Calcium and Sodium Homeostasis Flashcards
What is hypercalcaemia when PTHrP causes it
Known as humoral hypercalcaemia of malignancy when PTHrP is the cause
What cytokines produced by Multiple Myeloma activate osteoclasts
RANKL, IL-3, IL-6
One common sign of Multiple Myeloma
Pepperpot skull
How do granulomas cause hypercalcaemia
- Increased calcium concentration with PTH concentration
- Due to hydroxylation of Vit D in granuloma
what drugs can cause hypercalcaemia
Li, thiazide
What endocrine diseases can cause hypercalcaemia
(thyrotoxicosis, Addison’s disease)
Neuromuscular manifestations of hypocalcaemia
- Numbness and paraesthesia in fingertips, toes and around mouth
- Anxiety and fatigue
- Muscle cramps, carpo-pedal spasm, bronchial or laryngeal spasm
- Seizures
How does hypo and hyper calcaemia affect QT interval
Hypo=> prolongs, vv
effect of hypocalcaemia on eyes
Cloudiness of eyes lens and cataract
Causes of factitious hypocalcaemia
- Acute phase response (low albumin)
- Malnutrition or malabsorption
- Protein deficiency in diet
- Liver disease
- Reduced liver synthesis of albumin
- Nephrotic syndrome
- Albumin lost in urine
Causes of VDRR
- Deficient 1-hydroxylase (Vitamin D-resistant rickets type 1, VDRR type 1)
- Deficient receptor for calcitriol(Vitamin D- resistant rickets Type 2, VDRR type 2)
Other causes of rickets apart of VDRR
- Hypophosphataemic rickets
- Low Serum Phosphate→ Impaired mineralisation
- Excessive urine phosphate loss
- Phosphaturic hormone (FGF23)/ PHEX mutations
Hypophosphatasia ( low Alk Phosphatase)
Causes of 1* hypoparathyroidism
- Surgical damage or removal ( relatively common but usually transient)
- Suppressed secretion
- May be due to low Mg 2+,which is required for PTH action
- Caused by drugs, lost through GI tract etc.
- May be due to low Mg 2+,which is required for PTH action
- Inherited ( dont really need to know )
- Developmental Parathyroid Problems
- Genetic/ familial disorders eg. DiGeorge Syndrome
Treatment of hypoparathyroidism
- IV calcium may be required in acute situations
- Normally oral calcium and Vit D are given (Mg sometimes in less serious case)
- Vitamin D may be given in various forms
- By IM injection if malabsorption is present (can give large bolus to repair more quickly) or stores are required to be repleted more quickly
- As 1 OH form if renal function is impaired
- Close monitoring of plasma calcium concentration necessary
- Vitamin D may be given in various forms
What does reduced Cardiac output result in
Reduced Effective Circulating Volume
3 diseases causing interstitial oedema and how does this relate to water and salt gain/loss. Is hyponatraemia here hypervolaemic or hypo
Heart failure, liver failure, Nephrotic syndrome
water> salt gain
HYPER
What does hypothyroidism cause wrt water balance
pure water gain
common cause of malignant ectopic secretion of ADH
Small Cell Lung Carcinoma
Most common cause of hypernatremia
Hypovolaemia
What is a more likely cause of CDI
Head injury compared to pit tumour
Metabolic causes of NDI
Hyokalemia or Hypercalcaemia
How to treat NDI
Supraphysiological ADH, diuretics, NSAIDs
What is cholecalciferol and where is it found and converted
Vitamin D, gets converted by 25 hydroxylase in the liver to calcidiol
What enzyme is present in the kidney and what does it do wrt vitamin D metabolism
1a-hydroxylase
Converts 25(OH) Vit D to 1,25 (OH)2 VItamin D
What is calcitonin a useful marker of
Thyroid medullary cancer
what are the manifestation of hypercalcemia
“Stones, bones. abdominal moans, and psychic groans”
Muscle weakness (and constipation) ⇒both striated and smooth muscles
Anorexia, nausea, vomiting, mood change, depression
Abdominal pain
Renal effects- dehydration and renal stone formation,
What are the possible causes of hypercalcemia
Primary hyperparathyroidism - 90% solitary (benign)adenoma, some hyperplasia (of one or both glands), carcinoma
How are PTH, phosphate and bicarbonate, ALk Phosp levels in primary hyperparathyroidism
What causes these effects on phosphate and bicarbonate?
-
inappropriately increased PTH
- PTH not always high, may be high-normal
- Reduced serum phosphate and HCO3- (see below) also causes complexed calcium to be freed up and released into ionised fraction due to inhibition of proximal tubule reabsorption of Po4- and bicarbonate
Alk phos high or normal due to bonr resorption
Effect of primary hyperparathyroidism on pH level and what effect doe this have on the body?
Causes mild acidosis due to reduced uptake of bicarbonate, s which causes calcium to be leached from the bone, decreases calcium binding to albumin
Treatment of hyperparathyroidism
FIRST LINE is to rehydrate by IV - brings calcium concentration down
Can give loop diuretics like furosemide to inhibit distal ca2+ reabsorption
Can also give bisphosphonates- inhibit osteoclast action and hence bone resorption (Key drug for longer-term control after re-hydration)
What drug can inhibit osteoclast action
Calcitonin
What drugs can inhibit conversion of Vitamin D to calcitriol
Glucocorticoids
How do metastatic tumours cause hypercalcaemia
They locally stimulate bone resorption via osteoclast activation
diagnosis of hypercalcaemia from malignancy- what are the common investigations
Raised Ca2+ with suppressed PTH , high phosphate, high alk phosp
treatment of hypercalcaemia from malignancy
Rehydrate patient, use bisphosphonates to lower calcium in blood , treat underlying malignancy
What problems can hypocalcemia cause apart for mental and neuromuscular and cardiac functions
Eye probelms- cloudiness of eye lens and cataract
What is the most readily measured vitamin D metabolite
25-hydroxy-vitamin D released into plasma from the liver
how does Vitamin D deficiency affect phosphate
Reduces gut absorption of calcium which results in lower calcium levels in blood and higher PTH levels which result in increased bone resorption and increased phosphate wasting
diff between osteoporosis and osteomalalcia
less bone but histologically normal vs abnormal histology with wide seams of uncalcified osteoid
Essentially normal biochemistry vs Abnormal biochemistry→ low plasma vit D3, low calcium, high PTH
Sim between osteoporosis and osteomalalcia
Both have reduced bone density and susceptibility to fracture
What are the main causes of euvolaemic hyponatraemia and is there water or salt loss or gain
SIADH, hypothyroid, iatrogenic. pure water gain
What can dilutional hyponatraemia cause
Cerebral oedema
What are common causes of more salt loss than water loss
Is this hypo or hypervolaemic
diarrhea can be salt rich
HYPO
What are two non malignant causes of ectopic SIADH secretion
TB and pneumonia
What drugs can cause SIADH
thiazide diuretic, carbamazepine, amitriptyline
Why should hyponatraemia be corrected slowly
- Central Pontine Myelinolysis
- Devastating/fatal condition associated with rapid correction of hyponatraemia → due to nerve fibres in pons losing their myelin sheath
Treatment of hypervolaemic hyponatraemia
Diuretics like furosemide, fluid restriction
Treatment of euvolaemic hyponatraemia
- Treat underlying cause
- Stop IV fluids
- Thyroxine replacement
- Fluid restriction!!!
- Down to 500ml/day
- Rarely demeclocycline
What is the proportion of water to salt in colon
Musch higher proportion of water as salt is already absorbed in the small bowel
What infections can cause SIADH and DI
meningitis and encephalitis
What drug can cause NDI
Lithium carbonate which blocks receptors in nephron
Treatment for DI
- DDAVP exists ( nasal spray)
- Works in CDI
- For NDI
- Supraphysiological ADH may work
- Diuretics
- NSAIDs
Does addison’s result in hypo or hypernatraemia
hyponatraemia
Should rehydration be given for DI
No
What are the effects of PTH on calcium levels and how
Increases
- More calcium resorbed in Kidney (LOH, DCT and CD)
- Vit D3 activated to stimulate ca2+ absorption in gut
- Bone resorption
