Diabetes insipidus and SIADH

Question 1

What is diabetes insipidus?

Answer 1

The passage of large volumes (>3l/day) of dilute urine due to impaired water resorption by the kidney, due to reduced ADH secretion from the posterior pituitary (cranial) .or nephrogenic (impaired response of the kidney to ADH).
(OHCM)

Question 2

What causes cranial DI?

Answer 2

1. Idiopathic
2. Congenital: defects in ADH gene; DIDMOAD/Wolfram’s syndrome (rare)
3. Tumour: craniopharyngioma, metastases, pituitary.
4. Trauma (as in lecture), can be temporary if nerve endings grow back
5. Hypophysectomy
6. Autoimmune hypophysitis
7. Infiltration (histiocytosis, sarcoidosis)
8. Haemorrhage
9. Infection eg meningioencephalitis.
   (OHCM)

Question 3

What causes nephrogenic DI?

Answer 3

1. Inherited
2. Metabolic: low K, high Ca
3. Drugs: lithium, demeclocycline.
4. CKD
5. Post-obstructive uropathy.
   (OHCM)

Question 4

Give 2 actions of vasopressin.

Answer 4

1. Vasoconstriction
2. Increases water reabsorption, which concentrates urine (antidiuresis)
   These increase blood pressure.

Question 5

Give 3 symptoms of DI.

Answer 5

Polyuria
Polydipsia (can be uncontrollable)
Dehydration
Hypernatraemia: lethargy, weakness, irritability.

Question 6

Give 3 investigations for DI.

Answer 6

U&E - check for dilutional hyponatraemia.
Glucose to exclude DM
Serum and urine osmolalities - plasma osmolality is high with dilute urine.
CDI: MRI head, test AP function.

Question 7

How is DI diagnosed?

Answer 7

1. Urine output >3L/day

2. 8 hour water deprivation test: tests the kidneys’ ability to concentrate urine.

Question 8

Describe the management of cranial DI.

Answer 8

Desmopressin - synthetic analogue of ADH.

Look for other pathology using MRI and AP function tests.

Question 9

Describe the management of nephrogenic DI.

Answer 9

1. Treat the cause
2. Bendroflumethiazide PO
3. NSAIDs lower urine vol and plasma Na+ by inhibiting prostaglandin synthase. Prostaglandins locally inhibit the action of ADH.

Question 10

Describe the emergency management of DI.

Answer 10

1. Plasma U&E, serum and urine osmolalities.
2. Monitor urine output
3. Carefully lower Na to avoid brain injury if severely hypernatraemic.
   (OHCM)

Question 11

How much of the total body fluid is intracellular? Give your answer in L and a percentage of total body fluid.

Answer 11

28L ICF/42L TBW

= 2/3.

Question 12

How much of the total body fluid is intravascular? Give your answer in L and a percentage of extracellular fluid.

Answer 12

3.5L IVF/14L ECF (/ 42L TBW)
= 25%
(lecture)

Question 13

What regulates the release of vasopressin normally?

Answer 13

Osmoreceptors in the hypothalamus.

Question 14

What regulates the release of vasopressin in an emergency?

Answer 14

Baroreceptors in the brainstem and great vessels.

Question 15

How does vasopressin work?

Answer 15

Vasopressin binds to G-protein coupled 7 transmembrane domain receptors:
V1a receptor in the vasculature (-> vasoconstriction?)
V1b in the pituitary (secretion?)
V2 in the renal collecting tubules, causing an intracellular signalling cascade resulting in aquaporin-2 channels, through which water is reabsorbed to concentrate the urine.

Question 16

How is plasma concentration measured?

Answer 16

Osmolality (mOsmol/kg) - the number of molecules, not the size, even though albumin has a different effect to sodium.
Measured by an osmometer which measures freezing point.

Question 17

Desmopressin - class, mechanism, route of admin, side-effects?

Answer 17

Desmopressin is a synthetic analogue of ADH. Causes antidiuresis - pharmacology is that of ADH action.
Tablets: 100-600mcg/day VS nasal spray 10-20 VS injection 1-2mcg/day.
SEs: Headache, diarrhoea, hyponatraemia (->seizures).

Question 18

What could cause hyponatraemia in a patient without dehydration?

Answer 18

No oedema: SIADH (25%), water overload

Oedema: nephrotic syndrome, cardiac failure

Question 19

What happens in SIADH?

Answer 19

ADH continues to be secreted in spite of low plasma osmolality or large plasma volume.

Question 20

What are 3 symptoms of SIADH?

Answer 20

Hyponatraemia - headache, weakness and nausea to agitation, fitting and coma.
Faster speed of onset = worse symptoms.

Question 21

How is SIADH diagnosed?

Answer 21

No dehydration, no oedema, no diuretics.
Concentrated urine (Na+ >20mmol/L, osmolality >100mOsmol/kg)
It is overdiagnosed - consider differential.

Question 22

What could cause hyponatraemia in a patient with dehydration?

Answer 22

Kidneys: Addison’s disease, renal failure.
Other: Diarrhoea, vomiting

Question 23

Give 3 causes of hyponatraemia.

Answer 23

Malignancy - lung small-cell, pancreas
CNS disorders - meningoencephalitis, stroke
Chest disease - TB, pneumonia
Endocrine - hypothyroidism (not true SIADH)
Drugs - SSRIs, opiates

Question 24

Describe the investigations for hyponatraemia.

Answer 24

Urinary Na+ (tells you whether na/H2o are being lost by the kidneys (>20mmol/l) or other organs)
Urine osmolality (if >100mmol/kg, it is SIADH)

Question 25

Give an artefactual cause of hyponatraemia.

Answer 25

Sample was from a drip arm

Question 26

Give an iatrogenic nause of hyponatraemia.

Answer 26

Glucose infusion without saline, causing hypotonicity and hyponatraemia, especially if on thiazide diuretics.

Question 27

Describe the management of hyponatraemia.

Answer 27

1. Diagnose and treat underlying cause.
2. Replace Na and water at same rate they were lost
3. Fluid restriction if not dehydrated
4. Cautious rehydration if dehydrated - avoid central pontine myelinolysis.

Question 28

How does demeclocycline work?

Answer 28

It is an ADH antagonist, so causes urine dilution.

Question 29

How does tolvaptan work?

Answer 29

Promotes water excretion without loss of electrolytes. Effective in treating hyponatraemia including SIADH but expensive.

Question 30

Describe the management of SIADH.

Answer 30

1. Treat cause
2. Restrict fluid
3. Salt/ loop diuretic if severe.

Question 31

What is the difference between acute and chronic hyponatraemia? Give the difference in their management.

Answer 31

Acute is 24 hour onset, rapid correction is safer, may occur after subarachnoid haemorrhage.
Chronic is there the CNS adapts, so correction must be SLOW (avoid CPM)