Schatzie is a 3-year-old, FS miniature schnauzer that presented with long-term polydipsia and polyuria (PU/PD). According to patient history provided by the owner, Schatzie was acting normally aside from her PU/PD. 

Upon initial physical exam at the clinic, Schatzie's main problems seemed to be (from most clinically serious in decreasing order):

1) Hyponatremia and hypochloremia

• With occasional vomiting and diarrhea when replacement sodium was added to diet.

This grouping of issues is ranked as the most severe because of the effects that they can have on Schatzie's body over time if the issues aren't addressed, in addition to the fact that these issues could point to a bigger problem. Other clinical issues such as lethargy, seizures, and coma could eventually occur if the electrolyte imbalance isn't corrected. Additionally, these conditions could point to some type of condition that is causing water retention within the body, which could mean that another body system controlling the body's water intake and absorption was being affected.¹

Generally, hyponatremia can occur because of either water retention, or because of solute loss within the body through methods such as vomiting and diarrhea. Because Schatzie's vomitting and diarrhea is intermittent, water retention is the more likely cause of the condition. Hypochloremia is often associated with hyponatremia because of the fact that most sodium is taken in with chloride in the form of NaCl. 

2) Polyuria and polydipsia

Increased thirst and urination could point to a serious condition occurring in some organ system of the body along the urinary processing pathway, such as the kidneys, the brain, or the urinary tract itself. The inability to properly concentrate urine could suggest kidney failure, while a pituitary tumor or similar neoplasia could be causing a malfunction in the patient's water regulating system. If these conditions are left untreated, they could prove fatal. 

3) Incidental brain findings from MRI, which included:

• Moderate bilateral symmetrical dilation of the lateral ventricles
• Mild bulging of the caudoventral cerebellum with evidence of herniation

These findings could point to a more serious condition starting to develop, such as a brain tumor, encephalitis, or meningitis. If left untreated, these conditions could also prove fatal to Schatzie. 

Other problems that were not considered as clinically serious, but that should still be mentioned include:

• Slightly turbid urine
• Dry and wiry fur 
• Low chemistry bicarbonate levels (with generally lowered values for all other chemistry values) 
• Slight cardiomegaly (of the right side of the heart)

From diagnostic imaging, other issues were noted, such as 

• Presence of a dorsal soft tissue membrane narrowing Schatzie's larynx that was seen on radiographs
• Slight enlargement of the medial retropharyngeal lymph node

Most of these issues can be connected to the more serious clinical problems as secondary conditions. 

1. The most probable differential is Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), possibly associated with hydrocephalus:

• Normally, ADH is secreted by the hypothalamus in the brain. When water is ingested, there is a dilution of the blood plasma within the circulation (seen in biochemistries as a decrease in plasma osmolality (P_osm)). This change is detected by osmoreceptors in the hypothalamus, and causes ADH release by the posterior pituitary to be inhibited.¹

How ADH release affects plasma osmolality.¹

• When ADH ceases to be released, the aquaporins within the nephrons of the kidney are inhibited, and thus, less water in circulation is reabsorbed. 
• In patients with SIADH, decreased plasma osmolality does not cause inhibition of ADH release from the hypothalamus. The patient will still feel thirsty, even after drinking adequate amounts of fluids. This continuous fluid intake will eventually result in an overhydration within the body, leading to a dilution of body solutes, such as sodium (dilutional hyponatremia). 
• SIADH has many possible causes, including drugs, especially tranquilizers and antineoplastic chemotherapeutics; encephalitis; neoplasia that produce ADH ectopically; and intrathoracic lesions with compromised venous return to the great vessels and pressure receptors.² 
• SIADH is most likely occurring in Schatzie in part because of the dilation of her brain's lateral ventricles, and mild caudal occipital malformation with herniation, as seen on the MRI that was taken. These changes could be a result of excess cerebral spinal fluid on the brain, a condition referred to as hydrocephalus.¹
• These changes in her brain could possibly be putting more pressure on the area, and in turn affecting the ability of her brain's osmoreceptors to pick up on signaled changes in plasma osmolality.

The differential of SIADH is supported by several clinical signs seen during the various aspects of Schatzie's examination including: 

• Polydipsia/polyuria: Because ADH is not being inhibited when Schatzie takes in fluids, she will be continually thirsty. As a direct result, she will produce more urine.³ 
• Hyponatremia/hypochloremia (and other chemistry values on the low end of the reference range): Because ADH is still being released, as Schatzie takes in more and more fluids, they will dilute the solute levels within her circulation.
• Because sodium is the main solute of plasma, it is what is mainly affected by this dilution, and hyponatremia will occur. Because chloride is most often introduced into the body with sodium as NaCl, chloride levels within the plasma will also be diluted by the excess fluid intact. Similarly, the excess fluid also slightly dilutes levels of all other solutes in circulation, hence why all values are on the low end of the given reference ranges.⁴
• Intermittent diarrhea and vomitting: These signs are simply other consequences of an existing electrolyte imbalance occurring within the body because fluids and electrolytes are not being processed correctly through the body. 
• Slight cardiomegaly on the right side: Hyponatremia caused by SIADH would signal the kidneys to produce more renin within the body, increasing the overall blood pressure within Schatzie's system, and possibly causing the right-sided heart enlargement as seen on radiographs. 
• A video explaining further the intricacies of SIADH can be found linked here.

2. A possible secondary differential is some type of brain lesion, small tumor, or a pituitary cyst causing ADH to be inappropriately secreted in the brain, and thus causing Schatzie's clinical signs. However, because advanced imaging has already been done and showed no signs of these occurances, not recognizing these types of issues on the imaging results would have to be attributed to human error, which is less likely than another differential being the cause. 

Because ADH is not being inhibited, Schatzie is taking in more water. The posterior pituitary via the hypothalamus is not being signaled by a decrease in P_osm to inhibit the release of ADH. Thus, thirst is left unregulated, and Schatzie's brain is telling her she is still thirsty. The lack of ADH inhibition is the cause of her polydipsia. The extra hydration is causing a dilution of the electrolytes within circulating plasma. Because sodium is the main component of this plasma, the decrease in its concentration is most noticeable on the biochemistry results. In addition to the blood biochemistry and the urinalysis performed, radiographs, and a MRI were also performed. 

The MRI was performed to check for possible pituitary tumors, other neoplastic abnormalities, or brain issues that could’ve possibly been affecting Schatzie’s health, and causing her clinical signs. In most instances, some type of neoplasia or related disease would be the primary cause of signs like Schatzie's.

In a similar study examining clinical signs similar to Schatzie's in a 13-month-old Bichon Frise, MRI was used to test for brain involvement in the clinical diagnosis of SIADH. Results from both MRI, and the similarities that they have, are shown below. 

MRI results from the Shiel study showing marked symmetrical dilation of the lateral ventricles in a 13-month-old Bichon Frise.²

Results from Schatzie's MRI, showing dilation of lateral ventricles and mild caudal occipital malformation.³

In addition to the tests that had already been performed, an ADH blood test, to determine exactly how much ADH was being circulated would be useful in determining is SIADH was the actual cause of Schatzie's clinical signs. An ADH suppression test, with monitored blood and urine osmolality measurements over an extended period of time would be useful to determine when spikes of ADH were happening when they shouldn't be. Tests looking for vitamin deficiencies (since certain deficiencies could lead to similar clinical signs as SIADH) would also be useful to rule out possible other, secondary conditions. 

Other eventual side effects of SIADH (in addition to the diagnostic testing results) include behavioral changes (confusion, lethargy, convulsions, coma), muscle weakness, consistent nausea and abdominal cramping, postural hypotension, and consistent vomitting.¹ 

Schatzie's condition could be managed in several ways. Firstly, fluid restriction would allow for her body's electrolyte levels to normalize, and for the side effects of hyponatremia to subside. Hypertonic saline could also be administered to both keep Schatzie adequately hydrated, but also increase sodium and chloride levels without having to supplement the diet directly.²

Careful use of dieuretic drugs would decrease reabsorption of water within the system and would allow for any electrolyte imbalances to normalize. Additionally, ADH receptor antagonist drugs could be used to block the ADH from having an effect on the kidney's nephrons, thus decreasing water reabsorption. 

There were several basic scientific principles that needed to be understood before being able to interpret Schatzie's clinical signs. Perhaps the most important principle was that of how ADH regulates thirst within the body. This pathway is discussed multiple times in other areas of the case write-up. 

Another basic scientific principle that was relevant in this case was understanding how electrolytes work within the body, and how an imbalance can affect various aspects of an animal's physiology. Because the balance of electrolytes is so closely intertwined with the amount of hydration in an animal (and thus the plasma concentration), an extreme increase in the amount of fluid in circulation (such as in Schatzie's case) could cause an imbalance. Symptoms of such an imbalance would only worsen as more an more electrolyte's levels were diluted to miniscule levels. 

There were several issues that occurred when attempting to decide on appropriate differentials for this case. One issue was not knowing enough about either kidney or brain disorders to really connect the different clinical signs into one differential on first glance. The clinical signs were rather vague, and that opened up the differential possibilities to a lot of conditions that fit many of the clinical signs, but not all of them. Hopefully, with a more in-depth knowledge base about such topics later in my veterinary career, it will be easier to draw connections between organ systems, and thus make a more educated diagnosis. 

Another issue was not really being confident in my knowledge of what different portions of the brain do within the dog’s body, and thus how the incidental findings on Schatzie’s MRI would affect her overall differential. I spent a long while trying to make something more out of the incidental findings than what I actually needed to, and thus wasted a lot of time on researching the actual probable diagnosis further. 

¹Shiel, R. (2009). Syndrome of Inappropriate Antidieuretic Hormone Secretion Associated with Congenital Hyrocephalus in a Dog. J Am Anim Hosp Assoc. 45:249-252. Doi10.53260450249

²Brofman, PJ. (2003). Granulomatous amebic meningoencephalitis cause the syndrome of inappropriate secretion of antidiuretic hormone in a dog. J Vet Intern Med. 17:230-234. http://www.lloydinc.com/media/filer_private/2012/02/13/vol14_issue1_2004.pdf

³Kang, M. (2012). Syndrome of Inappropriate Antidiuretic Hormone Secretion Concurrent with Liver Disease in a Dog. J Vet Med Sci 74(5): 645–649, 2012 doi: 10.1292/jvms.11-0483

⁴Van Vonderen, I. (1997). Intra- and Interindividual Variation in Urine Osmolality and Urine Specific Gravity in Healthy Pet Dogs of Various Ages. J Vet Intern Med. 11:1;30-35. J.1939-1676.1997.tb00070.x

⁵Ayoub, JA. (2013). Association between urine osmolality and specific gravity in dogs and the effect of commonly measured urine solutes on that association. Am J Vet Res. 74(12):1542-5. doi: 10.2460/ajvr.74.12.1542.

Image references:

¹"How ADH release affects plasma osmolality". Retrieved April 26, 2016. Web. http://medical-dictionary.thefreedictionary.com/vasopressin

²"Shiel study MRI image". Retrieved April 25, 2016. Web. http://www.jaaha.org/doi/pdf/10.5326/0450249

³"Schatzie MRI results". Retrieved April 24, 2016. Web. https://cgscholar.com/community/community_profiles/vet-cases/community_publications/118316