Pathophysiology of calcium-phosphorus metabolism

Calcium98 %Phosphorus 86 %Norm 2,35 2,75 mmol/lNorm 1,22 2,2 mmol/lRole - Bones - Tooth - Blood coagulation - Membranes permeability - Nervous impulses pass - Muscle contraction - Enzymes activation (succinatdegydrogenasa, lecetinasa) Role - Bones - Tooth - ATP, Ph) - Phosphorillation of carbohydrates - DNA and RNA synthesis - Phospholipids of membranes - Phosphate buffer

10 (4)6 (2)

Daily need 1,0-1,2 g Depends on: - entrance (main source milk food) - absorption (max. duodenum, main quantity intestine), only 30 % of Ca absorbs from food - excretion (intestine, kidney) Daily need 1,5 g Source all food (there is no exogene deficit) Absorption - 70 % from used food Phosphorus of fish absorbs in 100 % Calcium 98 %Phosphorus 86 %Norm 2,35 2,75 mmol/lNorm 1,22 2,2 mmol/l

10 (4)6 (2)

Hormone regulation of calcium-phosphorus metabolismParathyroid hormone (PTH)Organ-target: bones, kidneys

Function of PTH - increase of Ca concentration in plasma

Mechanisms: 1. Releasing of by bones (activation of osteoclasts resumption of bones)2. Increase of reabsorbing in kidneys3. Activation of vit. D synthesisand increase of absorption in the intestine Vitamin DThyreocalcitonin

Organ-target - bones

Function - decrease of Ca concentration in plasma

Violation of calcium-phosphorus metabolismHypocalciemiaHypercalciemiaHypophosphatemiaHyperphosphatemia

ETIOLOGY Hypoparathyreosis (primary, secondary, tertiary)Pseudohypoparathyreosis (increasing of sensitivity of receptors to PTH)Hyperphosphatemia (insoluble salts of Ca phosphate form in children who were fed on cow's milk)D3 hypovitaminos (deteriorating of absorption of in GIT, which are at the controlling of vit. D)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)HypocalcaemiaPathological state, at the quantity of in blood less than 2,35 mmoll/l

Cramps Clinical manifestations of hypocalcaemiaTetanusThe process of tetanus potentiation at the motor neurons and interneuron of spinal cord violateConduction of impulses at reflex arch become easier Activate a reflex muscles contraction on mechanical and other stimuli Spasm of larynx, bronchus

asphyxia

deathCoronarospasm (cardiotetanus) angina

Stop of heart

RicketAcquired forms- Lack of vit. D in food - Lack of insolation insufficient of synthesisCongenital forms (calcipenia form )

Dependence on vit. D type 1 (reason hereditary defect of synthesis vit. D in kidneys)There is easy to treat by synthetic vit. D

- Dependence on vit. D type 2 (reason insensitivity of target organs to 1,25()2 D Very difficult clinical manifestationClinical manifestations of hypocalcaemia

Osteomalacia The bones become soft (as a result of metabolic violations of and in organic part of bones)Osteodythtrophy OsteoporosisAthrophia of bonesIncreasing of quantity Ca in bloodDecreasing of quantity PTHActivate of resorption of bone

Activate of osteoclastes which: - produce a lot of organic acids especially citric for solution hydroxilapatit- produce lisosomal enzymes for solution organic matrix

Implications: frequent fractures, disability Clinical manifestations of hypocalcaemia

How does look osteoporosis?

HypercalciemiaPathological state, at the quantity of in blood more than 2,75 mmoll/lETIOLOGYPrimary hyperparathyrosis (appear at multiple adenomatosis of endocrine glands, inheritance autossomal-dominant disease)

Hypervitanosis D (overdoses of drugs doses cause to excessive absorption in GIT)

Heavy and massive fractures the balance between construction of bone (slowing) and resorption (without changes)

Clinical manifestations of hypercalciemiaOsteodystrophy (Recklinhauzen disease)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. Cystosis swelling in the distal ends of both fibula bones MechanismHyperparatireosis increasing of in blood waste of from bones by resorbtion osteoporosis overgrowth of connective tissue (but isnt deposited) - osteofibrosis

Clinical manifestations of hypercalciemiaKINDSCALCINOSIS (, calcification) accumulation of insoluble salts of In soft tissuesThe main case alkalosis in tissueCellularExtracellularLocalGeneralMetaplasticDystrophyMetabolicMatrix for calcification Mitochondria

Lisosomes

Collagen and elastic fibers

Glicozaminglican

Clinical manifestations of hypercalciemiaThe main reason - hypercalciemiaMetastasic calcinosis The main case alkalosis conditionAppearsVessels (arteries )MyocardiumLungsMucous of stomachKidneys

Substances which are emitted or contacted these organs acids. These tissues have a high alkalinity for saving a normal state.

Metastasic calcinosis

Calcinosis of aortic valve

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 Dystrophic static calcinosis (petrification)Mechanism: alkalinity conditions increased absorption from blood The increased activity of phosphatases, which prodused from necrotic cells formation of insoluble salts of

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 couldnt 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.

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

Implications of calcinosisNegativePositiveCalcinosis atherosclerotic plaque provokes thrombosisCalcinosis of tendons violation of muscles constrictionLungs and heart like an armor violation of function of these organs

Petrification of tuberculosis center sign of healing

Clinical manifestations of hypercalciemiaCALCIPHILAXIA The state of increased sensitivity of organism to Increased quantity of Ca H.Selye (1960-1963) described the phenomenon andcreated an experimental model Sensitizing factor hypercalcaemiaDecisive factor degranulation of mass cells, mechanical damage, salts of l, FeThis phenomenon promotes the localization of process of organ calcification That cam explain the systemic destruction of the cardiovascular system

Hypophosphatemia (norm of P in blood 1.22 2.2 mmoll/l)ETIOLOGYChronic kidneys insufficiency (loosing by kidneys)Diseases of GIT (vomiting, malabsorption syndrome )Hypovitaminosis D (increased absobtion in the GIT)Liver diseasesUsing of insulin at treatment of diabetes mellitus and ketoacidosis (Increase of glucose phosphorylation increase of extracellular using)Restoring of nutrition after full starvation (mechanism is same like previous point)Pathological state, at the quantity of in blood less than 1.22 mmoll/l

Clinical manifestations of hypophosphatemia(long-term decline of )Rickets (in children)/osteomalacia (in adults)X-linked hypophosphatemiaAutossomal-dominant hypophosphatemialdamage of the bonesAutossomal-dominant hypophosphatemial ricketFanconis syndrome (group of diseases, which are manifested general dysfunction of renal tubules + lossing of )The main sign of all forms of rickets heredity defect of enzymes synthesis, which are responsible for transportation of in kidneysClinical manifestations:- Hypophosphatemia - Bones become soft- Delay of growth- In difficult case + violation of functions of liver, heart, brain and development of coma (reason violation of phosphorylation and deficit macroergs )

HyperphosphatemiaETIOLOGYIntensive capture of by kidneys (CKI, hypoparathyreosis, hyperthyroidism)Over use of from the bones (rapid bone growth, healing of fractures, tumor of bones)Intensive absorption in GIT (D hypervitaminosis, acute intestinal obstruction)Massive destruction of cells (hemolytic anemia, leucosis)Pathological state, at the quantity of in blood more than 2.2 mmol/lDont have independent value.Increasing of quantity of causes formation insoluble phosphates Ca in blood. Concentration of ionizing Ca decreases and hypocalcaemia is dominant in clinical manifestation