PU/PD Flashcards
Polydipsia definition
- Drinking more than 100 mLs/kg/day (grey zone is 50-100 mgs/kg/day)
Polyuria definition
- producing more than 50 mLs/kg/day of urine
Where is antidiuretic hormone produced and released?
- Produced by the hypothalamus
- Released by the posterior pituitary
What two things control water balance in the body?
- Osmolarity of plasma
- Circulating volume
What happens with osmolarity is increased?
- Thirst is stimulated
- ADH is produced
ADH action
- Works on the collecting tubules and duct of the kidney to increase
- Stimulates formation of aquaporins to move water into the renal medullary interstitium
How much of water filtered by the kidneys is reabsorbed?
> 99%
Kidneys and water balance during state of dehydration
- Can produce urine 7-8x the osmolality of plasma
- Plasma is 300 mOsm/L
- Concentrated urine is >2000 mOsm/L
Hypersthenuria urine concentration in dogs and cats
- Dog: >1.030
- Cat: >1.035 (closer to >1.050)
Isosthenuria urine concentration
1.008-1.012
But definitely be considering it still if USG is <1.017
Hyposthenuria urine concentration
- <1.008
- A little bit of a gray zone but <1.008 usually
- Resorption of solute > water
Gray zone of being minimally concentrated
- 1.012-1.030
- 1.030 is more of a cat thing
- 1.020 is more of a dog thing
When is isothenuria appropriate?
- If the patient needs to excrete water
- Primary polydipsia
What type of urine should a dehydrated patient have?
- Concentrated urine
DfDx for PU/PD (I don’t think we need to memorize this…yet)
- Diabetes mellitus
- Hyperthyroidism
- Hyperadrenocorticism
- Hypoadrenocorticism
- Acromegaly
- Primary hyperaldosteronism
- Diabetes insipidus - central
- Diabetes insipidus - nephrogenic
- Pheochromocytoma
- Hypercalcemia
- Neoplastic (intestinal leiomyosarcoma)
- Pyometra
- E. coli infections (urinary, sepsis)
- Hepatic disease
- Fanconi’s Syndrome
- Renal disease
- Hyperviscosity syndrome
- Polycythemia
- Post-obstructive diuresis
- Pyelonephritis
- Hypokalemia
- Hyponatremia
- Drugs (steroids, diuretics, anticonvulsants
- Psychogenic polydipsia
- Pain, heat, stress
- Hyperthermia
- Very low protein diets
Which diseases antagonize ADH to cause PU/PD?
- Cushing’s
- Primary Hyperaldosteronism
- Pheochromocytoma
- Hypercalcemia
- Neoplasia
- Pyometra/endotoxemia
- Hyperviscosity/endotoxemia
- Polycythemia
- Hypokalemia
Which diseases cause a loss of medullary gradient/osmotic diuresis to cause PU/PD?
- Diabetes mellitus
- Addison’s (losing so much sodium)
- Acromegaly
- Pyometra/endotoxemia
- Hepatic disease
- Fanconi’s
- Renal failure
- Post-obstructive diuresis
- Pyelonephritis
- Hyponatremia
- Low protein diet
Diseases with other or unclear causes of PU/PD
- Hyperthyroidism
- Psychogenic
- Pain, heat, stress
- Hyperthermia
Mechanism of PU/PD in Diabetes mellitus
- Glucose in urine causes osmotic diuresis leading to hypovolemia thus stimulating drinking
Mechanism of PU/PD in hyperthyroidism
- unclear
- Decrease medullary tonicity due to increased blood flow, psychogenic, concurrent renal insufficiency
Mechanism of PU/PD in Cushing’s
- glucocorticoids inhibit ADH release and renal response to ADH
Mechanism of PU/PD in Addison’s
- Mineralocorticoid deficiency causes chronic Na wasting, loss of medullary gradient
Mechanism of PU/PD in acromegaly
- Due to concurrent DM; glomerulonephropathy from Dr or excess GH
Mechanism of PU/PD in Primary hyperaldosteronism
- Unclear
- ADH resistance
- Hypokalemia
Mechanism of PU/PD in pheochromocytoma
- catecholamine induced inhibition of ADH release and renal ADH response
Mechanism of PU/PD in hypercalcemia
- Downregulation of aquaporin water channels and ADH inhibition
Mechanism of PU/PD in Neoplasia
- Paraneopalstic nephrogenic diabetes insipidus
Mechanism of PU/PD in pyometra/bacterial infections
- Bacterial (E. coli) endotoxin production competes with ADH at renal receptors, damages renal receptors, inactivation of adenylate cyclase, decrease Na and Cl transport into renal medullary interstitium
Mechanism of PU/PD in Hepatic disease (PSS)
- Unknown
- Loss of medullary gradient due to impaired urea nitrogen production
Mechanism of PU/PD in Fanconi’s syndrome
- Renal glucosuria causing osmotic diuresis
Mechanism of PU/PD in renal disease
- nephron dysfunction and compensatory increases in GFR to surviving nephrons
- Increased tubular fluid volume, decreased absorption of solutes leading to an osmotic diuresis and loss of medullary gradient
Mechanism of PU/PD in hyperviscosity syndrome/polycythemia
- increased blood volume and viscosity trigger release of atrial natriuretic peptide (ANP) secretion and stimulate baroreceptors
- ANP inhibits ADH release
Mechanism of PU/PD in post-obstructive diuresis
- Osmotic diuresis
Mechanism of PU/PD in pyelonephritis
- Destruction of countercurrent mechanisms and loss of medullary gradient; endotoxemia
Mechanism of PU/PD in hypokalemia
- Decreased renal ADH response, loss of medullary gradient
Mechanism of PU/PD in Hyponatremia
- Loss of medullary gradient
Mechanism of PU/PD in psychogenic PD
- Primary polydipsia resulting in pecondary polyuria
Mechanism of PU/PD in pain, heat, stress, hyperthermia
- Polydipsia resulting in secondary polyuria
Mechanism of PU/PD in very low protein diet
- Decreased urea nitrogen and resulting loss of medullary gradient
Diabetes insipidus overview
- Both a secondary condition and a primary disease
- Includes all alterations in ADH production and functionality
- Includes all of the PU/PD dfdx that affect ADH
Central DI
- ADH not being made
Nephrogenic DI
- Kidneys are not responding to ADH
- Receptors are not present or not responsive
Central diabetes insipidus
- Partial or complete deficiency of ADH
- Results in decreased ability or inability of the kidneys to conserve water and concentrate urine in response to increases in plasma osmolality
- Polyuria causes increased plasma osmolality because fluid is lost in excess of solute
- Increased osmolality stimulates thirst (polydipsia)
How common is central DI?
- Super rare
USG in Central DI
- USG is hyposthenuric, unless it’s partial
- if partial can be isosthenuric
Causes o fCentral DI
- Congenital, acquired, idiopathic
- Surgery, trauma, neoplasia
- e.g. pituitary surgery
Nephrogenic DI
- Lack of or impaired renal tubular responsiveness to ADH
- Primary or secondary
Primary nephrogenic DI
- Congenital defect in the nephron
- Mutation in ADH receptor or aquaporin
- RARE
- Hyposthenuric
Secondary nephrogenic DI
- MORE COMMON
- Causes are any conditions that affect ADH binding and function in the renal tubules, causing loss of medullary gradient, or causing osmotic diuresis
Approach to PU/PD
- Confirm it’s occurring
- Perform simple, high yield tests first
- Rule out causes of secondary NDI
- Then…and only then…consider CDI or primary NDI
How to confirm PU/PD?
- Water intake
- USG (first urination of the day)
- If you measure USG in the morning try to find out if the animal is drinking at night
Clues for underlying cause of PU/PD
- Look for clues based on patient history, PE, diet, drug history
- Basic lab work
- Ultrasound
- Evaluate for infection
- Additional endocrine testing
- Additional organ testing
Basic lab work screening
- Evaluate PCV, protein levels, electrolytes, calcium (iCa), renal values, liver values, glucosuria, pyuria, bacteriuria
Ultrasound
- Look for pyelonephritis, pyometra, hepatic, renal, endocrine, neoplasia
Infectious disease evaluation
- Cultures, Lepto serology
Additional endocrine testing
- LDDS, ACTH stim, thyroid levels (if cat)
Additional organ function testing for PU/PD
- Bile acids
- GFR study
Further possible clues for PU/PD
- Liver aspirate or biopsy, lymph node aspirates, bone marrow biopsy, etc.
If all of your testing is normal but you still have PU/PD, now what?
- Left with psychogenic vs primary DI
How to assess for Diabetes insipidus?
- Modified water deprivation test
- DDAVP response
- Remember that CDI or primary NDI is rare
- Psychogenic is MUCH MORE likely
Serum osmolality testing CDI vs psychogenic
- With CDI should be in the high-normal range or above normal (280-320 mOsm/kg)
- With psychogenic polydipsia would have a low-normal to below-normal serum osmolality (<275 mOsm/kg) caused by ingestion of water in excess of the kidneys’ ability to excrete it appropriately
Exogenous DDAVP
- Acts like ADH
Exogenous DDAVP Administration Response supportive of DI
- Increase in USG of at least 50% compared with pretreatment USG by day 5 to 7 or a specific gravity >1.030 supports the diagnosis of CDI
- May also result in concentrated urine with other disorders (psychogenic polydipsia, hyperadrenocorticism)
- You have to have ruled out everything else first
Modified water deprivation
- Used to determine whetehr endogenous ADH is appropriately released in response to dehydration and whether the kidneys can appropriately respond to ADH
What are drawbacks to modified water deprivation?
- Time consuming and labor intensive
- If done wrong, useless (need u cath, adequate staff to perform everything on time, in-house lab machines)
- If done wrong, dangerous (YOU CAN KILL PATIENTS).
Who is at risk of death in modified water deprivation?
- Hypernatremia, hyperosmolar, azotemia
- They keep urinating because they can’t stop
- Then you give them no water
- May be inhumane
- Monitor closely
Modified Water Deprivation Test procedures
- Gradually limit water intake over 3-5 days (dangerous)
- Then hospitalize and remove water completely. Monitor weight, PCV, TP, BUN, Na every 1-2 hours. If no concentration is reached, move to the next step.
- Give DAVP and monitor urine USG or urine osmolality. Offer small amounts of water 2 hours after administration. CDI is diagnosed when USG or urine osmolality increases by 50% or more.
Endpoint of water deprivation
- 5% dehydration of USG >1.025
- Either they have functional receptors and can produce
How not to do a water deprivation test?
- Take away water overnight then check a morning urine
- Take water away from the dog in hospital and just check a USG at the end of the day
- Start a modified water deprivation test without first gradually limiting water consumption for several days
Treatment for Acquired NDI
- Address the underlying cause!
Treatment for Central Diabetes insipidus
- Lifelong therapy!
- DDAVP (Desmopressin)
- Oral or nasal formulation, given as an eye drop or SC.
- Very expensive
Treatment for congenital Nephrogenic Diabetes insipidus
- Low-sodium diet
- Thiazide diuretics
- Free-choice water with NO RESTRICTION
- Allow constant access to water
- Ensure outside access to prevent accidents in the house
Thiazide diuretics and treatment of congenital nephrogenic diabetes insipidus
- Inhibit distal sodium resorption
- Causes volume contraction
- Increased proximal tubular sodium and water resorption
Prognosis of acquired NDI
- Depends on underlying disease
Prognosis of Congenital NDI
- good with constant water availability
Prognosis of acquired central DI
- Dependent on lesion
- If secondary to trauma, resolves within 2 weeks usually
Prognosis of congenital central DI
- Great with treatment
Endocrine diseases that do NOT cause PU/PD
- Hypothyroidism
- Primary hyperparathyroidism (if not hypercalcemic)
- Hypoparathyroidism
Endocrine diseases that DO cause PU/PD
- Diabetes mellitus
- Hyperthyroidism
- Hyperadrenocorticism
- Hypoadrenocorticism
- Primary hyperaldosteronism
- Acromegaly
- Diabetes insipidus
- Primary hyperparathyroidism (if hypercalcemic)
