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صدق الله العظيم 85االسراء اية
ByBy
Dr. Abdel Aziz M. HusseinDr. Abdel Aziz M. HusseinAssist Prof of Medical Assist Prof of Medical
PhysiologyPhysiology
Osteoclast
Total Body Ca+2
1000 – 1200 gm (70 Kg adult man)
Bone and Teeth
(99%) (1000 g)
Body fluids (ICF and ECF)
(1%) (1 g)
9 – 11 mg/dl
Non-diffusible (45%)
(bound with albumin)
Diffusible (55%)
Complexed with PO4
(10%)
Ionized (45%)
Active part
Un-exchangeable Ca+2 pool
Un-exchangeable Ca+2 pool
Exchangeable Ca+2 pool
Exchangeable Ca+2 pool
Ca+2 intakeCa+2 intake
Ca+2 lossCa+2 loss
• Ca+2 has fundamental importance to all biological systems.
1.Participates in numerous enzymatic reactions.
2.Important for hormone secretion.3.Acts as a mediator of hormonal
effects.
4. Essential for neurotransmission
5. Essential for ms contraction
6. Essential for blood clotting.
7. Essential for formation of bone and teeth.
Source:•Chief cells of parathyroid
gland Chemistry:
•Polypeptide hormone (84 aa)
• The prime function of PTH is to keep a normal
Ca+2 level in plasma (9-11 mg %).
• It also maintains a constant ratio between
Ca+2 and inorganic phosphate PO4-, so that;
• Solubility product = Ca x PO4 = K (constant).
Osteoblast Osteoclas
t
PCT
a) Kidney:a) Kidney:1. Increases reabsorption of Ca+2 and Mg+2 from DCT 2.Inhibits PO4 reabsorption from PCT. 3. Activates Vit. D by 1 α hydroxylase enzyme in PCT
b) Bone:b) Bone:1. Increases number and level of activity of osteoclasts
(bone destroying cells) in the skeleton →bone resorption 2.Increases pump of Ca+2 from bone matrix to ECF by
osteoblast
a) Small intestine :a) Small intestine :1. Increases absorption of Ca+2 (mediated by active
vitamin D (1, 25 DOH cholecalciferol)→ activated in the kidney by PTH.
2. Increases absorption of PO4 and Mg+2.
a) Plasma Ca level:• It the main regulator of PTH secretion.• ↓ Plasma Ca level → ↑ PTH secretionb) Plasma Mg level: as Cac) Plasma PO4 level: opposite to Cad) Nervous factors: β-adrenergic receptors agonists as isoproterenol→↑ PTH secretion
Source:• Parafollicular cells of
thyroid gland Chemistry:
• Polypeptide hormone (32 aa)
Thyrocalcitonin
Functions: ↓Blood Ca+2
↓Blood Ca+2
• Is the physiological antagonist to PTH with respect to Ca+2 i.e. lowers blood Ca+2
• Has the same effect of PTH on PO4 i.e. ↓es PO4 level • Has no effect on plasma Mg level.
a) Bones:1. Inhibits osteolysis by osteocytes and reduces
resorption by osteoclasts.2.Decreases Ca+2 mobilization from bone to blood as it
inhibits Ca+2 permeability of bone cells. b) Kidneys:
1.Increases urinary excretion of Ca+2 and PO4.2. Inhibits Vit. D activation in the kidney.
c) Intestine:1.Decreases Ca+2 absorption from the intestine.
2.Inhibits the gastric motility and gastrin secretion.
i)Plasma Ca+2:•The major stimulus to its secretion is a rise in serum Ca+2
•e.g. its plasma concentration ↑es 2-10 times after acute rise of serum Ca+2 of as little as 1 mg%. ii) GIT hormones:•Several GIT hormones (gastrin is the most potent) stimulate calcitonin secretion during ingestion of food.
Biosynthesis:•Formed in skin
by UVR•Activated at
liver and kidney to form
1,25 DOCC
• The intestine is the principal target of vitamin Da)On intestine:
• Stimulates the absorption of both Ca+2 and PO4-.
b)On bone:• Bone is the 2nd major target of vitamin D.
• Provides Ca+2 and PO4- to initiate the crystallization of bone osteoid at bone surfaces.
c)On kidney:• Increases renal tubular reabsorption of both
Ca+2 and PO4-.
• Sex hormones are involved in the pubertal growth spurt and closure of the epiphyses
a)Estrogens: • Protect female skeleton from the development of
osteoporosis:1.Inhibits PTH mediated bone resorption 2.↓es the amount of bone-resorbing cytokines such as
interleukin 1 and 6 in bone.3.↑es serum PTH due to the hypocalaemic effect of
the inhibition of bone resorption. b)Androgens;• Protect men from the development of osteoporosis
A. At physiological levels, glucocorticoids are necessary for skeletal growth.
B. Chronic excess have deleterious effects on Ca+2 homeostasis)
1. Decrease renal tubular Ca+2 absorption.2. Inhibit intestinal Ca+2 absorption.3. Inhibit osteoblastic bone formation.
1. Stimulate bone growth2. Stimulate Ca+2 and PO4 absorption from
intestine
• Stimulate bone growth and ossification • Hypothyroidism delay bone growth and
hyperthyroidism causes bone resorption
Disturbances of Ca+2 homeostasis
Hypercalcemia As in
hyperparathyroidism and bone
tumours
HypocalcemiaAs in
hypoparathyroidism and lack of vit D
Tetany Rickets, osteomalacia
