Polyuria

Urine output of >3 litres per day.  Note that it is usually accompanied by urinary frequency, but that frequency itself may not indicate polyuria (i.e. frequently passing small vs large volumes).

Pathophysiology

  • In general, polyuria can be a result of anything that causes
    • Increased water intake (polydipsia)
    • Decreased ADH (antidiuretic hormone) secretion (central diabetes insipidus)
    • Decreased peripheral ADH sensitivity (nephrogenic diabetes insipidus)
      • ADH promotes water reabsorption in the renal collecting ducts
    • Solute diuresis (most commonly seen in uncontrolled diabetes mellitus- where high glucose concentrations cause a passive diuresis)

Assessment

  • History
    • Define the extent of polyuria and distinguish between urinary frequency i.e. how much urine
    • If polyuria is present, explore this
      • Onset, Duration, Progression, Triggers, Exacerbating/Alleviating factors
      • Associated symptoms- specifically thirst/drinking (polydipsia); weight changes, (also night sweats)
    • Specific things to ask about include
      • Any recent IV fluids/tube feeds; recent catheterisation/urinary obstruction; recent head trauma/surgery or stroke
        • Note patients can be polyuric following urinary obstruction
    • PMHx
      • Diabetes mellitus
      • Psychiatric disorders – on lithium treatment
      • Sickle cell disease
      • Sarcoid/amyloidosis
      • Hyperparathyroidism
      • Hypertension – on diuretics
      • Alcohol and caffeine intake
      • Smoking history
  • Examination
    • General examination of
      • Blood pressure/pulse
      • Weight
      • Mucous membranes (dry?)
      • Skin (dry, pigmented lesions, ulcers/nodules)
    • Neurological/psychiatric exam (doesn’t have to be extensive but may be further explored if there is any suspicion or positive findings
      • e.g. papilloedema; visual fields etc

Red Flags

  • Abrupt onset or onset in children
  • Night sweats, weight loss (particularly where there is a smoking history too)
  • Psychiatric disorder

Investigations

  • Serum or fingerprick (BM) glucose measurement and urinalysis to rule out diabetes mellitus
  • Where hyperglycaemia is absent
    • U&Es including serum Calcium
      • Hypernatraemia suggests excess water loss due to diabetes insipidus
      • Hyponatraemia suggests excess free water intake (polydipsia)
    • Urine osmolarity
      • usually low with water diuresis and high with solute diuresis
  • If a diagnosis is not yet clear, a water deprivation test can be done
    • (NB only to be done as an inpatient under supervision)
      • Typically a baseline set of weight, bloods and observations are performed in the morning.  The patient is then deprived of water.  Where possible, hourly samples of urine are tested for osmolarity and sodium concentrations.  Once the patient shows signs of deprivation (i.e. orthostatic hypotension; postural tachycardia; >=5% weight loss OR if the urinary concentration does not increase by >30mOsm/kg), baseline measurements are repeated and a bolus of exogenous ADH administered.  One hour later, measurements are repeated again.
    • Interpretation
      • Normal
        • Maximal urine osmolarity after dehydration (>700mOsm/kg), and osmolarity does NOT increase >5% following ADH injection
      • Central diabetes insipidus
        • Urine osmolarity unchanged during water deprivation but concentrates following ADH administration
      • Nephrogenic/peripheral diabetes insipidus
        • Urine osmolarity shows no significant change after either water deprivation or ADH administration
      • Psychogenic polydipsia
        • Initial urine osmolarity is low (<100mOsm/kg), but urine concentration will normalise with water deprivation (essentially normal response)
    • Other tests which may be appropriate include
      • Pituitary function tests
      • Serum lithium concentration
      • Autoantibody screen

Causes

polyuria

  • Other causes include
    • Cushing’s syndrome/disease
    • CKD
    • Hypercalcaemia
    • Fanconi’s syndrome

Hyponatraemia and Syndrome of Inappropriate Antidiuretic hormone production (SIADH)

Background

  • Hyponatraemia is the most common electrolyte disturbance encountered.  Up to 30% of hospitalised patients will be hyponatraemic.  SIADH is the most common cause.
  • Usually asymptomatic but can manifest as anorexia, nausea, vomiting, confusion, lethargy, seizures and coma.
    • Severity of symptoms are usually representative of the rate of change rather than the severity of change (chronic hyponatraemia is rarely symptomatic)

Classifications of hyponatraemia

  • Hypovolaemic (sodium deficit with a relatively smaller water deficit)
    • e.g. renal sodium loss; diuretic therapy (esp thiazide diuretics); adrenocortical failure (e.g. Addison’s disease); GI sodium losses (diarrhoea/vomiting); burns
      • i.e. cause is often apparent (except perhaps in Addison’s/hypoadrenalism)
    • may have features of hypovolaemia e.g. thirst, dizziness, weakness, dry mucous membranes, reduced urine output etc
  • Euvolaemic (water retention alone)
    • Polydipsia; excessive electrolyte-free (e.g. 5% dextrose solution) infusions; SIADH (see below); hypothyroidism
  • Hypervolaemic (sodium retention with relatively greater water retention)
    • Congestive heart failure; cirrhosis; nephrotic syndrome; chronic renal failure

SIADH

Physiology

  • During resting states (normal homeostasis)- ADH is produced in the hypothalamus and stored in the posterior pituitary
  • Osmoreceptors in the hypothalamus detect changes in the ECF osmolality (most commonly as a result of serum sodium concentrations)
  • In the hyperosmolar state, they stimulate ADH secretion.  In the hypoosmolar state, they result in decreased production of ADH.
  • The action of ADH is primarily renal: increasing the number of aquaporin receptors in the collecting tubule, allowing for a greater reabsorption of water and dilution of the blood i.e. lower sodium concentration is actually due to higher ECF water content than actual number of moles of sodium
  • SIADH is characterised by
    • hyponatraemia
    • inappropriately elevated urine osmolality (>100mmol/kg) (can be higher than plasma osmolality)
    • excessive urine sodium concentrations (>30mmol/l)
    • decreased serum osmolality (<270mmol/kg)
    • in a euvolaemic patient, with no evidence of renal, cardiac or hepatic disease potentially associated with hyponatraemia

Causes

  • Tumours
  • CNS disorders e.g. stroke, trauma, infection, psychosis, porphyria
  • Pulmonary disorders: pneumonia, tuberculosis, obstructive lung disease
  • Drugs: anticonvulsants; psychotropics; antidepressants; cytotoxics; oral hypoglycaemics; opiates
  • Idiopathic

Investigations

  • Plasma and urine electrolytes/osmolaltiy
    • NB U&Es should be measured more than once in case of false positives
      • Low Na
      • Potassium- can be raised in Addison’s
  • Imaging can be useful e.g. CXR in heart failure

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Management

  • Correct any underlying cause e.g. stop diuretic
    • Beware of correcting too rapidly- particularly in chronically hyponatraemic patients (no more than 8-10 mmol/l/day)
      • can cause myelinolysis (demyelination)
  • If hypovolaemic- fluid replacement (0.9% saline)
    • NB beware of subsequent diuresis and rapid conversion to hypernatraemia (if this occurs, give desmopressin (ADH analogue) and 5% glucose (water))
  • If normovolaemic/hypervolaemic
    • Fluid restrict (500-1000ml/day)
      • Consider adding furosemide if symptomatically hypervolaemic
      • Consider adding NaCl tablets/3% saline if the urine osmolality exceeds that of plasma
  • NB If also hypokalaemia, potassium will raise both K and Na in the serum.

Hypercalcaemia

Background

  • Hypercalcaemia is mostly asymptomatic and is commonly an incidental finding after investigation for another reason.  It is relatively uncommon- so all cases should be investigated further
  • A note about calcium measurements:
    • About 50% of serum calcium is bound to plasma proteins (majority of which is albumin) and organic ions e.g. citrate/phosphate.  The rest is free and under hormonal control.
    • Labs routinely measure total serum calcium (free and bound).  However, they also routinely report a Corrected Calcium level which is the calcium level adjusted to the level of binding products e.g. albumin
      • E.g. if albumin is low, the corrected calcium levels increase (as more is free/unbound)
      • Both are relevant, but the corrected calcium levels show a more accurate representation of the physiological calcium levels (NB In practice, the two are often extremely close in the majority of patients.  Differ mainly in patients with underlying liver/kidney disease)

Presentation

  • Levels >2.21 (normal) but <2.8mmol/l
    • Patients may have polyuria/polydipsia; dyspepsia (calcium stimulates gastrin release); depression/low mood; mild cognitive impairment (may be acute or chronic)
  • Levels < 3.5mmol/l
    • + Muscle weakness; constipation; anorexia; nausea; fatigue (all general effects of calcium in muscle physiology)
  • Levels >3.5mmol/l
    • + Abdominal pain; vomiting; dehydration; lethargy; cardiac arrhythmias (shortened QT interval); pancreatitis; coma
  • Patients can also present with stone disease if the levels are chronically and insidiously raised.

Investigation

  • Repeat serum calcium (confirm hypercalcaemia)
    • Also look at albumin and urea levels (if raised, possible dehydration)
    • Other factors to inspect include Alk Phos; TFTs (thyrotoxicity)
  • Serum PTH
    • Raised/normal- diagnostic for primary hyperparathyroidism
      • Further tests may be considered by a specialist e.g. Urinary 24 hour calcium
        • Raised or normal suggest hyperparathyroidism
        • Low suggests familial hypocalciuric hypercalcaemia (found particularly in young people with a family history)
    • Low- consider another cause
      • Most commonly malignant hypercalcaemia
        • Radionucleotide bone scan is useful to look for malignant bone disease
  • Calcidiol testing can be done if no clear diagnosis is found from other tests (looking for Vit D toxicity
  • Other tests for complications which may be warranted include renal USS (for stone disease- may be an indication for removal of parathyroid glands); bone mineral density
  • Parathyroid imaging (USS, spect technetium scan)

Causes

  • Primary hyperparathyroidism is the most common cause (0.1-0.3% of the population)
  • Malignancy (myeloma or bony metastases)- suggested by rapidly progressive hypercalcaemia; second most common
  • Drugs e.g. lithium, thiazide diuretics
  • Rarer causes include
    • Tertiary hyperparathyroidism in end-stage renal disease
    • Granulomatous disease e.g. sarcoid, tuberculosis
    • Lymphoproliferative disorders
    • Vit D toxicity
    • Thyrotoxicosis
    • Addison’s disease
    • Familial Hypocalciuric Hypercalcaemia (1 in 78000) (see below)

Management (of hypercalcaemia)

  • If the patient is asymptomatic and hypercalcaemia is mild, identification of the underlying cause (+/- treatment) is all that is required
  • With acute/severe hypercalcaemia (>3mmol/l)
    • Rehydrate with saline (this can reduce the calcium by 0.5mmol/l
    • If severe, IV bisphosphonates e.g. disodium pamidronate or zoledronic acid may be helpful
      • Note that if this is due to hyperparathyroidism, bisphosphonates will only reduce calcium from bone resorption, not from renal reabsorption.

Familial Hypocalciuric Hypercalcaemia

  • Autosomal dominant disorder caused by inactivating mutation of the calcium sensing receptor gene, which reduces the ability of the parathyroid gland to sense calcium concentrations and an inability of renal receptors causing increased reabsorption of calcium.
    • Important to diagnose as these patients do NOT require parathyroid surgery
    • As well as calcium, PTH and urinary calcium tests, genetic tests may be available.
    • Patients only ever have mild hypercalcaemia (extremely rare to be symptomatic due to FHH) and no treatment is required.

Failure to Thrive and Short Stature

Failure to Thrive

Features

This is when a child has poor weight gain/growth and falls through the centile groups.  Head circumference is usually preserved relative to height (compared to some other causes of growth restriction in neonates e.g. IUGR), which is also conserved relative to weight.  (I.e. these children look small but normal proportions).  NB Head circumference may be increased relative to weight/height.

This is a common presentation of children by concerned parents, often around 10-12 month stage.

Cause

  • It is most commonly due to failure of nutrition (especially worldwide) and problems with (breast)feeding need to be addressed.
  • If there are any signs of abuse/neglect, suspicion should be raised and addressed.
  • Not uncommonly, children reported failing to thrive are actually constitutionally small and there has been an error of recording details at birth.
  • Diseases of almost any organ system can cause FtT
    • detailed history and examination- to assess for pathological causes is important.  E.g. evidence of diarrhoea, UTI, thyroid disease, renal disease, anaemia etc

Investigations

If nutrition and stature have been excluded as causes, further investigations should be done, including:

  •  Full blood works (FBC/U&E/LFT/TFT/Coeliac screen/immunoglobulins etc)
  • Stool cultures and stool reducing substances
  • Urinalysis
  • Sweat test (if not already done)

Management

  • The mainstay of management is increasing nutritional intake (if this is the underlying problem- if not, treat this appropriately first)
    • try also to encourage good diet habit and encourage eating (ignore when child doesn’t eat)
    • Snacks may be used- particularly if they are calorie dense

Potential Complications

  • Malnutrition can lower the body’s natural host defences and predispose to infection.  Unfortunately this can cause further malnutrition and a cycle can spiral down.
  • Refeeding syndrome can occasionally occur in these kids, so care should be taken when increasing their nutritional intake

Short Stature

Definition

A child with height <3rd centile.

Cause

Most commonly (almost by definition) is genetic short stature.  The next most common is probably constitutional growth restriction (i.e. normal growth velocity but abnormal for parent height).

However, any chronic disease can cause short stature, particularly hypothyroidism (normally can be diagnosed >2 years old- with associated weight gain) and Growth Hormone (GH) deficiency (diagnosed by insulin test).