Loobani AcademyAbstract
Diabetic ketoacidosis (DKA) is a severe, life-threatening complication diabetes mellitus (DM) that is caused by an absolute or relative deficiency of insulin.A 13 years old dog (Name: Dumplings) with local purulent skin and infected ulcers on right hind limbs.Before coming to our hospital, he had been treated as a simple superficial dermatosis and bandage up the affected part for 4 days.The situation was worse during this days.In this case, we diagnosis as Diabetic ketoacidosis, and after the therapy, patient had gradually become stabilized.It was a big challenge to diagnose and treat in my clinical experience, and the cure rate depend on the condition of the therapeutic schedule and the body.
Key words
Diabetes: Diabetic ketoacidosis (DKA), diagnosis, purulent infection
day 5 master feeling dog never see symptoms improved, depressed and in spirit, appetite waste, hence to come to our hospital. After auxiliary examination, the dog was initially diagnosed as diabetic ketoacidosis (DKA). Subsequently, the dog was treated with fluid rehydration, anti-inflammatory and insulin, and the body condition gradually stabilized.
1.Basic information
Name: HUA HUA
Breed: Poodle
Sex: Female (castrated)
Age: 13 years old
Body weight: 4.7kg
History: regular vaccination and deworming on time
2.Before therapy
Owner took her to have a bathing 4 day ago.Puppy stylin found a ulcer on the skin of the right hind limb, which was purulent infection.So he see a veterinarian in the other animal hospital and the vet there treat as a simple trauma with surgical saline flushing.After 4 days of therapy, there was no changing of the symptom of the infected skin, and the patient started to be depression, losing appetite.So transferring to our hospital to have a further examination.
3.Correlation examination
3.1 physical examination
Body weight 5.8kg, temperature 37.5℃, respiratory rate was 40/min.heart rate: 124 beats/min.mouth mucosa was pink, capillary refill time（CRT）>2s.body condition score（BCS）was 4/9. The patient was presented with depression.dry coat and nose. Abdominal palpation was found nervous and increased of abdomen.There were serve dental calculus and gingivitis in oral examination. A area of ulcer we can see on the skin of right hind limb, which was suppurative.
3.2 laboratory examination
3.2.1 Complete Blood Count(CBC)examination
Table 1 The result of the CBC examination（Day1）
Project | Result | Reference Range |
WBC | 10 | 6-17×109/L |
RBC | 3.68 | 5.5-8.5×1012/L |
HGB | 80 | 120-180g/L |
HCT | 23.8 | 37-55% |
MCV | 64.7 | 66-77fL |
MCH | 21.7 | 19.9-24.5pg |
MCHC | 336 | 300–360g/L |
PLT | 543 | 200-500×109/L |
LYM% | 5.4 | 12–30% |
OTHR% | 85.5 | 60-77% |
EO% | 8.8 | 2–10% |
LYM | 1.5 | 1.5-4.8×109/L |
OTHR | 23.9 | 3–11.5×109/L |
EOS | 2.5 | 0.1-1.25×109/L |
3.2.2 Blood smear microscope under 100x
CBC examination showed a obvious anemia in patient, MCV decreased combined with blood smears microscope picture where were found different size of red bloods cells, we can have a preliminary judgement, it may be non-regenerative anemia in this report. To the white blood count index, we can see the rise of the white blood cells, as well as a right shift of the white blood cell nucleus in the microscope.It may suggesting the possible existence of infection and inflammation.Thrombocytopenia may be associated with neutrophilia and an underlying endocrine disorder.
3.2.3 Canine CRP examination
Table 2 The result of the CRP examination（Day1）
Project | Result | Reference Range |
CRP | 107.8 | <20mg/L |
The result of the CRP infer there was acute sever inflammation in the body, which was consistent with the result of CBC examination.
3.2.3 Idexx Catalyst biochemistry CHEM15
Table 3 The result of the biochemistry CHEM15（Day1）
Table 3 The result of the biochemistry CHEM15（Day1）
Project | Result | Reference Range |
GLU | 34.01 | 3.89-7.95mmol/L |
CREA | 775 | 44-159umol/L |
BUN | 34.4 | 2.5-9.6mmol/L |
BUN/CREA | 11 |
|
PHOS | 4.35 | 0.81-2.2mmol/L |
CA | 2.30 | 1.98-3mmol/L |
TP | 78 | 52-82g/L |
ALB | 30 | 22-39g/L |
GLOB | 48 | 25-45g/L |
ALB/GLOB | 0.6 |
|
ALT | 49 | 10-125U/L |
ALKP | 1963 | 23-212U/L |
GGT | 6 | 0-11U/L |
TBIL | 12 | 0-15umol/L |
CHOL | 10.13 | 2.84-8.26mmol/L |
Biochemistry CHEM15 examination findings showed significant hyperglycemia, significant azotemia,and hyperphosphorus,combined with physical examination and the ratio of urea-nitrocreatinine, suggested the possibility of renal and prerenal azotemia. Alkaline phosphatase was significantly increased,but the result of GGT and total bilirubin were not significantly increased, cholesterol significantly increased,and there significant hyperglycemia at the same time, so it was suspected that it might be related to the steroid-induced increase of isoenzymes.
3.2.4 Electrolyte examination
Table 4 The result of the electrolyte examination
Project | Result | Reference Range |
pH | 7.108 | 7.25-7.40 |
pCO2 | 24.1 | 33-51mmHg |
HCO3-act | 7.5 | 13-25mmol/L |
Na+ | 136 | 139-150mmol/L |
K+ | 5.0 | 3.0-4.2mmol/L |
Cl- | 117 | 106-127mmol/L |
AnGap | 16 | 10-27 |
Osm | 280 | 280-310mOsm/kg |
Significant metabolic acidosis was observed in electrolytes examination. Mild hyponatremia and mild hyperkalemia may be associated with diabetes and kidney disease.
3.2.5 Blood pressure
The systolic blood pressure was 124mmHg as measured by a Doppler blood pressure monitor.
3.2.6 Diascopy and Fine needle aspiration examination
(A)
(B)
Picture 1. (A)A large number of degenerative neutrophils and several macrophages are seen.(B)and(A)The same slide sample, but with intracellular bacteria, suggests suppurative granulomatous inflammation caused by bacterial infection.
3.2.8 Urinalysis
Project | Result | Reference Range |
Gravity | 1.022 | 1.035-1.050 |
BLD | ++ | – |
BIL | Neg. | – |
UBG | Neg. | – |
KET | ++ | – |
GLU | ++++ | – |
pH | 5 | 6.0-7.0 |
In the urinalysis, we found the urine glucose and ketone were significantly increased, which means positive, the gravity of urine was lower than the reference range, and a large number of granular tubes were visible, suggesting diabetes, and there may be kidney injury or tubular disease. Mild occult blood.
4.Diagnosis
In conclusion with the consulting, clinical symptom,physical and laboratory examination, we have a preliminary diagnosis of diabetic ketoacidosis(DKA), and may concurrence with kidney and other endocrine disease.But the important thing was the treatment of DKA of patient now.
5.Treatment
The therapeutic goals of DKA animals are as follows:
1. Correct dehydration and electrolyte disorders:
(1) Replacement solution: Sodium lactate Ringer 250ml, ivgtt, 60ml/h: (If the concentration of sodium ion is >130mmol/L, sodium Ringer lactate should be used as the liquid; if the concentration of sodium ion is <130mmol/L, 0.9% normal saline should be used as the liquid)
(2) Maintenance solution: sodium lactate Ringer 360ml, ivgtt, 20ml/h: (Due to the electrolyte on the first day indicating mild hyperkalemia, no additional potassium chloride injection was added into the maintenance fluid, and further adjustment would be decided after the result of the electrolyte in the follow-up review. 1.5 to 2 times the amount of maintenance fluid is recommended in some cases)
(3) When the hydration status was corrected, the maintenance solution was continuously injected: sodium lactate Ringer 360-400ml+4ml10% potassium chloride injection, ivgtt, 20ml/h.
2. After 6h of the fluid therapy, adequate insulin was required to inhibit lipolysis, ketone body production, and the liver gluconeogenesis in the patient body.The dog was treated with the following insulin regimen: Insulin glargine (0.6U/kg/q12h) was injected subcutaneously, and blood glucose was monitored every 2h. When blood glucose was greater than 250mg/dL, short-acting insulin (0.1U/kg) was intramuscular injected, and hypoglycemia was monitored at the same time, with the goal of temporarily controlling blood glucose within 150-250mg/dL. Insulin treatment after stable blood glucose: 0.5-1U/kg, sc, q12h, blood glucose control below the renal threshold.
3.Correcting the acidosis of electrolyte: Sodium bicarbonate was not used to relieve acidosis in this case, and the current level of acidosis can be corrected by infusion and insulin. Blood gas results at 12h, 24h and 48h after treatment with fluid rehydration and insulin.
4.Treatment of complications:
(1) Improve renal perfusion through infusion and improve the situation of the azotemia;
(2) Using antibiotics to treat infection (abscess of the right leg) and control inflammation: amoxicillin clavulanate potassium, 18.5mg/kg, sc, qd.
(3)Painful management : Using analgesia, Butorphine, 0.2mg/kg, im, q8h;
(4)Provide iron-containing nutritional supplements to improve anemia;
(5)Provide carbohydrates (glucose) to allow continued insulin use without hypoglycemia.
Result of the case
On the third day after treatment, the acidosis of electrolyte was almost relieved. However, the elevated of the concentration of potassium ion in the dogs without adding more potassium chloride in the process of infusion, which may be suspected to be related to the co-existing kidney disease. And after 4 days of treatment, the patient had recover and go home.
6.Conclusion
Many dogs with DKA are presented as newly diagnosed diabetics.The mean age at diagnosis is 9-10 years of age.No sex or breed predisposition has been identified for DKA but they do exist for DM
Etiology and Pathophysiology
Insulin deficiency and increased levels of diabetogenic hormones (e.g. glucagon, cortisol, growth hormone, catecholamines) lead to abnormal glucose metabolism and hyperglycemia. In an insulin-deficient state, glucose transport into the cells is inadequate. Cells cannot use glucose for energy, which leads to cellular starvation. The body then starts to use adipose tissue as an alternate source of energy.Hormone-sensitive lipase is usually inhibited by insulin. With insulin deficiency, it facilitates the degradation of triglycerides and the formation of free fatty acids. Free fatty acids undergo beta oxidation within the cell to form acetyl-CoA. Acetyl-CoA accumulates in the liver where it is converted into acetoacetyl-CoA and ketone bodies, such as beta hydroxybutyrate, acetoacetate, and acetone.
The pathogenesis of DKA is not based on an insulin deficiency alone.An increase in diabetogenic hormones plays a significant role.Glucagon, growth hormone, and epinephrine stimulate lipolysis, thus increasing the amount of free fatty acids available for ketone formation.Glucagon and epinephrine also stimulate hepatic glycogenolysis and gluconeogenesis, as well as inhibit insulin-mediated glucose uptake by cells, which contributes to exacerbation of hyperglycemia.One study showed that 5/7 dogs with DKA had detectable endogenous insulin levels, and two of these dogs had insulin concentrations within the normal range. Therefore, other hormones are significant contributors to the development of DKA.
While the initial formation of ketone bodies serves as a protective mechanism against cellular starvation, eventually their utilization for energy is decreased due to limited cellular uptake. When ketone bodies continue to form and their utilization decreases, they start to accumulate.Ketone bodies are strong acids and their accumulation can quickly lead to metabolic acidosis. Ketonuria and osmotic diuresis from glucosuria leads to loss of sodium, potassium, and water in urine. These losses contribute to dehydration, hypovolemia, and further accumulation of ketones and glucose in the blood. Nausea, vomiting, and anorexia occur from stimulation of the chemoreceptor trigger zone by ketonemia and hyperglycemia, and contribute to the dehydration. Marked electrolyte abnormalities ensue.
Many patients with DKA are newly diagnosed diabetics. In one study, 65% (82/127) of dogs with DKA were diagnosed at the time of initial discovery of DM.Approximately 70% of dogs and 90% of cats with DKA have concurrent diseases. Some of the most common concurrent diseases noted in dogs include hyperadrenocorticism, pancreatitis, and bacterial urinary tract infections.
The choice of therapy
Treatment includes the specific therapy and supportive therapy.(1)Specific therapy:
Goals of therapy are to correct fluid deficits; correct electrolyte abnormalities; provide insulin; correct acidosis; and identify and treat underlying causes and concurrent diseases.(2)Supportive therapyConcurrent illnesses must be identified and treated appropriately. Antibiotics are indicated if a urinary tract or other bacterial infection is present. Antinausea medications are administered as needed for recurrent vomiting. Analgesics may be considered for dogs with pancreatitis.
Monitoring
Patients with DKA initially require hospitalization and intensive monitoring. Blood glucose levels are evaluated q 1-2 hours at first, then q 4-6 hours. Alternatively, a continuous glucose monitoring system can be used.It is important to frequently assess blood glucose to ensure that hyperglycemia is not resolving too rapidly. A sudden decrease in blood glucose can lead to rapid changes in osmolality with neurologic complications. It is also important to ensure that hypoglycemia does not develop.
Electrolytes are evaluated at least 1-2 times daily and more frequently in patients with significant derangements.Vital parameters (e.g. temperature, pulse rate and quality, respiratory rate and effort, hydration status, mentation, urine output, body weight) are also assessed multiple times daily to ensure fluid therapy is adequate.Urine or serum ketones can be evaluated at least once daily to assess response to therapy and resolution of ketonemia/ketonuria.
Prognosis
In one study of 127 dogs treated for DKA, 70% survived to be discharged from the hospital.5 Median hospitalization duration was 6 days.Non-survivors had lower ionized calcium, hematocrit, and venous pH compared to survivors.It is important to communicate with owners that therapy for DKA typically requires several days of hospitalization, and that a long-term commitment is also needed to treat DM once the animal is discharged from the hospital.
