renal function and excessive pro­tein catabolism.

          Essay # 6. Congenital Tubular Function Defects in Kidney:

          a. Diabetes Insipidus:

          (i) This disease is developed due to the non- production of ADHr. The individual passes large volume of urine (5-20 litres in 24 hours). The individual has to drink large amount of water to make up the loss.

          (ii) The reabsorption of water in the distal tu­bules does not take place in the absence of ADH.

          b. Vitamin D Resistant Rickets:

          (i) The tubular reabsorption of phosphate does not take place under this condition.

          (ii) Excessive loss of phosphate in urine leads to the development of a type of rickets which does not respond to usual doses of Vitamin D.

          c. Renal Glycosuria:

          In this condition, the tubular reabsorption of glu­cose is affected. Although the blood sugar is within normal level but glucose is excreted in urine due to defective reabsorption by the tubules.

          d. Idiopathic Hypercalcinuria:

          Calcium is not reabsorbed by the renal tubules in this condition. Hence, large amounts of calcium are excreted in the urine. Renal calculi may be de­veloped owing to the presence of large amounts of calcium in urine.

          e. Salt losing Nephritis:

          (i) Large amounts of sodium and chloride ions are excreted in urine in this condi­tion due to the defect in the tubular reab­sorption of these ions resulting in severe dehydration, hyponatremia and hypo-chloremia.

          (ii) Blood urea is increased due to the reduced glomerular filtration rate.

          (iii) This condition does not respond to aldos­terone administration but responds to parenteral administration of sodium chlo­ride solution.

          f. Renal Tubular Acidosis:

          (i) In this condition, the urine becomes alka­line or neutral due to the defect in the so­dium and hydrogen ion exchange mecha­nism in the distal tubules. There is a loss of sodium in the urine.

          (ii) The acidosis is accompanied by excessive mobilization and urinary excretion of cal­cium and potassium.

          (iii) These abnormalities led to clinical mani­festation of dehydration, hypokalemia, defective mineralisation of bones and nephrocalcinosis.

          (i) A number of defects in tubular reabsorp­tion exist in this condition. The defects are renal amino acid in renal glycosuria, hyperphosphaturia, metabolic aciduria, with increased urinary excretion of Na, Ca and K.

          (ii) In some individuals, cystinosis prevails due to the abnormality of cystine metabo­lism in which cystine crystals are depos­ited in macrophages in the liver, kidney, spleen, bone marrow, lymph nodes and cornea.

          h. Hartnup Syndrome (Hard Syndrome):

          (i) In this condition, a number of amino ac­ids are not reabsorbed owing to the defect in tubular reabsorption mechanism.

          (ii) Disturbances in tryptophan metabolism is suggested by the presence of increased amounts of tryptophan, indican and in­dole acetic acid in urine.

          (iii) The clinical symptoms are of niacin defi­ciency—a pellagra like skin lesions and mental deficiency.

          i. Nephrogenic Diabetes Insipidus (Water-Losing Nephritis):

          This condition is due to congenital defect in water reabsorption in the distal tubules and may, there­fore, resemble true diabetes insipidus.

          Essay # 7. Uremia –Clinical Kidney Condition:

          The renal failure develops the clinical condition uremia. This condition occurs both in the chronic renal failure and acute failure. The concentration of urea and other NPN constituents in plasma are increased depending on the severity of this condi­tion.

          In chronic renal disease, excretion of acid (hy­drogen ion) and also of phosphate ion is impaired. This results in the steady development of acidosis in uremia.

          In acute renal failure, the urine output is very low (300 ml or less in 24 hours). This leads to a steady increase in urea and NPN constituents and electrolytes (K + and Na + ) in plasma. There is rapid development of acidosis too.

          The important findings of severe chronic uremia or acute uremia are:

          a. High concentration of urea and other NPN constituents.

          b. High serum potassium concentration.

          c. – Water retention leading to generalised edema.

          Uremic coma occurs in serious cases:

          The concentration of urea and other NPN constituents of blood are very much increased (i.e., 10 times the nor­mal level) in severe renal failure.

          The potassium ion level may be slightly increased in chronic uremia. But in acute uremia, the concentration in serum is very much increased. Potassium is released from the cells due to the break­down of cellular proteins. This released potassium passes into the blood and in­terstitial fluid.

          When the concentration of potassium ion increases to 8 m. Eq/litre, it exerts a cardiotoxic effect resulting in the dilatation of the heart and when potassium ion concentration reaches at 12 to 15 mEq/ litre, the heart is likely to be stopped. This happens in severe uremia.

          iii. Water Retention and Edema:

          If the uremic patient drinks water and consumes other fluids, the water is retained in the body. If salt is not consumed, water retention in­creases in both the intracellular and extra­cellular fluid resulting in extracellular edema.

          The metabolic processes in the body produce daily 50 to 100 m mol of more metabolic acid than alkali. This ex­tra metabolic acid is excreted mainly through the kidneys. Acidosis develops rapidly in acute uremia. The patient faces ‘Coma’ due to severe acidosis.

          Essay # 8. The Artificial Kidney:

          During recent years, the artificial kidney has been developed to such an extent that several thousand patients with permanent renal insufficiency or even total kidney removal are being maintained in health for years.

          The artificial kidney passes blood through very minute channels bounded by thin membranes. There is a dialyzing fluid on the other side of the membrane into which unwanted substances present in the blood pass by diffusion. The blood is pumped continually between two thin sheets of cellophane the dialyzing fluid is on the outside of the sheets.

          The cellophane is porous enough to allow all con­stituents of the plasma except the plasma proteins to diffuse freely in both directions—from plasma into the dialyzing fluid and from the dialyzing fluid into the plasma.

          The rate of flow of blood through the artificial kidney is several hundred ml per minute. Heparin is infused into the blood as it enters the kidney to prevent clotting of blood. To prevent bleeding as a result of heparin, an anti-heparin substance, such as protamine, is infused into the blood as it is re­turned to the patient.

          Sodium, potassium and chloride concentrations in the dialyzing fluid and in normal plasma are identical but in uremic plasma, the potassium and chloride concentrations are considerably greater. These two ions diffuse through the dialyzing membrane so rapidly that their concentrations fall to equal those in the dialyzing fluid within three to four hours, expo­sure to the dialyzing fluid.

          On the other hand, there is no phosphate, urea, urate or creatinine in the dialyzing fluid.

          When the uremic patient is dialyzed, these substances are lost in large quanti­ties into the dialyzing fluid, thereby removing major proportions of them from the plasma. Thus, the constituents of the dialyzing fluid are such that those substances in excess in the extracellular fluid in uremia be removed at rapid rates, while the es­sential electrolytes remain quite normal.

          Utility of Artificial Kidney:

          The artificial kid­neys can clear 100 to 200 ml of blood urea per minute which signifies that it can function about twice as rapidly as two normal kidneys together whose urea clearance is only 70 ml per minute. However, the artificial kidney can be used for not more than 12 hours once in three to four days be­cause of danger from excess heparin and infection to the subject.

          Essay # 9. Hormones of the Kidney:

          a. Not only the kidney performs excretory functions but it acts as an endocrine or­gan. It liberates many hormones which affect other organs and tissues and some hormones which locally act within the kid­ney itself. It also destroys several hor­mones which are liberated from other en­docrine organs.

          b. The juxtaglomerular cells of the renal cor­tex produce the proteolytic enzyme rennin and secrete it into the blood. Rennin acts on a2-globulin which is normally present in blood plasma, although it is pro­duced in the liver.

          Rennin splits off a polypeptide fragment called angiotensin I which is decapeptide containing 10 amino acids. Another enzyme of the lung acts on angiotensin I to split off 2 amino acids and thus form the octapeptide angiotensin II.

          Angiotensin increases the force of the heartbeat and constricts the arterioles. It raises blood pressure and causes contrac­tion of smooth muscle. It is destroyed by the enzyme angiotensinases present in normal kidneys, plasma and other tissues. Recent studies suggest that rennin angi­otensin system is important in the mainte­nance of normal blood pressure.

          c. Prostaglandins are the other hormones of the kidney. They cause relaxation of smooth muscles. They cause vasodilata­tion and a decrease in blood pressure. They also increase renal blood flow. Kininogen which is produced by the kidney has an antihypertensive effect.

          d. The two hormones erythropoietin and erythrogenin have an effect on bone mar­row to stimulate production of red cells. Kidney plays an important role in the re­lease of erythropoietin and thus in con­trol of red cell production. Hypoxia stimu­lates production of erythropoietin.


          11.11: Endocrine Regulation of Kidney Function - Biology

          Maintaining a proper water balance in the body is important to avoid dehydration or over-hydration (hyponatremia). The water concentration of the body is monitored by osmoreceptors in the hypothalamus, which detect the concentration of electrolytes in the extracellular fluid. The concentration of electrolytes in the blood rises when there is water loss caused by excessive perspiration, inadequate water intake, or low blood volume due to blood loss. An increase in blood electrolyte levels results in a neuronal signal being sent from the osmoreceptors in hypothalamic nuclei. The pituitary gland has two components: anterior and posterior. The anterior pituitary is composed of glandular cells that secrete protein hormones. The posterior pituitary is an extension of the hypothalamus. It is composed largely of neurons that are continuous with the hypothalamus.

          The hypothalamus produces a polypeptide hormone known as antidiuretic hormone (ADH), which is transported to and released from the posterior pituitary gland. The principal action of ADH is to regulate the amount of water excreted by the kidneys. As ADH (which is also known as vasopressin) causes direct water reabsorption from the kidney tubules, salts and wastes are concentrated in what will eventually be excreted as urine. The hypothalamus controls the mechanisms of ADH secretion, either by regulating blood volume or the concentration of water in the blood. Dehydration or physiological stress can cause an increase of osmolarity above 300 mOsm/L, which in turn, raises ADH secretion and water will be retained, causing an increase in blood pressure. ADH travels in the bloodstream to the kidneys. Once at the kidneys, ADH changes the kidneys to become more permeable to water by temporarily inserting water channels, aquaporins, into the kidney tubules. Water moves out of the kidney tubules through the aquaporins, reducing urine volume. The water is reabsorbed into the capillaries lowering blood osmolarity back toward normal. As blood osmolarity decreases, a negative feedback mechanism reduces osmoreceptor activity in the hypothalamus, and ADH secretion is reduced. ADH release can be reduced by certain substances, including alcohol, which can cause increased urine production and dehydration.

          Chronic underproduction of ADH or a mutation in the ADH receptor results in diabetes insipidus. If the posterior pituitary does not release enough ADH, water cannot be retained by the kidneys and is lost as urine. This causes increased thirst, but water taken in is lost again and must be continually consumed. If the condition is not severe, dehydration may not occur, but severe cases can lead to electrolyte imbalances due to dehydration.

          Another hormone responsible for maintaining electrolyte concentrations in extracellular fluids is aldosterone, a steroid hormone that is produced by the adrenal cortex. In contrast to ADH, which promotes the reabsorption of water to maintain proper water balance, aldosterone maintains proper water balance by enhancing Na + reabsorption and K + secretion from extracellular fluid of the cells in kidney tubules. Because it is produced in the cortex of the adrenal gland and affects the concentrations of minerals Na + and K + , aldosterone is referred to as a mineralocorticoid, a corticosteroid that affects ion and water balance. Aldosterone release is stimulated by a decrease in blood sodium levels, blood volume, or blood pressure, or an increase in blood potassium levels. It also prevents the loss of Na + from sweat, saliva, and gastric juice. The reabsorption of Na + also results in the osmotic reabsorption of water, which alters blood volume and blood pressure.

          Aldosterone production can be stimulated by low blood pressure, which triggers a sequence of chemical release, as illustrated in Figure 1. When blood pressure drops, the renin-angiotensin-aldosterone system (RAAS) is activated. Cells in the juxtaglomerular apparatus, which regulates the functions of the nephrons of the kidney, detect this and release renin. Renin, an enzyme, circulates in the blood and reacts with a plasma protein produced by the liver called angiotensinogen. When angiotensinogen is cleaved by renin, it produces angiotensin I, which is then converted into angiotensin II in the lungs. Angiotensin II functions as a hormone and then causes the release of the hormone aldosterone by the adrenal cortex, resulting in increased Na + reabsorption, water retention, and an increase in blood pressure. Angiotensin II in addition to being a potent vasoconstrictor also causes an increase in ADH and increased thirst, both of which help to raise blood pressure.

          Figure 1. ADH and aldosterone increase blood pressure and volume. Angiotensin II stimulates release of these hormones. Angiotensin II, in turn, is formed when renin cleaves angiotensin. (credit: modification of work by Mikael Häggström)

          In summary: Hormonal Regulation of the Excretory System

          Water levels in the body are controlled by antidiuretic hormone (ADH), which is produced in the hypothalamus and triggers the reabsorption of water by the kidneys. Underproduction of ADH can cause diabetes insipidus. Aldosterone, a hormone produced by the adrenal cortex of the kidneys, enhances Na + reabsorption from the extracellular fluids and subsequent water reabsorption by diffusion. The renin-angiotensin-aldosterone system is one way that aldosterone release is controlled.


          Textbook of Nephro-Endocrinology

          Textbook of Nephro-Endocrinology, Second Edition, continues to be the definitive translational reference in the field of nephro-endocrinology, investigating both the endocrine functions of the kidneys and how the kidney acts as a target for hormones from other organ systems. It offers researchers and clinicians expert analyses of nephro-endocrine research and translation into the treatment of diseases such as anemia, chronic kidney disease (CKD), rickets, osteoporosis, and hypoparathyroidism.

          Changes to this edition include new chapters focused on hypercalcemia/hypocalcemia and the interaction of dialysis, chronic renal disease, and endocrine diseases. All chapters have been updated to include more preclinical data and more tables and schema that help translate this data into clinical recommendations. The section on hormones and renal insufficiency discusses insulin/diabetes, growth hormone, sex steroids, thyroid hormone, acid–base disturbances, and pregnancy.

          Textbook of Nephro-Endocrinology, Second Edition, continues to be the definitive translational reference in the field of nephro-endocrinology, investigating both the endocrine functions of the kidneys and how the kidney acts as a target for hormones from other organ systems. It offers researchers and clinicians expert analyses of nephro-endocrine research and translation into the treatment of diseases such as anemia, chronic kidney disease (CKD), rickets, osteoporosis, and hypoparathyroidism.

          Changes to this edition include new chapters focused on hypercalcemia/hypocalcemia and the interaction of dialysis, chronic renal disease, and endocrine diseases. All chapters have been updated to include more preclinical data and more tables and schema that help translate this data into clinical recommendations. The section on hormones and renal insufficiency discusses insulin/diabetes, growth hormone, sex steroids, thyroid hormone, acid–base disturbances, and pregnancy.


          25.10 The Urinary System and Homeostasis

          All systems of the body are interrelated. A change in one system may affect all other systems in the body, with mild to devastating effects. A failure of urinary continence can be embarrassing and inconvenient, but is not life threatening. The loss of other urinary functions may prove fatal. A failure to synthesize vitamin D is one such example.

          Vitamin D Synthesis

          In order for vitamin D to become active, it must undergo a hydroxylation reaction in the kidney, that is, an –OH group must be added to calcidiol to make calcitriol (1,25-dihydroxycholecalciferol). Activated vitamin D is important for absorption of Ca ++ in the digestive tract, its reabsorption in the kidney, and the maintenance of normal serum concentrations of Ca ++ and phosphate. Calcium is vitally important in bone health, muscle contraction, hormone secretion, and neurotransmitter release. Inadequate Ca ++ leads to disorders like osteoporosis and osteomalacia in adults and rickets in children. Deficits may also result in problems with cell proliferation, neuromuscular function, blood clotting, and the inflammatory response. Recent research has confirmed that vitamin D receptors are present in most, if not all, cells of the body, reflecting the systemic importance of vitamin D. Many scientists have suggested it be referred to as a hormone rather than a vitamin.

          Erythropoiesis

          EPO is a 193-amino acid protein that stimulates the formation of red blood cells in the bone marrow. The kidney produces 85 percent of circulating EPO the liver, the remainder. If you move to a higher altitude, the partial pressure of oxygen is lower, meaning there is less pressure to push oxygen across the alveolar membrane and into the red blood cell. One way the body compensates is to manufacture more red blood cells by increasing EPO production. If you start an aerobic exercise program, your tissues will need more oxygen to cope, and the kidney will respond with more EPO. If erythrocytes are lost due to severe or prolonged bleeding, or under produced due to disease or severe malnutrition, the kidneys come to the rescue by producing more EPO. Renal failure (loss of EPO production) is associated with anemia, which makes it difficult for the body to cope with increased oxygen demands or to supply oxygen adequately even under normal conditions. Anemia diminishes performance and can be life threatening.

          Blood Pressure Regulation

          Due to osmosis, water follows where Na + leads. Much of the water the kidneys recover from the forming urine follows the reabsorption of Na + . ADH stimulation of aquaporin channels allows for regulation of water recovery in the collecting ducts. Normally, all of the glucose is recovered, but loss of glucose control (diabetes mellitus) may result in an osmotic dieresis severe enough to produce severe dehydration and death. A loss of renal function means a loss of effective vascular volume control, leading to hypotension (low blood pressure) or hypertension (high blood pressure), which can lead to stroke, heart attack, and aneurysm formation.

          The kidneys cooperate with the lungs, liver, and adrenal cortex through the renin–angiotensin–aldosterone system (see Figure 25.14). The liver synthesizes and secretes the inactive precursor angiotensinogen. When the blood pressure is low, the kidney synthesizes and releases renin. Renin converts angiotensinogen into angiotensin I, and ACE produced in the lung converts angiotensin I into biologically active angiotensin II (Figure 25.23). The immediate and short-term effect of angiotensin II is to raise blood pressure by causing widespread vasoconstriction. angiotensin II also stimulates the adrenal cortex to release the steroid hormone aldosterone, which results in renal reabsorption of Na + and its associated osmotic recovery of water. The reabsorption of Na + helps to raise and maintain blood pressure over a longer term.

          Regulation of Osmolarity

          Blood pressure and osmolarity are regulated in a similar fashion. Severe hypo-osmolarity can cause problems like lysis (rupture) of blood cells or widespread edema, which is due to a solute imbalance. Inadequate solute concentration (such as protein) in the plasma results in water moving toward an area of greater solute concentration, in this case, the interstitial space and cell cytoplasm. If the kidney glomeruli are damaged by an autoimmune illness, large quantities of protein may be lost in the urine. The resultant drop in serum osmolarity leads to widespread edema that, if severe, may lead to damaging or fatal brain swelling. Severe hypertonic conditions may arise with severe dehydration from lack of water intake, severe vomiting, or uncontrolled diarrhea. When the kidney is unable to recover sufficient water from the forming urine, the consequences may be severe (lethargy, confusion, muscle cramps, and finally, death) .

          Recovery of Electrolytes

          Sodium, calcium, and potassium must be closely regulated. The role of Na + and Ca ++ homeostasis has been discussed at length. Failure of K + regulation can have serious consequences on nerve conduction, skeletal muscle function, and most significantly, on cardiac muscle contraction and rhythm.

          PH Regulation

          Recall that enzymes lose their three-dimensional conformation and, therefore, their function if the pH is too acidic or basic. This loss of conformation may be a consequence of the breaking of hydrogen bonds. Move the pH away from the optimum for a specific enzyme and you may severely hamper its function throughout the body, including hormone binding, central nervous system signaling, or myocardial contraction. Proper kidney function is essential for pH homeostasis.

          Everyday Connection

          Stem Cells and Repair of Kidney Damage

          Stem cells are unspecialized cells that can reproduce themselves via cell division, sometimes after years of inactivity. Under certain conditions, they may differentiate into tissue-specific or organ-specific cells with special functions. In some cases, stem cells may continually divide to produce a mature cell and to replace themselves. Stem cell therapy has an enormous potential to improve the quality of life or save the lives of people suffering from debilitating or life-threatening diseases. There have been several studies in animals, but since stem cell therapy is still in its infancy, there have been limited experiments in humans.

          Acute kidney injury can be caused by a number of factors, including transplants and other surgeries. It affects 7–10 percent of all hospitalized patients, resulting in the deaths of 35–40 percent of inpatients. In limited studies using mesenchymal stem cells, there have been fewer instances of kidney damage after surgery, the length of hospital stays has been reduced, and there have been fewer readmissions after release.

          How do these stem cells work to protect or repair the kidney? Scientists are unsure at this point, but some evidence has shown that these stem cells release several growth factors in endocrine and paracrine ways. As further studies are conducted to assess the safety and effectiveness of stem cell therapy, we will move closer to a day when kidney injury is rare, and curative treatments are routine.


          Watch the video: ENDOCRINE FUNCTIONS OF KIDNEY (August 2022).