The Case: Unresolving Edema
A 4-year-old neutered male Jack Russell terrier mix with an unremarkable medical history was presented for a distended abdomen and vomiting after drinking water. The dog had been seen 6 days earlier by the referring veterinarian for vomiting that resolved without treatment. No diagnostics had been performed at the first visit; at the second visit, blood analysis was performed.
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WBC: 5.8 x 103/L (range, 4.0–15.5)
Neutrophils: 1.9 x 103/µL (range, 2.06–10.6)
Albumin: 1.1 g/dL (range, 2.7–4.4)
Total protein: 3.9 g/dL (range, 5.0–7.4)
Calcium: 7.9 mg/dL (range, 8.9–11.4)
DAY 1Physical ExaminationTemperature: 101.4⁰FHeart rate: 140 bpmRespiratory rate: 35 bpmWeight: 9 lb, BCS 5/9Hydration: estimated 5%–7% dehydrationAbdominal palpation: suspected fluid wavePulse: slightly weak femoral pulsesBright, alert, responsive
DiagnosticsBlood pressure: 100 mmHg (Doppler)Flash abdominal ultrasound
Small bladder, but dog had urinated en route to hospital
Free fluid noted
Abdominocentesis/dipstick values
Clear fluid
Specific gravity: 1.000
Protein: 30+
Potassium: 4.1 mEq/L
Creatinine: 0.5 mg/dL
Cytology: no cells or bacteria
Serum biochemistry profile (abnormal findings)
pH: 7.34 (range, 7.35–7.45)
PO2: 77 (range, 85–100)
HCO3: 18.9 (range, 20–24)
BEecf: -7.0 (range, -5–0)
Treatment
Fluids: Plasma-Lyte* (11 mL/hr)
Low-fat diet
Rule-outs included protein-losing enteropathy, portosystemic shunt, and glomerular disease. Planned supportive care for 2 days followed by further workup.
Related Article: Canine Protein Losing Enteropathy
DAY 2Physical ExaminationTemperature: 101.9⁰FHeart rate: 140 bpmRespiratory rate: 40 bpmWeight: 9.48 lbSubcutaneous edema noted on ventrum with fluid accumulation surrounding the prepuce, lower thorax, and abdomen. Fluid leaked from those areas when pressure was applied.
DiagnosticsSNAP cPL: negativeAlbumin: 1.3 g/dL (range, 2.7–4.4)Serum biochemistry profile (abnormal values)
Hematocrit: 34.0% (range, 36–60)
Hemoglobin: 11.6 g/dL (range, 12.0–17.0)
BEecf: -2.0 mmol/L (range, -5–0)
PO2: 26 mmHG (range, 85–100)
SO2: 46% (range, >90)
TreatmentFluids: Plasma-Lyte* (15 mL/hr)Feeding: maintained a good appetite for low-fat food
DAY 3Physical ExaminationTemperature: 100.6⁰FHeart rate: 140 bpmRespiratory rate: 40 bpmWeight: 10.1 lbSubcutaneous edema was still present and had accumulated under right axilla.
DiagnosticsAlbumin: 1.3 g/dL (range, 2.7–4.4)
TreatmentSame as day 2
Related Article: Protein-Losing Nephropathy & Lameness in a Dog
DAY 4Physical ExaminationTemperature: 101.2⁰FHeart rate: 140 bpmRespiratory rate: 40 bpmWeight: 9.24 lbSubcutaneous edema persisted in inguinal area/right hindlimb.
DiagnosticsAbdominal ultrasound
Liver subjectively hypoechoic
Large volume of anechoic effusion present
Bile acids testingPremeal bile acids: 29.0 µmol/L (range, <10); postmeal bile acids: 16.5 µmol/L (range, <20)In-house urinalysisSpecific gravity: 1.042Protein: 3+SNAP 4Dx: negative × 4Urine protein:creatinine ratio/urinalysis/serum biochemistry profile/urine culture sent to outside laboratories. Had been preparing for endoscopy at time of urinalysis, which was halted when proteinuria was noted.List of differential diagnoses included protein-losing nephropathy +/- protein-losing enteropathy.
TreatmentIntravenous fluids discontinuedEnemas in preparation for endoscopyDrained 150 mL abdominal fluid prior to abdominal ultrasound to improve visualizationAspirin: 2.5 mg q24h PO
DAY 5Physical ExaminationTemperature: 102.2⁰FHeart rate: 120 bpmRespiratory rate: 36 bpmWeight: 10.3 lbBlood pressure: 114 mmHGEdema had progressed from previous day, but skin was no longer “weeping.”
Diagnostic Results (abnormal findings)Serum biochemistry profile
Total protein: 3.1 g/dL (range, 5.0–7.4)
Albumin: 1.2 g/dL (range, 2.7–4.4)
Albumin:globulin ratio: 0.6 (range, 0.8–2.0)
Creatinine: 0.4 mg/dL (range, 0.5–1.6)
Calcium: 7.2 mg/dL (range, 8.9–11.4)
Amylase: 1914 U/L (range, 290–1125)
Urine Testing
Albumin: >30 mg/dL (range, <2.5); microalbuminuria
Urine protein:creatinine ratio: 11.3 (range, <0.5)
Protein: 3+
Glucose: trace
Occult blood: 3+
Fine granular casts/LPF: 0–1
Hyaline casts/LPF: 0–3
TreatmentAspirin: 4 mg q24h PODoxycycline: 25 mg q12h POEnalapril: 2.5 mg q12h POOmega-3 fatty acids: 200 EPA q24h POLow-fat dietThe plan was to:
Consider endoscopy for PLE if the patient improved.
Consider a fecal α-proteinase assay to determine if the protein loss was occurring through the GI tract as well as a repeat urine protein:creatinine ratio in 2 weeks if patient survived.
Owners elected humane euthanasia 5 days later because of respiratory distress and continued cutaneous edema.
*A multiple electrolyte intravenous solution
The Specialist’s OpinionDavid F. Senior, BVSc, DACVIM & DECVIM (Companion Animal)
When confronted with a patient with edema, Starling forces across the plasma membrane of peripheral capillaries should be considered. The main forces are intravascular hydrostatic pressure and plasma oncotic pressure; however, increased interstitial oncotic pressure, altered capillary permeability (both most often sequelae of inflammation), loss of skin elasticity (applicable in aged human patients), and lymphatic obstruction (tumors) may be contributing factors.
Right-Sided Heart FailureFor ascites and edema, the physical examination should focus on the possibility of right-sided heart failure as a cause of increased intracapillary hydrostatic pressure. Investigation would include careful evaluation for the presence of venous distention, jugular pulses, cardiac murmurs, and a gallop rhythm. An echocardiogram allows evaluation for right-sided heart failure and intrathoracic masses that could impinge on venous return and lymphatic drainage.
Evaluation of plasma albumin addresses the possibility of reduced plasma oncotic pressure. In this patient, severe hypoalbuminemia indicated that reduced plasma oncotic pressure could be a primary reason for ascites and edema.
Causes of HypoalbuminemiaHypoalbuminemia can be caused by insufficient production, excessive loss, or redistribution of albumin (accumulation of inflammatory exudates in the abdomen or thorax). The most common causes of hypoalbuminemia relate to excessive loss of albumin due to protein-losing enteropathy or protein-losing nephropathy. Excessive loss of albumin due to extensive burns, pyothorax, and peritonitis is less common and is a clearly discernible end result of the primary disease. Protein-losing enteropathy is usually associated with a history of diarrhea but this is not always the case. The hallmark of protein-losing nephropathy is proteinuria, readily diagnosed with a urine chemistry dipstick test and confirmed by performing a urine protein:creatinine ratio.
Protein-Losing NephropathyOnce the presence of protein-losing nephropathy is established, a systematic diagnostic search for primary underlying causes that could be corrected should be undertaken. Typical primary causes of secondary glomerulonephropathy include heartworm disease, hyperadrenocorticism, systemic lupus erythematosus, chronic inflammation (prostatitis, pyoderma, abscesses, neoplasia, etc). Whether or not a primary correctable, underlying cause can be established, supportive care includes medication to reduce proteinuria (angiotensin-II blockade) and thrombosis (anticoagulants or platelet inhibitors).
PS: The case report gives scant detail about physical examination findings, which, with all our sophisticated tests, can be overlooked.
Another important point is that it is physiologically impossible for abdominal fluid to have a specific gravity of 1.000. Accurate assessment of this value requires measurement using a refractometer. Dipstick evaluation of SG is considered unreliable, and this is a good example of obvious error.
David F. Senior, BVSc, DACVIM, DECVIM-CA, is dean of Advancement and Strategic Initiatives at Louisiana State University School of Veterinary Medicine. After graduating from and completing a clinical internship at University of Melbourne, he worked in a predominantly dairy/beef practice in Alberta Canada for 4 ½ years before completing a residency in small animal internal medicine at University of Pennsylvania and then spent many years on faculty at University of Florida College of Veterinary Medicine, where he specialized in diseases of the urinary tract. Dr. Senior is the long-time conference coordinator of the NAVC.
The Generalist’s OpinionBarak Benaryeh, DVM, DABVP
Protein-losing enteropathy (PLE) and protein-losing nephropathy (PLN) are complex disorders and exploring these in detail would be well beyond the scope of a case discussion. The clinician did a good, thorough workup. Improvements that could have been made in this case are being slightly more aggressive in stabilizing the patient early on and running some additional initial diagnostics.
Initial StabilizationColloids: When the dog first presented with an abdominal effusion and low total proteins (globulin and albumin), the likely cause of the ascites was transvascular fluid leakage. The ideal treatment to counterbalance low oncotic pressure is a colloid fluid. Crystalloid fluids will continue to leak across the vascular space whereas colloids help retain fluid within the vasculature. Colloid choices include hetastarch, dextrans, plasma, and human albumin. Plasma tends to be poorly effective in cases of PLE as it continues to leak out of the damaged gut. Human albumin, although very effective, is extremely expensive. Hetastarch and dextrans remain good choices.
Abdominocentesis: Abdominocentesis was performed for diagnostic purposes on day 1. On day 4, 150 milliliters of fluid were drained to improve the dog’s comfort. Draining abdominal fluid is not a true treatment in cases of ascites as it does nothing for the course of disease, but it can be palliative in the short term. Given that this dog’s blood gases were suggestive of poor oxygen perfusion, it is possible that ascites was interfering with respiration and earlier drainage may have been of clinical benefit.
DiagnosticsInitial diagnostics that were performed included a complete blood count and serum biochemical profile as well as blood gases. In addition, a flash abdominal ultrasound and diagnostic abdominocentesis were performed. Days later, additional diagnostic tests were performed, but many were not run until day 4 or 5 and some tests, such as fecal α-proteinase were considered but never ordered. In a critical case such as this, with severe protein and vascular fluid loss, it is ideal to gain as much information as possible early in the course of disease. A urinalysis should be performed as part of the initial database, ideally before administration of any fluids. In addition, thoracic radiographs and an abdominal ultrasound can rule out neoplasia and look for sources of protein loss. If possible, the ultrasound should be performed by a trained radiologist, as there are certain findings, such as the appearance of submucosal streaks in the gastrointestinal tract, that can be difficult to identify but helpful in the diagnosis of PLE. Urine protein:creatinine ratio plays a key role in determining PLN and should be analyzed as a first-step diagnostic with low blood proteins and any presence of protein in the urine.
All these tests should be ordered within the first day or two. The definitive diagnosis is ultimately made through intestinal biopsy and/or a kidney biopsy, neither of which were performed in this case given the decision to euthanize.
PLE and PLN are very difficult to manage and referring these cases to an internal medicine specialist should be strongly considered. Neither condition is inexpensive to manage, and owners should be aware and willing to run the necessary diagnostics discussed above. PLN carries a poorer prognosis than PLE and the two diseases concurrently carry a very poor prognosis. In all cases, aggressive management should be instituted from the outset. Given the severity of this dog’s condition, it is possible that even the most aggressive intervention would not have helped.
Barak Benaryeh, DVM, DABVP, is the owner of Spicewood Springs Animal Hospital. He graduated from University of California–Davis School of Veterinary Medicine in 1997 and completed an internship in Small Animal Medicine, Surgery, and Emergency at University of Pennsylvania. Dr. Benaryeh has also taught practical coursework to first-year veterinary students and was a primary veterinary surgeon for the Helping Hands Program, which trains assistance monkeys for quadriplegic people. Dr. Benaryeh is certified by the American Board of Veterinary Practitioners in Canine and Feline Practice.