Water Metabolism and Diabetes Insipidus

Question 1

Water consumption and urine production are controlled by complex interactions between…

6 Answers

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 1

1. Plasma osmolality
2. Fluid volume in the vascular compartment
3. Thirst centre
4. Kidney
5. Pituitary gland
6. Hypothalamus

Question 2

Diabetes insipidus results from…

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 2

Deficiencies in secretion of vasopression OR its ability to interact normally with receptors located in the distal and collecting tubular cells

Question 3

Diabetes insipidis results from either a deficiency in secretion of vasopression OR its ability to interact normally with receptors in the kidney. What is the result of either of these scenarios clinically?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 3

This results in an impaired ability to conserve water and concentrate urine

Which results in the production of large volumes of hypotonic dilute urine

Which results in compensatory polydipsia to minimise dehydration

Question 4

The physiologic regulation of vasopressin synthesis and secretion is governed by which two major factors?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 4

1. Extracellular fluid osmolality
2. Blood pressure and volume

Extracellular fluid osmolality (and water homeostasis) is primarily regulated by ADH
Blood pressure and volume are in a large part regulated by the RAAS

Question 5

Vasopressin is the main hormone involved in the regulation of…

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 5

Water homeostasis and osmolality

Question 6

Water homeostasis and osmolality are primarily regulated by which hormone?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 6

Vasopressin

Question 7

What is the system that has a large responsibility in regulating blood pressure and volume?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 7

The RAAS system

Question 8

How does vasopressin secretion respond to changes in plasma osmolality?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 8

Small increases in osmolality result in increased production and secretion of vasopressin

Small decreases in osmolality result in decreased production and secretion of vasopressin

Changes occur in parallel

Question 9

The neurohypophysis contains a set of hypothalamic nuclei (supraoptic and paraventricular) responsible for the synthesis and secretion of oxytocin and vasopressin. These nuclei are composed of…

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 9

1. The magnocellular neurons
2. Axonal cell processes (form the supraopticohypophysial tract)
3. The termini within the posterior lobe of the pituitary

Question 10

What is the function of the magnocellular nuclei?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 10

They secrete vasopressin and oxytocin in response to appropriate stimuli

Stimulus comes from high pressure baroreceptors in the carotic sinus and aortic arch and low pressure volume receptors in the atria and pulmonary venous system

Question 11

Vasopressin and oxytocin are produced by which structure?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 11

The magnocellular neurons in the neurohypophysis

Question 12

Describe how neurogenic input from high pressure arterial baroreceptors and low pressure volume receptors affect the release of vasopressin

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 12

Baroreceptors and volume receptors normally inhibit the magnocellular neurons. Decrease in this tonic inhibition results in the release of vasopressin

Question 13

Decreased tonic inhibition of high pressure baroreceptors and low pressure volume receptors results in the release of vasopressin the action of which is…

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 13

To stimulate V1a receptors on blood vessels, the result of which is vasoconstriction. The purpose of this is the effectively increase circulating plasma volume

ADH also acts on the kidneys to retain water but the main hormonal regulator of blood volume is the RAAS (stimulates renal sodium resorption)

Question 14

What is the general molecular composition of arginine vasopressin?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 14

Six member disulfide ring with a three membered tail on which the terminal carboxyl group is amidated

Question 15

What is the difference in structure between arginine vasopressin and the synthetic compound desmopressin acetate (DDAVP)

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 15

D-arginine is substituted for L-arginine at position 8
The terminal amino group is removed from cysteine

Question 16

What is DDAVP?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 16

Desmopressin acetate (synthetic form of ADH)
AKA Deamino D-arginine vasopressin

Question 17

The production of vasopressin (and oxytocin) is associated with specific binding proteins called…

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 17

Neurophysins

Question 18

The neurophysin peptide (vasopressin / oxytocin) combination is often referred as…

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 18

Neurosecretory material

Question 19

Describe the transport and release of vasopressin starting at the magnocellular neurones

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 19

1. One molecule of neurophysin II binds one molecule of vasopressin (neurosecertory material)
2. Neurosecretory material is transported along the the axons of the hypothalamo-neurohypophyseal nerve tract
3. Stored in granules in nerve terminals in the posterior pituitary
4. Electrical stimulation of magnocellular neurons results of release into the blood stream via exocytosis
5. Neurophysin-vasopressin combination dissociates in plasma releasing free vasopressin (the majority of this hormone exists unbound in plasma)

Question 20

What are the mechanisms by which vasopressin is metablised and excreted?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 20

1. AVP binds to specific receptors after which they undergo proteolytic degradation
2. Renal excretion is a secondary method (approx 1/4 of metabolic clearance)

Question 21

The actions of AVP are mediated via the binding of receptors on the end organs of response. What are these receptors, what are the resulting actions, and how are these results acheived?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 21

1. V2 cAMP dependent receptors on the epithelia of the renal collecting duct. This mediates the diuretic action of AVP. It also stimulates the production of factor VIII and von Willebrand factor
2. V1a phosphatidylinositol dependent receptors on blood vessels. This mediates the vasoconstrictive actions of ADH
3. V3/V1b stimulates the secretion of ACTH from the anterior pituitary

Question 21

Where are the primary cells that sense changes to osmolality located?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 21

In the brain. Specifically cells in the organum vasculosum of the lamina terminalis and in areas near the anterior wall of the third cerebral ventricle

Question 22

The primary cells that sense change to osmolality are located in the brain. What is anatomically significant about the cells of this region?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 22

The cells in this region are perfused by fenestrated capillaries. Thus the blood brain barrier at this stie is deficient. The cells are therefore influenced by the composition of plasma rather than cerebrospinal fluid. Thus they are able to respond rapidly to changes in osmolality by increasing/reducing the production / secretion of vasopressin.

Question 23

How large must be the change in plasma osmolality to change the secretion of vasopressin?

Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 23

As little as a 1% increase or decrease in plasma osmolality is sufficient to stimuate and increase or decrease in AVP release from the store of hormone in the posterior pituitary

Question 24

What is the half life of AVP? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 24

Approximately 15 minutes

Question 25

Describe how AVP leads to the insertion of aquaporins in the apical membrane of the renal tubular epithelial cells ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 25

1. AVP binds V2 receptors on the basolateral surface of the cell 2. Activation of the V2 receptor triggers membrane adenylate cyclase function. This enxyme converts ATP to cAMP 3. cAMP activates protien kinase A 4. PKA triggers the insertion of aquaporins into the luminal surface of the renal tubular epithelial cells

Question 26

What is the result of aquaporin insertion into the apical membrane of renal epithelial tubular cells? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 26

Water permeability is increased. This allows osmotic water flow (not active water flow) from the tubular lumen into the hypertonic medullary interstitium

Question 27

AVP increases osmotic water flow from the tubular fluid of the collecting duct into the medullary interstitium. In this circumstance, how is medullary hypertonicity maintained? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 27

The vasa recta resorbs this water from the medullary interstitium thereby maintaining the osmotic gradient / hypertonicity of the renal medulla

Question 28

What are the factors that impact the amount of water reabsorbed from the distal nephron? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 28

1. Plasma AVP concentration 2. Existence of a significant osmotic gradient in the renal interstitium (i.e. adequate renal medullary hypertonicity)

Question 29

How does a reduction in / loss of renal medullary hypertonicity affect the action of AVP? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 29

Movement of water from the distal tubular lumen into the renal interstitium is passive. A reduction in medullary hypertonicity reduces the osmotic gradient required for this passive resoprtion of water. This means that a loss of renal medullary hypertonicity may inhibit vasopressin's antidiuretic effects.

Question 30

Why does medullary washout alone rarely result in significant polyuria? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 30

This is because a majority of the fluid coming from the loop of Henle can still be resorbed isotonically in the distal convoluted tubule and proximal collecting duct

Question 31

What is solute diuresis? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 31

This is a process that occurs when large volumes of filtered solutes reduce impair the ability of fluid to be reabsorbed in the proximal tubule. The resulting large amount of fluid presented to the distal nephron then overwhelms its capacity for water reabsorption resulting in diuresis even in the presence of large concentrations of vasopressin. This can occur in the presence of high dietary intakes of sodium, or in the presence of poorly reasborbed solutes such as mannitol, urea, or glucose.

Question 32

What are mechanisms that stimulate thirst? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 32

1. Increased ECF osmolality (via osmoreceptors in the anterior hypothalamus) 2. Decreases in intravascular volume (via high and low baroreceptors in the thorax) 3. Angiotensin II

Question 33

By how much must plasma osmolality increase to stimulate thirst? | This value is from a study in humans ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 33

2-3%

Question 34

What satiates thirst? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 34

This requires restoration of normal plasma osmolality (major role) and blood volume

Question 35

What defines polyuria and polydipsia clinically? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 35

Polydipsia: water intake > 100ml/kg/day Polyuria: Urine output > 2ml/kg/hr (>50ml/kg/24hrs) Keeping in mind there is potential for urine production to be abnormal within the normal reference ranges in some individuals

Question 36

What are the classifications of primary polyuric disorders? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 36

1. Primary pituitary and nephrogenic diabetes insipidus (NDI) 2. Secondary NDI 3. Osmotic diuresis induced polyuria 4. Intereference with the hypothalamic-pituitary secretion of AVP

Question 37

What is the most common form of diabetes insipidus? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 37

Acquired secondary NDI

Question 38

What are the mechanisms by which secondary NDI can occur? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 38

1. Interference with the normal interaction of AVP and renal tubular AVP receptors 2. Problems with the generation of intracellular cAMP 3. Problems with renal tubular cell function 4. Loss of the renal medullary interstitial concentration gradient

Question 39

## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Question 40

What is the mechanism by which diabetes mellitus stimulates osmotic diuresis and compensatory polydipsia? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 40

1. Relative or absolute insulin deficiency results in hyperglycaemia 2. Capacity for renal tubular reabsorption of glucose is exceeded 3. Glucose appears in the urine and acts as an osmotic diuretic causing increased water loss into the urine 4. Water loss results in hypovolaemia 5. Hypovolaemia stimulates thirst and increased water intake

Question 41

What is renal tubular glycosuria? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 41

A rare congenital tubular disorder in which there is an inability for glucose to be reabsorbed from the ultrafiltrate

Question 42

What are the clinical findings that would increase the suspicion of renal tubular glycosuria? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 42

1. Polyuria and polydipsia 2. Persistent glycosuria 3. Normal blood glucose and serum fructosamine concentrations

Question 43

What are the potential reasons for the development of polyuria in patients with pyometra? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 43

Bacterial endotoxins may 1. Compete with AVP for V2 receptor binding sites 2. Interfere with the insertion of aquaporin-2 water channels into the apical membrane of renal tubular epithelial cells 3. Cause reversible renal tubular cell lesions

Question 44

Why does hypercalcaemia result in polyuria? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 44

Increased calcium is associated with down regulation of aquaporin-2 water channels and decreased function of AVP. It results in: 1. Inhibited binding of AVP to its receptor binding site 2. Damage to AVP receptors in the renal tubules 3. Inactivation of adenylate cyclase 4. Decreased transport of sodium and chloride into the renal medullary interstitium

Question 45

How do glucocorticoids affect the production of AVP at the level of the hypothalamus? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 45

Glucocorticoids work at the level of the hypothalamus and / or neurohypophysis to inhibit AVP release. They do this by: 1. Increasing the osmotic threshold for for AVP release 2. Decreasing the sensitivity of the AVP response to increasing osmolality

Question 46

Besides its action at the level of the hypothalamus, what are potential mechanisms by which glucocorticoids cause polyuria? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 46

1. Increase GFR (potentially via altered renal autoregulation - not from this reference) 2. Altered proximal tubular epithelial sodium transport 3. Increased free water clearance 4. Cause resistance to the effects of AVP in the kidney

Question 47

Besides the increase in circulating steroid hormones, how might a pituitary tumour present in Cushing's disease result in polyuria? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 47

There is potential that the presence of a pituitary macrotumor may directly compress the magnocellular neurons resulting in a deficiency of AVP

Question 48

What are the potential mechanisms by which polyuria occurs in pyelonephritis? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 48

1. Direct destruction of renal tissue (and thus the countercurrent mechanism in the renal medulla) via infection and inflammation 2. Bacterial endotoxins may compete for AVP binding sites (as with pyometra)

Question 49

How does hyperaldosteronism result in polyuria? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 49

The mechanism for this is not clear

Question 50

What is CDI? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 50

Central diabetes insipidus It is a polyuric syndrome that results from a lack of sufficient AVP to concentrate urine for water conservation

Question 51

What is the result of an absolute deficiency in AVP (compared to partial deficiency)? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 51

Persistent hyposthenuria Severe diuresis USG remains

Question 52

What is the result of a partial deficiency in AVP (compared to an absolute deficiency)? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 52

This is known as partial CDI Persistent hyposthenuria and severe diuresis as long as there is unlimited water access USG can increase into the isosthenuric range (1.008 - 1.015) with water restriction but cannot generally concentrate above 1.015 - 1.020 (even with severe dehydration)

Question 53

What is the relationship between AVP and USG in patients with partial CDI? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 53

Maximum USG in periods of dehydration is inversely related to the severity of the deficiency in AVP secretion

Question 54

What us the pathophysiology of CDI? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 54

This requires destruction of AVP production sites (the supraoptic or paraventricular nuclei of the hypothalamus) and/or the major ducts (axons) that carry AVP to the axon terminals in the posterior pituitary (neurohypophysis)

Question 55

What is the aetiology of CDI? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 55

It can result from any condition that damages the neurohypophyseal system D: Hypothalamic pituitary malformation A: Cysts N: Neoplasia I: Idiopathic (most common),Inflammation, Parasite migration, Transsphenoidal hypophysectomy T: Head trauma

Question 56

What is the common signalment for the development of CDI? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 56

Appears at any age in any breed of any gender

Question 57

Trauma induced transection of the pituitary stalk often results in transient CDI. What affects the duration of CDI in this circumstance? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 57

Duration depends on the location of the transection of the hypophyseal stalk relative to the hypothalamus. Transections more proximally (closer to the median eminence) results in a longer duration because it is associated with a longer time frame for the hypothalamic axons to undergo regeneration and begin secreting AVP again.

Question 58

When should trauma induced CDI be suspected? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 58

1. When severe polydipsia and polyuria develop within 48 hours of head trauma 2. When hypernatraemia, hyposthenuria, and hypertonic dehydration develop in a traumatised patient being treated with IV fluids

Question 59

Transient or permanent DI is a common result of transsphenoidal hypophysectomy performed for the treatment of pituitary dependent hyperA in dogs. What are the statistics cited in this chapter for this outcome? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 59

One study evaluating 127 dogs with pituitary dependent hyperA 1. Postoperative CDI was transient in 78% of dogs with DDAVP discontinued 2 weeks after surgery in 47% and eventually discontinued in 31% (THESE NUMBERS DO NOT MAKE SENSE TO ME > LOOK UP ORIGINAL ARTICLE) 2. CDI was present until death or final follow up in 22% of dogs

Question 60

Neoplastic destruction of the magnocellular neurons may cause CDI. What percentage destruction must occur for DI symptoms to become apparent? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 60

90% of the magnocellular neurons must be destroyed

Question 61

In one study, what influence the incidence of postoperative permanent CDI in dogs undergoing transsphenoidal surgery for hyperA? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 61

Occurence was strongly influenced by the size of the tumour; larger tumour = more likely

Question 62

Does CDI have a hereditary component? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 62

Though it is well established in puppies and kittens, a hereditary link has not been documented

Question 63

Define NDI ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 63

Nephrogenic diabetes insipidus This is a polyuric disorder that results from impaired responsiveness of the nephron to the actions of AVP

Question 64

Describe the general concentrations of plasma AVP in cases of NDI ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 64

Plasma AVP concentrations are normal or increased in NDI

Question 65

How would you establish a diagnosis of congenital NDI? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 65

Findings of high plasma AVP concentrations in the presence of hypotonic polyuria and a lack of responsiveness to DDAVP

Question 66

How common is primary NDI in cats and dogs? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 66

It is rare. There have only been a few reports in the dog and none in the cat

Question 67

Familia NDI has been reported in a family of Huskies. What was the underlying mechanism for the disease in this case? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 67

The affected puppies had normal V2 receptor numbers, but there was a tenfold decrease in their binding affinity for AVP

Question 68

When can primary NDI be considered as a differential diagnosis in older patients? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 68

Only when polyuria and polydipsia has been present for the animals entire life

Question 69

Define primary polydipsia ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 69

(Compulsive water consumption) Syndrome characterised by ingestion of excess water. It results in compensatory polyuria to prevent water intoxication

Question 70

What is the aeitology of primary polydipsia in the dog and cat? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 70

There appears to be a psychogenic basis in dogs (this is uncommon). This has not been reported in cats. Hypothalamic lesions affecting the thirst centre have not been documented in dogs or cats

Question 71

Describe the urine concentrating ability if dogs with primary polydipsia ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 71

Urine concentration can exceed 1.030 during water deprivation

Question 72

Why might it take a prolonged period for dogs with primary polydipsia to show an increase in USG during water deprivation? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 72

This is because primary polydipsia results in concurrent renal medullary solute washout

Question 73

What does the identification of concentrated urine imply about the mechanism of action of AVP? ## Footnote Chapter 1: Textbook of Canine and Feline Endocrinology

Answer 73

1. Hypothalamic AVP production 2. Pituitary AVP secretion 3. Renal tubular responsiveness to AVP