Disorders of calcium and sodium regulation Flashcards
what are the main mechanism that regulate water status
- Thirst
- Anti-diuretic hormone (ADH) from posterior pituitary gland
_____ and _____ regulation is closely linked
sodium
water
plasma osmolality is tightly regulated through _____
sodium
ADH is released by the posterior pituitary in response to what things?
- Decreased plasma volume (sensed by baroceptors in atria/veins/carotids)
- Increased plasma osmolality (sensed by osmoreceptors in hypothalamus)
ADH acts mainly via which receptor
AVPR2
Where is AVPR2 found and what are its action
- Basolateral membrane of kidney collecting ducts
- Inserts aquaporin channels to increase renal water reabsorption
what is the effect of aldosterone on the kidneys
increases sodium reabsorption through ENaC- so water reabsorption happens too because water follows sodium and potassium excretion in the distal nephron
This increase in sodium status also increases plasma volume and raises blood pressure
what is hyponatraemia defined as
Serum sodium < 135 mmol/l
what is the cause of hyponatraemia
Almost always due to disorder of water balance
- Inability to suppress ADH release so inappropriate retention of water (opposite of Diabetes insipidus)
Renal impairment
- Diuretic effect (especially thiazides)
what are the 3 main reasons for hyponatraemia
- Na and water deficit (hypovalaemia)
- Water excess (euvolemia)
- Na and water excess (hypervalaemia)
what are the causes of hypovalaemia (Na and water deficit)
1) Renal Losses: Diuretic excess Mineralcorticoid deficiency Salt-losing nephritis Ketonuria Osmotic diuresis
2) Extra renal losses:
Vomiting
Diarrhoea
Pancreatitis
what are the causes of euvolemia (Water excess)
Glucocortioid deficiency Hypothyroidism Pain Psychiatric disorders Drugs
what are the causes of hypervalaemia (Na and water excess)
Nephrotic syndrome
cardiac failure
Acute and chronic renal failure
cirrhosis
What is ‘Syndrome of inappropriate anti-diuretic hormone (SIADH)’
Excess ADH or inappropriate ADH for plasma osmolality
Why is SIADH the commonest cause of low plasma sodium
due to increased body water- dilutes plasma osmolality
what are the causes of SIADH
Cancer: lung/lymphoma/leukaemia
Chest disease: pneumonia
CNS disorders: infections, injury
Drugs: opiates, thiazides, anti-convulsants, proton pump inhibitors, anti-depressants
How to diagnose SIADH
Presence of these:
- Hyponatraemia with inappropriate low plasma osmolality
- Urine osmolality> plasma osmolality
- Urine sodium> 30 mmol/l
- pivotal for DIAGNOSIS (both would be high)
- no recent use of diuretic agents
Absence of adrenal, thyroid, pituitary or renal insufficiency
why is it important that intracellular and extracellular osmolality must be equal
When the serum [Na] is low, water moves into cells to increase plasma osmolality causing cell swelling
what happens to the brain when there is a sudden decrease in Na
Cerebral Oedema (swelling)
what happens to the brain when there is a sudden increase in Na
Osmotic demyelination syndrome (water moves out of brain to bring down plasma osmolality)
What are the neurological clinical features of Hyponatraemia
Begins as being asymptomatic but as plasma Na falls brain swelling occurs leading: - Mild confusion - Gait instability - Marked confusion - Drowsiness - Seizures
what is the management of hyponatraemia
1) Severe and acute
Unconscious or seizures- symptoms
Give infusion of hypertonic (3%) saline
Can increase sodium quickly
2)Less severe +/- chronic (common)
Establish causes- e.g. diuretics
Fluid Restriction- increase in fluid will cause further hyponatraemia
Increase Na slowly- if sodium increased too quickly then risk of osmotic demyelination
2nd line Treatment:
AVPR2 antagonists (‘vaptans’)- antagonise effect of ADH
Very expensive
What are the cuases of hypernatraemia
Most usually due to water loss (‘dehydration’) and inability to access water
Main causes:
Insensible/sweat losses (severe burns/sepsis)
GI losses- severe diarrhoea or vomiting
Diabetes Insipidus
Osmotic diuresis due to hyperglycaemia
what is the management of hypernatraemia
Treat Cause Estimate total body water deficit if possible and correct loss Avoid overly rapid correction - Aim for ↓ 10 mmol/l in 24 hours - Concern is cerebral oedema Use IV 5% dextrose
What are the sources of Calcium
GI tract
Bones
Kidney
How does the GI tract contribute to Calcium homeostasis
Absorbed throughout small intestine from dietary sources (only approx 10% absorbed)
Vitamin D dependent
How does bone contribute to Calcium Homeostasis
Body Calcium reservoir
Regulates plasma Ca via action of osteoblasts and osteoclasts
How does Kidney contribute to Calcium Homeostasis
Free Ca filtered by glomerulus
97-99% is reabsorbed
What role does Vitamin D play in calcium homeostasis
Increases GI absorption
Increases bone resorption
Increased renal reabsorption
WHat role does PTH play in calcium regulation
When decreased Plasma calcium Levels:
Parathyroid glands release PTH, which acts on:
1) Bones
Resorption
Release of Calcium and Phosphate
2) Kidneys
Increased Phosphate excretion
Increased Calcium Reabsoprtion
Increased Calcitriol Formation–> Increased CaHPO4 absorption
what is hypercalcaemia
High calcium levels in blood
what are the clinical features of hypercalcaemia
Neurological:
- Confusion
- Fatigue
- Stupor, coma
- Decreased concentration
o MSK:
- Muscle weakness
- Bone pain
- Osteopenia/osteoporosis
o GI:
- Anorexia, Nausea and vomiting
- Bowel hypomotility and constipation
- Pancreatitis
- Peptic ulcer disease
o Renal:
- Polyuria
- Polydipsia
- Nephrolithiasis and nephrocalcinosis
- Nephrogenic DI
- Acute and chronic renal insufficiency
- Distal renal tubular acidosis
What are the ECG changes in hypercalcaemia
Shortened QTc interval
Bradycardia- slow heartbeat
–> becomes a life threatening problem
what are the causes of hypercalcaemia
Primary Hyperpararhyroidism:
- Due to single parathyroid adenoma with raised PTH and Ca
Malignancy:
secretion of PTH-related peptide (produced by cancers)
Breast, lung and multiple myeloma are commonest tumours
Also, seen in bone metastases due to direct osteolysis
what is the diagnosis of hypercalcaemia
Measure PTH
If ↓ then malignancy likely
If ‘normal’ or ↑ then primary hyperparathyroidism
what is the management of hypercalcaemia
rehydration, biphosphonates, other agents
Treat underlying cause
1) Rehydration
- Patients often hypovolaemic
- Hypovolaemia impairs renal clearance of calcium
- Isotonic (0.9%) saline infusion corrects hypovolaemia
- Be careful of fluid overload
- Hourly bags of saline to bring Ca down to normal
2) Biphosphonate Therapy
- Inhibit bone resorption by inhibiting osteoclasts activity
- Agent of choice for treating hypercalcaemia of malignancy or acute hypercalcaemia
- Zolendronic acid is most commonly used
- Delayed effect, maximal at 2-4 days after treatment
3) Other agents Calcitonin - Increases renal calcium excretion - Decreases bone resorption of calcium - Only effective for 48 hours- so can be used while waiting for bisphosphonate to work
Glucocorticoids
- Inhibit vitamin D production
Parathyroidectomy
- Only if resistant to treatment
- Rarely indicated urgently and Carried out further down the line
what are the complications of acute hypocalcaemia
Tetany
- Increased neuromuscular excitability
- Peri-oral numbness, muscle cramps, tingling of hands/feet
- If severe: carpopedal spasm, laryngospasm, seizures
Cardiac complications
- Dysrhythmia
- hypotension
- Prolonged QT on ECG
what are the causes of hypocalcaemia
Low PTH
- After parathyroid/ thyroid surgery
- Autoimmune hypoparathyroidism
High PTH
- Vitamin D deficiency
- Chronic renal failure
- Loss of Calcium
Drugs
Hypomagnesaemia
Leads to PTH resistance
what is the management of hypocalcaemia
Intravenous calcium replacement if tetany or cardiac manifestations May also need magnesium infusion Chronic management: Vitamin D replacement (D2 or D3) Oral calcium salts Treat underlying cause
