Ca and PO4 metabolism

Question 1

What is the distribution of Ca and PO4 in the body?

Answer 1

 50% of the total calcium in serum is
present in the ionized form.
 99% of calcium and 85% of phosphore in
the organism are lacalised in bones.

Question 2

What regulates blood levels of Ca metabolism?

Answer 2

PTH and vitamin D

Question 3

What is the Ca concentration in the serum?

Answer 3

Total serum Ca: 2,1–2,6 mmol/l (8,5–10,5 mg/dl)

Ionized Ca: 1,1–1,3 mmol/l (4,4–5,2 mg/dl)

Question 4

How does PTH control Ca levels?

Answer 4

 Hypercalcemia

 Hypophosphatemia

Question 5

What regulates PTH secretion?

Answer 5

release is controlled by active vit D3

secretion is controlled by Mg and catecholamines

Question 6

What are the effects of PTH on the body?

Answer 6

 Bone – resorption of calcium and phosphate
from bones
 Intestinal mucosa – increase of intestinal
calcium absorption by renal production of 1,25-OH Vitamin D
 Kidney –increases the reabsorption of
calcium and inhibits the reabsorption of
phosphate (thus promotes renal phosphate
excretion). PTH stimulates vitamin D
hydroxylation in the kidney.

Question 7

How is calcitonin regulated in the body?

Answer 7

secreted by parafollicular C cells of the thyroid gland

regulated by serum calcium (increased Ca2+ level stimulate CT release)

Question 8

What are the effects of calcitonin (CT)?

Answer 8

 Hypocalcemia

 Hypophosphatemia

Question 9

What is the effect of excess secretion of CT?

Answer 9

Secretion of extremely high calcitonin levels by
medullary thyroid carcinoma has no effect on
mineral homeostasis.

Question 10

What are the biological effects of calcitonin on the body?

Answer 10

 Bones - the major effect of the hormone is
to inhibit osteoclastic bone resorption.
 Kidney – CT inhibits the reabsorption of
phosphate, increases the renal excretion of
calcium.
 It is important as a tumor marker in
medullary thyroid carcinoma.

Question 11

How is the medullary thyroid carcinoma test conducted?

Answer 11

Stimulation tests – up-regulation of
calcitonin production
Test with pentagastrin (0,5ug/kg body weight
(i.v.) in 5 sec.) or fast intravenous supplementation of gluconate calcium (2 mg of calcium/kg body weight iv over 1 minute).

Question 12

What vitamin controls the levels of calcium in the body?

Answer 12

1,25-OH Vitamin D is the most important

metabolite, and is the most biologically active.

Question 13

What are the effects of 1,25-OH Vitamin D

Answer 13

 Hypercalcemia

 Hyperphosphatemia

Question 14

How are the target tissues affected by 1,25-OH Vitamin D?

Answer 14

 Intestine – the transport of calcium through the
cytosol requires a vitamin-D-inducible protein
called calbindin.
 Bone – 1,25OH-D plays a role in regulating bone
formation and resorption (promotes phosphate
deposition).
 Kidney – it stimulates calcium and phosphate
reabsorption by the kidney tubules.
 Parathyroid glands – decreased vitamin D
production stimulates secretion of PTH.

Question 15

How is the presence of hypercalcemia defined by lab values?

Answer 15

Level of total calcium in blood > 2,7 mmol/l

or level of ionised calcium > 1,3 mmol/l

Question 16

What are some important causes of hypercalcemia?

Answer 16

 Primary hyperparathyroidism
 Tertiary hyperparathyroidism in chronic renal failure
 Malignancies
 Sarcoidosis – it increases 1,25OH-D production
 Endocrinopathies (thyrotoxicosis, adrenal
insufficiency, pheochromocytoma)
 Drug-induced (iatrogenic)– especially thiazide
diuretics which increase calcium reabsorption in the
kidney (and loss of potassium)
 Idiopathic hypercalcemia

Question 17

What is a hypercalcemic crisis?

Answer 17

 Calcium level in blood over 3.5mmol/l
 Clinical symptoms: short QT interval,
polyuria, polydipsia, nausea, vomites,
shock, coma.
 Biochemical test: hypercalcemia,
hypophosphatemia, dehydratation,
electrolytes imbalance, metabolic acidosis

Question 18

What is the etiology of primary hyperparathyroidism?

Answer 18

single parathyroid adenoma 80%,
primary hyperplasia 15%,
parathyroid carcinoma 1-2%

Question 19

What are the symptoms of primary hyperparathyroidism? 5

Answer 19

 Kidney – renal stones, nephrocalcinosis, polyuria,
polydipsia, uremia
 Bone – osteitis fibrosa, osteoporosis
 Gastrointestinal tract – constipation, nausea, vomiting,
peptic ulcer, pancreatitis
 Psychiatric – lethargy, fatigue, depression, psychoses
and others
 Others - hypertension, itching, keratitis, soft tissue
calcification

Question 20

What are the lab values indicating primary hyperparathyroidism? 6

Answer 20

 Calcium level in blood > 2,6 mmol/l
 Hypercalciuria – normally 6 mmol/24h
 Phosphor level- in lower norm range or
decreased
 PTH level – increased over 60pg/ml
 Alkaline phosphatase level – increased
 Tests of kidney function – creatinine,
clirens of creatinine.

Question 21

What is hungry bone syndrome?

Answer 21

 In patients with severe hyperparathyroid
bone disease after successful parathyroidectomy.
 Increased uptake of calcium and
phosphate by the bones.

Question 22

What is secondary hyperparathyroidism?

Answer 22

increased PTH secretion is associated with hypocalcemia

 Decreased resorption of calcium from the
intestine
 Chronic kidney failure (decreased vit D
production, hyperphosphatemia)
 Decreased concentration of vit D in blood

Question 23

What is renal osteodystrophy?

Answer 23

 Chronic renal diseases result in reduced
circulating levels of vitamin D metabolites,
and high levels of phosphate in the serum.
They bound calcium (soft tissue calcification)
– two reasons for hypocalcaemia.
 Hypocalcaemia and low levels of 1,25OH-D
stimulate PTH production – secondary
hyperparathyroidism.
 bones gradually become thin and weak with
increased risk of bone fractures

Question 24

Secondary hyperparathyroidismbiochemical parameters?

Answer 24

 Increased PTH level
 Hypocalcemia eventually calcium level at
the low normal range
 Hyperphosphatemia
 Increased level of alkaline phosphatase
 Parameters of renal function

Question 25

What are the blood parameters of hypocalcemia?

Answer 25

Level of total calcium in blood < 2,2 mmol/l,

or level of ionised calcium < 1,1 mmol/l

Question 26

What are the causes of hypocalcemia?

Answer 26

 Normal magnesium level in blood
 Hypoparathyroidism
 Resistance to PTH action – pseudohypoparathyroidism,
renal insufficiency (secondary hyperparathyroidism)
 Vitamin D deficiency or resistance to vitamin D action
 Acute hyperphosphatemia, transfusion of citrated blood
 „Hungry bones syndrome” – idiopatic increased uptake of
calcium and phosphate by the bones.
 Decreased magnesium level
 Impaired intestinal absorption
 Alcoholism

Question 27

What are the symptoms of hypocalcemia?

Answer 27

 Neuromuscular manifestation – tetany,
paresthesias, laryngeal spasm, latent
tetany, generalized seizures,
pseudotumor cerebri,
 Cardiac effect – prolongation of the QT
interval
 Subcapsular cataract
 Skin – is dry and flaky and nails are brittle

Question 28

What is primary hypoparathyroidism?

Answer 28

 Lack or not efficient production of biological
active from of PTH.
 Pathophysiology:
 Hypocalcemia – decreased calcium mobilisation
form the bones, decreased absorbtion form the
digestive syndrome, decreased production of
metabolites of vit D3 in kidney; inhibited renal
readsorption of calcium
 Hyperphosphatemia – inhibits production of vit D3
metabolites in kidney; accumulation of calcium
phosphate in soft tissues.

Question 29

What are the lab results of hypoparathyroidism?

Answer 29

 Hypocalcemia in blood
 Hyperphosphatemia with phosphaturia
 Low PTH concentration in blood
 Decreased level of 1,25(OH)2D3

Question 30

What is pseudohypoparathyroidism?

Answer 30

Rear inherited syndrome characterized by end-organ
resistance to PTH.
Types:
 1A – lack of 1 allel of gene for subunit of protein G
(inheritance AD); 50% reduction of effectiveness of
PTH binding to adenyl cyclase (resistance to PTH).
Often is correlated with resistance to TSH, LH, FSH.
Biochemical parameters: hypocalcemia,
hyperphosphatemia, increased level of PTH.
 1B – isolated resistance to PTH

Question 31

How is phosphate metabolized?

Answer 31

 Phosphor is deposited in skeleton as hydroxyapatite,
 15 % is distributed among extra skeletal sites
like phosphoproteins, phospholipids, and nucleic acids
 In blood, phosphorus exists as the phosphates, H2PO4
- and HPO42-, but its concentration is measured as phosphorus, with a normal range of 0,87 – 1,45 mmol/l (2.5 -4.5 mg/dl).

Question 32

How is phosphate metabolism hormonally controlled?

Answer 32

 Kidney - PTH and CT increase phosphorus excretion, and Vitamin D decreases its excretion.
 Intestine - Vitamin D increases absorption as well as PTH.
 Bone – PTH stimulates phosphor release into the blood

Question 33

What phosphate level indicates hypophosphatemia?

Answer 33

Phosphate level of less than 2.5 mg/dl (0.87

mmol/l).

Question 34

What are causes of hypophosphatemia?

Answer 34

 hyperparathyroidism,
 Hypothyroidism,
 impaired kidney function,
 diuretics for a long time,
 severe undernutrition,
 diabetic ketoacidosis,
 severe alcohol intoxication,

Question 35

What phosphate level indicates hyperphosphatemia?

Answer 35

Phosphate level of higher than 4.5 mg/dl (1.45 mmol/l).

Question 36

What are causes of hyperphosphatemia?

Answer 36

 kidney failure
 primary hypoparathyroidism
 bone diseases (fractures, neo)
 acromegaly
 sarcoidosis
 severe burns