Renal Regulation Of Calcium, Phosphate, and Magnesium PDF

Renal Regulation of Potassium, Calcium, ▪~0.9% total body calcium is intracellular Phosphate, and Magnesium ▪~0.1% is present in the extracellular fluid volume Extracellular fluid: 4.2 mEq/L...

Renal Regulation of Potassium, Calcium, ▪~0.9% total body calcium is intracellular Phosphate, and Magnesium ▪~0.1% is present in the extracellular fluid volume Extracellular fluid: 4.2 mEq/L Chemical Anatomy of Serum Calcium seldom rising or falling more than ±0.3 mEq/L ▪Total serum calcium (8.4-10.2 mg/dl) is composed many cell functions are sensitive to changes in of three distinct “compartments”: extracellular fluid potassium concentration an increase in plasma potassium concentration 1. Ionized (48%) of only 3 to 4 mEq/L can cause cardiac o physiologically active in muscle arrhythmias contraction, blood coagulation and Higher concentrations can lead to cardiac intracellular adhesion arrest or fibrillation 2. Protein bound (46%): o Albumin: hypoalbuminemia may result in falsely low levels (may correct by adding 0.8 for the reduction of albumin by 1 unit below 4 g/dL) 3. Complexed with inorganic compounds (7%) o e.g. citrate or phosphate Calcium flux between body compartments Intestinal Calcium Absorption Two major mechanisms for Ca absorption: Potassium is reabsorbed in the proximal 1. Between cells (paracellular): tubule and in the ascending loop of Henle, so a. Passive only about 8 percent of the filtered load is b. Quantitative significant when delivered to the distal tubule intake is high 2. Through cells (Transcellular): Distribution of calcium in the body a. Active ▪Total body content of calcium is 1,000-1,200 g b. Influenced by calcitriol c. Calbindin: acts as an intracellular ▪99% of the body calcium resides in bone sink to reduce the microvilli [Ca] ▪1% of this is freely exchangeable with the calcium in extracellular fluids 1 vlbr Renal Regulation of Calcium Balance Factors that affect renal regulation of calcium Only the ionized and the complexed calcium may be directly affected by the kidneys Filtered load 10g of calcium a day Normally only 200mg are found in the urine 98-99% are absorbed by the kidneys Where is the calcium absorbed? Renal Handling of Calcium Hormonal Regulation of Calcium Homeostasis Different segments of the nephron are tasked with calcium reabsorption Involves two hormones: o PTH 1. 60-70% proximal convoluted tubule ▪ produced by parathyroid glands 2. 20% cortical segments of the loop of Henle o Calcitriol ▪ produced by the kidneys 3. 10% distal convoluted tubule Actions in three organs: (BIK) 4. 5% collecting duct o Bone o Intestine Segment Specific Mechanisms of Calcium Re- o Kidneys absorption Calcium Sensing Receptor is the key sensor Proximal tubule: (PT) coordinating the various feedback loops in o Passive diffusion (80% paracellular) kidneys and parathyroid glands o Active transport (10-15%) Parathyroid hormone (PTH) Thick ascending loop of Henle: TAHL Major physiological regulation of calcium level o A paracellular mechanism accounts for Secreted by the parathyroid glands in response the transport of calcium in this to hypocalcemia, hyperphosphatemia, and/or segment ↓ calcitriol Collecting Duct: (CD) Changes in serum calcium are the primary o A transcellular mechanism accounts for stimulus the transport of calcium in this o sensed by the Calcium Sensing segment Receptor Expression in parathyroid glands tightly Mechanisms of calcium absorption per segment regulated at the translation and transcription (summary) levels It increases serum calcium by three different mechanisms: 1. Stimulates bone resorption 2. Enhances GI absorption of calcium and phosphorus by stimulating renal production of calcitriol 3. Augments renal calcium reabsorption Vitamin D Nomenclature Vitamin D o cholecalciferol (from UV radiation) and/or ergocalciferol (dietary sources) 2 vlbr  25-Hydroxyvitamin D: Alterations in Calcium Balance Have Clinical o the 25-hydroxylated metabolites of Consequences vitamin D; also known as ercalcidiol or calcidiol; abbreviated as 25(OH)D Calcitriol: o 1,25-dihydroxycholecalciferol; abbreviated as 1,25(OH)2D3 Vitamin D analogs o derivatives of vitamin D2 and vitamin D3 , of which the clinically investigated synthetic derivatives include ▪ Doxercalciferol ▪ Paricalcitol ▪ Alfacalcidol ▪ Falecalcitriol Manifestations of abnormal calcium levels ▪ 22-oxacalcitriol (maxacalcitol) Vitamin D metabolism and action Phosphorus turnover and physiology Phosphorus stores and levels Total body stores ~ 700g (85% in bone, 14% intracellular, 1% extracellular) Extracellular: 70% is organic, 30% inorganic Inorganic: 15% is protein bound, 85% complexed with cations or free (this is measured in chemistry labs) Normal concentration 2.5-4.5 mg/Dl 3 vlbr Phosphorus flux between body compartments Segment Specific Mechanisms of Phosphorus Handling: PT Factors that alter renal regulation of phosphorus Intestinal Phosphorus Absorption Two major mechanisms for Ca absorption: 1. Between cells (paracellular): a. Passive b. Quantitative significant when intake is high 2. Through cells: a. Active b. Influenced by calcitriol c. Calbindin: acts as an intracellular sink to reduce the microvilli [Ca] Regulation of Renal P Excretion Transcellular transport mechanisms Clinical alterations of Phosphorus balance Renal Handling of Phosphorus Different segments of the nephron are tasked with phosphorus reabsorption 1. 85% proximal convoluted tubule 2. 10% loop of Henle 3. 3% distal convoluted tubule 4. 2% collecting duct 4 vlbr  Magnesium Total body stores: 24g 99% intracellular Normal magnesium concentration is 1.7-2.6 mg/dL (or 0.7-1.05 mmol/L) Only 70% of serum magnesium is free (the rest is complexed to albumin) Multiple functions due to its role as an enzymatic cofactor Renal Handling of Magnesium ▪Kidneys filter 2000-4000 mg/d Filterable component is the free serum magnesium (70% of total level) Different segments of the nephron are tasked with magnesium reabsorption 1. 10-20% proximal convoluted tubule 2. 70% loop of Henle 3. 10% distal convoluted tubule Magnesium and the TAHL Responsible for 40-70% of magnesium reabsorption Paracellular mechanism similar to the calcium 5 vlbr