POLYURIA POLYDIPSIA Reto Neiger Klinik fr Kleintiere Innere

POLYURIA / POLYDIPSIA Reto Neiger Klinik für Kleintiere (Innere Medizin) Justus-Liebig Universität Giessen Denmark September 2014

Definition POLYDIPSIA (PD) Increased thirst: mostly due to polyuria Rarely a primary problem - psychogenic - neurological - hyperrenism POLYURIA (PU) Increased production of urine (low SG) Due to disorder of water homeostasis with abnormal cellular and plasma osmolality Denmark September 2014

Specific gravity (SG) vs Osmolality (Osmo) Osmo SG 1000 280 320 1008 1012 Hypo- 1035 Isosthenuric Denmark September 2014

Osmolality vs specific gravity Mostly very good correlation • increasing osmolality increasing USG EXEPTIONS • high [Proteins] 1 g/d. L 0. 003 -0. 005 • high [Glucose] 1 g/d. L 0. 004 -0. 005 4 Denmark September 2014

afferent efferent Prox. Tub Medulla Cortex Glomerulus Dist. Tub Collecting duct Loop of Henle Denmark September 2014

300 afferent efferent Cortex 300 Na. Cl H 2 O Dist. Tub 300 Medulla urea Prox. Tub Glomerulus Collecting duct Loop of Henle Denmark September 2014

300 efferent afferent Cortex 300 Na. Cl H 2 O Dist. Tub 300 Medulla urea Prox. Tub Glomerulus Collecting duct Loop of Henle Denmark September 2014

H 2 O Na. Cl Ascending thick limb H 2 O Interstitium Descending thin limb Na. Cl Denmark September 2014

300 300 300 300 300 300 Denmark September 2014

400 400 200 400 400 200 200 Equilibrium Denmark September 2014

300 200 400 400 Denmark September 2014

350 350 150 500 500 300 300 Equilibrium Denmark September 2014

300 200 350 300 350 500 300 500 Denmark September 2014

325 325 125 425 425 225 425 425 600 600 225 400 Equilibrium Denmark September 2014

300 325 125 225 325 225 425 425 600 225 400 600 Denmark September 2014

312 375 125 475 225 425 513 513 700 225 400 Equilibrium Denmark September 2014

300 efferent afferent Glomerulus Cortex 300 Na. Cl H 2 O Prox. Tub Dist. Tub 80 urea 300 200 900 900 Loop of Henle 1200 Interstitium Medulla 300 Collecting duct Denmark September 2014

Countercurrent mechanism Denmark September 2014

300 efferent afferent Glomerulus Cortex 300 Na. Cl H 2 O Prox. Tub Dist. Tub 80 urea 300 200 900 900 Loop of Henle 1200 Interstitium Medulla 300 Collecting duct Denmark September 2014

Lumen Collecting duct cells O H 2 O O H 2 Denmark September 2014

Lumen TJ H 2 O TJ = Tight Junctions Water tight Collecting duct cell H 2 O Denmark September 2014

Lumen Collecting duct cell AVP= Arginin-Vasopressin (ADH AVP H 2 O PKA ATP V 2 -Receptor G-Protein AVP c. AMP H 2 O PKA= Proteinkinase A Denmark September 2014

Lumen Collecting duct cell AQP 2 = Aquaporinkanäle H 2 O PKA ATP V 2 -Receptor G-Protein AVP c. AMP H 2 O AQP 2 Denmark September 2014

H 2 O 300 V 2 -Receptor Interstitium Lumen Collecting duct cell AVP O H 2 O 900 1200 Denmark September 2014

Urine Osmolality Stockham and Scott: Fundamentals of Veterinary Clinical Pathology 2008 Denmark September 2014

1. Osmotic Diuresis Medulla Cortex Differential diagnosis Denmark September 2014

Differential diagnosis Normoglycaemia 1. Osmotic Diuresis Glucose 100% Glucose Freely filtered Glucose No Glucose Denmark September 2014

Differential diagnosis Hyperglycaemia (> renal threshhold) Not 100% Glucose 1. Osmotic Diuresis Glucose Freely filtered Glucose Glucose Denmark September 2014

Differential diagnosis Hyperglycaemia (> renal threshhold) Not 100% Glucose Freely filtered 1. Osmotic Diuresis Diabetes mellitus Renal glucosuria Glucose Glucose Denmark September 2014

Cortex Differential diagnosis Medulla 2. Lack of AVP Denmark September 2014

Differential diagnosis Medulla Cortex 2. Lack of AVP Diabetes insipidus Denmark September 2014

Diabetes insipidus • Central diabetes insipidus • Renal diabetes insipidus • Congenital rarely in dogs and cats • Acquired rarely in dogs and cats very rare in dogs and cats • Acquired very common in dogs and also in cats Denmark September 2014

Lumen Collecting duct cell Central D. Inspipidus AVP H 2 O Renal D. Inspipidus H 2 O Denmark September 2014

Differential diagnosis Medulla Cortex 2. Lack of AVP Diabetes insipidus Secondary renal D. i. Hypercalcaemia Hypercortisolism Pyometra Pyelonephritis Hypokalaemia Hyperthyroidism Denmark September 2014 Acromegaly

Differential diagnosis Medulla Cortex 3. Chronic kidney Disease (CKD) Denmark September 2014

CKD Compensation Total kidney mass 33%25% 100% Loss of concentrating ability (Isosthenuria) Creatinine Blind Window azotaemia Denmark September 2014

Differential diagnosis Medulla Cortex 4. Medullary Washout Liver disease Hypoadrenocorticism Marked hyponatraemia Chronic PU/PD Denmark September 2014

Differential diagnosis Medulla Cortex 5. Primary Polydypsia Denmark September 2014

Plan for animal with PU/PD Confirmation that problem exists 2. Inspection of data base for clues 3. Performance of special diagnostic tests 4. Performing urine concentrating tests 1. Denmark September 2014

1. Confirmation of problem v Differentiate PU from stranguria, pollakiuria, dysuria v Measure water intake at home v Analyse urine specific gravity Species Dog Cat H 20 intake < 100 ml/kg/d < 75 ml/kg/d Urine output 20 -45 ml/kg/d 20 -40 ml/kg/d Urine SG > 1030 > 1035 Denmark September 2014

2. History and physical examination v. Intact female: r/o pyometra v. Lymphadenopathy: r/o hypercalcemia v. Weigh loss, tachycardia, restless: r/o hyperthyroidism, diabetes mellitus v. Alopecia, potbelly, muscle weakness, hepatomegaly: r/o hypercortisolaemia v. Drugs: r/o steroids, diuretics, primidone, salt supplementation Denmark September 2014

2. Inspect minimum data base • Urine specific gravity • Glucosuria • Bacteriuria / pyuria • Azotaemia • Hypercalcaemia • Electrolyte changes • Values pointing towards liver disease • Values pointing towards hypercortisolaemia Denmark September 2014

3. Special diagnostic tests v. Liver function tests v. Bile acid stimulation test, ammonia tolerance test v. Tests for hypercortisolaemia v. Low Dose Dexamethasone Suppression test v. ACTH-Stimulation test v. Cortisol: creatinine-ratio in urine v. Calcium v. Measure ionised calcium v. GFR study v. Creatinine clearence Denmark September 2014

4. Water deprevation test • Contraindication: • Renal disease (Azotemia) • Dehydration • Rule out all other causes of PU/PD • Equipment: • Refractometer (for urine specific gravity) • Exact scale (to measure weight of animal) • Catheter to empty bladder • ADH for i. m. injection Denmark September 2014

Protocol • Reduce water intake slowly to 75 ml/kg/d • Remove water and food • Empty bladder and measure spec. gravity (SG) of urine • Obtain exact weight of dog (kg) and write down • Empty bladder q 1 -2 h; measure SG and kg every time • Stop if >5% dehydrated (or SG >1030) • Give ADH (2 -5 U i. m. ) and continue 1 -2 h Denmark September 2014

USG Water deprivation test 1050 Normal 1040 Psychogenic polydipsia 1030 Complete central DI 1020 Partial central DI 1010 Nephrogenic DI 1000 0 1 2 3 ± Hours 4 5 6 ADH-inj. 7 8 Denmark September 2014

Urine specific gravity > 1035 No PU/PD Glucosuria positive D. m. , 1°Glucosuria, Drugs, Stress Pyuria/Bacteriuria positive Pyelonephritis, Pyometra, Prostatitis Azotemia positive CKD, Addison, Hyperthyroid, … Hypercalzemia positive Malignancy(LSA), Hyperparathyroid. Addison, Granulomatous, … Neutrophilia positive Pyometra, Cushing, Pyelonephritis Electrolyte change positive Addison, Hypokaliemia, … ACTH-ST / LDDST positive Hypercortisolism Liver function test positive Hepatopathy Water deprivation test 1°Polydipsia Central DI Renal DI Denmark September 2014