Parathyroid.docx

Parathyroid anatomy most species have 2 pairs rats and pigs have 1 pair located on poles of thyroid gland lobes chief cells: secrete PTH (parathyroid hormone) oxphil cells: larger than chief cells, unknown function, oxidative, and hydrolytic enzymatic activity Hormone chemical structure and synthesi...

Parathyroid anatomy most species have 2 pairs rats and pigs have 1 pair located on poles of thyroid gland lobes chief cells: secrete PTH (parathyroid hormone) oxphil cells: larger than chief cells, unknown function, oxidative, and hydrolytic enzymatic activity Hormone chemical structure and synthesis most are proteins or peptides rER synthesizes pre-prohormones (inactive version) golgi cleaves prohormone and then into hormones they are then packaged into secretory vesicles and await secretion PTH synthesis Step 1: calcium sensing receptors (GPCR) on the gland's membrane surface sense decline in blood ionized calcium (iCa) level Step 2: low levels of iCa trigger release of PTH (high levels inhibit PTH release Step 3: rER synthesizes pre-proPTH and converts it into proPT Step 4: golgi cleaves proPTH into PTH and it's secreted via exocytosis metabolized by liver and kidney half-life 5-10mins Phosphate (general info) parathyroid gland is major gland involved in it's metabolism ATP/AMP within cell membrane and intracellular compartments nucleic acid buffer system 85% bones (mineralized here), 14% intracellular, 1% ECF Calcium (general info) parathyroid gland is major gland involved in it's metabolism muscle contraction nerve cell activity blood coagulation enzyme activation membrane stability structural with teeth and bones hormone release with exocytosis 99% bone, <1% intracellular, 0.1% ECF Calcium: Phosphate Ratio (within blood plasma) phosphate binds to calcium, thus reducing available ionized calcium more phosphate= more calcium= less ionized calcium less phosphate= less calcium= more ionized calcium (think: more ionized calcium= less available calcium for phosphate to bind to) when calcium and phosphate are not balanced, the body will start taking calcium from other parts of the body (like the bones) to help maintain homeostasis Pool of Calcium: Bones 99% stored as hydroxyapatite crystals (containing water, phosphate, calcium) Pool of Calcium: Intracellular <1% bound to proteins in ER and Mitochondria higher intracellular calcium levels= more cell activity Pool of Calcium: ECF (blood and interstitial fluid) 0.1% of the pool of calcium is within the ECF Within this is: 50%: ionized calcium (regulated & most important blood calcium) 40%: bound to proteins (albumin) 10%: bound to other anions Calcium-Phosphate Metabolism calcium regulation involved ionized calcium movement between ECF and bones, GI tract (increase calcium resorption), or, kidneys (resor and release ions) hormones involved in maintaining homeostasis: calcitonin, PTH, calcitriol (active vitamin D) PTH Actions increase calcium and decrease phosphate in ECF direct impact on bone and kidney calcium metabolism indirect impact on GI tract metabolism (absorption) of calcium via calcitriol PTH with Bones (direct) Step 1: PTH binds to osteoblast receptor, stimulating production of osteoclast-activating factors Step 2: Causing activation of (nearby) osteoclast to digest organic matrix of the bone (AKA: bone resorption) Step 3: Results in release of iCa and phosphate into the blood PTH promotes movement of iCa across osteocyte-osteoblast membrane where the osteocyte pumps iCa from fluid within canaliculi bone fluid into ECF and into blood. Vitamin D Metabolism Step 1: Starts with Vitamin D3 (made within the skin using UV or can be obtained from eggs or oily fish) or with Vitamin D2 (only obtained via diet) Step 2: Either one enters the liver and is converted into calcidiol Step 3: Calcidiol enters the kidneys and is converted into calcitriol (active Vitamin D version) due to PTH action on the renal cells PTH with Kidneys (direct) PTH acts on distal convoluted tubules to increase calcium reabsorption PTH acts on proximal convoluted tubule and decreases renal phosphate reabsorption PTH acts on kidney's activation of vitamin D by stimulating the kidney enzyme (1-alfa-hydroxilase) to convert calcidiol to calcitriol (active vitamin D) Calcitriol: General Info active version of vitamin D it is lipophilic and requires transport proteins increases calcium absorption within the GI tract enhances PTH with bone metabolism of calcium Bones: General Info osteocyte: biomineralization (move calcium in and out of tissue) and maintain bone tissue osteoblast: create bone tissue/matrix osteoclast: destroy bone tissue (reabsorb bones) osteogenic cell: stem cells osteoclast differentiate from monocytes (hemopoietic stem cells) osteocyte differentiate from osteoblast (mesenchymal stem cells) Calcitonin: General Info Produced by parafollicular cells (AKA: C-Cells) in the thyroid gland as protein hormones Increased ionized calcium levels within the blood, stimulates calcitonin release It counter balances PTH by having the goal of decreasing ionized calcium levels within blood. Here are examples: Decreasing calcium movement from bones to the ECF which results in an inhibitory effect on osteoclast reabsorption. Increasing phosphate movement into bones from ECF, thus increasing (calcium) storage. Increasing renal excretion of calcium and phosphate via urine GI hormones (gastrin, secretin, CCK) stimulate calcitonin release when too much calcium is being absorbed within the intestines PTH with GI Tract (indirect) Calcitriol stimulates active transport of dietary calcium across intestinal epithelium and regulates ionized calcium levels entering the blood from diet. Without calcitriol, animals won’t have enough calcium to support bone structure. Exception: hind gut fermenters (horses and rabbits). They regulate blood calcium by increasing or decreasing urine loss, resulting in chalky white urine. They are also able to constantly absorb calcium within their intestines. Primary Hyperparathyroidism: General Information This is the excessive secretion of PTH by abnormal chief cells within the parathyroid gland (parathyroid adenomas) Causes persistent hypercalcemia and negative feedback control is lost Hypercalcemia impacts kidneys, neuromuscular system, and GI tract Symptoms: Polydipsia and polyuria because the kidneys no longer respond to ADH (anti-diuretic hormone) Calcinuria leads to secondary UTI and urolithiasis (bladder stones or bladder crystals) Decreased excitability of PNS/CNS, causing decreased excitability of GI smooth muscles, and resulting in decreased cell membrane permeability of muscles Cardiac arrhythmias (bradycardia) Diagnosed with urinalysis (crystalluria) or blood serum chemistry that would show elevated total and ionized calcium levels Secondary hyperparathyroidism (within horses) Referred to as: Nutritional secondary hyperparathyroidism (NSH) or “Big Head Disease” This disease is the result of hyper mobilization of calcium from the skeleton under the influence of PTH. This happens because the lack of calcium within the diet causes PTH to start taking it from the bones. Can also be due to increased levels of phosphorus, inverted calcium-phosphate ratio, or increased oxalate levels in forages Oxalates prevent the digestion and absorption of calcium Nutritional Metabolic Bone Disease (NMBD) within reptiles and amphibians AKA: Nutritional secondary hyperparathyroidism (NSHP) Predisposing factors: Low dietary calcium and vitamin D3 intake Inverted calcium-phosphate ratio Lack UV-B light exposure Inappropriate temperature gradient Inappropriate diets cause excessive PTH production in response to hypocalcemia. This causes calcium to be reabsorbed form the bones and results in weakened bones Hypoparathyroidism This is when there is a deficiency of PTH It’s cause can be idiopathic (the most common cause), where the parathyroid gland is destroyed. It can also be caused by surgical destruction of the parathyroid gland or trauma, or agenesis Low PTH levels cause decreased calcitriol production, hypocalcemia, and hyperphosphatemia Symptoms (mild to severe) include: fever, pain, muscle weakness, cramps, seizures, neuromuscular and neurological signs, cardiac manifestations, skeletal deformities, and other bone effects Diagnosed with serum biochemistry which will show hyperphosphatemia, decreased total and ionized calcium levels, and undetectable PTH