Endocrine ParaThyroid VP Summer 2023 Ross University PDF

Cellular Biology & Homeostasis ENDOCRINE-PARATHYROID VP Summer 2023 Clara Camargo, DVM 1. Locate the parathyroid glands and briefly describe the macro and microanatomy of them. 2. Understand the physiological relevance of calcium and phosphate to maintain body homeostasis 3. Understand the s...

Cellular Biology & Homeostasis ENDOCRINE-PARATHYROID VP Summer 2023 Clara Camargo, DVM 1. Locate the parathyroid glands and briefly describe the macro and microanatomy of them. 2. Understand the physiological relevance of calcium and phosphate to maintain body homeostasis 3. Understand the synthesis, regulation and transport of PTH. 4. Describe the effects of the parathyroid hormones on target tissues/organs. 5. Understand the role of PTH on calcitriol activation and the importance of it on calcium metabolism. 6. Understand the relationship between PTH and calcitonin and their effects on calcium and phosphate homeostasis. 7. Understand the symptoms of the main pathologies related to the parathyroid hormones (hyperparathyroidism, hypoparathyroidism and secondary nutritional hyperparathyroidism) TEMINOLOGY AND ABREVIATIONS AMP (Adenosine Monophosphate) Osteoblast ATP (Adenosine Triphosphate) Osteoclast Bone canaliculi Osteocyte Calcitonin Osteogenic cell (stem cell) Calcitriol Osteolysis ECF (extra cellular fluid) Parathyroid chief cells GI (gastrointestinal) Parathyroid oxyphil cells G-protein coupled receptor Preprohormone Hypercalcemia Prohormone Hypocalcemia PTH (parathyroid hormone) Hormone iCa (Ionized calcium) PARATHYROID GLANDS - ANATOMY ENDOCRINE SYST EM PARATHYROID GLAND - ANATOMY Most species have 2 pairs  Pigs and rats have only one pair Location varies between species  Usually at the poles of the 2 lobes of the thyroid glands ENDOCRINE SYST EM CHEMICAL STRUCTURE OF HORMONES (Recall) E N D O C RI NE S Y S Y E M 1. PROTEIN OR PEPTIDE HORMONES • Makes up the majority of hormones o Ex: Insulin, ACTH, PTH, CCK o LH, FSH and TSH (glycoproteins) • Are synthesized as a larger molecule (PRE-PROHORMONE->PROHORMONE) inside of the ER and Golgi apparatus o Packaged into secretory granules awaiting for secretion https://www.creative-diagnostics.com/Cytokines-Hormones.htm PARATHYROID GLAND There are 2 types of parathyroid cells in the glandular tissue 1. CHIEF CELLS  Produce PTH or Parathormone or Parathyroid hormone 2. OXYPHIL CELLS  Unknown function, larger than chief cells, present oxydative and hydrolitic enzyme activity ENDOCRINE SYST EM PTH SYNTHESIS Parathyroid cells are very sensitive to a decline in blood iCa [Ca2+]  Calcium-sensing receptors on gland membrane surface  G-Protein coupled receptors (cAMP-PKA-gene transcription) PTH synthesis is similar to other protein  Decrease in blood [iCa] (hypocalcemia) stimulates PTH release  Normal or increased [iCa] in blood (hypercalcemia) – inhibition of PTH release hormones o Prepro-PTH is synthesized in rER and then cleaved to pro-PTH o The “pro” portion is removed (in the Golgi) and the resulting PTH is secreted by exocytosis  Metabolized by liver and the kidneys  Half-life of 5-10 min PARATHYROID GLAND – Calcium and Phosphate ENDOCRINE SYST EM Main gland involved in the Calcium (Ca2+) & Phosphate (PO4) metabolism o These ions play a major role in physiological homeostasis PHOSPHATE PO4 CALCIUM • Buffer system • Muscle contraction • Composition of cell membrane and • Nerve cell activity • Release of hormones by exocytosis • Activation of several enzymes • Blood coagulation • Maintenance of membrane stability • Structural integrity of bones and teeth • 99% in bones; <1% Intracellular; 0.1% ECF intracellular components • Nucleic acid • Adenosine Triphosphate (ATP) • Adenosine Monophosphate (AMP) • 85% in bones; 14% Intracellular; 1% ECF POOL OF CALCIUM  99% in bones  (in the form of hydroxyapatite crystals, which contain calcium, phosphate, and water)  <1% Intracellular  Bound to proteins, within ER or mitochondria  Increased intracellular calcium concentrations are indicative of increased cell activity ENDOCRINE SYST EM  0.1% ECF (insterstitial fluid and blood)  50% is ionized (iCa)  Biologicallyactive form  Precisely regulated  40% bound to proteins  Mainly albumin  10% is combined with other anions The most important pool for physiological control of calcium concentrations in the blood CALCIUM - PHOSPHATE METABOLISM The regulation of calcium levels involves control of the movement of calcium between the ECF and 3 organs: o Bones o Kidneys o GI tract  3 hormones are involved in this process o PTH (parathyroid hormone) o Active VIT D (Calcitriol – steroidlike molecule) o Calcitonin (thyroid hormone) ENDOCRINE SYST EM PTH ACTIONS ENDOCRINE SYST EM The net effect of PTH is to increase calcium and decrease phosphate concentrations in ECFs o Direct effect on bone and kidney metabolism of calcium o Indirect effect on GI metabolism of calcium • Via calcitriol BONES ENDOCRINE SYST EM Types of bone cells OpenStax College Cross-section of bone Osteoblasts - responsible for the formation of new bone tissue (bone developing and remodeling) Osteocytes - biomineralization (local mineral deposition at the bone matrix), differentiated from osteoblasts (mesenchymal stem cells) Osteoclasts - degrade bone tissue (remodeling or pathological processes). Differentiated from monocytes (hematopoietic stem cell) PTH ACTIONS - DIRECT EFFECTS ON BONE ENDOCRINE SYST EM 1. Promotes the transfer of Ca2+ across the osteoblast-osteocyte membrane  Osteocytes pump Ca2+ from the fluids within bone canaliculi → into the extracellular fluid → blood PTH ACTIONS - DIRECT EFFECTS ON BONE ENDOCRINE SYST EM 2. Binds to receptors on bone osteoblast cells and stimulates the production of osteoclast-activating factor  Causes activation of nearby osteoclasts  Moves toward the bone and begin to digest the organic matrix – bone resorption  Releases Ca2+ and PO4 into the blood OpenStax College PTH ACTIONS - DIRECT EFFECTS ON KIDNEYS 1. Acts on the distal convoluted tubules increasing absorption of calcium 2. Acts on the proximal convoluted tubules decreasing renal reabsorption of phosphate 3. Acts on VIT D activation by the kidneys  Vit D must be transformed by liver and kidneys to become biologically activated  PTH stimulates the kidney enzyme 1-alfa-hydroxilase which converts calcidiol 25(OH)D → calcitriol 1,25(OH)₂D  Calcitriol increases absorption of calcium by the GI tract  Also enhances effects of PTH on bone metabolism of calcium ENDOCRINE SYST EM VITAMIN D METABOLISM ENDOCRINE SYST EM UV PTH Because of its lipid nature, calcitriol is carried in plasma by transcalciferin (produced in the liver) 1-alfa-hydroxilase VIT D BECOMES AN ACTIVE HORMONE UNDER PTH ACTION ON RENAL CELLS PTH ACTIONS - INDIRECT EFFECT ON GI Calcitriol stimulates the active transport of dietary calcium across the intestinal epithelium  Without calcitriol most animals are unable to acquire enough calcium from the diet to support normal bone structure  By regulating [calcitriol] the animal can regulate Ca2+ entering the blood from diet  EXCEPT Hindgut fermenters (i.e., horse and rabbits) • Intestinal mechanisms to absorb calcium all the time • Regulate blood Ca2+ by increasing/decreasing urinary loss •Chalky white-colored urine ENDOCRINE SYST EM PTH REGULATION PTH secretion is mainly controlled by:  Free (ionized) calcium concentration in the blood  Decrease in iCa stimulates PTH secretion and vice-versa ENDOCRINE SYST EM CALCITONIN ENDOCRINE SYST EM • Calcitonin is produced by parafollicullar cells or C-cells in the THYROID gland o They are scattered throughout the body of the thyroid gland (among the follicles) • Synthesized as other protein hormones (Preprohormones – prohormones – hormones) • Increase in blood [iCa] stimulates calcitonin release • It counterbalances the effects of PTH C-cells THYROID GLAND CALCITONIN ACTIONS ENDOCRINE SYST EM Decreases the movement of calcium from the bone  from bone calcium pool (behind the osteoblast-osteocyte barrier) to the ECF  bone reabsorption through an inhibitory effect on osteoclasts Increases  movement of phosphate from ECF into bone  renal excretion of calcium and phosphate CALCITONIN REGULATION  Calcitonin secretion is regulated by calcium concentration in the blood Increased [Ca2+] stimulates calcitonin secretion ENDOCRINE SYST EM  GI hormones also stimulate the secretion of calcitonin EX: Gastrin, secretin, CCK Parathyroid gland PTH AN INCREASE IN CALCIUM + Calcitriol INCREASE ABSORPTION INCREASE ABSORPTION KIDNEYS GI TRACT A DECREASE IN CALCIUM + CALCITONIN Thyroid gland INCREASE EXCRETION INCREASE EXCRETION INCREASE MOBILIZATION BONES INCREASE STORAGE ENDOCRINE SYST EM • HYPERPARATHYROIDISM ENDOCRINE SYST EM Primary Hyperparathyroidism: is autonomous, excessive synthesis and secretion of parathyroid hormone (PTH) by abnormal chief cells of the parathyroid gland (parathyroid adenoma)  lead to persistent hypercalcemia Symptoms related to hypercalcemia, affect mainly kidneys, GI and neuromuscular system  Polydipsia and Polyuria - decreases ability of the kidneys to respond to antidiuretic hormone (ADH)  Calciuria that can lead to urolithiasis and secondary urinary tract infection (UTI)  Depresses the excitability of the central and peripheral nervous systems; decreases GI smooth muscle excitability; and decreases cell membrane permeability of muscles  Cardiac arrhythmias (bradycardia) can be caused by hypercalcemia Diagnosis:  Urinalysis (crystalluria)  Serum biochemistry (both total and ionized calcium levels are elevated) ENDOCRINE SYST EM HYPOPARATHYROIDISM Hypoparathyroidism is absolute or relative deficiency Symptoms mild to severe, related to calcium of parathyroid hormone (PTH). deficiency  fever, pain,  muscle weakness, autoimmune destruction of parathyroid and other  cramps, seizures, causes (trauma, agenesis, surgical destruction…)  neuromuscular and neurologic signs,  cardiac manifestations,  skeletal deformities and bone effects  Can be idiopathic (most common), caused by  Inappropriately low levels of PTH classically result in hypocalcemia, hyperphosphatemia, and decreased calcitriol Diagnosis: serum biochemistry  low total and ionized calcium  Undetectable intact PTH concentrations  Hyperphosphatemia is also common Secondary Hyperparathyroidism in horses FYI ENDOCRINE SYST EM Kentucky Equine Reseach Prevent Nutritional Secondary Hyperparathyroidism in Horses The condition occurs due to  a dietary calcium deficiency Nutritional secondary hyperparathyroidism  excess levels of phosphorus (NSH), also known big-head disease, is  an inverted calcium-to-phosphorus ratio in the caused by excessive mobilization of calcium from the skeleton under the influence of parathyroid hormone total diet  high levels of oxalates in forages which interfere with digestion and absorption of calcium PARATHYROID PATHOLOGIES FYI ENDOCRINE SYST EM Nutritional metabolic bone disease in reptiles and amphibians (NMBD)  Nutritional secondary hyperparathyroidism (NSHP) Unappropriated diet can cause: Excessive production of parathyroid hormone (PTH) from the parathyroid gland in response to hypocalcemia. Calcium is then resorbed from the bone, resulting in a weakening of the bones. PARATHYROID PATHOLOGIES FYI ENDOCRINE SYST EM Nutritional secondary hyperparathyroidism occurs as a result of dietary or husbandry mismanagement. The most implicated factors are:  prolonged deficiency of dietary calcium or vitamin D3  imbalance of the calcium-phosphorus ratio in the diet (usually an excess of phosphorus)  inadequate exposure to ultraviolet (UVB) radiation in diurnal animals From: Reptile and parrots forum https://ourreptileforum.com/community/threads/metabolicbone-disease-nutritional-secondaryhyperparathyroidism.5386/ Parathyroid Glands and Hyperparathyroidism https://www.youtube.com/watch?v=sD9st1ZPFrQ Clara Camargo, DVM [email protected] Best Wishes Be Well, Be Kind & Be Awesome ©2021 Ross University School of Veterinary Medicine. All rights reserved.