The kidney as an endocrine organ Illsley Y1 2022-2023 (2).pptx

The kidney as an endocrine organ (including adrenal function) Year 1 2022-2023 Charlotte Illsley In this session To extend and consolidate earlier consideration of renal function and bone metabolism (will also discuss in thyroid session) To introduce the function of the kidney as an endocrine organ...

The kidney as an endocrine organ (including adrenal function) Year 1 2022-2023 Charlotte Illsley In this session To extend and consolidate earlier consideration of renal function and bone metabolism (will also discuss in thyroid session) To introduce the function of the kidney as an endocrine organ To emphasise the roles of erythropoietin, vitamin D3 and the renin-angiotensin system in the homeostatic control of body systems To consider structure/function relationships in the adrenal gland To generate an overview understanding of the main groups of adrenal cortical and medullary hormones and their function To create a general awareness of the significance of disorders of these hormones in human disease processes The kidney Mineralcorticoids (aldosterone) Glucocorticoids (cortisol) Androgens Catecholamines (adrenaline and noradrenaline) As well as the filtration and reabsorption that the kidney does (see previous session), it also has key endocrine functions The kidney produces hormones The adrenal glands (ad = on top, renal = kidney) also have key endocrine functions Renin Erythropoietin Calcitriol By EEOC - cancer.gov, Public Domain, https://commons.wikimedia.org/w/i ndex.php?curid=1394171 Erythropoietin Erythropoietin is synthesised mainly by the kidney Secreted by the kidney Produced in response to hypoxia (and low level continuous release) Promotes erythropoiesis (red blood cell production) in the bone marrow Binds to receptors on RBC progenitors (more specific than a stem cell) Binding promotes proliferation, differentiation (into RBCs) and survival of the progenitor cells By Mountaineer - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php? curid=5730546 Used (illegally) by athletes – why? By McSmit - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php? curid=7704806 Calcitriol/Vitamin D3 Calcitriol is the active metabolite of vitamin D3 When we eat vitamin D3 or make it in our skin (as a result of sun exposure), it needs to be activated (hydroxylated) in the kidneys, producing the hormone, calcitriol Increases blood Ca2+ levels: It increases the Ca2+ absorbed in the GI tract It promotes reabsorption of Ca2+ in the kidneys It stimulates Ca2+ release from bone Calcitriol/Vitamin D3 Calcitriol is a steroid hormone so acts intracellularly (it’s fat soluble so can cross the plasma membrane) It binds the calcitriol receptor (aka vitamin D receptor) which increases transcription of a gene encoding a Ca 2+ binding protein, allowing more Ca2+ to be transported from the intestines into the blood NB – although calcitriol causes release of Ca 2+ from the bone, bones tend to take up more Ca2+ than they lose because there is more Ca2+ in the blood (apart from when there is dietary lack of Ca 2+ and/or when the transport out of the GI tract isn’t working properly) Calcitriol/Vitamin D3 We will talk more about Ca2+ levels and bone in the thyroid session, but for now be aware: Calcitonin is a peptide hormone produced in the thyroid, released when Ca2+ in the plasma is high and reduces it (does the opposite to calcitriol) Its key role is to prevent Ca2+ loss from the skeleton Parathyroid hormone (PTH) is released from parathyroid glands in response to low plasma Ca2+ levels, increasing availability of Ca2+ PTH and calcitriol work towards the same goal (increasing plasma Ca2+) Renin Renin secreted by cells in the juxtaglomerular apparatus (kidney) Renin is a protease enzyme It hydrolyses angiotensinogen to angiotensin I Regulates blood pressure by regulating fluid balance Released as a result of low blood pressure in afferent arterioles (sympathetic stimulation) OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php? curid=30148646 Renin-AngiotensinAldosterone System (RAAS) When blood pressure drops (e.g. dehydration or blood loss), renin is released to start the RAAS Renin cleaves angiotensinogen (produced constitutively and released by liver) to release angiotensin I Angiotensin I is further cleaved by angiotensin converting enzyme (ACE) to produce angiotensin II (this happens in the lungs) By Mikael Häggström - All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php? Renin-AngiotensinAldosterone System (RAAS) Angiotensin II: Causes vasoconstriction of vessels Causes more constriction of glomerular efferent than afferent arterioles (in the kidney) to maintain GFR By Mikael Häggström - All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php? Renin-AngiotensinAldosterone System (RAAS) Angiotensin II: Causes high concentrations of NaCl to be maintained in the medulla of the kidney (more water reabsorbed) Stimulates Na+ channels to reabsorb more Na+ from the nephron (more water follows) Stimulates release of aldosterone from the adrenal cortex Aldosterone also increases reabsorption of Na+ and water in the nephron By Mikael Häggström - All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php? Renin-AngiotensinAldosterone System (RAAS) Angiotensin II: Causes release of anti-diuretic hormone (ADH) aka vasopressin (made in hypothalamus, released from pituitary gland) ADH causes water reabsorption from the nephron and also stimulates thirst All of these things make us reabsorb more water and increase blood pressure (increased fluid volume) By Mikael Häggström - All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php? Renin-AngiotensinAldosterone System (RAAS) ACE inhibitors stop the conversion of angiotensin I to angiotensin II so lower blood pressure Atrial natriuretic peptide (ANP) has the opposite effect of the RAAS – it is made and released by muscle cells in the heart as a response to increased blood pressure ANP causes increased Na+ excretion and thus increased water loss in urine By Mikael Häggström - All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php? The adrenal gland Different hormones are released from different areas of the adrenal gland NB epinephrine and norepinephrine = adrenaline and noradrenaline By EEOC - cancer.gov, Public Domain, https://commons.wikimedia.org/w/index.php? curid=1394171 By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148154 Adrenal hormones – steroid hormones Steroid hormones are lipid soluble hormones which can act inside the target cells (they can get through the membrane) By doing this they can change the transcription of DNA in the cell, changing the proteins expressed The main groups of steroid hormones are corticosteroids and sex steroids Adrenal hormones – steroid hormones Corticosteroids: Mineralcorticoids regulate mineral balance, e.g. aldosterone which we have discussed in the RAAS (previous slides) – from adrenal cortex Corticosteroids: Glucocorticoids regulate glucose balance, e.g. cortisol. We covered cortisol in the stress session – refer back to this (remember it increases glucose in the blood) – from adrenal cortex Androgens (male sex hormones) including dehydroepiandrosterone (DHEA) – these are converted into e.g. testosterone or estrogens in the gonads (which have a more potent effect) – from adrenal cortex Adrenal hormones – catecholamines Catecholamines (adrenaline and noradrenaline) – we covered these a bit in the stress session and will come back to them in the autonomic nervous system session later this year From adrenal medulla These mediate the fight or flight response in the autonomic nervous system Renal hormones – human disease By EEOC - cancer.gov, Public Domain, https://commons.wikimedia.org/w/index.php? curid=1394171 Tumours in the kidney can result in over-secretion of renin -> high BP Chronic kidney disease: Anaemia is common in people with CKD as they don’t make enough erythropoietin -> fewer red blood cells So is lack of calcitriol which leads to various issues associated with Vit D deficiency (bone, immune system etc) – these people need supplements Renin Erythropoietin Calcitriol Adrenal hormones – human Mineralcorticoids (aldosterone) disease Glucocorticoids (cortisol) Hypoaldosteronism is decreased aldosterone levels (various causes) -> loss of Na+, hypotension, circulatory insufficiency treated with mineralcorticoid supplements and salt Lack of cortisol (e.g. Addison’s disease) – see stress session Also Cushing’s disease where too much ACTH is released from pituitary (usually tumour) -> too much cortisol Too much cortisol -> e.g. high BP, weight gain, stretch marks in skin, etc. (check saliva cortisol levels) Androgens Catecholamines (adrenaline and noradrenaline) By EEOC - cancer.gov, Public Domain, https://commons.wikimedia.org/w/index.php? curid=1394171 Adrenal hormones – human disease Mineralcorticoids (aldosterone) Congenital adrenal hyperplasia (CAH) – various genetic disorders resulting in over or under production of corticosteroids and sex steroids CAH can result in early or late puberty, ambiguous genitalia, infertility and many others CAH causing inadequate mineralcorticoids, similar symptoms to hypoaldosteronim – salt loss and dehydration Glucocorticoids (cortisol) Androgens Catecholamines (adrenaline and noradrenaline) By EEOC - cancer.gov, Public Domain, https://commons.wikimedia.org/w/index.php? curid=1394171 In this session To extend and consolidate earlier consideration of renal function and bone metabolism (will also discuss in thyroid session) To introduce the function of the kidney as an endocrine organ To emphasise the roles of erythropoietin, vitamin D3 and the renin-angiotensin system in the homeostatic control of body systems To consider structure/function relationships in the adrenal gland To generate an overview understanding of the main groups of adrenal cortical and medullary hormones and their function To create a general awareness of the significance of disorders of these hormones in human disease processes