Transcript Document

Pathophysiology of calcium-phosphorus
metabolism
Calcium
Са10 (РО4)6 (ОН2)
98 %
86 %
Norm
1,22 – 2,2 mmol/l
Norm
2,35 – 2,75 mmol/l
Role
- Bones
- Tooth
- Blood coagulation
- Membranes permeability
- Nervous impulses pass
- Muscle contraction
- Enzymes activation
(succinatdegydrogenasa,
lecetinasa)
Phosphorus
Role
- Bones
- Tooth
- ATP, КPh)
- Phosphorillation of
carbohydrates
- DNA and RNA synthesis
- Phospholipids of
membranes
- Phosphate buffer
Calcium
Са10 (РО4)6 (ОН2)
Phosphorus
86 %
98 %
Norm
2,35 – 2,75 mmol/l
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)
Norm
1,22 – 2,2 mmol/l
Daily need – 1,5 g
Source – all food
(there is no exogene
deficit)
Absorption - 70 % from
used food
Phosphorus of fish
absorbs in 100 %
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 synthesis
and increase of absorption
in the intestine
Vitamin D
Thyreocalcitonin
Organ-target - bones
Function - decrease of
Ca concentration in
plasma
Violation of
calcium-phosphorus metabolism
Hypocalciemia
Hypercalciemia
Hypophosphatemia
Hyperphosphatemia
Hypocalcaemia
Pathological state, at the quantity of Са in blood
less than 2,35 mmoll/l
ETIOLOGY
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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)
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 on mechanical and other stimuli
Spasm of larynx, bronchus
asphyxia
death
Coronarospasm (cardiotetanus)
Cramps
angina
Stop of heart
ClinicalГіпокальциемія
manifestations of
hypocalcaemia
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
Гіпокальциемія
Clinical manifestations
of hypocalcaemia
Osteodythtrophy
Osteomalacia
The bones become soft
(as a result of metabolic
violations of Са and Р in
organic part of bones)
Osteoporosis
Athrophia of bones
Increasing of quantity Ca in blood
Decreasing 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
How does look osteoporosis?
Hypercalciemia
Pathological state, at the quantity of Са in blood
more than 2,75 mmoll/l
ETIOLOGY
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Primary hyperparathyrosis (appear at multiple adenomatosis of
endocrine glands, inheritance autossomal-dominant disease)
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Hypervitanosis Dз (overdoses of drugs doses cause to excessive
absorption Са in GIT)
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Heavy and massive fractures – the balance between construction
of bone (slowing) and resorption (without changes)
Clinical manifestations of hypercalciemia
Osteodystrophy (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
Mechanism
Hyperparatireosis – 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 hypercalciemia
CALCINOSIS
(звапнення, calcification) – accumulation of insoluble salts of Са
In soft tissues
The main case – alkalosis in tissue
KINDS
Cellular
Extracellular
Local
General
Matrix for calcification
1.
Mitochondria
2.
Lisosomes
1.
Collagen and elastic fibers
2.
Glicozaminglican
Metaplastic
Dystrophy
Metabolic
Clinical manifestations of hypercalciemia
Metastasic calcinosis
The main reason - hypercalciemia
The main case – alkalosis condition
Appears
1.
2.
3.
4.
5.
Vessels (arteries )
Myocardium
Lungs
Mucous of stomach
Kidneys
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
Dystrophic static calcinosis (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: 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.
Metabolic calcinosis (інтерстиціальне звапнення)
Pathogenesis unknown
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 hypercalciemia
CALCIPHILAXIA
The state of increased sensitivity of organism to
Increased quantity of Ca
1.
2.
H.Selye (1960-1963) described the phenomenon and
created an experimental model
Sensitizing factor – hypercalcaemia
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
Hypophosphatemia
(norm of P in blood 1.22 – 2.2 mmoll/l)
Pathological state, at the quantity of Р in blood
less than 1.22 mmoll/l
ETIOLOGY
1.
2.
3.
4.
5.
6.
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 of glucose phosphorylation – increase of extracellular Р using)
Restoring of nutrition after full starvation (mechanism is same like
previous point)
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 )
Hyperphosphatemia
Pathological state, at the quantity of Р in blood
more than 2.2 mmol/l
ETIOLOGY
1.
2.
3.
4.
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 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