Biological Function of Inorganic Elements Lectures 1-4 PDF

Biological function of inorganic elements Dr. Sherin Bakhashab Dr. Bahiya Osrah  Composition of Body Fluids  Water is the main component of all body fluids making up 45- 75% of the total body weight.  A-Function of water:  1-Water is a solvent for many ionic compounds and neutral mol...

Biological function of inorganic elements Dr. Sherin Bakhashab Dr. Bahiya Osrah  Composition of Body Fluids  Water is the main component of all body fluids making up 45- 75% of the total body weight.  A-Function of water:  1-Water is a solvent for many ionic compounds and neutral molecules  2-Regulation of body temperature by evaporating the moisture in the lungs and from the skin  3- Water is important to maintain the structure and functions of macromolecule ex; protein  4-Water is the main constituent of the body fluids  Body Fluids Components B- Total body water: Total body water is distributed between two main compartments: 1--Intracellular fluid (ICF) compartment: fluid found within (inside) the cells comprises 60% of all body fluids. 2--Extracellular fluid (ECF) compartment: all fluids found outside the cells, comprises 40% of all body fluids. It is distributed between plasma and interstitial fluid. https://courses.lumenlearning.com/ap2/chapter/body-fluids-and-fluid-compartments-no-content/ Extracellular fluid can be subdivided into : a-Plasma b-Interstitial c.-lymph fluid d-Transcellular fluids: These are fluids present inside organs such as liver, salivary gland , mucous membranes of the respiratory and gastrointestinal tract, cerebrospinal fluid (CSF) and other body fluids.  Composition of Body Fluids  Solutes are broadly classified into: 1. Electrolytes are inorganic salts, all acids and bases, and some proteins 2. Nonelectrolytes – examples include glucose, lipids, creatinine, and urea  Electrolytes have greater osmotic power than nonelectrolytes  Water moves according to osmotic gradients Hypotonic solutions have less solutes and more solvent while hypertonic solutions have more solutes and less solvent. Electrolyte Composition of Body Fluids Na Cl K  Extracellular Fluids 1. ECFs are similar except for the high protein content of plasma 2. Sodium (Na+) is the major cation 3. Chloride (Cl-)is the major anion  Intracellular Fluids 1. Have low sodium and chloride 2. Potassium (K+) is the chief cation 3. Phosphate (PO4-) is the chief anion Extracellular and Intracellular Fluids Sodium and potassium concentrations in extra- and intracellular fluids are nearly opposites Sodium, Potassium and Chloride Sodium is the principle cation in the ECF. Potassium is the principle cation in ICF. Chloride is the main anion in the ECF. Sources and requirements: 1. Na and Cl are obtained from NaCl of food (cheese, bread, whole grain). 2. K is found in large quantities in beef, chicken, some fruits and potatoes. 3. The daily intake of NaCl is about 2.5 g (2300mg) according to the FDA American dietary guidelines recommended for adults and 98% is eliminated by the faeces.  Sodium, Potassium and Chloride  Distribution: The total amount of Na in the body is about 4000 mmoles. 50% are present in ECF (2000 mmoles) 3% are present in ICF (140 mmoles) 47% are present in bone (1900 mmoles) The total amount of K in the body is about 4300 mmoles. 98% are present in ICF (4200 mmoles) 1% is present in ECF (50 mmoles) 1% is present in bones (50 mmoles)  Blood levels  Most Na and Cl are present in the blood plasma, while most of the K is present in the red blood cells. Plasma Red cell level level (mmole/L) (mmole/L) Sodium 6 ± 140 37 Chloride 6 ± 100 53 Potassium 0.9 ± 4.4 110 www.bloodcednter.stanford.edu  Functions H/K ATPase Production of gastric HCl by the parietal cells: The process of acid secretion begins with the hydrolysis of water to form one H+ and OH- in the cytoplasm of parietal cells. Secretion of H+ into the lumen is an active process driven by H+ /K+ ATPase. The pump exchanges H+ for K+. Then Cl- ions diffuse through open chloride channel. * CA = Carbonic anhydrase  Amy C. Engevik,et al. 2020 The Physiology of the Gastric Parietal Cell  Functions Maintenance of normal acid-base balance (Chloride shift)  During normal metabolic activity, acids are continually being formed, which should be neutralized and excreted through lungs and kidneys to maintain the acid-base equilibrium. Plasma Functions  Functions  The red cell membrane is permeable to HCO3- but impermeable to K+.  HCO3- diffuse outside the RBCs in exchange for chloride ions (Cl-) which shifts into the cell in order to maintain electrical ions neutrality across the erythrocyte membrane.  Cl- ions are neutrilized by K+ while sodium bicarbonate is formed in the plasma.  This process occurs when CO2 tensions is increased and this explains the higher chloride content in venous RBCs than arterial RBCs.  In arteries, where CO2 tension is reduced, the reverse occurs, i.e., the Cl- leaves the cells and enters the plasma.  Active transport system for Na+ and K+ Na-K pump  Pumping Na+ ions out and K+ in against strong concentration gradients called Na+ - K+ pump.  It requires ATP as source of energy  Active transport in cells controls the concentration gradient, muscle contraction, nerve impulse, and drives the active transport of sugars and amino acids.  ATP drives the transfer of Na+ and K+ across the membrane by the following mechanism:  Important features of the pump  For each ATP hydrolysed, 3 Na+ are removed from the cell and 2K+ enters the cell.  Na+ triggers phosphorylation, whereas K+ triggers dephosphorylation. Transport of sugars and amino acid by Na+ flow  Transport of sugar (glucose) into the cell is coupled by simultaneous entry of Na+. Na-K pump  Transport of sugars and amino acid by Na+ flow  Na+ and glucose bind to a specific transport protein and enter together by symport carriers.  Na+ enters the cell are pumped out by Na+ - K+ pump.  The rate of glucose transport depends on the Na+ concentration gradient across the membrane.  Symports driven by Na+ are widely used by the animal cells to transport amino acids.  This symport system is present in the plasma membrane of intestinal and kidney cells.  Most symports and antiports are driven by Na+ gradients generated by Na+ - K+ pump.  Symport is the type of transport in which two compounds can move simultaneously across a cell membrane in the same direction  While in opposite direction called antiport  Na+ and Cl- absorption Na+ and Cl- are present in the luminal content of small intestine. Na+ moves into brush border of the intestinal cell by a carrier (glucose) mediated mechanism. Na+ is then released by Na+ - K+-ATPase present in the lateral and basal cell membrane. Cl- follow Na+ into the cell to maintain the ionic equilibrium. Small Intestine anatomy  https://www.youtube.com/watch?v=kM3zVCm8jT8  The most important function of the small intestine is absorption of nutrients from food that passes through the tract.  The villi in the intestinal tract are small finger like projections and protrusions of epithelial cells which increase the surface area significantly.  This large surface area allows for efficient uptake of nutrients. This efficiency is increased even more because each cell in the villi have microvilli on their surface.  K absorption Most of K is absorbed in small intestine (77%). K+ absorption in small intestinal epithelium is passive process, as it passes between the cells and tight junctions. Absorption is driven according to electrochemical gradient, i.e, following ingestion of K+ the concentration in lumen will be greater than that in ECF.  Na, K and Cl excretion  Na and Cl are eliminated mainly in the urine and to a lesser extent in the perspiration (sweating).  K is normally eliminated in the urine.  Reabsorption of electrolytes, mainly Na, by the distal tubular cells (kidney) is under the control of adrenal cortical hormones aldosterone and deoxycorticosterone. Let’s talk a little bit about Kidney Anatomy https://www.youtube.com/watch?v=fkkc_HVAVlo Types of Nephrons Aldosterone Do you remember ?? Action of Aldosterone on Na transport  When the concentration of electrolytes and osmotic pressure of plasma fall below certain level, the adrenal cortex secretes hormones which increase the reabsorption of Na salts, therefore restoring electrolytes to plasma and increasing osmotic pressure. Aldosterone Adrenal The Na Reabsorption gland outcome: Na  When plasma electrolytes and osmotic pressure rise aboveincreased normal, the adrenal cortex secretes less hormones, permitting the excretion of more Na salts and lowering osmotic pressure. Adrenal Na Reabsorption The outcome: gland Na decreased Na Excretion  Disorders of Sodium metabolism  A) Sodium deficiency (hyponatremia)  Low Na concentration in blood < 136 mmol/L. 1. External Na loss: such as due to vomiting, diarrhoea, sweating, skin diseases. In such cases, dehydration accompanied with electrolytes loss, therefore the patient should receive sufficient amount of water and salts. 2. Primary renal Na loss:  Diuretic phase of acute renal failure (eg. Post-renal transplantation): normally this stage is short-lived (lasting few days) but it may occasionally be prolonged.  Chronic renal failure with salt restriction Disorders of Sodium metabolism 3. Secondary Na renal loss are essentially induced by hormone or diuretic as in: i.Addison’s disease due to decreased aldosterone.  Secondary Na renal loss are essentially induced by hormone or diuretic as in: ii. Congenital adrenal hyperplasia (CAH) due to impaired mineralocorticoid (corticosteroid produced by adrenal cortex and involved in maintaining the salt/water balance) synthesis (deficiency of some enzymes) CAH: is genetic disorder caused by mutations in genes that code for enzymes involved in making the steroid hormones in the adrenal glands such as 21-hydroxylase. iii. Diuretic abuse--> drugs used to help kidney in producing more urine and excrete salts  Symptoms and treatment Symptoms are nonspecific and can include: Mental changes Headache Nausea and vomiting Tiredness Muscle spasms and seizures  Severe hyponatremia can lead to coma and can be fatal. Treatment of hyponatremia involves intravenous fluid and electrolyte replacement  Disorders of Sodium metabolism  B) Sodium excess (hypernatremia) High Na concentration in blood > 145 mmol/L. 1.With oedema:  Pregnancy: sodium retention  Disorders of Sodium metabolism 1. Without oedema:  Acute Na loading: rare, caused by inappropriate Na administration to highly dependant individuals.  Renal Na retention due to:  Excess mineralocorticoids (aldosterone)  Primary hyperaldosteronism (eg. Adenoma: is a benign tumour (non-cancer) of epithelial tissue with glandular origin). Tumour lead the adrenal gland to produce too much hormone of aldosterone.  Secondary hyperaldosteronism eg. Renin-secreting tumour. Secretion of excessive renin (secreted by kidney to regulate blood pressure) lead to hyperaldosteronism. me secreted and stored in kidney to promote angiotensin production Increase Na reabsorption Decrease K (increase excretion) https://www.britannica.com/science/renin-angiotensin-system  How about K ?  Disorders of Potassium Balance  Hypokalemia refers to a decrease in plasma potassium level below 3.5 mmol/L.  Causes of hypokalemia: Pseudohypokalemia -Extreme leukocytosis (increase in leukocytes (WBC) above normal range), infection or leukemia Decreased K intake Increased K losses -Non-renal: Skin: by diaphoresis (excessive sweating, can be a symptom of various conditions, infection, certain cancers, side effect of some medication) Gastrointestinal: diarrhea and vomiting -Renal Decrease blood flow Clinical manifestations-associated symptoms Cardiovascular: -Hypertension (K reduce blood vessel tension, lower blood pressure) -Arrhythmias (irregular pattern ECG of heart beats) Neuromuscular: 1.Smooth muscle: 2.Skeletal muscle: -Weakness -Paralysis Endocrine system: -Glucose intolerance (↓insulin release and sensitivity) Hypokalemia is associated with impaired insulin secretion and decreased glucose uptake, hyperglacemia, lost the ability of beta cells to sense the changes in plasma glucose level. (H.W hint) Renal: - Decrease blood flow  Hyperkalemia Hyperkalemia refers to an increase in plasma levels of potassium in excess of 5.0 mmol/L. Causes of hyperkalemia: 1. Excessive intake: rare as sole cause 2. Impaired renal K+ excretion -Endogenous or exogenous K+ -Drugs that impair K+ excretion  Clinical manifestations Cardiovascular abnormalities– untreated hyperkalemia lead to fatal cardiac arrhythmias, heart attack Neuromuscular -Weakness -Paralysis Renal/electrolyte -Decreased ammonia production in the proximal tubule leading to decrease ammonia excretion and cause metabolism acidosis -Metabolic acidosis: is a condition that occurs when the body produces excessive quantities of acid or when the kidneys are not removing enough acid from the body. In hyperkalemia, acidosis can develop by the transcellular shift of K+ when intracellular K+ is exchanged for extracellular H+.  References  http://www.austincc.edu/apreview/EmphasisItems/Electrolytefluid balance.html#bodyfluids  Bioinorganic chemistry: A short course, by Rosette M. Roat- Malone.  Lecture 4 Macrominerals Calcium Dr. Sherin Bakhashab  Calcium  Sources: 1. Milk and milk products (the richest sources) 2. Beans, leafy vegetables and egg yolk Requirements: 3. Adult men and women: 800 mg/ day 4. Children, pregnant and lactating women: 800 – 1200 mg/day  Absorption 1. Calcium is absorbed by an active transport mechanism in the small intestine. 2. Absorption requires calcium binding protein present in the intestinal mucosal cells  Regulation of Calcium Absorption Plasma calcium levels are tightly regulated in the body and altered levels are a stimulus for changing calcium handling in kidney and bone. 1. Vitamin D (1, 25 dihydroxycholecalciferol = calcitriol): through the formation of calcium binding protein and increase calcium absorption in the small intestine 2. Parathyroid hormone: through the conversion of vitamin D to 1, 25 dihydroxycholecalciferol in the kidney. Regulation of Calcium Absorption https://med.virginia.edu/ginutrition/wp-content/uploads/sites/199/2015/11/ JavorskyArticle-March-06.pdf  Factors affecting calcium absorption A. Factors promoting calcium absorption 1. High protein diet: amino acids form with calcium a soluble calcium salts that can be easily absorbed 2. pH: an acidic pH in the upper small intestine is essential for calcium absorption 3. High dietary lactate (soy food, sauerkraut, yogurt) or citrate (lemon) that form soluble salts with calcium. B. Factors inhibiting calcium absorption 1. High dietary phosphate (Nuts, whole grains, seafood), oxalate (black beans, quinoa, kiwi, spinach) which form insoluble salts with calcium. 2. Alkalinity: excess intake of alkalies as in the treatment of peptic ulcer (stomach and first part of the small intestine ulcer caused by digestive action of stomach acid) decreases calcium absorption. Medication that reduce and neutralize stomach acid. Peptic ulcer cause by infection with H.pylori bacterium and prolong use of NSAID medication (eg. Ibuprofen) 3. Impaired fat absorption NSAID: Non-steroidal anti-inflammatory drug  Body Calcium 1. Calcium is the most abundant mineral in the body ( about 1200 g). 2. Most of calcium present in the skeleton (bones and teeth) 99%. 3. Calcium salts in bones are not inert. They are in a constant state of turnover in skeleton being deposited in sites of bone formation and released at sites of bone resorption. In adult male about 700 mg calcium enter and leave bones each day.. 4. The remaining 1% of calcium are present in body fluids and other tissues.  Blood Calcium 1. Blood calcium level ranges from 9-11 mg/dl. (dl=0.1L unit of volume) 2. Blood calcium lies entirely in the plasma (RBCs don’t contain calcium). 3. Plasma calcium is present in 3 forms: a) Ionized 50% (diffusible): Its deficiency causes tetany. b) Non-ionized 5% (diffusible): complexed with organic ions e.g. Citrate. c) Non-ionized 45% (non-diffusible): it is bound to protein mainly albumin. Its deficiency occurs with conditions of hypoproteinaemia (low protein level) and Tetany: overlycauses no tetany.nerves cause involuntary (uncontrolled movement) stimulated muscle cramps and contractions Factors affecting blood calcium level :  Hormonal regulation: 4 hormones are concerned with regulation of blood calcium.  These are:  1) parathyroid hormone  2) calcitriol  3) calcitonin  4) katacalcin   Factors Affecting Blood Calcium A. Hormonal regulation: 4 hormones are concerned with regulation of blood calcium. Synergistically These are:  Parathyroid hormone: It increases blood calcium level through: Mobilization of calcium from bones (bone resorption), releases Absorption of calcium from intestine through conversion of vitamin D into calcitriol (active vitamin D) in the kidney Reabsorption of calcium by renal tubules Act  Calcitriol (1,25-dihydroxycholecalciferol): It increases blood calcium level through: Absorption of calcium from intestine, we need calcitriol (active form vitamin D) Reabsorption of calcium by renal tubules Mobilization of calcium from bones outco me Ca +2 https://med.virginia.edu/ginutrition/wp-content/uploads/sites/199/2015/11/ JavorskyArticle-March-06.pdf  biologically inactive. pidermas bsorb UV and convert to previtamin D3 apidly convert to inactive D3 n epidermal keratinocytes with production f 1,25 Step 1 in liver hydroxylation steps Step 2 in kidney By enzyme located in proximal tubules 1 alpha-hydr Active form Robert U. Simpson, 2011  Bone resorption outcom Seru m e ca+2 H.W hint When we have Blood level Osteoclast And how it connected to PTH Bone deposition Calcitriol outcome Seru Osteoblast Calcitonin m ca+2  Factors Affecting Blood Calcium  Calcitonin and katacalcin:  These two hormones are secreted by the parafollicular or ‘C’ cells of the thyroid gland.  They are released in response to hypercalcemia and decrease blood calcium level through inhibition of its mobilization from bones or increasing calcium deposition in bones. en we have high blood Ca+2 level  calcitonin  to have an outcome of lowering blood Ca+2 Outco me Ca +2 Factors affecting plasma calcium deposition  Factors Affecting Blood Calcium B. Other factors:  Blood pH: ionization of calcium occurs at normal blood pH (7.4). Alkalosis decreases ionized calcium.  Plasma proteins: in cases of hypoproteinaemia, the non-diffusible calcium decreases.  Functions of Calcium  Unionized calcium: comprise the structure of bones and teeth.  Ionized calcium: It is important for a) Transmission of nerve impulses. b) Contraction of muscles. c) Decrease the neuromuscular excitability. Then if there is a Deficiency of ionized calcium leads to tetany. Neurons become unstable with increased excitability lead to hand spasms. d) Blood clotting. e) Maintenance of cell membrane permeability. f) Activation of certain enzymes e.g. pyruvate kinase. g) Mediation of some hormone responses e.g. Ca+2 acts as intracellular messenger (second messenger) or can be combined with calmodulin as third messenger. Functions of Calcium  Excretion 1. Most of calcium is excreted with faeces. 2. Small amount is excreted in urine.  Alterations of plasma calcium A. Hypercalcaemia: it is caused by 1. Primary hyperparathyroidism: usually due to adenoma (tumour gland like cells of the epithelial tissue). 2. Excess intake of vitamin D or calcium or both. Usually it is due to overdose of vitamin D. 3. Bone diseases: such as malignancy, leukaemia, multiple myeloma (bone marrow cancer). 4. Other causes: thyrotoxicosis (excess circulating thyroid hormone), Cushing's syndrome (excess cortisol/stress hormone for long time)(cortisol increase bone resorption and bone density decrease due to more osteoclast and high stress hormone or fight or flight mode block calcium from entering the bone. 5. increase ACTH (adenocorticotropic hormone from anterior pituitary gland under stress stimulate adrenal gland increase cortisol) glucocorticoids increase bone resorption gut absorption increased  increase calcium in plasma). B. Hypocalcaemia: it causes hyper-excitability of the nervous tissue, neuromuscular irritability that leads to tetany, rickets (bone pain and poor bone growth) and osteoporosis. It is caused by 1. Hypoparathyroidism. 2. Kidney diseases where activation of vitamin D is inhibited. 3. Pseudohypoparathyroidism: caused by deficient PTH receptors, and with high serum PTH.  Parathyroid Thyroid hormone Calcitriol=vitamin gland D Calcitonin  Mobilization of Ca+2 increase  inhibits bone calcium from PO4-2 decrease bones (bone Ca+2 mobilization  Increase bone Mg+2 increases resorption), decrease releases Ca+2  Absorption of PO4-2 deposition calcium from decrease  Decrease intestine through intestine conversion of absorption vitamin D into  Promotes calcitriol (active Aldosterone: vitamin D) in the kidney Mg+2: It decreases kidney plasma Mg excretion level  Reabsorption of calcium by renal by increasing its tubules excretion by the kidney.  Increase PO4 excretion Increase Na، Cl reabsorption Decrease K (increase excretion)