Homeostasis mechanism, blood

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

In some adults, iron overload can be the result of a genetic defect (idiopathic hemochromatosis) that causes malfunction of the normal homeostasis mechanism and, in turn, excessive absorption of iron. Iron overload can also be caused by too many blood transfusions, which results in too much iron in the various iron-containing organs. 

Pharmacologically mediated adverse effects can be placed into one of three categories (1) primary pharmacodynamic (PD) effects, (2) secondary PD effects, and (3)those either not linked to the primary PD effect or caused by an unknown mechanism. Primary pharmacodynamic adverse effects are those which represent an overexpression of the primary, intended pharmacological effect of the xenobi-otic. An example of an adverse primary PD effect occurs when an overdose of insulin, a critical hormone involved in the homeostasis of blood glucose, is administered. A deficiency of insulin results in diabetes mellitus and is expressed by hyperglycemia. Overdosing of insulin results in hypoglycemia, which can have immediate and severe clinical consequences. 

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

In anemia of critical illness, the mechanism for RBC replenishment and homeostasis is altered by, for example, blood loss or cytokines, which can blunt the erythropoietic response and inhibit RBC production. 

General outlines of the cellular actions of sympathomimetics are presented in Tables 6-3 and 9-3. Sympathomimetics have prominent cardiovascular effects because of widespread distribution of a and 3 adrenoceptors in the heart, blood vessels, and neural and hormonal systems involved in blood pressure regulation. The net effect of a given sympathomimetic in the intact organism depends not only on its relative selectivity for cx or 3 adrenoceptors and its pharmacologic action at those receptors any effect these agents have on blood pressure is counteracted by compensatory baroreflex mechanisms aimed at restoring homeostasis. 

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