Diagnostic approach to polyuria and polydipsia (PUPD)

Question 1

Define Polyuria and Polydipsia?

Answer 1

• Polyuria = Increased urination
• Polydipsia = Increased thirst

Question 2

Most animals with PUPD have?

Answer 2

Primary polyuria causing a secondary compensatory polydipsia – they drink more because they have lost water and are thirsty, because they cannot concentrate their urine

Question 3

Thirst and urination are determined by interplay of:

Answer 3

Plasma osmolality (tonicity of the blood), especially plasma sodium

•Determines blood pressure – baroreceptors (pressure) and osmoreceptors (water)

Hypothalamic - Pituitary gland – ADH axis

•Regulates water reabsorption in collecting duct

Renal function

•Needed to produce concentrated urine

Question 4

Clinical signs of PUPD – what do owners see?

Answer 4

• Seen to drink more often from bowl
• Need to fill water bowl more often
• Drinking from puddles, shower, glasses
• Longer than normal stream of urine
• Need to urinate more frequently (may see as incontinence)

Question 5

Discuss Primary polydipsia?

Answer 5

• RARE
• Psychogenic polydipsia – horse>others
• Hepatic insufficiency/ portosystemic shunt – can give changes in mentation causing PD
• Central lesion effecting hypothalamus
• Dietary change e.g. wet to dry

–No compensatory PU

•Compensation for increased loss eg heat

–No compensatory PU

Question 6

List causes of Primary polyuria?

Answer 6

• Hepatic disease
• Hyperthyroidism (C)
• Hyperadrenocorticism*
• Hypoadrenocorticism
• Hypokalemia
• Hypercalcaemia*
• Diabetes mellitus (DM)*
• Diabetes insipidus (DI)
• Pyometra*

–Cause 2ndary nephrogenic disabetes inspidus in the male seen with prostatitis.

• Pyelonephritis
• Post-obstructive
• Renal disease*
• Iatrogenic

* = most common in dogs

C= cats only

Question 7

How else can causes of primary polyuria be categorised?

Answer 7

•Renal

•Hepatic

•Endocrine – diabetes mellitus, diabetes insipidus, hyperthyroidism, hyperadrenocorticism, hypoadrenocorticism

•Infectious – pyelonephritis, pyometra

•Electrolytes – hypokalemia, hypercalcaemia

• Iatrogenic – diuretics, steroids etc
• Hyperviscosity syndromes: interefere with ADH production

Question 8

What is ADH’s role in PU/PD caused by Primary central diabetes insipidus?

Answer 8

Primary central diabetes insipidus

–Congenital, very rare (secondary central also v rare from tumours)

–No ADH produced so cannot concentrate urine

Question 9

What is ADH’s role in PU/PD caused by Nephrogenic diabetes insipidus?

Answer 9

Nephrogenic diabetes insipidus

–Only common as an acquired disease (pyometra and protastitis)

–Congenital, exceptionally rare!

–No ADH receptors so no ADH action in DCT

Question 10

what is young animal urine like?

Answer 10

Young animals, v dilute urine, almost like water.

Question 11

Discuss what causes Reduced sensitivity to ADH that causes Failure of tubule to respond to ADH?

Answer 11

Reduced sensitivity to ADH

–E.coli toxins in pyelonephritis and pyometra

–Hyperadrenocorticism

Question 12

Discuss what causes Interference with action of ADH at tubule that causes Failure of tubule to respond to ADH?

Answer 12

Interference with action of ADH at tubule

–Hypercalcaemia

–Hypokalemia

Question 13

Discuss what causes ADH receptor downregulation that causes Failure of tubule to respond to ADH?

Answer 13

ADH receptor downregulation

–Obstuction of ureters/ bladder

–Hypokalemia

Question 14

What is osmotic diuresis?

Answer 14

Increased excreted solute with high osmotic potential needs dilution

Question 15

What can lead to osmotic diuresis?

Answer 15

• Diabetes mellitus (glucose)
• Chronic kidney disease (BUN) multifactoral animals with renal disease of variable degrees of PU/PD
• Post-obstructive diuresis (BUN) e.g blocked cat build up lots of electrolytes behind obstruction and then when freed it floods out.
• Liver failure inc portosystemic shunt (cortisol, other solutes not broken down)

Question 16

What is Reduced medullary concentration gradient?

Answer 16

Unable to concentrate urine in Loop of Henle

Question 17

What can lead to reduced medullary concentration gradient?

Answer 17

Long period of PU of any cause (reduced BUN present in medulla)

• Including fluid therapy and corticosteroids

Liver failure (reduced BUN production)

Hypoadrenocorticism (hyponatremia) Addisons: pre-renal azotaemia as they cannot retain Na so they cant increase their USG.

Hyperthyroidism (increased renal blood flow)

Question 18

Look at this if you feel like it?

Answer 18

Question 19

What is a Reduced medullary concentration gradient?

Answer 19

Unable to concentrate urine in Loop of Henle

Question 20

What causes Reduced medullary concentration gradient?

Answer 20

• Long period of PU of any cause (reduced BUN present in medulla)
• Including fluid therapy and corticosteroids
• Liver failure (reduced BUN production)
• Hypoadrenocorticism (hyponatraemia)
• Hyperthyroidism (increased renal blood flow)

Question 21

History check

If the owner has noticed a change in urinary behaviour, ask them to describe what has changed:

Answer 21

–Any change in food, treats, management?

–Is the animal on any medications which may cause PUPD?

–Straining to urinate?

–Small volume of urine frequently or big ones?

–Urine on the bed in the morning?

–Conscious/unconscious urination?

–Discoloured/smelly urine?

Question 22

Step 1. Is it really PUPD?

Answer 22

Is it drinking more than it should?

–Ask owners to measure intake over 24h

•Measure over 2-3 days which makes for easier calculation

–Normal = 40-60ml/kg/d (but compare relative to what is normal to the dog. Has the owner said it is drinking more this is enough to trigger investigation)

–PD is 100ml/kg a day roughly twice normal.

Is its urine concentrated?

–Get a free catch sample and check with your refractometer –NOT dipstick!

–typically >1.035 to be concentrated (relative to the patient)

Question 23

In step 1 if the USG is acceptable what do we do?

Answer 23

If the USG is acceptable (moderately concentrated):

–Thorough clinical examination - palpate relevant areas e.g. thyroid, kidneys, liver.

–go back to the clients for a better history of the nature of the problem (often pollakiuria/dysuria)

Question 24

If it is PUPD, or the USG is low or both, continue to step 2.

What is step 2?

Answer 24

Is there glucose in the urine on your dipstick?

–If so, this animal may have diabetes mellitus.

–ALWAYS check with a concurrent blood glucose (there are rare causes of primary renal glycosuria)

–Check not contamination from the container!

–Remember stressed cats…..

–If not, go to step 3.

–Renal threshold for cats of glucose: 12mmol/L

Question 25

What is step 3?

Answer 25

**Step 3 – is there evidence of chronic kidney disease?** * Is the animal in poor body condition? * Skin tent? Small kidneys if palpable? * Halitosis/oral ulceration * USG 1.008-1.012? –Concentrated urine less than 1.008. A hyposthenuric urine suggest kidneys are still working and diluting urine. –Or is the USG commensurate with the level of dehydration? If suspicious, check: Blood urea nitrogen AND serum creatinine with serum phosphate (remember high BUN could just be from dehydration/ high protein meal)

Question 26

Step 4– review the clinical examination and signalment. ## Footnote Which animals are likely to get which diseases? DAMNITV?

Answer 26

**Young animals?** * Congenital abnormality: cPSS, congenital renal disease **Female entire dogs?** * Pyometra **Old cats?** * CKD, hyperthyroidism, Lymphoma, diabetes, primary hypertension (not common on its own) **Old dogs?** * HyperAC, neoplasia (stuff causing hypercalcaemia), diabetes, kidney disease, liver disease

Question 27

Got a suspicion of pyometra? Next steps....

Answer 27

Pyometra – diagnostic imaging

Question 28

Got a suspicion of Hypercalcaemia? Next steps....

Answer 28

**Hypercalcaemia** – check serum and ionised Ca and phosphate then look at differentials

Question 29

Got a suspicion of Liver disease ? Next steps....

Answer 29

Liver disease – bile acid stimulation test

Question 30

Got a suspicion of Hyperadenocorticism? Next steps....

Answer 30

Hyperadenocorticism – ACTH stim

Question 31

Got a suspicion of Hypoadrenocorticism? Next steps....

Answer 31

**Hypoadrenocorticism** – ACTH stim (if wanted to rule it out measure basal cortisol)

Question 32

Got a suspicion of Hyperthyroidism? Next steps....

Answer 32

**Hyperthyroidism** – total T4

Question 33

Got a suspicion of Pyelonephritis? Next steps....

Answer 33

**Pyelonephritis** – sediment/urine culture (but may be negative......)

Question 34

Discuss the Water deprivation test?

Answer 34

* There is a “water deprivation test” which has been used to diagnose diabetes insipidus in the past * It is now thought best to rule out all other differentials and then trial treat with DDAVP rather than use this test * Also consider ADH assay along with blood and urine osmolality measurements

Question 35

Summary?

Answer 35

* There is a finite list of causes of PUPD – follow a systematic approach * Always check urine specific gravity on a refractometer, not the dipstick * Bear in mind that common things are much more likely than the weird ones

Question 36

**“Sally”, 10yo F Staffordshire bull terrier** * Drinking more for last 2 weeks * Off colour and vomiting, normal faeces * Possible weight loss? * Not sure whether spayed **Clinical examination** * Mucus membranes slightly tacky * Thoracic auscultation normal * Abdomen tense, difficult to palpate * No visible vaginal discharge * Temperature 39.2C **What is the problem list?**

Answer 36

**Probable primary problems** * Polydipsia, likely due to polyuria * Vomiting * [Mild pyrexia] **Probable secondary problems (indirect manifestations of disease)** * Weight loss (likely reduced intake/cachexia) * Inappetance (likely due to nausea) * 5% dehydration (likely due to PUPD)

Question 37

What are the Differential diagnoses - (PUPD) for this case?

Answer 37

**Renal** **Hepatic** **Endocrine** – diabetes mellitus, diabetes insipidus, hyperthyroidism, hyperadrenocorticism, hypoadrenocorticism **Infectious** – pyelonephritis, pyometra **Electrolytes** – hypokalemia, hypercalcaemia **Iatrogenic** – diuretics, steroids etc

Question 38

What are the Differential diagnoses for vomiting in this case?

Answer 38

**Primary GI tract problem** –Inflammatory, infectious, obstructive, motility disorder, toxic **Intra-abdominal, extra GI problem** –Pancreatitis, diabetes mellitus, hepatitis, renal disease, pyometra, splenitis, hypoadrenocorticism, obstruction from large mass **Extra-abdominal** –Fear, pain, vestibular disease, toxic

Question 39

The next steps in this case was?

Answer 39

* Urinalysis? USG 1.020 inappropriately concentrated for a dog with PU/PD * Biochemistry to rule out renal disease and diabetes mellitus? - Mild pre-renal azotemia – dehydration - No evidence of diabetes mellitus

Question 40

Case outcome for case 1?

Answer 40

Pyometra

Question 41

**Case 2** * Harry, 5yo MN labarador * PUPD for 4 weeks * Marked weight loss * Clinical examination otherwise unremarkable **Problem list** * PUPD * Weight loss –Inadequate intake –Unable to digest/metabolise food –Metabolism in excess of intake •Nothing remarkable on clinical examination! Look at the biochem?

Answer 41

Glucose not above renal threshold Moderate azotaemia Both calciums are high (3 types of calcium: complex calcium, protein bound and ionised calcium) ionised is the physiologically relevant. Hypercalcaemia which is physiologically relevant and azotaemia Most animals with kidney disease will not have a marked hypercalcaemia (Rare) Hypercalcaemia is nephrotoxic which is directly damaging the tubules, reducing renal perfusion and mineralisation= secondary damage to kidneys from hypercalcaemia

Question 42

What are case 2s new problems?

Answer 42

* Azotaemia * Hypercalcaemia (ionized and total) * Hyperphosphotemia

Question 43

What are the Differential diagnoses for hypercalcemia?

Answer 43

**Hogs In Yard** **H**yperparathyroidism **O**steolysis **G**ranulomatous disease **S**purious sample **I**diopathic (cats) **N**eoplasia **Y**oung animals **A**ddisons (Hypoadrenocorticism) **R**enal disease **D** Hypervitaminosis D

Question 44

Can we narrow down the list?

Answer 44

* Harry is hypercalcemic and hyperphosphatemic * In most diseases, the normal Ca-Ph balance is maintained * This balance is lost in: –Renal failure –Hypervitaminosis D

Question 45

Could Harry have primary renal failure?

Answer 45

Question 46

What did case 2 have?

Answer 46

**Hypervitaminosis D** Major differential diagnoses: fish oil toxicity causing Hypervitaminosis D Owner had been giving these and had been causing the problem

Question 47

How was case 2 managed for hypercalcemia?

Answer 47

* Aggressive IV fluids (0.9% NaCl) * Frusemide? * Prednisolone? * Bisphosphonates? * Hope that there hasn’t been too much renal calcification....... **Harry survived, but with chronic renal damage**

Question 48

Discuss Hypervitaminosis D?

Answer 48

Vitamin D toxicity refers to the effects of excessive intake of bioactive metabolites of vitamin D. Toxicity caused by ergocalciferol(vitamin D2) or cholecalciferol (vitamin D3) can occur from excessive dietary supplementation (most common in young growing dogs) for treatment of primary hypoparathyroidism. Both of these forms of vitamin D have a slow onset of action and prolonged duration, making correct dosing difficult. Treatment is directed at discontinuing the supplement or decreasing the dose of vitamin D. Toxicity caused by calcitriol (1,25-dihydroxyvitamin D), the most active form of vitamin D, most commonly occurs after treatment of primary hypoparathyroidism. Calcitriol is also the active ingredient in some rodenticides, but these products are no longer widely available in the USA. In dogs, a newly emerging cause of vitamin D toxicity is ingestion of the calcitriol analogue, calcipotriene (also called tacalcitol), which is a topical preparation used to treat psoriasis in people. Calcipotriene toxicity in dogs can result in severe metastatic calcification in the GI tract, kidney, and other tissues; the condition is commonly fatal.