11. Minerals Flashcards
Cut off value of RDA to differenciate between major and trace minerals?
If the daily requirement is more than 100 mg, they are called major elements or macrominerals.
If the requirement of certain minerals is less than 100 mg/day, they are known as minor elements or microminerals or trace elements.
Explain Factors affecting Ca absorption?
B. Factors causing increased absorption
i. Vitamin D: Calcitriol induces the synthesis of the carrier protein (Calbindin) in the intestinal epithelial cells, and so facilitates the absorption of calcium (Fig. 35.1).
ii. Parathyroid hormone: It increases calcium transport from the intestinal cells.
iii. Acidity: It favors calcium absorption.
iv. Amino acids: Lysine and arginine increase
calcium absorption.
C. Factors causing decreased absorption
i. Phytic acid: Hexaphosphate of inositol is present in cereals. Fermentation and cooking reduce phytate content.
ii. Oxalates: They are present in some leafy vegetables, which cause formation of insoluble calcium oxalates.
iii. Malabsorptionsyndromes:Fattyacidisnot absorbed, causing formation of insoluble calcium salt of fatty acid.
iv. Phosphate: High phosphate content will cause precipitation as calcium phosphate. The optimum ratio of calcium to phosphorus which allows maximum absorption is 1:2 to 2:1 as present in milk.
Functions of Calcium?
- Activation of enzymes
Calmodulin is a calcium binding regulatory protein, with a molecular weight of 17,000 Daltons. Calmodulin can bind with 4 calcium ions. Calcium binding leads to activation of enzymes. Calmo- dulin is part of various regulatory kinases. - Muscles
Calcium mediates excitation and contraction of muscle fibers. Different types of calcium channels are shown in Figure 35.2. Upon getting the neural signal, calcium is released from sarcoplasmic reticulum. Calcium activates ATPase; increases action of actin and myosin and facilitates excitation- contraction coupling. The trigger of muscle contraction is the interaction of calcium with Troponin C (see Chapter 52). The active transport system utilizing calcium binding protein is called calsequestrin. Calcium decreases neuromuscular irritability. Calcium deficiency causes tetany. - Nerve conduction
Calcium is necessary for transmission of nerve impulses from presynaptic to postsynaptic region. - Secretion of hormones
Calcium mediates secretion of insulin, parathyroid hormone, calcitonin, vasopressin, etc. from the cells. - Second messenger
Calcium and cyclic AMP are second messengers of different hormones (see Table 44.1). One example is glucagon. Calcium is used as second messenger in systems involving G proteins and inositol triphosphate. - Vascular permeability
Calcium decreases the passage of serum through capillaries. Thus, calcium is clinically used to reduce allergic exudates.
Fig. 35.4. Different forms of calcium in serum - Coagulation
Calcium is known as factor IV in blood coagulation cascade. Prothrombin contains gamma-carboxy glutamate residues which are chelated by Ca++ during the thrombin formation (see Chapter 33, under vitamin K). - Myocardium
Ca++ prolongs systole. In hypercalcemia, cardiac arrest is seen in systole. This fact should be kept in mind when calcium is administered intravenously. It should be given very slowly. - Bone and teeth
The bulk quantity of calcium is used for bone and teeth formation. Bones also act as reservoir for calcium in the body. Osteoblasts induce bone deposition and osteoclasts produce deminerali- zation. - Calpains
Calpains are a family of calcium-dependent, cysteine proteases (proteolytic enzymes) seen ubiquitously in mammals.
Causes and manifestations of hypocalcemia?
Causes of Hypocalcemia 1. Deficiency of Vitamin D Decreased exposure to sunlight Malabsorption, dietary deficiency Hepatic diseases Decreased renal synthesis of calcitriol Nephrotic syndrome (binding protein lost) Anticonvulsant therapy 2. Deficiency of Parathyroid Hypoparathyroidism (primary, secondary) Pseudohypoparathyroidism 3. Increased Calcitonin Medullary carcinoma of thyroid 4. Deficiency of Calcium Intestinal malabsorption Acute pancreatitis Infusion of agents complexing calcium Alkalosis decreasing ionized calcium 5. Deficiency of Magnesium 6. Increase in Phosphorus Level Renal failure Phosphate infusion Renal tubular acidosis 7. Hypoalbuminemia
Symptoms of Hypocalcemia
- Muscle cramps
- Paresthesia, especially in fingers
- Neuromuscular irritability, muscle twitchings
- Tetany (Chvostek’s sign, Trousseau’s sign)
- Seizures
- Bradycardia
- Prolonged QT interval
Causes and manifestations of hyperalcemia?
Causes 1. Hyperparathyroidism 2. Multiplemyeloma 3. Paget’sdisease 4. Metastatic carcinoma of bone 5. Thyrotoxicosis,Addison'sdisease 6. Benignfamilialhypercalcemia 7. Dehydration 8. Prolongedimmobilization 9. Tuberculosis,leprosy,sarcoidosis 10. Milk-alkalisyndrome 11. Drugs Thiazide diuretics Excess vitamin D or vitamin A Excess calcium given IV Lithium therapy Theophylline
Symptoms
- Anorexia,nausea,vomiting
- Polyuria and polydypsia (ADH antagonism)
- Confusion, depression, psychosis
- Osteoporosis and pathological fracture
- Renal stones
- Ectopic calcification and pancreatitis
- Serum alkaline phosphatase may be increased
Explain Mucosal Block Theory?
i. Duodenum and jejunum are the sites of absorption. Iron metabolism is unique because homeostasis is maintained by regulation at the level of absorption and not by excretion (Fig. 35.9). No other nutrient is regulated in this manner. In other words, iron is a one-way element.
ii. When iron stores in the body are depleted, absorption is enhanced. When adequate quantity of iron is stored, absorption is decreased. This is referred to as mucosal block of regulation of absorption of iron.
iii. Only ferrous (and not ferric) form of iron is absorbed. Ferric iron is reduced to ferrous iron by ferric reductase, an enzyme present on the surface of enterocytes. Ferrous iron in the intestinal lumen binds to mucosal cell protein, called divalent metal transporter-1 (DMT-1). This bound iron is then transported into the mucosal cell. The rest of the unabsorbed iron is excreted (Fig. 35.9).
iv. Insidethemucosalcell,theferricironisformed and is complexed with apoferritin to form ferritin. It is kept temporarily in the mucosal cell. If there is anemia, the iron is further absorbed into the bloodstream. If transferrin is saturated with iron, any iron accumulated in the mucosal cell is lost when the cell is des- quamated. The fraction of iron absorbed and retained is decided by the iron status. When iron is in excess, absorption is reduced; this is the basis of “mucosal block” (Fig. 35.9).
v. This mechanism of iron absorption from intestinal lumen to the mucosal cell is different from the iron release from intestinal cell to the bloodstream (Fig. 35.9). Iron in the ferritin is released, then crosses the mucosal cell with the help of a transport protein called, ferro- portin. But this can happen only when there is free transferrin in plasma to bind the iron. Iron crosses the cell membrane as ferrous form. In the blood it is re-oxidized to ferric state, and transported by transferrin.
Explain Factors affecting absorption of Fe?
i. Mucosal regulation
ii. Stores regulation
iii. Erythropoietic regulation
iv. There is reciprocal relationship between synthesis of ferritin and transferrin receptor (TfR).
How is Lab diagnosis of IDA done?
i. Serum iron level: It is depressed in iron deficiency, acute and chronic infections, carcinomas, hypothyroidism and Kwashiorkor.
ii. Total iron binding capacity (TIBC): It is elevated in hypochromic anemias, acute hepatitis and pregnancy.
iii. Soluble transferrin receptor level (TfR): It has distinct advantages over the other parameters because inflammatory states will not alter sTR levels. The level of sTR is increased in iron deficiency anemia, hemolytic anemia and polycythemia. Decreased values are seen in aplastic anemia and chronic renal failure.
Explain Wilson’s disease?
i. Wilson’s Disease: Ceruloplasmin level in blood is drastically reduced in Wilson’s hepato- lenticular degeneration. The incidence of Wilson’s disease is 1 in 50,000. The basic defect is in a gene encoding a copper binding ATPase in cells (ATP7B gene in liver cells). This is required for normal excretion of copper from liver cells; in its absence, copper is accumulated in cells, leading to copper deposits in liver and brain (see Chapter 28). Adminis- tration of penicillamine, which helps in chelation and excretion of copper, may help the affected persons. As zinc decreases copper absorption, zinc is sometimes used therapeutically in Wilson’s disease, to reduce copper load in the body.
Presence of Kayser-Fleicher rings in the eye which are copper deposits in the cornea.
Explain Menke’s Kinky Hair Syndrome?
It is an X-linked defect (affects only male children). It is a condition in which dietary copper is absorbed from GI tract; but cannot be transported to blood due to absence of an intracellular copper binding ATPase (muta- tion in ATP7A gene). Please note that the proteins present in liver and in extrahepatic tissues are different. This explains the difference in clinical manifestations of Wilson’s disease and Menke’s disease. Copper is not mobilized from intestinal cells as well as in other tissue cells. The copper that has entered into the cell is not able to get out of the cells, and so it accumulates. Hence copper is not available for metabolism, resulting in defective cross-linking of connective tissue. Vascular and connective tissues are affected, and child dies usually in infancy. Injections of copper salts may be effective as a treatment.
Which are theSe containing enzymes and proteins?
In mammals, glutathione peroxidase (GP) is the important selenium containing enzyme. RBC contains good quantity of glutathione peroxidase.
Thyroxin is converted to T3 by 5’-de-iodinase, which is a selenium containing enzyme. In Se deficiency, this enzyme becomes less active, leading to hypothyroidism.
The UGA codon (see Chapter 41) is acting as the codon for direct insertion of seleno-cysteine into selenium containing
enzymes. Seleno-cysteine is directly incorporated into the protein during biosynthesis. So, seleno-cysteine may be considered as the 21st amino acid
Explain Therapeutic uses of Li?
Lithium is used in treating manic depressive psychosis (bipolar disorders), the dose being 25-500 mg/day. Lithium will counteract both mania and depression.
