Kidney as an endocrine gland and its non excretory fuctions

In this presentation, you will get the insight to the kidney as an endocrine gland along with some of its non excretory functions.

1. Kidney as an endocrine gland Usra Hasan A13156217001 M.Sc. Medical Physiology 3 rd Semester 2 nd Year

2. Contents Introduction Endocrine functions Non-excretory functions References

3. Introduction The kidney is one of the most vital organ in human body. It plays an essential role in the maintenance in higher organisms, not only through regulating the blood pressure and body fluid homeostasis and clearing the wastes,  The kidney serves as an important endocrine target organ for several hormones , thereby controlling the extracellular fluid volume, electrolyte balance, acid-base balance, and blood pressure. Kidneys secrete many hormonal substances in addition to erythropoietin and thrombopoietin .

4. Kidney perform several functions, which are majorly categorized into Excretory function Homeostatic function Metabolic function Endocrine function

5. Endocrine Functions

6. Kidney secrete and synthesize several hormones and enzymes, which play a vital role in the functioning of system. The kidneys produce three important hormones, which affect many processes in the kidneys, namely Erythropoietin Thrombopoietin Renin Calcitriol Prostaglandins

7. In addition to synthesis , the kidneys also contribute to the  degradation  of certain  hormones – such as  insulin or  parathyroid hormone . It synthesize insulinase , an enzyme, which cleaves insulin, and eventually degrades it. It also produces enzymes , such as kallikreins , which produce hormones in other, distant sites. The kidney is also an important producer of “ local hormones ” or autocrine and paracrine molecules, such as prostaglandins, etc. Not only that, the kidney is the primary target organ for various hormones like  aldosterone, angiotensin, and the natriuretic peptides . It is also affected by other hormonal diseases. 

8. The kidney secretes Renin , a key enzyme of the renin-angiotensin system ( RAS ) that leads to the production of a potent pressor hormone angiotensin, and produces the following hormones and humoral factors. Kallikreins , a group of serine proteases that act on blood proteins to produce a  vaso -relaxing peptide bradykinin. Erythropoietin ( EPO ), a peptide hormone essential for red blood cell (RBC) formation by the bone marrow. 1,25- (OH)2 vitamin D3 , the active form of vitamin D essential for calcium homeostasis, which is produced by the proximal tubule cells via the enzyme 1α-hydroxylase.

9. Renin Angiotensin System Renin is an enzyme that is produced by the granular cells of the afferent arteriole at the JGA (juxtaglomerular apparatus), have autocrine and paracrine effects. Angiotensinogen , produced by the liver , gets converted into  Angiotensin I , by the action of renin secreted the kidney, now present in the circulatory system. Angiotensin I in turn gets converted into angiotensin II by the action of an enzyme secreted by lungs, called angiotensin converting enzyme (ACE). ACE is important in raising blood pressure. People with high blood pressure are sometimes prescribed ACE inhibitors to lower their blood pressure. Angiotensin II  acts on the blood vessels of the body, and cause  vasoconstriction . Vasoconstriction in turn results into increase in the blood pressure.

10. Also,  Angiotensin II  acts via receptors in the  adrenal glands  to stimulate the secretion of  aldosterone . Aldosterone is also known as the salt retaining hormone , promotes retention of sodium ions and water in the body. It also causes loss of potassium ions from the body. It all results into the immediate effect of renin on the blood pressure , due to angiotensin II  stimulated vasoconstriction and aldosterone stimulated potassium loss . Aldosterone is structurally similar to  progesterone , a steroid, which binds to the aldosterone receptor and weakly stimulates Na +  reabsorption and increased water recovery. Angiotensin II also causes the release of a hormone called  anti-diuretic hormone  (ADH), commonly called vasopressin.

11. ADH is a hormone released from the posterior pituitary gland that causes an increase in blood pressure .  It vasoconstricts our blood vessels, which causes increased blood pressure,  also increases water absorption from the distal tubule and collecting ducts . It promotes the recovery of water, decreases urine volume, and maintains plasma osmolarity and blood pressure, 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.

12. Erythropoietin System Erythropoietin is a peptide hormone which  regulates erythropoiesis . Structure and function It is a  glycoprotein  containing 165 amino acids,  receptors present on the membranes of  red blood cell precursors . Binding of the hormone  reduces apoptosis  of these cells – multiple cells survive and can therefore complete their development into mature erythrocytes. Synthesis and inactivation In adults, approximately 85 % of erythropoietin is synthesized in the kidneys  (interstitial cells) , the remaining 15% amount in the  liver  (peri-venous hepatocytes) .

13. The liver plays a key role in the production of erythropoietin during the fetal period. But in adulthood, the liver is no longer able to compensate for a potential decrease in production in the kidneys. The main stimulus to produce erythropoietin is a  decrease in the partial pressure of oxygen  in the blood flowing through the two organs. Hypoxia leads to prostaglandin formation which in turn stimulates erythropoietin formation . Hormone production is also supported by  androgens  (testosterone) , and  catecholamines  (β – receptors). The main location of  inactivation  of erythropoietin is the  liver .

14. Regulation   Usual stimulus is hypoxia , but hormone can also be stimulated by cobalt salts & androgens. Secretion of hormone is facilitated by alkalosis that develops at high altitudes. Like renin secretion, erythropoietin secretion is facilitated by catecholamines via a beta-adrenergic mechanism.

15. Biosynthesis Of 

16. Calcitriol (1,25- dihydroxycholecalciferol) Calcitriol is a calciotropic hormone secreted by renal proximal tubular cells . It stimulates intestinal calcium absorption and bone mineralization . The drug form is used for treatment of osteoporosis and renal failure . It is also produced outside the kidney in small amounts by many other tissues including placenta and activated macrophages. Mechanism and Synthesis It is generated in the skin of animals when light energy is absorbed by a precursor molecule 7-dehydrocholesterol . 7-dehydrocholesterol gets converted into pre-calciferol in the presence of sunlight radiation.

17. The first of these steps  occurs in the liver  and involves the  enzyme vitamin D3 25-hydroxylase  (CYP2R1) , which  catalyzes  synthesis of  25-hydroxyvitamin D3  (25(OH)D3) , the  main circulating form of vitamin D . The  25 (OH)D3  molecule then acts as the substrate for  25(OH)D3 1αhydroxylase   (CYP27B1) , which  catalyzes  synthesis of  1α,25-dihydroxyvitamin D3 , an active form of vitamin D3 [2]. 25 (OH)D3  and  1α,25-dihydroxyvitamin D3  receive  hydroxylation  by  CYP24  at the position of C-24 as degradation steps.

18. Functions helps in the process of calcium & phosphate absorption in gut. helps in the reabsorption of calcium from distal nephrons. effect on bone mineralization. increases the number & activity of the osteoclasts, so net effect is mobilization of calcium from bone. additional effects on the production of calcitriol include an increase by  prolactin , which stimulates  lactogenesis , a process which requires large amounts of calcium.

19. Prostaglandins Prostaglandins, and the structurally related molecules prostacyclins , thromboxanes  and leukotrienes, are called eicosanoids because they contain 20 carbon atoms (Greek eikosi = 20). These hormones are relatively short-lived and hence act locally near to their site of synthesis in the body. They are derived from the common precursor arachidonate. It is secreted from kidney are PGA2 & PGE2. They decrease blood pressure by systemic vasodilatation, diuresis & natriuresis. Prostaglandins seem to act via two separate mechanisms. Secreted prostaglandins bind to specific cell surface G-protein coupled receptors, and generally increase cAMP levels. Prostaglandins may also bind to nuclear receptors and alter gene transcription.

20. Synthesis is controlled by two enzymes. The first enzyme, phospholipase A2, required for the synthesis of all ecosinoid molecules.  The second enzyme depends on the type of molecule. Cyclooxygenase is the main regulated enzyme for prostaglandin and thromboxane synthesis, while leukotriene synthesis is regulated by 5-lipoxygenase. Phospholipase A2 is inhibited by glucocorticoids. Cyclooxygenase is inhibited by aspirin and several other widely used drugs.

21. Functions stimulate inflammation, modulate synaptic transmission between nerve cells, and induce sleep. Although aspirin (acetylsalicylic acid) has been used for centuries to decrease inflammation, pain and fever. Aspirin inhibits the synthesis of prostaglandins by irreversibly inhibiting prostaglandin synthase. Prostaglandins appear to form a major part of the signaling pathway in fever induction. Prostaglandins appear to be involved in some pain pathways; inhibition of COX (probably COX-2) is thus analgesic. Prostaglandins are required for normal implantation of the fertilized oocyte.  involved in initiation of labor. Prostaglandins are used for labor induction. Normal kidneys do not appear to require prostaglandins. However, kidneys in individuals with chronic liver, heart, or kidney disease do require prostaglandin biosynthesis in the kidney. some anti-ulcer drugs appear to function by increasing prostaglandin synthesis.

22. References https://www.rose-hulman.edu/~brandt/Chem430/Prostaglandins.pdf https://www.sciencedirect.com/science/article/pii/B9780128010280002361 http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/vitamind.html https://study.com/academy/lesson/renin-angiotensin-aldosterone-system-raas-pathway-functions-terms.html https://courses.lumenlearning.com/ap2/chapter/endocrine-regulation-of-kidney-function/ Ganong Guyton n hall Sembulingam

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