Pathophysiology of calcium-phosphorus metabolism

Calcium98 %

Са10 (РО4)6 (ОН2) Phosphorus86 %

Norm2,35 – 2,75 mmol/l

Norm1,22 – 2,2 mmol/l

Role - Bones- Tooth- Blood coagulation- Membranes permeability- Nervous impulses pass- Muscle contraction- Enzymes activation (succinatdegydrogenasa, lecetinasa)

Role - Bones- Tooth- ATP, КPh)- Phosphorillation of carbohydrates- DNA and RNA synthesis- Phospholipids of membranes- Phosphate buffer

Са10 (РО4)6 (ОН2)

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 foodPhosphorus of fish absorbs in 100 %

Calcium 98 %

Phosphorus86 %

Norm2,35 – 2,75 mmol/l

Norm1,22 – 2,2 mmol/l

Hormone regulation of calcium-phosphorus metabolism

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 synthesisand increase of absorption in the intestine

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 synthesisand increase of absorption in the intestine

Vitamin DVitamin D Thyreocalcitonin

Organ-target - bones

Function - decrease of Ca concentration in plasma

Thyreocalcitonin

Organ-target - bones

Function - decrease of Ca concentration in plasma

Violation of calcium-phosphorus metabolism

Hypocalciemia

HypercalciemiaHypophosphatemia

Hyperphosphatemia

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 Са in GIT, which

are 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)

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 Са in GIT, which

are 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)

HypocalcaemiaHypocalcaemia

Pathological state, at the quantity of Са in blood less than 2,35 mmoll/l

Pathological state, at the quantity of Са in blood less than 2,35 mmoll/l

Cramps

Cramps

Clinical manifestations of hypocalcaemiaClinical manifestations of hypocalcaemia

TetanusTetanus

The process of tetanus potentiation

at the motor neurons and interneuron of spinal cord violate

The process of tetanus potentiation

at the motor neurons and interneuron of spinal cord violate

Conduction of impulses at reflex arch become easier Conduction of impulses at reflex arch become easier

Activate a reflex muscles contraction on mechanical and other stimuli Activate a reflex muscles contraction on mechanical and other stimuli

Spasm of larynx, bronchus

asphyxia

death

Spasm of larynx, bronchus

asphyxia

death

Coronarospasm (cardiotetanus)

angina

Stop of heart

Coronarospasm (cardiotetanus)

angina

Stop of heart

ГіпокальциеміяГіпокальциемія

Ricket

Acquired forms

- Lack of vit. Dз in food

- Lack of insolation – insufficient of synthesis

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 type 2

(reason – insensitivity of target organs to 1,25(ОН)2 Dз

Very difficult clinical manifestation

Clinical manifestations of hypocalcaemia

Clinical manifestations of hypocalcaemia

ГіпокальциеміяГіпокальциемія

Osteomalacia The bones become soft

(as a result of metabolic violations of Са and Р in organic part of bones)

Osteomalacia The bones become soft

(as a result of metabolic violations of Са and Р in organic part of bones)

Osteodythtrophy

OsteoporosisAthrophia of bones

OsteoporosisAthrophia of bones

Increasing of quantity Ca in bloodIncreasing of quantity Ca in blood

Decreasing of quantity PTHDecreasing of quantity PTH

Activate 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

Activate 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 hypocalcaemiaClinical manifestations of hypocalcaemia

How does look osteoporosis?

HypercalciemiaHypercalciemia

Pathological state, at the quantity of Са in blood

more than 2,75 mmoll/l

Pathological state, at the quantity of Са in blood

more than 2,75 mmoll/l

ETIOLOGY Primary hyperparathyrosis (appear at multiple adenomatosis of

endocrine glands, inheritance autossomal-dominant disease)

Hypervitanosis Dз (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)

ETIOLOGY Primary hyperparathyrosis (appear at multiple adenomatosis of

endocrine glands, inheritance autossomal-dominant disease)

Hypervitanosis Dз (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)

Clinical manifestations of hypercalciemiaClinical 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.

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

Cystosis swelling in the distal ends of both fibula bones

MechanismHyperparatireosis – increasing of Са in blood – waste of Са from bones by resorbtion – osteoporosis – overgrowth of connective tissue (but Са isn’t deposited) - osteofibrosis

MechanismHyperparatireosis – increasing of Са in blood – waste of Са from bones by resorbtion – osteoporosis – overgrowth of connective tissue (but Са isn’t deposited) - osteofibrosis

Clinical manifestations of hypercalciemiaClinical manifestations of hypercalciemia

KINDS

CALCINOSIS (звапнення, calcification) – accumulation of insoluble salts of Са

In soft tissuesThe main case – alkalosis in tissue

CALCINOSIS (звапнення, calcification) – accumulation of insoluble salts of Са

In soft tissuesThe main case – alkalosis in tissue

CellularExtracellularCellularExtracellular

LocalGeneralLocalGeneral

MetaplasticDystrophyMetabolic

MetaplasticDystrophyMetabolic

Matrix for calcification

1. Mitochondria

2. Lisosomes

1. Collagen and elastic fibers

2. Glicozaminglican

Matrix for calcification

1. Mitochondria

2. Lisosomes

1. Collagen and elastic fibers

2. Glicozaminglican

Clinical manifestations of hypercalciemiaClinical manifestations of hypercalciemia

The main reason - hypercalciemiaThe main reason - hypercalciemia

Metastasic calcinosis Metastasic calcinosis

The main case – alkalosis conditionThe main case – alkalosis condition

Appears1. Vessels (arteries )2. Myocardium3. Lungs4. Mucous of stomach5. Kidneys

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

state.

Appears1. Vessels (arteries )2. Myocardium3. Lungs4. Mucous of stomach5. Kidneys

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

state.

Metastasic calcinosis 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

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)Dystrophic static calcinosis (petrification)

Mechanism: alkalinity conditions – increased absorption Са from blood – The increased activity of phosphatases, which prodused from necrotic cells

– formation of insoluble salts of Са

Mechanism: alkalinity conditions – increased absorption Са from blood – The increased activity of phosphatases, which prodused from necrotic cells

– formation of insoluble salts of Са

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.

Pathogenesis unknown

Metabolic calcinosis (інтерстиціальне звапнення)Metabolic calcinosis (інтерстиціальне звапнення)

Limestone deposits in skin, tendons, fascias, muscles, along

nerves and vessels

Implications of calcinosis

Negative Positive

Calcinosis atherosclerotic plaque – provokes thrombosis

Calcinosis of tendons –

violation of muscles constriction

Lungs and heart like an armor – violation of function of these

organs

Petrification of

tuberculosis center – sign of healing

Clinical manifestations of hypercalciemiaClinical manifestations of hypercalciemia

CALCIPHILAXIA The state of increased sensitivity of organism to

Increased quantity of Ca

CALCIPHILAXIA The state of increased sensitivity of organism to

Increased quantity of Ca

H.Selye (1960-1963) described the phenomenon andcreated an experimental model

1. Sensitizing factor – hypercalcaemia2. Decisive factor – degranulation of mass cells, mechanical

damage, salts of Аl, Fe

H.Selye (1960-1963) described the phenomenon andcreated an experimental model

1. Sensitizing factor – hypercalcaemia2. Decisive factor – degranulation of mass cells, 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

This 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)

Hypophosphatemia (norm of P in blood 1.22 – 2.2 mmoll/l)

ETIOLOGY1. Chronic kidneys insufficiency (loosing by kidneys)2. Diseases of GIT (vomiting, malabsorption syndrome )3. Hypovitaminosis D (increased absobtion in the GIT)4. Liver diseases5. Using of insulin at treatment of diabetes mellitus and ketoacidosis

(Increase of glucose phosphorylation – increase of extracellular Р using)6. Restoring of nutrition after full starvation (mechanism is same like

previous point)

ETIOLOGY1. Chronic kidneys insufficiency (loosing by kidneys)2. Diseases of GIT (vomiting, malabsorption syndrome )3. Hypovitaminosis D (increased absobtion in the GIT)4. Liver diseases5. Using of insulin at treatment of diabetes mellitus and ketoacidosis

(Increase of glucose phosphorylation – increase of extracellular Р using)6. Restoring of nutrition after full starvation (mechanism is same like

previous point)

Pathological state, at the quantity of Р in blood

less than 1.22 mmoll/l

Pathological state, at the quantity of Р in blood

less than 1.22 mmoll/l

Clinical manifestations of hypophosphatemia(long-term decline of Р)

Clinical manifestations of hypophosphatemia(long-term decline of Р)

Rickets (in children)/osteomalacia (in adults)

X-linked hypophosphatemia

Autossomal-dominant hypophosphatemial

damage of the bones

Autossomal-dominant hypophosphatemial ricket

Fanconi’s syndrome (group of diseases, which are manifested

general dysfunction of renal tubules + lossing of Р)

The main sign of all forms of rickets – heredity defect of enzyme’s

synthesis, which are responsible for transportation of Р in kidneys

Clinical 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 )

HyperphosphatemiaHyperphosphatemia

ETIOLOGY1. Intensive capture of Р by kidneys (CKI, hypoparathyreosis, hyperthyroidism)2. Over use of Р from the bones (rapid bone growth, healing of fractures, tumor of bones)3. Intensive absorption Р in GIT (Dз hypervitaminosis, acute intestinal obstruction)4. Massive destruction of cells (hemolytic anemia, leucosis)

ETIOLOGY1. Intensive capture of Р by kidneys (CKI, hypoparathyreosis, hyperthyroidism)2. Over use of Р from the bones (rapid bone growth, healing of fractures, tumor of bones)3. Intensive absorption Р in GIT (Dз hypervitaminosis, acute intestinal obstruction)4. Massive destruction of cells (hemolytic anemia, leucosis)

Pathological state, at the quantity of Р in blood

more than 2.2 mmol/l

Pathological state, at the quantity of Р in blood

more than 2.2 mmol/l

Don’t have independent value.

Increasing of quantity of Р causes formation insoluble phosphates Ca in blood.

Concentration of ionizing Ca decreases and hypocalcaemia is dominant in clinical manifestation

Don’t have independent value.

Increasing of quantity of Р causes formation insoluble phosphates Ca in blood.

Concentration of ionizing Ca decreases and hypocalcaemia is dominant in clinical manifestation