Physiology of Calcium Regulating Hormones: Zheng Flashcards
Recognize the physiological importance of calcium, define the compartmentalization and distribution of calcium, describe calcium exchange between tissue compartments
Hypocalcemia: hyperreflexia, spontaneous twitching, muscle cramps, tingling & numbness.
Hypercalcemia: constipation, polyuria, polydipsia, and neurologic signs of hyporeflexia, lethargy, coma, and death.
99% of Ca2+ is stored in bone. Of the Ca in the plasma compartment, 40% is bound to albumin. The remaining 60% is ultrafilterable. Of that ultrafilterable 60%, 50% is free, ionized Ca that is the only fraction that is biologically active.
PTH regulates [Ca] in serum. Ionized Ca concentration regulates PTH secretion from the parathyroid glands.
Ca v –> PTH ^ –> Ca released from bone, reabsorption in kidney and inhibits PO4 reabsorption which allows for greater plasma [ionized Ca] bc it is not complexed to PO4.
Mg also has a similar effect on PTH release.
PTH also activates 25-hydroxycholecalciferol to 1,25-dihydroxy… via 1a-hydroxylase, to absorb Ca from the small intestine.
1,000mg Ca taken in diet. 400 mg absorbed in small intestine. 300 mg secreted into small intestine. Net 100-150mg absorption.
1 kg Ca in bone. 600mg resorbed daily.
10g Ca filtered by kidneys daily. 9.9 g reabsorbed. 100mg lost in urine daily.
Loss has to = intake or you have imbalance.
Recognize the physiological importance of phosphate, define the compartmentalization and distribution of phosphate, describe phosphate exchange between tissue compartments
85% total PO4 stored in bone. 14% intracellular. 1% extracellular. Of extracellular, 55% is free in plasma (HPO4). 35% cation bound. 10% protein bound.
PO4 is primarily excreted in urine. 1100mg absorbed from small intestine. 200mg secreted into small intestine. 900mg excreted in urine. ~ 1/7 what is filtered by glomerulus.
Phosphate is one of the most abundant minerals in the body, and its serum levels are regulated by a complex set of processes occurring in the intestine, skeleton, and kidneys. The currently known main regulators of phosphate homeostasis include parathyroid hormone (PTH), calcitriol, and a number of peptides collectively known as the “phosphatonins” of which fibroblast growth factor-23 (FGF-23) has been best defined. Maintenance of extracellular and intracellular phosphate levels within a narrow range is important for many biological processes, including energy metabolism, cell signaling, regulation of protein synthesis, skeletal development, and bone integrity. The presence of adequate amounts of phosphate is critical for the process of apoptosis of mature chondrocytes in the growth plate. Without the presence of this mineral in high enough quantities, chondrocytes will not go into apoptosis, and the normal physiological chain of events that includes invasion of blood vessels and the generation of new bone will be blocked, resulting in rickets and delayed growth. In the rest of the skeleton, hypophosphatemia will result in osteomalacia due to an insufficient formation of hydroxyapatite.
Explain free calcium and phosphate in the plasma and the
relationship between them
Ca is complexed to PO4 in the plasma, so when plasma PO4 goes up, free ionized Ca goes down.
For every 10 atoms of Ca in bone, there are 6 molecules of PO4. Whether Ca and PO4 are laid down in bone or resorbed from bone depends on the product of their concentrations rather than their individual concentrations.
When the product exceeds the solubility product, bone is laid down, and vice versa.
Describe the relationship between plasma free calcium and PTH levels, and identify the major mechanism that
regulates PTH secretion.
As PTH levels rise (in plasma), Ca levels rise and phosphate levels fall. The major mechanism regulating PTH secretion is [Ca].
Hypocalcemia= ^ PTH secretion
Hypercalcemia= v PTH secretion
List the main peripheral actions of calcitonin; describe the relationship between plasma free calcium and calcitonin levels, and the regulation of calcitonin secretion
Calcitonin has essentially the opposite effects of PTH. Reduces plasma [Ca] and [PO4] by inhibiting osteoclast activity. Inhibits renal tubule reabsorption of Ca and PO4. NOT A MAJOR REGULATOR OF Ca LEVELS IN ADULTS.
List the different forms of vitamin D, describe the peripheral actions of calcitriol, describe the relationship between plasma free calcium and calcitriol levels, and
identify the major mechanisms that control vitamin D metabolism.
There is active (1,25-dihydroxycholecalciferol) and inactive (25-hydroxycholecalciferol AKA calcitriol) vitamin D. The inactive form is activated by 1a-hydroxylase as stimulated by PTH.
As plasma free [Ca] drops, PTH will stimulate the activation of active Vit. D.
Discuss the renal control (filtration, reabsorption, and excretion) of calcium and phosphate, and relate it to the renal actions of PTH, calcitriol, and fibroblast growth factor 23 (FGF23).
PTH causes more renal reabsorption of Ca and inhibits reabsorption of PO4.
Calcitriol (1,25-dihydroxy…) incr. renal absorption of BOTH Ca and PO4 as well as absorption of BOTH from the small intestine.
FGF23 acts on the kidney to decrease reabsorption of PO4 and decrease production of calcitriol, resulting in hypophosphatemia. FGF23 also reduces PTH secretion in a feedback loop.
States of hyperphosphatemia will result in rises in plamsa FGF23 to reverse the hyperphosphatemia by increasing renal excretion of PO4.
