Pathophysiology of disorders of mineral metabolism (chem path) Flashcards
What are the key hormones regulating mineral homeostasis (4)
Parathyroid hormone (PTH)
Calcitriol
Calcitonin
Fibroblast growth factor 23 (FGF23)
How does PTH regulate minerals?
It acts upon the bones and stimulate osteoclast resorption activity which increases concentration of calcium and phosphate.
Acts upon kidney and promote reabsorption of calcium and excretion of phosphate.
Also activates vitD which stimulates the intestines to absorb more calciuma and phosphate.
How does calcitriol regulate minerals?
It stimulates the intestines to absorb more calcium and phosphate. At high concentrations it also promotes bone resorption by osteoclast to produce more calcium and phosphate into circulation.
How does FGF23 regulate minerals?
It is secreted by osteocytes when calcitriol and phospate levels in circulation are high.
-It increases renal excretion of phosphates by inhibiting the sodium phosphate cotransporter.
- Also inhibits renal 1-alpha hydroxylase.
Net effect- decreases serum phosphate, phosphaturia and decreased serum calcitriol.
How does calcitonin regulate minerals?
It is secreted by the c cells in the thyroid when there are elevated calcium levels.
It inhibits bone resorption by inhibiting osteoclast activity.
Calcitonin is used as a marker for what condition?
Medullary thyroid carcinoma (MTC)
Confounding factors in calcium measurement(2)
Protein
pH
What occurs during alkalosis( high pH) leading to decreased free calcium ions?(4)
Hydrogen ions dissociate from albumin, calcium then binds to albumin.
Also causes an increase in complex calcium formation.
If more calcium binds to albumin, free ionized calcium falls, symptoms and signs of hypocalcaemia.
Note that the total calcium concentration does not change.
What happens during low pH?
In acidosis the concentration of free, ionized calcium increases, symptoms and signs of hypercalcaemia.
Two common causes of hypercalcaemia?
Malignant tumours
Primary hyperparathyroidism
Symptoms of hypercalcaemia(6)
-Hallucinations
-Confusion
-Constipation
-Muscle weakness
-Polyuria, polydipsia
-Arrhythmias
What are other causes of hypercalcaemia? (4)
Thyrotoxicosis- causes high calcium levels by stimulating osteoclastic activity.
Immobilisation-stimulates resorption
Thiazide diuretics- decreases renal excretion of calcium.
Chronic lithium therapy- increased PTH secretion.
VitD toxicity- increases calcium concentration in circulation, stimulate more absorption of calcium from gut.
What is familial hypocalciuric hypercalcaemia
An inherited autosomal dominant trait.
There is a defect in the Calcium Sensing Receptor (CaSR) gene.
Receptor cannot sense high levels of calcium, this may lead to hypercalcaemia.
What is hypocalcaemia?
Low levels of circulating calcium due to hypoparathyroidism, hypomagnesaemia, or vitD deficiency.
What does Vitamin D deficiency cause? (2)
Osteomalacia in adults and rickets in children.
What is the complex metabolic bone disease that hypocalcaemia is often associated with?
Chronic Kidney Disease- Mineral and Bone Disorder (CKD-MBD)
What is renal osteodystrophy? (3)
- Inability to excrete phosphates, leading to the stimulation of FGF23.
-Inhibition of alpha-1 hydroxylase.
-No activation of VitD.
-Low levels of calcium. - Low calcium levels stimulates high PTH secretion.
What causes acquired hypoparathyroidism?(4)
-Infiltrative conditions
-Autoimmune
-Surgery
-Idiopathic
What causes hyperphosphataemia in children?
Undiluted cow’s milk
True or false
Hypophosphataemia is common during alcohol withdrawal.
True
Homeostatic response in Hypophosphataemia
Suppression of FGF23.
What is the NB function of magnesium?
It is important for the maintenance of structures of nucleic acids, proteins and ribosomes.
What is caused by extracellular magnesium depletion?
Hyperexcitability
What increases urinary excretion of magnesium?
ECF volume expansion, hypercalcaemia, hypermagnesaemia.
What do very high magnesium concentration cause
Cardiac arrest and respiratory paralysis
In which instances is hypermagnesaemia induced?
In ICU to:
-reduce bronchospasm in severe asthma.
-reduce fitting in pre-eclampsia.
What causes hypomagnesaemia, physiologically?
Circulating magnesium binding to albumin
What are the causes if hypomagnesaemia? (5)
-Cirrhosis
-Malabsorption, malnutrition
-Diuretic therapy
-Alcoholism
-Drug toxicity
What are the clinical features of hypomagnesaemia? (5)
Tetany, agitation, ataxia, tremor, cardiac arrhythmias.
What do we call the disease where there is an increase in both the osteoblastic and osteclastic activities.
Pagets disease of bone
