Pathophysiology of calcium-phosphorus metabolism

1. Pathophysiology of calcium-phosphorus metabolism Ph.D., MD,Assistant ProfessorHanna Saturska

2. Calcium98 % Phosphorus86 % Norm1,22 – 2,2 mmol/l Norm2,35 – 2,75 mmol/l Role- Bones- Tooth- ATP, КPh)- Phosphorillation of carbohydrates- DNA and RNA synthesis- Phospholipids of membranes- Phosphate buffer Role- Bones- Tooth- Blood coagulation- Membranes permeability- Nervous impulses pass- Muscle contraction- Enzymes activation (succinatdegydrogenasa, lecetinasa)

3. Phosphorus86 % Calcium 98 % Norm1,22 – 2,2 mmol/l Norm2,35 – 2,75 mmol/l Daily need – 1,5 gSource – all food(there is no exogene deficit)Absorption - 70 % from used foodPhosphorus of fish absorbs in 100 % Daily need – 1,0-1,2 gDepends on:- entrance (main source – milk food)- absorption (max. – duodenum, main quantity – intestine), only 30 % of Ca absorbs from food- excretion (intestine, kidney)

4. Parathyroid hormone (PTH) Organ-target: bones, kidneys Function of PTH-increase of Ca concentration in plasma Mechanisms: 1. Releasing of Са by bones (activation of osteoclasts – resumption of bones) 2. Increase of Са reabsorbing in kidneys 3. Activation of vit. Dз synthesis and increase of absorption in the intestine Vitamin D Hormone regulation of calcium-phosphorus metabolism Thyreocalcitonin Organ-target -bones Function -decrease of Ca concentration in plasma

5. Violationof calcium-phosphorus metabolism Hypocalciemia Hypercalciemia Hypophosphatemia Hyperphosphatemia

6. Hypocalcaemia Pathological state, at the quantity of Са in blood lessthan 2,35 mmoll/l ETIOLOGY • Hypoparathyreosis (primary, secondary, tertiary) • Pseudohypoparathyreosis (increasing of sensitivity ofreceptors to PTH) • Hyperphosphatemia (insoluble salts of Ca phosphate form – in children who were fed on cow's milk) • D3 hypovitaminos (deteriorating of absorption of Са in GIT, whichare at the controlling of vit. Dз) • Illness of GIT (diarrhea, steatorrhea) • Hyperproduction of thyreocalcitonin (medullary thyroid cancer) • Chronic renal failure(leads to loss of Ca and decrease of sensitivity to PTH)

7. Clinical manifestations of hypocalcaemia Tetanus The process of tetanus potentiation at the motor neurons and interneuron of spinal cord violate Conduction of impulses at reflex arch become easier Activate a reflex muscles contraction onmechanical and other stimuli Spasm of larynx, bronchus asphyxia death Coronarospasm (cardiotetanus) angina Stop of heart Cramps

8. Clinical manifestations of hypocalcaemia Гіпокальциемія Acquired forms - Lack of vit. Dз in food - Lack of insolation –insufficient of synthesis Ricket Congenital forms (calcipenia form ) – Dependence on vit. Dз type 1 (reason – hereditary defect of synthesis vit. Dз in kidneys) There is easy to treat by synthetic vit. Dз - Dependence on vit. Dз type2 (reason – insensitivity of target organsto 1,25(ОН)2 Dз Very difficult clinical manifestation

9. Clinical manifestations of hypocalcaemia Гіпокальциемія Osteodythtrophy Osteoporosis Athrophiaof bones Osteomalacia The bones become soft (as a result of metabolic violations of Са and Р in organic part of bones) Increasing of quantity Ca in blood Decreasing of quantity PTH Activate ofresorption of bone Activate ofosteoclastes which: - produce a lot of organic acids especially citric for solutionhydroxilapatit - produce lisosomal enzymes for solutionorganic matrix Implications: frequent fractures, disability

10. How does look osteoporosis?

11. Hypercalciemia Pathological state, at the quantity of Са in blood morethan 2,75 mmoll/l ETIOLOGY • Primary hyperparathyrosis (appearat multiple adenomatosis of endocrine glands, inheritance autossomal-dominant disease) • HypervitanosisDз (overdoses of drugs doses cause to excessive absorption Са in GIT) • Heavy and massive fractures – the balance between construction of bone (slowing) and resorption (without changes)

12. Clinical manifestations of hypercalciemia Osteodystrophy (Recklinhauzen disease) Cystosis swelling in the distal ends of both fibula bones Recklinhauzen disease – hyperparathyreoid osteodystrophy in 24 years old female. Damaging of lower jaw. The patient complains only on not pain deformation of face. Roentgenexam of whole skeleton revealed multiple changes. Mechanism Hyperparatireosis – increasing of Са in blood – waste of Са from bonesby resorbtion – osteoporosis – overgrowth of connective tissue (but Са isn’t deposited) - osteofibrosis

13. Clinical manifestations of hypercalciemia CALCINOSIS (звапнення, calcification) – accumulation of insoluble salts of Са In soft tissues The main case – alkalosis in tissue KINDS Metaplastic Dystrophy Metabolic Cellular Extracellular Local General Matrix for calcification Mitochondria Lisosomes Collagen and elastic fibers Glicozaminglican

14. Clinical manifestations of hypercalciemia Metastasic calcinosis The main reason - hypercalciemia The main case – alkalosis condition Appears Vessels (arteries ) Myocardium Lungs Mucous of stomach Kidneys Substanceswhich are emitted orcontacted these organs – acids. These tissues have a high alkalinity forsaving a normal state.

15. Metastasic calcinosis Calcinosis of aortic valve

16. Dystrophic staticcalcinosis (petrification) It arises in necrotic and dystrophic tissues - tuberculosis center , infarctions, dead fetus, chronic focus of inflamations (lungs and heart like an armor ), focuses of atherosclerosis, scar tissue Mechanism: alkalinityconditions – increased absorption Са from blood – The increased activity of phosphatases, which prodused from necrotic cells – formation of insoluble salts of Са

17. The woman gave birth stone baby! A resident of Morocco Zara became pregnant in 1959 at the age of 26. Nine months of pregnancy passed without complications. The contractions were long and very painful, and, fearing for her life, her husband took Zara to the hospital. In the hospital room Zara saw as young woman in the throes died, doctors couldn’t save her child. Fearing that a similar fate awaits her as well, Zara escaped from the hospital. Over the next few days the contractions continued, but the long-awaited baby was never born. Many years later, when Zara was 75 years old, the pain suddenly returned, and the woman went to doctors. Ultrasound examination revealed the presence of abdominal foreign body, the origin of which doctors could not explain. There have been more thorough examination of the Zara, which resulted in doctors admitted that the solid mass in the her body - nothing like petrified body of her child, who was not born. It was necessary to conduct operation because the subsequent delay would inevitably lead to the death of the patient. The operation continued four hours. The doctors managed to pull out of a woman's body fetus weighing just over 3 kilograms and 42 centimetres in length. Thus, in 46 years, "Stone Child" of Zara has finally emerged into the light. This phenomenon is very rare, to 1900 were described only 38 such cases, today they number no more than 300. The oldest fossilized fetus was found during excavations of burial sites in the U.S., his age is more than 1000 years.

18. Metabolic calcinosis (інтерстиціальне звапнення) Limestone deposits in skin, tendons, fascias, muscles, along nerves and vessels Pathogenesis unknown

19. Implications of calcinosis Positive Negative Calcinosisatherosclerotic plaque – provokes thrombosis Petrification of tuberculosis center –sign ofhealing Calcinosisof tendons – violation of muscles constriction Lungs and heart like an armor – violation offunction of these organs

20. Clinical manifestations of hypercalciemia CALCIPHILAXIA The state of increased sensitivity of organism to Increased quantity of Ca H.Selye (1960-1963)describedthe phenomenon and created an experimental model Sensitizing factor – hypercalcaemia Decisive factor – degranulation of masscells, mechanical damage, salts of Аl, Fe This phenomenon promotes the localization of process of organ calcification That cam explain the systemic destruction of the cardiovascular system

21. Hypophosphatemia(normof P in blood 1.22 – 2.2 mmoll/l) Pathological state, at the quantity of Р in blood lessthan 1.22 mmoll/l ETIOLOGY • Chronic kidneys insufficiency (loosing by kidneys) • Diseases of GIT (vomiting, malabsorption syndrome ) • Hypovitaminosis D (increased absobtion in the GIT) • Liver diseases • Using of insulin at treatment of diabetes mellitus and ketoacidosis (Increase ofglucose phosphorylation – increase of extracellular Р using) • Restoring ofnutritionafter full starvation (mechanism is same like previous point)

22. Clinical manifestations of hypophosphatemia(long-term decline of Р) Rickets (in children)/osteomalacia (in adults) X-linkedhypophosphatemia The main sign of all forms of rickets – heredity defect of enzyme’s synthesis, which are responsible for transportation of Р in kidneys Autossomal-dominanthypophosphatemial damage of the bones Clinical manifestations: - Hypophosphatemia - Bones become soft - Delay of growth - In difficult case + violation of functions of liver, heart, brainand development of coma (reason – violation of phosphorylation and deficit macroergs ) Autossomal-dominanthypophosphatemial ricket Fanconi’s syndrome (group of diseases, whichare manifested generaldysfunction of renal tubules + lossing of Р)

23. Hyperphosphatemia Pathological state, at the quantity of Р in blood morethan 2.2 mmol/l ETIOLOGY • Intensive capture of Р by kidneys (CKI, hypoparathyreosis, hyperthyroidism) • Over use of Р from the bones (rapid bone growth, healing of fractures, tumor of bones) • Intensive absorption Р in GIT (Dз hypervitaminosis, acute intestinal obstruction) • Massive destruction of cells(hemolytic anemia, leucosis) Don’t have independentvalue. Increasing of quantityof Р causes formation insoluble phosphates Ca in blood. Concentration of ionizing Cadecreasesand hypocalcaemia is dominant in clinical manifestation

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