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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
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)
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:
http://www.cristina.prof.ufsc.br
PRESERVE O DIREITO AUTORAL CITANDO A FONTE.
Fisiologia do Sistema Endócrino
REGULAÇÃO ENDÓCRINA DA
CALCEMIA
(níveis plasmáticos de cálcio)
Hormônios:
Paratireoideano (PTH)
Calcitriol e
Calcitonina
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. 42-1 Berne et al., 2004
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
Órgãos e hormônios envolvidos na regulação da calcemia
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/
Glândulas Paratireóides
Secreção de Paratormônio
Paratireóides
Paratormônio
(PTH)
extraído, enquanto disponível, de: http://www.owensboro.kctcs.edu/gcaplan/anat2/Study%20Guides/APII%20Endocrine%20Glands.htm
Regulação da calcemia pelo Paratormônio (PTH)
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/
Regulação da calcemia pelo Calcitriol
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/
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, 684-700. Figura extraída de:
http://www.nature.com/nrc/journal/v7/n9/fig_tab/nrc2196_F1.html Caso interesse uma cópia do artigo original, escreva-me.
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: http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/calcium.html
Absorção da Vitamina D
Nutrition
(veja legenda no próximo slide)
UVB
Diet
vitamin D3 and D2
Skin
Vitamin D3
7-dehydroxycholesterol
Vitamin D3 +
VDBP or albumin
Small
intestine
Bile salts and
conjugated vitamin D
25-hydroxylase
25-OHD
1-hydroxylase
Enterocyte
Chylomicron
+
vitamin D
Reabsorption of
bile salts and
conjugated
vitamin D
Terminal
metabolites
ileum
veja legenda adiante
1,25-(OH)2 vitamin D
Active form of vitamin D
or Calcitriol
X-3
Extraído, enquanto disponível gratuitamente, de: http://www.gastroslides.org/default.asp
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. 25-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,25dihydroxyvitamin 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 2:308-315.;
Crawford BA et al (2006) Vitamin D replacement for cirrhosis-related bone disease. Nature Clinical Practice Gastroenterology and Hepatology 3: 689-699.;
Pappa, Helen M; Bern, Elana; Kamin, Daniel; Grand, Richard (2008). Nutrition. 24(2), 176-183.
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: http://www.cytochemistry.net/Endocrine_System/thyroid_and_parathyroid.htm#Locate
Alguns conceitos sobre fisiologia do tecido ósseo
Remodelagem óssea
extraído, quando disponível, de: http://www.medes.fr/Eristo/Osteoporosis/BoneRemodeling.html
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
AS CÉLULAS ENVOLVIDAS NA REMODELAGEM ÓSSEA
Progenitoras da matriz óssea
precursor de osteoblastos
precursor de osteoclastos
Osteoblastos
iniciam a
formação óssea
Osteoblastos
Formação de
osso novo
Osteoclasto
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. 2006.
http://www.nutritionandmetabolism.com/content/3/1/36#
AS CÉLULAS ENVOLVIDAS NA REMODELAGEM ÓSSEA
Progenitoras da matriz óssea
precursor de osteoblastos
precursor de osteoclastos
osteócitos
monitoram estresse
mecânico ósseo
Osteoblastos
Formação de
osso novo
Osteoclasto
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. 2006.
http://www.nutritionandmetabolism.com/content/3/1/36
AS CÉLULAS ENVOLVIDAS NA REMODELAGEM ÓSSEA
Progenitoras da matriz óssea
precursor de osteoblastos
precursor de osteoclastos
osteoclastos
reabsorvem osso
Osteoblastos
Formação de
osso novo
Osteoclasto
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
As células no microambiente ósseo
extraído, enquanto disponível, de: http://www.abdn.ac.uk/medicine_therapeutics
Formação e resorção óssea
extraído, enquanto disponível, de: http://www.abdn.ac.uk/medicine_therapeutics
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: http://www.medes.fr/Eristo/Osteoporosis/BoneRemodeling.html
O ciclo da remodelagem óssea
extraído, enquanto disponível, de: http://www.abdn.ac.uk/medicine_therapeutics
Porque ocorre a remodelagem óssea?
extraído, quando disponível, de: http://www.abdn.ac.uk/medicine_therapeutics
Remodelagem óssea e regulação
da massa óssea
extraído, enquanto disponível, de: http://www.abdn.ac.uk/medicine_therapeutics
Efeito da idade na massa óssea e risco de
ocorrência de fraturas
http://www.nutritionandmetabolism.com/content/3/1/36
Decrease in peak bone mass with age and increase in fracture risk with increasing
age. Valsamis et al, 2006
Osso e regulação da homeostase
do cálcio
extraído, enquanto disponível, de: http://www.abdn.ac.uk/medicine_therapeutics
OS HORMÔNIOS REGULADORES DA REMODELAGEM ÓSSEA
Progenitoras da matriz óssea
precursor de osteoblastos
precursor de osteoclastos
Glicocorticóides
Estrógenos
Andrógenos
GH/IGF-1
Osteoblastos
Formação de
osso novo
+
1,25 OHD
PTH
+
Estrógenos
Calcitonina
Tiroxina
Vitamina A
Osteoclasto
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. 2006.
http://www.nutritionandmetabolism.com/content/3/1/36#
Remodelagem óssea
Conheça este WEBsite que possui várias animações muito
interessantes, além de textos:
http://courses.washington.edu/bonephys/physremod.html
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: http://www.pediatric-orthopedics.com/Topics/Bow_Legs/bow_legs.html
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