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Fisiologia do Sistema Endócrino Regulação endócrina da Calcemia

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Apresentação em tema: "Fisiologia do Sistema Endócrino Regulação endócrina da Calcemia"— Transcrição da apresentação:

1 Fisiologia do Sistema Endócrino Regulação endócrina da Calcemia
   Profa. Adjunto do Depto. Ciências Fisiológicas-CCB-UFSC Como citar este documento: PINTO, Cristina Maria Henrique. Fisiologia Humana: Endocrinofisiologia. Disponível em: <http://www.cristina.prof.ufsc.br>. Acesso em: coloque a data aqui

2 Bibliografia recomendada Livros-textos:
ESQUEMAS PARA FACILITAR O ESTUDO E O ACOMPANHAMENTO DE MINHAS AULAS Bibliografia recomendada Livros-textos: “Fisiologia” Costanzo, 2007, 3ª Ed. (Ed. Elsevier) “Fundamentos de Fisiologia”, Berne et al, 2006, 4ª Ed.(Ed. Elsevier) “Berne & Levy: Fisiologia” Koeppen & Stanton, 2009, 6ª Ed. (Ed. Elsevier) “Fisiologia” Berne et al., 2004, 5ª Ed. (Ed. Elsevier) “Tratado de Fisiologia Médica” Guyton & Hall, 2006, 11ª Ed. (Ed. Elsevier) “Fisiologia” Aires, M. M., 2008, 3ª Ed. (Ed. Guanabara Koogan) “Fisiologia: texto e atlas” Despopoulos e Silbernagl, 2003 (Ed. Artmed)

3 PRESERVE O DIREITO AUTORAL CITANDO A FONTE.
AS FIGURAS AQUI UTILIZADAS FORAM RETIRADAS DE WEBSITES E, QUANDO POSSÍVEL, SÃO SEGUIDAS PELO ENDEREÇO NA INTERNET. PARA CONSULTA A TEXTOS E OUTROS RECURSOS ONLINE, VEJA EM: PRESERVE O DIREITO AUTORAL CITANDO A FONTE.

4 Fisiologia do Sistema Endócrino
REGULAÇÃO ENDÓCRINA DA CALCEMIA (níveis plasmáticos de cálcio) Hormônios: Paratireoideano (PTH) Calcitriol e Calcitonina

5 Órgãos e mecanismos envolvidos na regulação da Calcemia (níveis de cálcio no sangue)
Os números referem-se aos níveis da cálcio diários em humanos. Repare o balanço entre a ingestão e a excreção de cálcio assim como para a remoção e reposição de cálcio nos ossos (remodelagem óssea). Fig Berne et al., 2004

6 Visão geral do intercâmbio de cálcio...
... entre diferentes compartimentos teciduais em uma pessoa com ingestão de 1.000mg de Cálcio por dia. Grande parte do cálcio ingerido é normalmente eliminada pelas fezes, embora os rins tenham a capacidade de excretar quantidades abundantes de cálcio por meio da redução Guyton e Hall, 2006

7 Órgãos e hormônios envolvidos na regulação da calcemia

8 Glândulas Paratireóides Secreção de Paratormônio
(PTH) extraído, enquanto disponível, de:

9 Regulação da calcemia pelo Paratormônio (PTH)

10 Regulação da calcemia pelo Calcitriol

11 Metabolismo da Vitamina D
Photochemical synthesis of vitamin D3 (cholecalciferol, D3) occurs cutaneously where pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3 (pre-D3) in response to ultraviolet B (sunlight) exposure. Vitamin D3, obtained from the isomerization of pre-vitamin D3 in the epidermal basal layers or intestinal absorption of natural and fortified foods and supplements, binds to vitamin D-binding protein (DBP) in the bloodstream, and is transported to the liver. D3 is hydroxylated by liver 25-hydroxylases (25-OHase). The resultant 25-hydroxycholecalciferol (25(OH)D3) is 1-hydroxylated in the kidney by 25-hydroxyvitamin D3-1-hydroxylase (1-OHase). This yields the active secosteroid 1,25(OH)2D3 (calcitriol), which has different effects on various target tissues23. The synthesis of 1,25(OH)2D3 from 25(OH)D3 is stimulated by parathyroid hormone (PTH) and suppressed by Ca2+, Pi and 1,25(OH)2D3 itself. The rate-limiting step in catabolism is the degradation of 25(OH)D3 and 1,25(OH)2D3 to 24,25(OH)D3 and 1,24,25(OH)2D3, respectively,which occurs through 24-hydroxylation by 25-hydroxyvitamin D 24-hydroxylase (24-OHase), encoded by the CYP24A1 gene. 24,25(OH)D3 and 1 ,24,25(OH)2D3 are consequently excreted. The main effects of 1,25(OH)2D3 on various target tissues are highlighted above. Extraída de: “Vitamin D signalling pathways in cancer: potential for anticancer therapeutics” Deeb et al., 2007 Nature Reviews Cancer 7, Figura extraída de: Caso interesse uma cópia do artigo original, escreva-me.

12 Biossíntese do Calcitriol
(Hormônio derivado da Vitamina D ou 1,25(OH)2-Vitamina D) Vitamin D is a fat-soluble vitamin that exists in various forms. Some forms are relatively inactive in the body, and have limited ability to function as a vitamin. Exposure to sunlight is an important source of vitamin D. Ultraviolet (UV) rays from sunlight trigger vitamin D synthesis in the skin. The liver and kidney help convert vitamin D to its active hormone form, also called CALCITRIOL. + PTH + PTH Dietary Sources. Only a few foods naturally contain significant amounts of vitamin D, including fatty fish and fish oils. Other dietary sources include fortified milk and margarine, liver, butter, cream and egg yolks. Veja mais em:

13 Absorção da Vitamina D (veja legenda no próximo slide)
Nutrition Diet vitamin D3 and D2 UVB Skin Vitamin D3 7-dehydroxycholesterol Enterocyte Chylomicron + vitamin D Vitamin D Absorption Vitamin D and Calcium Metabolism. The active form of vitamin D is 1,25 (OH)2 vitamin D. There are multiple feedback loops to tightly regulate vitamin D and calcium OHD and 1,25 (OH)2 vitamin D is metabolized by 24-hydroxylase to the inactive metabolites, 24,25-hydroxyvitamin D3 and 1,24,25-dihydroxyvitamin D 3. The enzyme, 24-hydroxylase, is stimulated by 1α,25- dihydroxyvitamin D3. 1α,25-dihydroxyvitamin D3 feedback inhibits parathyroid hormone production. PTH tightly regulates 1,25(OH)2 vitamin D3 by inhibiting 1hydroxylase. 1,25(0H)2 vitamin D3 controls calcium and phosphate homeostasis through the kidney, intestine, and bone. The level of 1,25 (OH)2 vitamin D3 is controlled by PTH, and serum calcium and phosphate. PTH is secreted when there are low levels of serum calcium. PTH then causes renal synthesis of 1,25 (OH)2 vitamin D by stimulating 1hydroxylase. Low levels of phosphate stimulate production 1,25 (OH)2 vitamin D independent of PTH. There is also an inhibitory feedback loop from 1,25 (OH)2 vitamin D on itself in response to serum levels of calcium and phosphate. The most important function of 1α,25-dihydroxyvitamin D is the absorption of calcium from the intestine. It also acts on the kidney and bone to regulate calcium and phosphate homeostasis. There are also other noncalcemic physiologic functions. Calcium is ionized at low pH in gastrointestinal tract so absorption is increased by exposure of food to gastric acid. Calcium absorption is also increased by substances that form soluble complexes with calcium such as amino acids and bile salts. Absorption is decreased by insoluble complexes such as oxalate and long-chain fatty acids. Patients with gastrointestinal and liver diseases are at risk for low vitamin D levels. Patients may have low vitamin D intake or skin absorption, loss of absorptive surface, fat malabsorption, bile salt deficiency, and loss of liver function which may cause reduced vitamin D levels. Lim WC et al (2005). Mechanisms of Disease: vitamin D and inflammatory bowel disease. Nature Clinical Practice Gastroenterology and Hepatology 2: Crawford BA et al (2006) Vitamin D replacement for cirrhosis-related bone disease. Nature Clinical Practice Gastroenterology and Hepatology 3: Pappa, Helen M; Bern, Elana; Kamin, Daniel; Grand, Richard (2008). Nutrition. 24(2), Vitamin D3 + VDBP or albumin Small intestine Reabsorption of bile salts and conjugated vitamin D metabolites Bile salts and conjugated vitamin D Terminal ileum 25-hydroxylase 25-OHD veja legenda adiante 1-hydroxylase 1,25-(OH)2 vitamin D Active form of vitamin D or Calcitriol X-3 Extraído, enquanto disponível gratuitamente, de:

14 Legenda da figura anterior:
Vitamin D Absorption Vitamin D and Calcium Metabolism. The active form of vitamin D is 1,25 (OH)2 vitamin D. There are multiple feedback loops to tightly regulate vitamin D and calcium OHD and 1,25 (OH)2 vitamin D is metabolized by 24-hydroxylase to the inactive metabolites, 24,25-hydroxyvitamin D3 and 1,24,25-dihydroxyvitamin D 3. The enzyme, 24-hydroxylase, is stimulated by 1α,25- dihydroxyvitamin D3. 1α,25-dihydroxyvitamin D3 feedback inhibits parathyroid hormone production. PTH tightly regulates 1,25(OH)2 vitamin D3 by inhibiting 1hydroxylase. 1,25(0H)2 vitamin D3 controls calcium and phosphate homeostasis through the kidney, intestine, and bone. The level of 1,25 (OH)2 vitamin D3 is controlled by PTH, and serum calcium and phosphate. PTH is secreted when there are low levels of serum calcium. PTH then causes renal synthesis of 1,25 (OH)2 vitamin D by stimulating 1hydroxylase. Low levels of phosphate stimulate production 1,25 (OH)2 vitamin D independent of PTH. There is also an inhibitory feedback loop from 1,25 (OH)2 vitamin D on itself in response to serum levels of calcium and phosphate. The most important function of 1α,25-dihydroxyvitamin D is the absorption of calcium from the intestine. It also acts on the kidney and bone to regulate calcium and phosphate homeostasis. There are also other noncalcemic physiologic functions. Calcium is ionized at low pH in gastrointestinal tract so absorption is increased by exposure of food to gastric acid. Calcium absorption is also increased by substances that form soluble complexes with calcium such as amino acids and bile salts. Absorption is decreased by insoluble complexes such as oxalate and long-chain fatty acids. Patients with gastrointestinal and liver diseases are at risk for low vitamin D levels. Patients may have low vitamin D intake or skin absorption, loss of absorptive surface, fat malabsorption, bile salt deficiency, and loss of liver function which may cause reduced vitamin D levels. Lim WC et al (2005). Mechanisms of Disease: vit D and inflammatory bowel disease. Nature Clinical Practice Gastroenterology and Hepatology 2: ; Crawford BA et al (2006) Vitamin D replacement for cirrhosis-related bone disease. Nature Clinical Practice Gastroenterology and Hepatology 3: ; Pappa, Helen M; Bern, Elana; Kamin, Daniel; Grand, Richard (2008). Nutrition. 24(2),

15 Regulação da calcemia pela Calcitonina
Parafollicular cells are also called "C cells".  They are found in the interstitial spaces outside the thyroid follicles in the middle third of the lateral lobes.  As all endocrine cells, they lie next to capillaries so they can secrete their hormone into the bloodstream.  The hormone they produce is "CALCITONIN".  They respond to high blood levels of calcium.  When calcium levels are too high, they secrete calcitonin and this hormone inhibits osteoclastic activity. What is the function of osteoclasts? Osteoclastic activity releases calcium that goes into the blood stream for use by the cells in the body. How does it do this? Veja em:

16 Remodelagem óssea Alguns conceitos sobre fisiologia do tecido ósseo
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17 Remodelagem óssea Process of bone remodeling. Signals carried by canalicular and syncytial routes from interior osteocytes, and endocrine signals to resting osteoblasts and lining cells generate local paracrine cytokine signals to nearby osteoclasts and osteoclast precursors. Osteoclasts also recruit their own precursors by paracrine signals. The osteoclasts resorb an area of mineralized bone, and local macrophages complete the clean-up of dissolved elements. The process then reverses to formation as osteoblast precursors are recruited to the site and differentiate into active osteoblasts. These lay down new organic matrix and mineralize it. Thus, new bone replaces the previously resorbed mature bone Levy et al., 2006

18 AS CÉLULAS ENVOLVIDAS NA REMODELAGEM ÓSSEA
Progenitoras da matriz óssea precursor de osteoblastos precursor de osteoclastos Osteoblastos iniciam a formação óssea Osteoclasto Osteoblastos Formação de osso novo Resorção óssea Osteócito Development of osteoblasts and osteoclasts from bone marrow progenitors. Factors affecting the development and function of these cells, bone resorption by osteoclast and new bone formation by osteoblasts. Abbreviations: GH: growth hormone, IGF: insulin like growth factors,PTH: parathyroid hormone Valsamis et al

19 AS CÉLULAS ENVOLVIDAS NA REMODELAGEM ÓSSEA
Progenitoras da matriz óssea precursor de osteoblastos precursor de osteoclastos osteócitos monitoram estresse mecânico ósseo Osteoclasto Osteoblastos Formação de osso novo Resorção óssea Osteócito Development of osteoblasts and osteoclasts from bone marrow progenitors. Factors affecting the development and function of these cells, bone resorption by osteoclast and new bone formation by osteoblasts. Abbreviations: GH: growth hormone, IGF: insulin like growth factors,PTH: parathyroid hormone Valsamis et al

20 AS CÉLULAS ENVOLVIDAS NA REMODELAGEM ÓSSEA
Progenitoras da matriz óssea precursor de osteoblastos precursor de osteoclastos osteoclastos reabsorvem osso Osteoclasto Osteoblastos Formação de osso novo Resorção óssea Osteócito Development of osteoblasts and osteoclasts from bone marrow progenitors. Factors affecting the development and function of these cells, bone resorption by osteoclast and new bone formation by osteoblasts. Abbreviations: GH: growth hormone, IGF: insulin like growth factors,PTH: parathyroid hormone Valsamis et al #

21 As células no microambiente ósseo
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22 Formação e resorção óssea
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23 O ciclo da remodelagem óssea Two main types of cells are responsible for bone renewal: the osteoblasts involved in bone formation and the osteoclasts involved in bone resorption.  Activation: Preosteoclasts are stimulated and differentiated under the influence of cytokine and growth factors to mature into active osteoclasts.  Resorption: Osteoclasts digest mineral matrix, old bone.  Reversal: End of resorption   Formation: Osteoblasts are responsible for bone matrix synthesis (collagen). Two other non-collagenous proteins are also formed: ostocalcin and osteonectin.  extraído, enquanto disponível, de:

24 O ciclo da remodelagem óssea
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25 Porque ocorre a remodelagem óssea?
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26 Remodelagem óssea e regulação da massa óssea
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27 Efeito da idade na massa óssea e risco de ocorrência de fraturas
Decrease in peak bone mass with age and increase in fracture risk with increasing age. Valsamis et al, 2006

28 Osso e regulação da homeostase do cálcio
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29 - - + + Progenitoras da matriz óssea precursor de osteoblastos
OS HORMÔNIOS REGULADORES DA REMODELAGEM ÓSSEA Progenitoras da matriz óssea precursor de osteoblastos precursor de osteoclastos Glicocorticóides Estrógenos Calcitonina 1,25 OHD PTH - - Estrógenos Andrógenos GH/IGF-1 Tiroxina Vitamina A + + Osteoclasto Osteoblastos Formação de osso novo Resorção óssea Osteócito Development of osteoblasts and osteoclasts from bone marrow progenitors. Factors affecting the development and function of these cells, bone resorption by osteoclast and new bone formation by osteoblasts. Abbreviations: GH: growth hormone, IGF: insulin like growth factors, PTH: parathyroid hormone. Valsamis et al

30 Remodelagem óssea Conheça este WEBsite que possui várias animações muito interessantes, além de textos:

31 Deficiência na infância de Vitamina D/Calcitriol causa o Raquitismo
Raquitismo: Raquitismo é uma doença do metabolismo da Vitamina D, vital para a mineralização óssea. Deficiência de Vitamina D na dieta é a forma mais comum de raquitismo mas também pode ser devido a alterações genéticas que afetam os vários aspectos do metabolismo da Vitamina D. Veja mais em:

32 Fisiologia Endócrina Vivendo perigosamente...
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