![Calcium Homeostasis
• Calcium homeostasis refers to the regulation
of the concentration of calcium ions in the
extracellular fluid [Ca++]ECF. This parameter is
tightly controlled because the calcium ions
have a stabilizing effect on voltage-gated ion
channels.
• For instance, when [Ca++]ECF is too low
(hypocalcemia), voltage-gated ion channels
start opening spontaneously, causing nerve
and muscle cells to become hyperactive. The
syndrome of involuntary muscle spasms due
to low [Ca++]ECF is called hypocalcemic tetany.](https://image.slidesharecdn.com/biochem-170521133008/85/SOURCES-BIOCHEMICAL-FUNCTION-AND-CLINICAL-SIGNIFICANCES-OF-CALCIUM-AND-PHOSPHORUS-Ca-P-17-320.jpg)
![• Conversely, when [Ca++]ECF is too high (hypercalcemia), voltage-gated
ion channels don't open as easily, and there is depressed nervous
system function.Another problem of hypercalcemia is that calcium can
combine with phosphate ions, forming deposits of calcium
phosphate (stones) in blood vessels and in the kidneys](https://image.slidesharecdn.com/biochem-170521133008/85/SOURCES-BIOCHEMICAL-FUNCTION-AND-CLINICAL-SIGNIFICANCES-OF-CALCIUM-AND-PHOSPHORUS-Ca-P-18-320.jpg)
![Parathyroid Hormone
• A decrease in ionized calcium stimulates a release of parathyroid hormone
(PTH), which maintains calcium homeostasis by 1) increasing bone mineral
dissolution, thus releasing calcium and phosphorus, 2) increasing renal
reabsorption of calcium and excretion of phosphorus, and 3) enhancing the
gastrointestinal absorption of both calcium and phosphorus indirectly
through its effects on the synthesis of 1,25(OH)2D (calcitriol).
• In healthy subjects, this increase in serum PTH level in response to
hypocalcemia effectively restores serum calcium levels and maintains
normal serum phosphorus levels. PTH also enhances the conversion of
calcidiol [25(OH)-vitamin D] to calcitriol, which in turns decreases PTH
secretion at the level of the parathyroid glands completing the typical
endocrine feedback loop](https://image.slidesharecdn.com/biochem-170521133008/85/SOURCES-BIOCHEMICAL-FUNCTION-AND-CLINICAL-SIGNIFICANCES-OF-CALCIUM-AND-PHOSPHORUS-Ca-P-26-320.jpg)
SOURCES ,BIOCHEMICAL FUNCTION AND CLINICAL SIGNIFICANCES OF CALCIUM AND PHOSPHORUS (Ca & P)
- 3. • NOOR FAIZA😎 • HAFSA KHALID😉 • SHAIQA ZAFAR 😍 • AQSA MUSHTAQ 🙂 • MARYAM KHALID😁 • LAIBA ROOP PAUL 😂 GROUP MEMBERS:
- 4. MINERALS • CALCIUM AND PHOSPHORUS are basically minerals. “Minerals are naturally-occurring inorganic substances with a definite and predictable chemical composition and physical properties”
- 5. WHAT IS CALCIUM? • Calcium is a chemical element which is essential for living organisms, including humans. Calcium is a mineral found in many foods. • Calcium's chemical symbol is "Ca". • We need to consume a certain amount of calcium to build and maintain strong bones and healthy communication between the brain and various parts of the body.
- 6. • Calcium is one of the body's electrolytes, which are minerals that carry an electric charge when dissolved in body fluids such as blood (but most of the body's calcium is uncharged). • It is required for activation of several enzymes such as succinate dehydrogenase, ATPase and certain proteolytic enzymes.
- 8. WHAT IS PHOSPHORUS ? • Phosphorus is the second most plentiful mineral in our body. The first is calcium. Our body needs phosphorus for many functions, such as filtering waste and repairing tissue and cells.
- 10. What Does CALCIUM Do? Calcium(Ca) is required for the : • Muscle contraction, • Nerve conduction, • Hormone release, • Blood coagulation • In addition, specific Calcium concentration is required for various other metabolic processes.
- 11. SOURCES OF
- 12. Calcium Sources in Food • Milk and dairy products are not the only sources of calcium. Here is a list of foods that are good sources of calcium:
- 13. Food Amount Calcium (milligrams) Yogurt, plain, low fat 8 oz 415 Collards, frozen, boiled 1 cup 357 Skim milk 1 cup 306 Yogurt, plain, whole milk 8 oz 275 Black-eyed peas, boiled 1 cup 211 Canned salmon 3 oz 181 Calcium-set tofu 3 oz (¼ block) 163 Cheese food, pasteurized 1 oz 162 Trail mix (nuts, seeds, chocolate chips) 1 cup 159 Baked beans, canned 1 cup 154 Cottage cheese, 1% milk fat 1 cup 138 Iceberg lettuce 1 head 97 Green peas, boiled 1 cup 94 Soy milk 1 cup 93 Oranges 1 cup 72 Almonds 1 oz (24 nuts) 70
- 15. Some of the main sources of phosphorus are: • Seeds (Pumpkin & Squash) • Cheese (Romano) • Fish (Salmon) • Shellfish (Scallops) • Nuts (Brazil) • Beef & Veal (Lean Beef) • Low Fat Dairy (Nonfat Yogurt) • Soya Foods (Tofu) • Beans & Lentils
- 16. Functions of Calcium • Calcium salts provide rigidity to the skeleton. Calcium phosphate is a major component of the mineral complex (called hydroxyapatite) that gives structure and strength to bones. • Many neuromuscular and other cellular functions depend on the maintenance of the ionized calcium concentration in the ECF. • Blood clotting • absorbing vitamin B12
- 17. Calcium Homeostasis • Calcium homeostasis refers to the regulation of the concentration of calcium ions in the extracellular fluid [Ca++]ECF. This parameter is tightly controlled because the calcium ions have a stabilizing effect on voltage-gated ion channels. • For instance, when [Ca++]ECF is too low (hypocalcemia), voltage-gated ion channels start opening spontaneously, causing nerve and muscle cells to become hyperactive. The syndrome of involuntary muscle spasms due to low [Ca++]ECF is called hypocalcemic tetany.
- 18. • Conversely, when [Ca++]ECF is too high (hypercalcemia), voltage-gated ion channels don't open as easily, and there is depressed nervous system function.Another problem of hypercalcemia is that calcium can combine with phosphate ions, forming deposits of calcium phosphate (stones) in blood vessels and in the kidneys
- 20. Calcium pumps • Calcium pumps are a family of ion transporters found in the cell membrane of all animal cells. • They are responsible for the active transport of calcium out of the cell for the maintenance of the steep Ca2+ electrochemical gradient across the cell membrane. • Calcium pumps play a crucial role in proper cell signalling by keeping the intracellular calcium concentration roughly 10,000 times lower than the extracellular concentration. • Failure to do so is one cause of muscle cramps. • There are two calcium ATPase: 1. The plasma membrane Ca2+ ATPase and the sodium-calcium exchanger are together the main regulators of intracellular Ca2+ concentrations. 2. sarcoplasmic reticulum calcium atpase
- 21. What Does Phosphorus Do? You need phosphorus to keep your bones strong and healthy, to help make energy, and to move your muscles. In addition, phosphorus helps to: • build strong bones and teeth • filter out waste in your kidneys • manage how your body stores and uses energy • grow, maintain, and repair tissue and cells • produce DNA and RNA — the body’s genetic building blocks • balance and use vitamins such as vitamins B and D, as well as other minerals like iodine, magnesium, and zinc • assist in muscle contraction • maintain a regular heartbeat • facilitate nerve conduction • reduce muscle pain after exercise
- 22. Secondary Functions of Phosphorus • Phosphorus also acts as a buffer, neutralizing acids to maintain normal pH in the blood. Many enzymes and hormones also contain phosphorus as a structural component. Hemoglobin, the important oxygen-carrying protein in the bloodstream, also depends upon phosphorus contained in its structure for proper function.
- 23. Vitamin D • Vitamin D helps in absorption of calcium and phosphorus. • Vitamin D is called a ‘vitamin’ because of its exogenous source, predominately from oily fish in the form of vitamin D2 and vitamin D3. • It is really a hormone, synthesized by the skin and metabolized to an active hormone, calcitriol, by the kidney which then acts throughout the body. • In the skin, 7-dehydrocholesterol is converted to vitamin D3 in response to sun light, a process that is inhibited by sunscreen of SPF 8 or greater. • Once in the blood, vitamin D2 and D3 from diet or skin bind with vitamin D binding protein, and carried to the liver where they are hydroxylated to yield 25(OH)D, often called calcidiol. Calcidiol is then converted in the kidney to 1,25(OH)2D by the action of 1α-hydroxylase. • The 1α-hydroxylase in the kidney is regulated by nearly every hormone involved in calcium homeostasis, and its activity is stimulated by PTH, estrogen, calcitonin, prolactin, growth hormone, low calcium and low phosphorus. Its activity is inhibited by calcitriol, thus providing the ‘feedback’ loop that regulates calcitriol synthesis.
- 24. • The most important function is exerted on the small intestine, where calcitriol regulates the intestinal absorption of calcium and, to a lesser degree, phosphorus and inhibits PTH synthesis at the parathyroid gland. • The most important role of vitamin d is to maintain skeletal Calcium balance by promoting Ca absorption in intestine. • Promoting bone reabsorption by increasing osteoclasts number. • Maintenance of calcium and phosphate levels for bone formation. • Allowing proper functioning of parathyroid harmone.
- 26. Parathyroid Hormone • A decrease in ionized calcium stimulates a release of parathyroid hormone (PTH), which maintains calcium homeostasis by 1) increasing bone mineral dissolution, thus releasing calcium and phosphorus, 2) increasing renal reabsorption of calcium and excretion of phosphorus, and 3) enhancing the gastrointestinal absorption of both calcium and phosphorus indirectly through its effects on the synthesis of 1,25(OH)2D (calcitriol). • In healthy subjects, this increase in serum PTH level in response to hypocalcemia effectively restores serum calcium levels and maintains normal serum phosphorus levels. PTH also enhances the conversion of calcidiol [25(OH)-vitamin D] to calcitriol, which in turns decreases PTH secretion at the level of the parathyroid glands completing the typical endocrine feedback loop
- 27. CLINICAL SIGNIFICANCE OF CALCIUM • Deficiency of calcium can lead to weaker bones, tetany and seizures. • Deficiency can occur due to poor intake, malabsorption, vitamin D deficiency, hypoparathyroidism and renal disease. • Long term Deficiency can lead to osteomalacia and osteoporosis.
- 28. CLINICAL SIGNIFICANCE OF CALCIUM • HYPOCALCEMIA Definition “Hypocalcemia is an electrolyte imbalance in which the serum, or blood, calcium level is below the normal range. The normal serum calcium level is 8.5-10.5 mg/dl.”
- 30. Conditions: • Other conditions resulting to hypocalcemia are chronic liver disease, nephrotic syndrome, congestive heart failure, and malnutrition, osteomalacia and rickets, etc. but common causes are chronic renal failure and hypomagnesemia. • In chronic renal failure, hypoproteinemia, hyperphosphatemia, low serum vitamin D (reduced synthesis because of inadequate renal mass) and/or skeletal resistance to PTH contribute to hypocalcemia. Magnesium deficiency impairs PTH secretion and cause PTH end-organ resistance. Inherited resistance of PTH leads to pseudohypoparathyroidism and thus hypocalcemia e.g. in pseudohypoparathyroidism type I (Albright’s hereditary osetodystrophy) is due to reduction in guanine nucleotide regulatory complex in adenylate cyclase complex. Vitamin D deficiency is also associated with hypocalcemia and is due to impaired intestinal absorption of calcium and skeletal resistance to PTH. Clinically hypocalcemia presents with neuromuscular hyperexcitability, such as tetany, paresthesia, and seizures.
- 31. • Causes of Hypocalcemia • Hypocalcemia most commonly results when too much calcium is lost in urine or when not enough calcium is moved from bones into the blood. Causes of hypocalcemia include the following: • A low level of parathyroid hormone (hypoparathyroidism), as can occur when the parathyroid glands are damaged during thyroid gland surgery • Lack of response to a normal level of parathyroid hormone (pseudohypoparathyroidism) • No parathyroid glands at birth (for example, in DiGeorge syndrome) • Vitamin D deficiency (due to inadequate consumption or inadequate exposure to sunlight) • Kidney dysfunction, which results in more calcium excreted in urine and makes the kidneys less able to activate vitamin D • Inadequate consumption of calcium • Disorders that decrease calcium absorption
- 32. Severe symptoms of calcium deficiency disease include: • confusion or memory loss. • muscle spasms. • numbness and tingling in the hands, feet, and face. • depression. • hallucinations. • muscle cramps. • weak and brittle nails. • easy fracturing of the bones.
- 33. Treatment of Hypocalcemia • Calcium supplements • Sometimes vitamin D • Calcium supplements, given by mouth, are often all that is needed to treat hypocalcemia. If a cause is identified, treating the disorder causing hypocalcemia or changing drugs may restore the calcium level.
- 34. Hypercalcemia (Elevated Calcium Levels)
- 36. What are the causes of hypercalcemia? • One of the most common causes of high calcium levels (hypercalcemia), is an overproduction of parathyroid hormone, or hyperparathyroidism. • Hyperparathyroidism tends to be more common in women over 50. • It can be the result of all four parathyroid glands producing too much PTH (parathyroid hyperplasia), or one gland specifically producing an excessive amount of hormone (usually the result of a parathyroid adenoma, or benign tumor). • Hypercalcemia can occur due to other medical conditions. These conditions can vary in severity and chronicity, and may be life- threatening. Malignancy is a common cause of elevated blood calcium. Up to 20% of individuals with cancer will develop hypercalcemia at some point in their disease.
- 37. What Are the Symptoms of Hypercalcemia? You might not have any symptoms if you have mild hypercalcemia. If you have a more serious case, you might have symptoms that affect various parts of your body. Kidneys Symptoms related to your kidneys can lead to: • excessive thirst • excessive urination • pain between your back and upper abdomen on one side Abdomen Symptoms related to the abdomen include: • nausea • abdominal pain • decreased appetite • constipation • vomiting
- 38. Muscles • Calcium levels can affect your muscles, causing twitches and weakness. Skeletal System High calcium levels can also cause bone issues, including: • bone pain • height loss • bowed shoulders • curvature of the spine • fractures from disease
- 39. • Psychological Symptoms • Hypercalcemia can also cause psychological symptoms, such as depression, memory loss, and irritability.
- 40. TREATMENT • Severe Cases You might need hospital treatment if you have a severe case. The goal of treatment is to return your calcium level to normal. Treatment also aims to prevent damage to your bones and kidneys. Treatment options include the following: • Calcitonin is a hormone produced in the thyroid gland. It slows down bone loss. • Intravenous fluids keep you hydrated. • Corticosteroids are anti-inflammatory medications. They help your body handle having too much vitamin D. • Loop diuretic medications can help your kidneys function and get rid of extra calcium. • Intravenous bisphosphonates can keep your bones from breaking down. • Dialysis can be given to rid your blood of extra calcium and waste when you have damaged kidneys. This is only done if other treatment methods aren’t working.
- 41. CLINICAL SIGNIFICANCE OF PHOSPHORUS
- 42. Hyperphosphatemia • Hyperphosphatemia—that is, abnormally high serum phosphate levels—can result from increased phosphate intake, decreased phosphate excretion, or a disorder that shifts intracellular phosphate to extracellular space
- 43. Persons who are at risk for increased phosphorus levels • Kidney disease: Past or present hemodialysis; adherence to renal (low phosphorus) diet; use of oral phosphate binders • Cancer: Leukemia, lymphoma, bone tumors, other cancers, chemotherapy treatment • Endocrinopathies (hypoparathyroidism and pseudohypoparathyroidism) • Trauma Burns or heat-related illnesses Prolonged immobilization Metabolic or hematologic disorders, including genetic predisposition • Ischemic bowel (possible phosphorus elevations)
- 44. signs and symptoms • Fatigue • Shortness of breath • Anorexia • Nausea • Vomiting • Sleep disturbances
- 45. Primary hyperparathyroidism Primary hyperparathyroidism occurs because of some problem with one or more of the four parathyroid glands: • A noncancerous growth (adenoma) on a gland is the most common cause. • Enlargement (hyperplasia) of two or more parathyroid glands accounts for most other cases. • A cancerous (malignant) tumor is a rare cause of primary hyperparathyroidism. • Primary hyperparathyroidism usually occurs randomly, but some people inherit a gene that causes the disorder.
- 46. Secondary hyperparathyroidism • Secondary hyperparathyroidism is the result of another condition that lowers calcium levels. • Therefore, your parathyroid glands overwork to compensate for the loss of calcium. Factors that may contribute to secondary hyperparathyroidism include: Severe calcium deficiency. • Your body may not get enough calcium from your diet, often because your digestive system doesn't absorb the calcium from it. Severe vitamin D deficiency. • Vitamin D helps maintain appropriate levels of calcium in the blood, and it helps your digestive system absorb calcium from your food. Your body produces vitamin D when your skin is exposed to sunlight, and you consume some vitamin D in food. If you don't get enough vitamin D, then calcium levels may drop. Chronic kidney failure. Your kidneys convert vitamin D into a form that your body can use. • If your kidneys function poorly, usable vitamin D may decline and calcium levels drop. Chronic kidney failure is the most common cause of Secondary hyperparathyroidism
- 47. Hypophosphatemia • Hypophosphatemia is a serum phosphate concentration < 2.5 mg/dL (0.81 mmol/L). • Causes include alcoholism, burns, starvation, and diuretic use. Clinical features include muscle weakness, respiratory failure, and heart failure; seizures and coma can occur. Diagnosis is by serum phosphate concentration. Treatment consists of phosphate supplementation.
- 48. Severe chronic hypophosphatemia usually results from a prolonged negative phosphate balance. Causes include : • Chronic starvation or malabsorption, often in patients with alcoholism, especially when combined with vomiting or copious diarrhea • Long-term ingestion of large amounts of phosphate-binding aluminum, usually in the form of antacids
Editor's Notes
- #7: as succinate dehydrogenaseis the only enzyme that participates in both the citric acid cycle and the electron transport chain. ATPases are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion. Proteolytic enzymes (or proteases) refer to the variousenzymes that digest (break down into smaller units) protein. These enzymes include the pancreatic proteaseschymotrypsin and trypsin, bromelain (pineapple enzyme), papain (papaya enzyme), fungal proteases, and Serratia peptidase (the “silk worm” enzyme).
- #10: The amount of phosphate in the blood affects the level ofcalcium in the blood. Calcium and phosphate in the body react in opposite ways: as blood calcium levels rise, phosphate levels fall. A hormone called parathyroid hormone (PTH) regulates the levels of calcium and phosphorus in your blood.
- #17: a complex phosphate of calcium Ca5(PO4)3OH that occurs as a mineral and is the chief structural element of vertebrate bone
- #24: Calcium and vitamin D work together to protect your bones—calcium helps build and maintain bones, while vitamin D helps your body effectively absorb calcium
- #28: Osteomalacia: softening of the bones, typically through a deficiency of vitamin D or calcium Softening of bone, particularly in the sense of bone weakened by demineralization Osteoporosis weakens bone and increases risk of bones breaking. Bone mass (bone density) decreases
- #44: Leukemia is cancer of the blood or bone marrow (which produces blood cells) Lymphoma is a form of cancer that affects the immune system Endocrinopathy: A disease of an endocrine gland. Commonendocrinopathies include hyperthyroidism and hypothyroidism.