POLYURIATutorial

Dr Amir BabikerMBBS, MRCPCH (UK), CCT (UK),

Msc Endocrinology and Diabetes (Queen Mary University, London, UK)

Consultant Paediatric Endocrinologist, KKUHand Assistant Professor, KSU

Objectives• Definition of polyuria

• Causes of polyuria and Approach

• Types of diabetes: Assessment and Mmt

• Emergency management: DKA & hypoglycaemia

• Clinical Scenarios

Definition• Excessive or abnormally large production or passage of

urine (usually > 2000 ml/m2/day) or (> 5 ml/kg/hr).

• Surface area= Ht(cm) X Wt(kg)/3600

• Increased production and passage of urine may also be termed diuresis.

• Frequency is usually an accompanying symptom.

• Polydipsia (increased thirst)= Cause or effect.

Causes

(1) Increased fluid intake.

(2) Increased urinary solute execration.

(3) Impaired urinary concentration.

(4) Physiological

(1) INCRAESED FLUID INTAKE:– Iatrogenic– Compulsive water drinking (Psychogenic polydipsia)

(2) INCREASED URINARY SOLUTE EXCRETION – OSMOTIC DIURESIS: 1. Diabetes mellitus (DM)2. Mannitol treatment

– SALT LOSS:1. Adrenal insufficiency2. Aldosterone resistance3. Diuretics4. Cerebral salt wasting (CSW) or salt diuresis

(3) IMPAIRED URINARY CONCENTRATION: - INEFFICIENT ADH ACTION (DIABETES INSIPIDUS, DI): 1. Central (Neurogenic) DI 2. Nephrogenic DI

- RENAL DISORDERS: 1.UTI 2. Renal tubular acidosis (RTA) 3. Bartter and Gitelman Syndromes 4. Renal glucosuria 5. Chronic renal failure

Clinical and biochemical similarities

• DM and renal glucosuria

• DI and Psychogenic polydipsia

• UTI, aldosterone resistance, Bartter and Gitelman syndromes, and RTA

• Chronic renal failure and adrenal insufficiency

Approach

History

• Age of onset: Congenital/Acquired• Fever: UTI• Polydipsia: nocturnal, odd behaviour.• Salt craving: Adrenal insufficiency, CSW• Failure to thrive: DM, Nephrogenic D.I, RTA, CAH, Bartter • Hyperphagia or loss of appetite: DM• Head trauma, neurosurgery: Central D.I• Meningitis: Central D.I• Drug intake: Diuretics, Mannitol.

History

• Increased ICP: CNS tumors• Rash, Seborrhoea: Histiocytosis• Psychological problems: Psychogenic polydipsia• Polyuria, shock in newborn period: CAH• Muscle weakness: Hypokalaemia, RTA, Bartter• Constipation, paresthesia: Hypercalcemia• Abdominal cramps, arthralgia, etc: Sickle cell

anaemia

Examination

• Look for signs of dehydration and shock..

• Failure to thrive: DM, DI, RTA, CAH• Fever: UTI• DD: CNS malformations• Neurological deficits: CNS pathologies• Midline defects: Central DI

Examination

• Ambiguous genitalia: CAH• Rickets: RTA, Renal failure• Acidotic breathing: DM, CRF, RTA• Rash, Seborrhoea, ear discharge: Histiocytosis• Hyperpigmentation: Adrenal insufficiency• Muscle weakness, floppiness: Hypokalaemia:

RTA, Bartter

Investigations

24 hr hour urine output 2L/m2/day or >5ml/kg/hr POLYURIA Further investigations

Investigations

• Urine: • WBCs: UTI• Sugar: DM• Specific gravity: <1.015 – DI• Urine Osmolality: <300 mOsm/kg – DI

• CBC, U&Es, Calcium, Blood gas, Blood glucose, Plasma Osmolality, HbA1c, MRI brain, Renal USS, Genetic tests as indicated.

DI Vs Psychogenic polydipsia

DI - Likely

DI - Unlikely

DI and similar conditions

Water Deprivation test

DIPosm, Not able to concentrate urine

Water deprivation test

Psychogenic polydipsiaPosm, able to concentrate urine

DDAVP response test

Central DI

Nephrogenic DI

Posm >270 and <300 mOsm/kg

Management

• Central DI responds to DDAVP (IV, oral, Intranasal).

• NDI: DDAVP is ineffective. Hydrochlorothizide (HCTZ) +/- Amiloride and

indomethacin OR ttt of the cause• Adequate hydration is important.

• CWD: Psycological and behavioural treatment

DM

Condition 2 hour glucose Fasting glucose HbA1c

mmol/l(mg/dl) mmol/l(mg/dl) %

Normal <7.8 (<140) <6.1 (<110) <6.0

Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) &

<7.0(<126) 6.0–6.4

Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126) 6.0–6.4

DM ≥11.1 (≥200) ≥7.0 (≥126) ≥ 6.5

OR Symptoms of hyperglycaemia and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)

•A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above methods on a different day.

Diabetes mellitus is characterized by recurrent or persistent hyperglycaemia, and is diagnosed by demonstrating any one of the following:[

Types of DM

• T1DM (IDDM, Juvenile DM): Autoimmune, idiopathic

• T2DM (NIDDM, Adult onset):Obesity, Acanthosis nigricans, FH.

• Gestational DM• Other: Monogenic, congenital, neonatal,

2ry..etc

Other• Genetic defects of β-cell function

– MODY– Mitochondrial DNA mutations

• Genetic defects in insulin processing or insulin action– Defects in proinsulin conversion– Insulin gene mutations– Insulin receptor mutations

• Exocrine pancreatic defects– Chronic pancreatitis.– Pancreatectomy– Pancreatic neoplasia– Cystic fibrosis– Hemochromatosis– Fibrocalculous pancreatopathy

Other• Endocrinopathies

– Growth hormone excess (acromegaly)– Cushing syndrome– Hyperthyroidism– Pheochromocytoma– Glucagonoma

• Infections– Cytomegalovirus infection– Coxsackievirus B

• Drugs– Glucocorticoids– Thyroid hormone– β-adrenergic agonists– Statins

• Genetic syndromes: Down’s, Klinefilter, Laurence Moon Biedel, Prader Willi, Turner synd.

Management• Insulin:

• Regular and NPH (1/3 and 2/3)• Analogues (Mixed, ultra short, Detemir & Glargine)• Insulin pumps (CSII): Open and closed loops.

• Support (Diabetic team): • Education: CHO counting, I:CHO, Self care & injections,

hypos management, Sick day rules• Psychological• Annual review: Examination, Invx: Blood and urine, Eye

• Life style: • Diet (CHO = 50 - 60%, Fats: < 30%, Proteins 10 – 20%) • Sensible exercise

Concepts• Honeymoon phase or partial remission: weeks to 2 years, due to B cell hyperplasia.

• Early morning hyperglycaemia: with NPH & Regular (Somogyi & Dawn phenomena)

• Sick day rules:• Check Blood sugar every 2-4 hrs• Check ketones• Drink plenty of fluids• Need extra insulin to clear ketones• Never omit insulin• Hypoglycaemia may be a problem especially in young

children

DKA

Children with T1DM who have:

Hyperglycaemia (BG >11 mmol/l)

pH < 7.3

Bicarbonate < 15 mmol/l

With ketonaemia and/ or ketonuria.

and who has: Acidotic respiration, dehydration, drowsiness and/or abdominal pain/vomiting

DKA

They can die from :

Cerebral oedema: This is unpredictable, occurs more frequently in younger children and newly diagnosed diabetes and has a mortality of around 25%.

Hypokalaemia: This is preventable with careful monitoring and management

Aspiration pneumonia: NGT.

DKA Emergency management

1. Resuscitation 2. Confirm diagnosis 3. Investigations

Full Clinical Assessment

1. Assessment of dehydration (weight)

2. Conscious level

3. Physical examination (C oedema, infection, ileus)

4. Role of PICU (Age, LOC, severe acidosis, shock, staff)

DKA

Management:Fluids – volume, rate, type, oral fluids Insulin: 0.1 units/kg/hour (0.1ml/kg/hour:

Start after 1 hr of IV fluids.Potassium: 40 mmol/l, when the pt PUBicarbonate: rarely required, PH < 6.9 Phosphate: Not usually required. Continuing management.

DKA

Fluid volume:Requirement = Maintenance + Deficit – ResusDeficit (ml) = % dehydration x body weight

(kg) x 10 Maintenance requirements: 0 - 2 yrs 80 ml/kg/24 hrs 3 - 5 70 ml/kg/24 hrs 6 - 9 60 ml/kg/24 hrs 10 - 14 50 ml/kg/24 hrs adult (>15) 30 ml/kg/24 hrs

Hourly rate = 48 hr maintenance + deficit – resuscitation fluid already given

48

Example : A 20 kg 6 year old boy who is 10% dehydrated, and who has already had

20ml/kg saline, will require

10 (%) x 20 (kg) x 10 = 2000 mls deficit

plus 60 ml x 20 kg = 1200 mls maintenance each 24 hours

2 x 1200 mls = 1400 + 2000 = 4400 mls

minus 20kg x 20ml = 400 mls resus fluid

4000 mls over 48 hours = 83 mls/hour

DKA

Fluids required:

Blood Glucose Level Type of Fluid >14 mmol/l Normal saline 4 – 14 mmol/l During 1st 6 hours

5% Dex+ 0.9% saline After 1st 6 hours 5% Dex+ 0.45% saline

<4mmol/l 10% Dextrose

DKAObservations to be carried out:

Ensure full instructions are available to nursing staff emphasising the need for :

• strict fluid balance: Input/Output • testing for glucose & ketones

• hourly BP and basic observations

• hourly capillary blood glucose measurements

• U&E: after 2 hrs initially, then 4 hrly.

• twice daily weight.

DKA

• hourly or more frequent neuro observations initially

• reporting immediately to the medical staff, even at night, symptoms of headache or any change in either conscious level or behaviour

• reporting any changes in the ECG trace, especially T wave changes suggesting hyperkalaemia

Cerebral Oedema

headache & slowing of heart rate

change in neurological status (restlessness, irritability, increased drowsiness, incontinence)

specific neurological signs (eg. cranial nerve palsies)

rising BP, decreased O2 saturation

abnormal posturing

More dramatic changes such as convulsions, papilloedema, respiratory arrest are late signs associated with extremely poor prognosis

Cerebral Oedema Management If suspected inform senior staff immediately. The following measures should be taken immediately while arranging transfer to

PICU: • exclude hypoglycaemia as a possible cause of any behaviour change • give Mannitol 1 g/kg stat (= 2.5 ml/kg Mannitol 20% over 20 minutes) OR 3%

saline• restrict IV fluids to 50 % maintenance and replace deficit over 72 rather than 48

hours • the child will need to be moved to PICU (if not there already) • once the child is stable, exclude other diagnoses by CT scan• a repeated dose of Mannitol should be given after 2 hours if no response • document all events (with dates and times) very carefully in medical records

Hypoglycaemia

• Target blood glucose: 4 – 8 mmol/l.• Treat all blood glucose below 4 mmol/l to

avoid hypo unawareness.• Symptoms:

– Sympathetic: pallor, tachycardia, sweating, tremors

– Neuroglycopoenic: irritability, headache, nausea, seizure, stupor, coma

Hypoglycaemia

• Causes:– Missed or delayed meal– Exercise– Overdose of insulin– Impaired food absorption (CD)– Addison’s disease– Alcohol

• Treatment:– Oral CHO: glucose tabs, gel and fluids– I/M glucagon– 10% Dx 2 ml/kg bolus

CASE 1

• A 14 yr old girl had recurrent severe hypoglycaemias with 2 episodes leading to convulsions and hospital admission. She was diagnosed with T1DM at 9 yrs of age and was treated with BD injections of Novomix 30 at 30 U am and 18 U pm. No recent change in her diet or level of activity and she does not drink alcohol.

Questions and answers

• What Invx would you consider doing?– HbA1c– CD (TTG)– AAA– TFT

• If the results of these Invx proved normal, what further explanation could account for her recurrent hypoglycaemias?

– Insulin overdose. This adolescent was not coping well with DM management – improved with psychological support

Case 2An 11-year-old boy presented with an 8-week history of polyuria and

polydipsia. He was otherwise well apart from recent headaches. Investigations in clinic demonstrated the following:

• Serum sodium 142 mmol/L• Serum potassium 3.7 mmol/L• Serum urea 2.3 mmol/L• Serum creatinine 52 mol/L• Plasma osmolality 305 mOsm/kg• Plasma glucose 6.2 mmol/L• Urine sodium 16 mmol/L• Urine osmolality 78 mOsm/kg

Questions and answers(1) What further investigation is required to clarify the

diagnosis?(2) What additional investigations are then required?(1): Given that this child is spontaneously hyperosmolar,a formal water deprivation test is contraindicated.However, it is not clear whether this child has cranial or

nephrogenic DI - Desmopressin response test: His urinary osmolality increased from 75 to 530 mOsm/kg and there was a dramatic reduction in his urine output suggesting that he has cranial diabetes insipidus.

(2): Given a diagnosis of CDI and headache: MRI brain and Pituitary function tests.

Summary

• Polyuria: • Definition• Causes • Approach

• DI Vs Psychogenic polydipsia

• DM and its complications

Discussion