Ca MG PO Flashcards
MINERAL AND BONE METABOLISM
-mechanical support, protection, mineral reserve/storage for ca mg po4
-consists of bone cells: osteoclasts (resorption to mobilize minerals), osteoblasts (formation and mineralization of organic matrix)/ They are the bone turnover and remodeling
bone remodeling units
-hormonal control of mineral metabolism influenced by Parathyroid (PTH) and Vit D, thyroid hormones, calcitonin, estrogens, androgens, growth hormone, cortisol, insulin
-markers of bone formation/resorption (hormone metabolites, calcitonin, alkaline phosphatase isoenzymes, collagen cross-links, and PTH-related protein produced by certain tumours
-Women prone to osteoporosis, a disease in which bone resorption outstrips formation, and most elderly women will not realize they have it until a fracture occurs
Parathyroid hormone (PTH)
REGULATION OF MINERAL METABOLISM
-triggered by low ionized calcium levels.
-synthesized and secreted by the parathyroid glands
-regulator of blood calcium levels influences both calcium and phosphate balance
-targets bone, kidney, intestine (indirectly)
-release of Ca2+ from bone
-increased Ca2+ reabsorption from renal tubules
-decreased phosphate reabsorption
stimulates production of 1,25(OH)2D
REGULATION OF MINERAL METABOLISM
Vitamin D
-Renal synthesis occurs in response to PTH
-PTH and vitamin D act together to raise blood calcium and increase bone reabsorption (and phosphate levels), but the phosphate that is released from bone is incidental
-targets the intestine, bone
-increased absorption of both Ca2+ and phosphate
-Vitamin D obtained from the diet and exposure to sunlight
-Vitamin D3 is converted to 25-OH-D3 the inactive form of Vitamin D
-In the kidney, 25-OH-D3 is hydroxylated to form the biologically active form, 1,25-[OH]2-D3
REGULATION OF MINERAL METABOLISM
Calcitonin
-produced by the thyroid
-responds to increased free [Ca2+] in blood, in opposition to PTH and Vit D decreases bone resorption
-demonstrated by acute infusion of calcium
-promotes calcium salt disposition in bones
-pt with thyroid carcinoma (lots of calcitonin_ dont have hypocalcemia or hypophosphatemia
-pts with thyroidectomy (expect zero calcitonin) do not become hypercalcemic- no change in mineral metabolism
-no hormone or factor has been described as regulating magnesium homeostasis but it is influenced by PTH and Vit D
CALCIUM BIOCHEMISTRY
-can be found in 3 plasma pools but not equally protein bound , anion bound , free-ionized -pos charged binds to neg charged protein mostly ALB
-mostly found in bone 99% and the other 1% in body fluids - serum and IF (40% non diffusible 80/20 alb/glb). 10% complexed in anions and 50% free and diffusable)
-sequestered in the bone together with phosphate as a salt called hydroxyapatite
-Binding to protein is pH-dependent-Alkalosis (build up of excess base) increases binding, therefore decreases free calcium; acidosis decreases binding, therefore increases free calcium
-Distribution between bound and free is tightly regulated by PTH, vitamin D (hormone), and calcitonin in response to levels of free calcium (active form)
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INTRACELLULAR CALCIUM
very little amount
-muscle contraction by binding trop excitation-contraction coupling
-hormone secretion but if too much then membrane potential Na and K gates are not balances prevent calcium channels from opening causing muscle weakness
-glycogen metabolism cell division
-Calmodulin is a calcium-dependent protein that activates or deactivates enzyme systems by binding calcium, like an on-off switch
-Cam mediates inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response
-Cam can be found in the cytoplasm
-binds to those who cant bind calcium and will use CaM as a calcium sensor and signal transducer
-Cam used the calcium stores in the endoplasmic reticulum, and the sarcoplasmic reticulum
EXTRACELLULAR CALCIUM
-very high
-maintain intracellular calcium
bone mineralization
-stabilizes plasma membranes by influencing permeability and excitability
-regulates neuromuscular excitability
-increased Ca leads to muscle relaxation
may lead to mental depression, muscle weakness, in extreme cases may cause heart to stop
-decreased Ca leads to uncontrolled muscle “tetany” - lead to seizures, convulsive death
-coagulation cascade- prothrombin + Ca = thrombin > fibrinogen >fibrin (forming a meshwork to stop bleeding
- inorganic ion transfer - Ca2+ and cyclic AMP (cAMP) aid in the transfer of inorganic ions across cell membranes
HYPOCALCEMIA
-hypoalbuminemia (most common)
due to liver disease, malnutrition, etc.
-magnesium deficiency depressed PTH secretion
-chronic renal failure causing renal resistance to PTH leading to impaired synthesis of vitamin D
-vitamin D deficiency or resistance
decreased intestinal absorption (eg., steatorrhea) leads to decreased serum calcium
-“rickets” in children, “osteomalacia” in adults
hypoparathyroidism decreased PTH leads to decreased serum calcium
symptoms-neuromuscular, cardiac arrhythmias. cramps and seizures
HYPERCALCEMIA
malignancy
-direct tumor erosion of the bone
-secretion of PTH-rP (PTH related protein produced by tumors)
-can cause carcinomas, breast cancer
hyperparathyroidism
increased PTH leads to increased serum Ca
hypervitaminosis D -(vitamin D intoxication)
increased intestinal absorption leads to increased serum Ca
symptoms
neurological - depression, coma, gastrointestinal-nausea, vomiting, renal -stone formation
PHOSPHATE BIOCHEMISTRY
-85% in skeleton found in NA, phospholipids with serum levels dependent on meals and hormonal regulation
-15% found in cells and blood 80% in cells as phosphate esters and 20% in organic form (phosolipids) and inorganic di/hydrogen phosphate
INTRACELLULAR PHOSPHATE
-high-energy bond (ATP, NADP, NADPH)
- found in nucleotides, nucleic acids, phosphoproteins
-cell membranes
-regulation of metabolism of protein, fat, carbohydrate
-gene transcription
-cell growth
- affects formation of 2,3-DPG (indirect effect on the release of oxygen from hemoglobin)
-acts as buffer of blood
-helps with bone mineralization
HYPOPHOSPHATEMIA
-hyperparathyroidism (increased renal excretion)
-increased PTH leads to decreased P reabsorption causing decreasd serum P
-Fanconi Syndrome (renal phosphate wasting) it is the decrease of tubular reabsorption causing decreased serum P. Can be inherited or acquired through poisoning by tetracycline
-vitamin D deficiency (malabsorption)
decrease intestinal absorption leads to decreased serum P
HYPERPHOSPHATEMIA
-usually related to inability of kidneys to excrete
-renal failure due to increased P retention leading to increased serum P
-hypoparathyroidism caused by decreased PTH causing increased tubular reabsorption leading to increased serum P
-hypervitaminosis D caused by increase of intestinal absorption leading to serum P
-excessive intake
-neonates susceptible due to increased intake of cow milk or laxatives
FACTORS AFFECTING ABSORPTION OF CA & P
PROMOTING
PROMOTING absorption
vitamin D
-a steroid derivative therefore fat soluble (vitamin D is absorbed with dietary fat)
-sources: exposure of skin to sunlight, certain natural and fortified foods
-ascorbic acid (vit C) enhances vit D absorption
diet-fish liver oils, fatty fish, egg yolks, liver
-high protein diet increases Ca & P absorption
-increased dietary intake of Ca & P increases absorption
pregnancy
-physiological changes increases Ca absorption
-pH
acid pH leads to increased solubility of Ca salts causing increased absorption
major problem with absorption of Ca and P is actually a problem of Ca absorption alone as Ca forms insoluble salts with phosphate but phosphate can absorb itself so if Ca absorption is improved then phosphate absorption will follow
FACTORS AFFECTING ABSORPTION OF CA & P
inhibiting
-the elderly may have reduced absorptive ability
-impaired fat absorption means lower amount Vit D = lower Ca absorption
-formation of insoluble salts with phosphates or oxalates
