Ca lecture med school 2023 - handout.ppt

This presentation is for private study only. It should not be given as a public presentation or otherwise disseminated. To do so may place the presenter in breech of copyright ENDOCRINE CONTROL OF CALCIUM HOMEOSTASIS BSMS Medical students 2023 Dr Trevor Wheatley Consultant Endocrinologist & Honora...

This presentation is for private study only. It should not be given as a public presentation or otherwise disseminated. To do so may place the presenter in breech of copyright ENDOCRINE CONTROL OF CALCIUM HOMEOSTASIS BSMS Medical students 2023 Dr Trevor Wheatley Consultant Endocrinologist & Honorary Clinical Senior Lecturer Princess Royal Hospital University Hospitals Sussex Sussex, UK Why is Calcium Important? • Exocytosis – Neurotransmitter secretion – Hormone secretion • Physical properties of bone • Biochemical processes ( many ) • Blood clotting LEARNING POINT Hypocalcaemia Destabilizes Neurones So - If someone has a first fit Check the serum calcium Hypocalcaemia can cause seizures Physical Signs of Hypocalcaemia 1. CARPOPEDAL SPASM (Trousseau’s sign) A – cuff deflated B – Cuff Inflated 2. Chvostek’s Sign Present in 10% of normals Low plasma calcium increases the permeability of neuronal membranes to sodium Consequences of Hypercalcaemia • Acute – Thirst & Polyuria – Abdominal Pain • Chronic – Constipation – Musculoskeletal aches / weakness – Neurobehavioral symptoms – Renal calculi – Osteoporosis Measuring Serum Calcium • Protein Bound 40% –Albumin bound 90% – Globulin Bound 10% • Bound to Cations 10% – Phosphate & Citrate • Ionised ( free ) 50% Clinical Learning Points • The lab reports total serum Ca++ corrected for the Albumin concentration BUT • The corrected Ca++ may be inaccurate – If the Albumin concentration is < 20 g /l – In severe acute illness In these cases Measure Ionised Ca++ directly Calcium Level in the blood Controlled within a tight normal range ( 2.15 – 2.55 mmoles / l ) ? HOW Chief cells in the Parathyroid glands make Parathyroid hormone PTH Release is determined by Serum Calcium concentration QUESTION? How does the Parathyroid cell know when to make PTH? OR How does it know when the blood Ca++ is abnormal? Calcium Sensing receptor in the Parathyroid Chief Cells Calcium & PTH Secretion Ca++ Behaving like a Hormone! e.g. Less Calcium Molecules Altered Calcium Sensing Receptor formation Modified Chief cell processes Mg++ PTH secretion Low Magnesium prevents PTH release How Does Parathyroid Hormone Work? PTH (Type 1) RECEPTOR Biological effect Where are the PTH1 receptors? ie. Where is the biological effect? • BONE • KIDNEY BONE – Rapid Action of PTH Osteocytic Membrane Pump PTH Rapid Ca++ Release Calcium Release from Bone Stimulation of Osteoclasts PTH OSTEOBLAST Rank Ligand RANK OSTEOCLAST ACTIVATION Osteoclast Breaking Down Bone Ca++ released into bloodstream KIDNEY - ACTIONS OF PTH 1. Rapid Calcium Reabsorption • Calcium Reabsorption in • Loop of Henle • Distal Tubule • Collecting Ducts • PO4 Reabsorption ( proximal Tubule) 2. Renal Synthesis of Active Vitamin D SUN UVLb Diet Skin Vitamin D Cholecalciferol LIVER 25 OH Vitamin D Cod Liver oil Oily fish (wild) Mushrooms Fortified Foods RENAL ACTIONS OF PTH PTH 25 OH Vitamin D 1,25 OH Vitamin D Calcium Transporters & Binding Protein (Calbindin) in Gut cells Calcium absorption from gut The Kidney & Vitamin D 25 OH Vitamin D Osteocyte FGF 23 - 1,25 OH Vitamin D + PTH The Kidney & Phosphate Excretion Osteocyte FGF23 Renal Phosphate Excretion Calcium Metabolism Clinical Problems Primary Hyperparathyroidism DIAGNOSIS • Serum Calcium increased • Serum Phosphate reduced • PTH increased Ask re Family History Complications of Hyperparathyroidism - Osteoporosis - Bone cysts ( if severe) Complications of Hypercalcaemia Renal Stones Indications for Parathyroidectomy • • • • • • Osteoporosis Renal Calculi Hypercalciuria Age < 50 years Serum calcium > 2.8 mmol/l Consumer choice! Locating the Parathyroid adenoma Neck Ultrasound Locating the Parathyroid adenoma Sesta Mibi Parathyroid scan Adenoma 4D CT scan Parathyroid adenoma 18F-fluorocholine PET/CT Hypoparathyroidism • Serum Calcium low • PTH low / normal Causes of Hypoparathyroidism • Iatrogenic – Thyroidectomy – Radical neck surgery • Autoimmune • Hypomagnesaemia • Genetic mutations Secondary Hyperparathyroidism Common causes • Low / low normal serum Calcium + HIGH PTH – Low serum 25 OH vitamin D • Lack of sun exposure • Gastrointestinal problems – Malabsorption – Extensive surgery ( small bowel ) – Renal Failure Reduced Vitamin D concentration Rickets Ricketts Osteomalacia Looser’s Zone Vitamin D levels in the Elderly Elderly skin & Vitamin D production Vitamin D deficiency increases Falls & Fractures 1,25 Vit D Maintains blood Ca++ Concentration Maintains Bone Mineral density