PU/PD

Question 1

PU/PD has endocrine and non endocrine causes. Outline these:

Answer 1

Endocrine disease

• Diabetes mellitus
• Diabetes insipidus (nephrogenic/central)
• Hyperadrenocorticism
• Hypoadrenocorticism
• Hyperparathyroidism
• Hyperthyroidism

Non-endocrine disease

Renal disease

• AKI/CKD
• Pyelonephritis (upper UTI)

GI disease

• Particularly liver disease – congenital/inflammatory/failure

Genitourinary system

• Infectious/inflammatory disease – pyometra/prostatic abscess

Neurological system

• Inflammatory, traumatic, neoplastic, congenital, psychogenic

Lymphoreticular

• Hyperviscosity – proteins/cells

Pathophysiological processes

• Hypercalcaemia (Neoplasia primarily, inflammatory disease)
• Systemic inflammatory disease (inflammatory leucogram, high level proteins)
• Iatrogenic - medications

Question 2

From this history and physical exam what do you conclude?

History — Sam is an 11-year-old, 30kg, Labrador with a history of PU/PD for some years. He first became PU/PD around 3 years ago. — The clinical signs persisted for a further 8 months. — A further 3 months elapsed before Sam developed bald patches over his flanks and dorsum. These were non-pruritic and the hair was easily epilated. — A further 9 months elapsed and the owner brought Sam for vaccination having reported that the PU/PD had improved slightly. Unfortunately he had developed moderate left forelimb lameness.

Physical examination:

— Sam was quiet but alert, in lean body condition.

— Vital parameters were within normal limits.

— Oral mucus membranes were pink and moist with a normal CRT.

— Peripheral lymph nodes were within normal limits.

— Ocular mucus membranes were injected, as were the third eyelids.

— Thoracic auscultation was unremarkable.

— Cardiac auscultation was also unremarkable. — Abdominal palpation revealed thin skin but reasonable abdominal contour.

— There were no palpable abdominal abnormalities.

— Dermatological examination revealed a poor haircoat with patchy alopecia, although this was not symmetrical.

Answer 2

Slow onset and long standing condition. Therefore can rule out acute problems like infections and neoplasia as would be dead by 3 years.

Its is waxing and waning so cant be renal as that just gets worse over time. Endocrinopathies can wax and wane. Classic endocrine skin disease because it is non=pruritic because of the high steroids.

Not likely to be thyroid disease because has been going on for a while and most importantly it has PU/PD.

Injected mucous membranes (due to hypertension) and thin skin.

Strong suspicions for endocrinopathy specifically cushings.

Question 3

So how do we define polydipsia?

Answer 3

Normal water intake:

40-60ml/kg/day

Definition of polydipsia:

>100ml/kg/day

Question 4

The primary pathophysiologic mechanisms of PU include?

Answer 4

• Defect in osmoregulated ADH secretion (central/cranial/hypothalamic Diabetes insipidus)
• Reduction in the renal response to appropriate circulating concentrations of ADH (nephrogenic Diabetes insipidus)
• Excessive persistent fluid intake (Dipsogenic diabetes insipidus/primary polydipsia/psychogenic polydipsia)
• Osmotic diuresis due to tubular constituents (e.g glucose)

Question 5

The mechanisms which underpin PUPD?

Answer 5

Primary

• neurogenic/central DI
• nephrogenic DI (rare and presents at birth)
• Dipsogenic DI

Secondary NDI (commonest)

• Interference of action of ADH
  
  • Receptors, generation of cAMP in CD cells
• Renal tubular cell dysfunction, loss of medullary concentrating gradient because medulla gets fibrotic
• Interference with ADH secretion (steroids and phenobarbitone affect this)

Question 6

How does CKD cause PU/PD?

Answer 6

• Progressive loss of nephrons leads to compensatory changes which lead to further progressive damage.
• Increased fluid load presented to the distal tubules leads to less reabsorption of solutes e.g. urea and electrolytes which results in an osmotic diuresis. In addition changes within the medulla preclude generation of an effective hypertonic interstitium
• In addition tubular changes reduce sensitivity to ADH

Question 7

How does Hyperadrenocorticism cause PU/PD?

Answer 7

• A variety of mechanisms are suspected to be involved.
• GCs directly interfere with the secretion of ADH at the level of both hypothalamus and pituitary. This is via an increase in osmotic threshold and reduced response of ADH to increasing osmolality.
• GCs are also thought to interfere with ADH action within the distal tubules and collecting ducts. It is also possible that GCs are able to reduce the permeability of the tubules to water.
• In a small number of cases direct compression of the hypothalamus by a pituitary macroadenoma may alter ADH release

Question 8

How does hypoadrenocorticism cause PU/PD?

Answer 8

• Kidney function is normal in these cases and hypovolaemia may be severe.
• Suspected to be chronic Na wasting and reduction in the concentration gradient within the renal medulla. The influence of hypercalcaemia is also a factor. Ionised hypercalcaemia will lead to a secondary NDI.
• Generally the PD/PU is an early feature of the disease and by the time animals present they are collapsed and have more notable clinical signs associated with GI tract.
• Animals dehydrate due to the sodium wasting from inadequate mineralocorticoid concentrations. This leads to the development of a pre-renal azotaemia despite normal renal function.

Question 9

How does hypokalaemia cause PU/PD?

Answer 9

• Potassium concentration alters renal blood flow
• This may impair renal tubular potassium-linked transporters preventing solute accumulation in the interstitium and medulla
• There is also a blunting effect of ADH release and rendering of the distal tubule less sensitive to ADH (poss by effect on cAMP generation and downregulation of AQP)

Question 10

How does hyperthyroidism cause PU/PD?

Answer 10

• Thyroid hormone alters renal blood flow.
• The pathophysiology of PU/PD in hyperthyroidism remains to be ascertained. It is thought possibly to result from increased total medullary blood flow and thus reduced medullary solute concentration
• May also be psychogenic component and many animals suffer concurrent CKD

Question 11

How does post-obstructive diuresis cause PU/PD?

Answer 11

• Mainly seen in male cats after relief of urethral obstruction
• Marked elevation in urea leads to an osmotic diuresis. This is short lived and self limiting.

Question 12

How does Glycosuria cause PU/PD?

Answer 12

• Osmotic diuresis due to tubular glucose
• Importantly not all glycosuric animals are diabetic. Recent studies in cats have shown that <30% of cats presented with significant glycosuria to a teaching hospital had causes other than DM.
• Metabolic abnormalities can lead to intermittent/transient glycosuria in some animals. Reports of a number of dogs with fructose intolerance where glycosuria is noted following ingestion of fruit sugars which then resolves when this is cleared.

Question 13

How does liver disease cause PU/PD?

Answer 13

• Complex relationship with multiple factors responsible
• Impaired urea production reduces medullary tonicity, may also increase GFR.
• Impaired metabolism of ACTH and cortisol
• Impaired metabolism of Aldosterone and NH3
  
  • leads to sodium retention and primary PD
• Psychogenic component may also be present

Question 14

How does hypercalcaemia cause PU/PD?

Answer 14

• Calcium is thought to exert its influence on the distal tubule via its interaction with ADH via:
  
  • inhibition of adenylate cyclise,
  • damage renal tubules directly,
  • inhibit binding of ADH to tubules,
  • reduce Na/Cl transport in the interstitium

Question 15

How does pyometra/infection cause PU/PD?

Answer 15

Endotoxins (esp Coli) compete with ADH for binding sites (reversible)

Question 16

How does Pyelonephritis cause PU/PD?

Answer 16

• Endotoxins (esp Coli) compete with ADH for binding sites
• As above except additional tubular damage may be irreversible
• Inflammation may destroy countercurrent mechanism medulla

Question 17

How does polycythaemia cause PU/PD?

Answer 17

• Suspected to be due to increased threshold for ADH release which delays response to increasing osmolality
• Thought to be due to increases ANP and baroreceptor stimulation. These inhibit ADH release and CD response to ADH

Question 18

Where do you start with a PU/PD case?

Answer 18

• In the majority of clinical cases, PD is a result of PU
• A variety of medical conditions induce PD/PU which are COMMON causes
• Primary CDI/NDI are RARE causes
• Primary PD disorders are RARE causes

Question 19

A minimum database is required to be able to rule in or out common causes of PU/PD. What is this?

Answer 19

• Urinalysis (YOU CAN’T EVALUATE PD/PU WITHOUT IT)
  
  • USG MUST BE MEASURED
  • Full analysis including sediment, UPC and culture
  • It is important to establish how significant the protein concentration is in the urine
• cystocentesis sample is important after having established the presence of PD/PU
• Serum biochemistry
  
  • Should include urea, creatinine, phosphate, calcium, total protein, glucose, cholesterol, liver enzymes and electrolytes
• Thyroid hormone should be measured in older cats
• CBC to include differential count (not %)

Question 20

Interpret these results?

Answer 20

On DDx was liver disease and liver values are up here however in HyperAC you get a metbaollic hepatopathy. Glucocorticoid induced ALP enzyme. This is not an uncommon picture for a cushinoid dog.

Cholesterol increased in dogs with cushings and liver disease would not show high cholesterol.

Classic cushings biochem picture.

Question 21

Interpret these results?

Answer 21

Metabollic hepatopathy picture seen from endocrinopathies.

Entire female with high levels of progesterone causing type 2 diabetes. She was speyed and weaned off insulin over 3 months and cured.