Osteoclasts – are polynucleated macrophage like cells that digest bone matrix by secreting protease enzymes. They remodel and repair bone and they are target cells for PTH that promotes bone resorption and calcium mobilization.
Osteoblasts – are young bone forming cells, secreting collagen into the bone matrix. Once surrounded by bone matrix, their activity diminishes and they are considered to be mature, and are called osteocytes. Osteo blasts are usually found near bone surfaces.
Osteocyte – are found in or near the lacunae. They develop extensive processes ( filopodia), that run thru the canulicula, connecting with other osteocytes. These membraneous processes facilitate the exchange of nutrients, especially Ca between bone and blood.
PTH – a polypeptide hormone which is secreted by the chief cells of the parathyroid gland. PTH acts on bone, kidney, and intestine; to increase Ca levels in plasma.
Calcitinin – a large peptide hormone secreted by the parafollicular C cells of the thyroid. It is secreted in response to an increase in the plasma Ca level and it works to decrease Ca in plasma with in minutes. Calcitonin is very necessary in children but not so necessary in adults.
Vitiman D – a steroid hormone (fat soluble) which undergoes changes in 2 places 1st being in the liver to 25 – hydroxycholecalciferol (calcidiol), and 2nd in the kidney from 25… to 1,25 dihydroxycholecalciferol
(calcitriol), and this 2nd reaction is stimulated by and tightly controlled by PTH. Absorption of 1,25 di … occurs in the small intestine. This absorption occurs in response to the 1,25 di… stimulating the formation of 1) Ca binding proteins, 2) of Ca ATP ase, and 3) of alkaline phosphatase; all of which promote absorption of Ca & PO4 ions out of the lumen of the intestine into the plasma. The Ca is divalent and therefore cant cross the cell membrane of intestinal epithelium with out the above 3 mechanisms, which are activated by the 1,25 di… Therefore Ca absorption will occur at a rate determined specifically by the 1,25 di… described above. Problems in synthesis of 25…, or 1,25 di… or inability to make 1 – 3, can cause pathology.
Calcium – a cation, an alkaline earth metal ( reactive) in group 2a ( looses its 2 electrons easily to go to Ar) . oxidation state is +2 , ionic radius is @ 100 pm, atomic radius is 197 pm, 1st ionization level is 6.113 eV, electronegativity is 1.0, BP is 1494 C, MP is 842 C, Density is 1.55g/cc
Phosphorous is an anion with an electronegativity of 2.1( wants to hold onto electrons more than Ca does), and it’s a non metal so it wants to combine with calcium, is part of the bone salts, and is regulated by the kidney and PTH ( and vit D) . Is present in tooth enamel. Exists as PO4.
Fast exchange – PTH activates membrane bound Ca pump in the intestine, which pumps out Ca with out PO4.
Slow exchange - is the actual dissolving of bone via osteoclasts action.
Resorption - is where PTH causes demineralization ( release of bone salts) via osteoclasts which in turn allows tranpsort of Ca from bone into blood stream via the ostercytes. This is slow exchange.
Reabsorption – occurs when ECF Ca is dec. The Ca is reabsorbed into renal circulation from the tubules so that it can be distributed to the blood circulation. Ca absorbed from the collecting duct increases and excretion of Ca decreased. PO4 is reabsorbed from the proximal tubule and PO4 excretion is increased.
Absorption - occurs when ECF Ca is low. PTH level increases à Inc rate of formation 1,25 di… and increase the concentration of 1,25 di… stimulates the formation of Ca binding proteins and other factors in the epithelium of the small intestine which increases the rate of absorption of Ca from the lumen of the gut.
Rickets – is caused by inadequate absorption of Ca from the GI tract due to
Effect on bones PTH à extreme osteoclastic activity à weaker bone à increases physical stress on bone à rapid osteoblastic activity, but osteoid cant become calcified because of insufficient Ca and PO4 ions. Over time the newly formed uncalcified and weak osteoid takes place of older bone that is being resorbed Treat this by giving adequate amounts of Ca & PO4.
Osteomalacia – adult rickets, which is usually caused by steatorrhea ( fatty stool) and vit D is fat soluble so out it goes with the stool. Ca forms insoluble soap and fats in the presence of steatorrhea so both are excreted in the stool. Rarely will adults progress to tetany, but osteomaoicia can cause severe bone disability. VIT D resistant rickets or Renal rickets are caused by 1) failure to convert 25… to 1,25 di… and 2) congential hypophosphatemia which decreases reabsorption of PO4 by renal tubules.
Rickets and osteomalacia have impaired mineralization of bone as opposed to osteoarthritis which has reduction in bone mass rather than select reduction of mineral content.
Osteoporosis – occurs secondary to diminished organic bone matrix ( a reduction in bone mass). Osteoblastic activity is < than normal à depressed bone osteoid deposition, also hyper parathyroidism à inc osteoclastic activity can cause osteoporosis and the following things are seen:
Regulation of Ca level by
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