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Wendy Blount, DVM

Practical Clinical Pathology Proteins , Sugars & Fats. Wendy Blount, DVM. Glucose. Danger values - < 40 g/dl; > 1000 g/dl Hyperglycemia Brain dehydration due to hyperosmosis CNS signs (cerebral, brain stem) and seizures

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Wendy Blount, DVM

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  1. Practical Clinical PathologyProteins, Sugars & Fats Wendy Blount, DVM

  2. Glucose Danger values - <40 g/dl; >1000 g/dl • Hyperglycemia • Brain dehydration due to hyperosmosis • CNS signs (cerebral, brain stem) and seizures DDx Hyperglycemia other than DM and stress (especially in prediabetics): • Beta adrenergics (terbutaline, albuterol, etc.) • Corticosteroids • Glaucoma treatments – acetazolamide, etc. • Thiazide diuretics • Levothyroxine, progestagens, estrogens • Diazoxide, glucagon

  3. Diagnosing Diabetes Mellitus • Confirm Hyperglycemia • Stressed cats can have transient hyperglycemia (200-400) • Critically ill non-diabetic dogs can also have marked hyperglycemia (>400) • Stress hyperglycemia due to glucocorticoids, epinephrine and insulin resistance • Acute hyperglycemia has adverse effects on the immune system, coagulation, heart and brain • Chronic hyperglycemia is toxic to beta cells • Treat with judicious insulin PRN

  4. Diagnosing Diabetes Mellitus 2. Stress Hyperglycemia or DM? • “No glycosuria” makes DM unlikely • Stressed cats can have glycosuria • Renal threshold 180-220 mg/dl in the dog • 200-300 mg/dl in the cat • Ketones in the urine indicate catabolism – investigate DKA • DKA = Diabetic ketoacidosis • Any sick cat who has not eaten for days can have ketonuria • If all else fails, run a fructosamine • Fructosamine elevated with DM • Decreased with hyperthyroidism • Normal with stress hyperglycemia

  5. Continuous Glucose Monitoring (CGM) Systems (Flash) • Probe measures glucose in interstitial fluid continuously to plot a curve • Wireless transmission to a pager size display • Human device validated in dogs 2016 • Previous devices worn in a vest • Freestyle Libre is disposable • Available in the US as of Dec 2017 • Requires a prescription • Approved for people – off label for pets

  6. Nicole Tarantino, TechCollege Station TX

  7. Continuous Glucose Monitoring (CGM) Systems (Flash) Dr. Greg Matt, Houston TX

  8. Continuous Glucose Monitoring (CGM) Systems (Flash) Dr. Greg Matt, Houston TX

  9. Pattern Recognition - Diabetes Mellitus • Hyperglycemia (of course) • Indications of DKA • Low HCO3, low TCO2, low pH, high anion gap, ketonuria, vomiting, lethargy • Indicates: ICU care, higher level of IV potassium supplementation, more phosphates • Insulin carries K+ &Phos into the cell • Correcting acidosis worsens K+ & phos • Phos <1.5 can cause severe hemolysis • Low K+ can cause weakness and paralysis • Pancreatitis pattern – need fluid support • Fatty liver pattern – feed cats

  10. K+ & Phos in DKA Patient • Monitor PCV, K+ and Phos at least daily until stable, in DKA patients • More often if very low or unstable • Can use 0.5cc lithium heparin tubes to prevent exsanguination • Place jugular catheter for patient comfort • Draw blood without venipuncture • Replace K+ according to sliding scale • More K+ supplemented when acidotic • The lower Phos, the more KPhos:KCl you use • Don’t exceed 0.5 mEq/kg/hr potassium

  11. K+ & Phos in DKA Patient • Eating is important to maintaining K+/Phos • usually stabilize when the cat begins to eat • REMEMBER • KCl contains 2 mEq/ml potassium • KPhosphates contain 4 mEq/ml potassium • Use half the volume of KCl as KPhos for the same amount of potassium added to fluids • Be VERY CAREFUL of bicarbonate therapy • I almost never give bicarb to DKA patients • Bicarbonate can exacerbate low Phos and K • Regular insulin given PRN to keep glucose 100-250, checking glucose q2-4 hrs

  12. Hypoglycemia Signs of Hypoglycemia • Mild (glucose 50-80) • Lethargy, weakness • Poor appetite • Moderate (glucose 30-50) • Vomiting • Head tilt, ataxia • Severe (glucose <30) • Seizures, coma • Blindness – temporary or permanent • Signs can be relatively mild when insidious and/or chronic ( Insulinoma , Teddy )

  13. DDx Fasting Hypoglycemia < 60 mg/dl • Neoplasia (paraneoplastic hypoglycemia) • insulinoma • Hepatocellular carcinoma, hepatoma • Leiomyosarcoma, leiomyoma • Other tumors (especially hepatic metastasis) • Severe liver Disease • Sepsis • Hypoadrenocorticism • Toy Breed, juvenile hypoglycemia (alanine deficiency)

  14. DDx Fasting Hypoglycemia • Hunting dog hypoglycemia, glycogen storage disease • Severe polycythemia (>65%) • Pancreatitis • Severe malnutrition • Glucagon deficiency (failure of alpha cells – rare in pets) • Hypopituitarism • Dried chicken jerky treats • Seizures

  15. DDx Fasting Hypoglycemia • Toxicity • Xylitol • alpha lipoic acid • Insulin or oral hypoglycemics • Beta blockers – propranolol, atenolol • Ethylene glycol

  16. DDx Fasting Hypoglycemia • Artifactual hypoglycemia • Serum/plasma sits on the blood cells, which utilize glucose • decreases at 7mg/dl/hr • Spin blood within 30 minutes • Test glucose in serum/plasma within 48 hours • Sodium fluoride tubes prevent this • Glucometers run lower than lab machines

  17. Thumb Rules • Hypoglycemia usually relatively mild (>45 g/dl) for: • Addison's (ACTH stim) • Liver disease (bile acids) • Look for patterns on serum profile • Hypoglycemia more severe (<40) for: • Sepsis (pattern recognition) • Juvenile hypoglycemia • Neoplasia • Secondary to seizures • Most profound hypoglycemia is often due to insulinoma, or insulin overdose

  18. Diagnosis of Fasting Hypoglycemia • Repeat fasting glucose to confirm • Simultaneous insulin & glucose when glucose <50-60 to rule out insulinoma • Lower glucose = more confident assessment • Imaging • Thoracic radiographs • Abdominal rads often not helpful for insulinoma, as tumors often small (<3 mm) • Abdominal ultrasound for tumor location to guide surgery and to look for metastasis • Ultrasound 50-69% sensitive for insulinoma • CT no more sensitive than ultrasound for insulinoma

  19. Diagnosis of Fasting Hypoglycemia 4. Diagnostic Surgery • Insulinoma may or may not be grossly visible • Decrease tumor burden by removing visible tumors • Look for metastasis (biopsy or FNA) • Liver • Abdominal lymph nodes • Peripancreatic tissues • Empirically remove one lobe of pancreas if insulinoma highly suspected

  20. Pattern Recognition -Insulinoma • CBC and UA normal • Serum panel • Hypoglycemia - mean 38-42 mg/dl • Usually below 60 • Can be as low as 15 • The rest often normal • May assume serum sat on the cells • Early on, 12-24 hour fast may be required to detect hypoglycemia • Index of suspicion often low at the time of bloodwork

  21. Pattern Recognition Hypoglycemia • DDx Hypoglycemia in a puppy or kitten • Juvenile hypoglycemia • starvation • Portasystemic shunt • Sepsis • DDx Hypoglycemia Young adult dogs/cats • PSS or other hepatobiliary disease • Hypoadrenocorticism (dog >> cat) • Sepsis

  22. Pattern Recognition Hypoglycemia • DDx Hypoglycemia Geriatric dogs or cats • hepatobiliary disease • Beta cell neoplasia (insulinoma) • Extrapancreatic neoplasia • Hypoadrenocorticism • Sepsis

  23. Hyperlipidemia • Elevated triglycerides and gross lipemia • Gross lipemia at triglycerides >200 mg/dl • Assess only after a 12-hour fast Clinical Signs • GI upset, abdominal pain, pancreatitis • PU-PD • Ataxia, weakness, behavioral changes, seizures • Danger value - >1000 mg/dl • Lipemia retinalis, lipemia aqueous, corneal lipid

  24. Hyperlipidemia • Elevated triglycerides and gross lipemia • Gross lipemia at >200 mg/dl • Assess only after a 12-hour fast Clinical Signs • GI upset, abdominal pain, pancreatitis • PU-PD • Ataxia, weakness, behavioral changes, seizures • Danger value - >1000 mg/dl • Lipemia retinalis, lipemia aqueous, corneal lipid • Xanthoma

  25. Hyperlipidemia • Elevated triglycerides and gross lipemia • Gross lipemia at >200 mg/dl • Assess only after a 12-hour fast Clinical Signs • GI upset, abdominal pain, pancreatitis • PU-PD • Ataxia, weakness, behavioral changes, seizures • Danger value - >1000 mg/dl • Lipemia retinalis, lipemia aqueous, corneal lipid • Xanthoma

  26. Hyperlipidemia DDx High Triglycerides • Post-prandial elevation • Primary hyperlipidemia • miniature schnauzers, shelties >> cats • Secondary hyperlipidemia • Endocrine – hypothyroidism, hyperadrenocorticism, diabetes • Pancreatitis, cholestasis • Liver disease, nephrotic syndrome • Drugs • Glucocorticoids, estrogens • Phenobarbital, bromide • Megace in the cat

  27. Donna MedfordLaPorte TX

  28. Hyperlipidemia

  29. Hyperlipidemia Diagnostic work-up • First Tier Tests • CBC, serum profile with electrolytes, UA • cPL or CPLI • Thyroid panel: canine TSH, TT4, fT4; feline TT4, fT4 • Second Tier Tests • If signs of hyperadrenocorticism - Low Dose Dexamethasone Test or ACTH Stim • If hyperglycemia needs further investigation – fructosamine • If proteinuria – Urine P:C ration x 3 days • If signs of liver disease – bile acids • Trial Therapy for primary hyperlipidemia (handout) (Client Handout)

  30. Hypercholesterolemia DDx high cholesterol • Hypothyroidism • Hyperadrenocorticism • Diabetes mellitus • Liver Disease • Protein losing nephropathy • Drugs – corticosteroids, methimazole, phenytoin, thiazide diuretics, phenothiazines

  31. Hypocholesterolemia DDx low cholesterol • Liver Disease – portacaval shunt, cirrhosis • Lymphangiectasia • Selected neoplasias • Starvation • Drug therapy • L-asparaginase, azathioprine • Colchicine • Cholestyramine • Oral aminoglycosides

  32. Serum Proteins TP = albumin + globulins Albumin • Danger values - <1.0 g/dl • Major fluid shifts – pulmonary and peripheral edema, third space accumulation • Simultaneous loss of AT3 – thromboembolic disease • Pulmonary thromboembolism (PTE) • mesenteric thrombus • portal vein thrombus • If portal hypertension, ascites can occur at albumin <1.5 g/dl

  33. Serum Proteins DDx increased Albumin • Dehydration • Falsely increased ( refractometer) • Lipemia • severe hyperglycemia • Azotemia • Hyperchloridemia, hypernatremia • Severe hyperbilirubinemia

  34. Serum Proteins DDx hypoalbuminemia • Not making enough albumin • liver failure • anorexia, hyporexia • maldigestion, malabsorption (Protein Losing Enteropathy) • Severe malnutrition (starvation) • Albumin Loss • Protein losing enteropathy (PLE) • Protein losing nephropathy (PLN) – glomerular disease • Exudative wounds and lesions • External hemorrhage – including GI loss

  35. Serum Proteins DDx hypoalbuminemia • Albumin Consumption • Sepsis • Pancreatitis • Sequestration • body effusions - can cause or be caused by hypoalbuminemia • Due to increase hydrostatic pressure, decreased oncotic pressure or leaky vessels • Vasculitis – immune mediated, infectious (bacteria, rickettsial) • Secondary to hyperglobulinemia • Dilution from aggressive IV fluid therapy • Lab error • Human labs give falsely low values for canine albumin • Abaxxis also had problems for awhile

  36. Serum Proteins Stepwise work-up for low albumin • If no exudative skin lesions, do first tier tests • CBC, panel, UA, fecal flotation • K9 HW Test, Feline FeLV/FIV tests • Then indicated second tier tests • If liver pattern on panel – bile acids, blood ammonia • If proteinuria without pyuria or hematuria – Urine P:C • If profuse diarrhea, consider PLE • GI diagnostics – GI panel, intestinal biopsies • Or confirm with fecal alpha-1 protease inhibitor assay • If effusions, sample fluid • Transudate indicates effusion is likely due to hypoproteinemia • Modified transudate or exudate means other factors are in play

  37. Serum Proteins Drugs that alter albumin • Decreased albumin: • Estrogens • Anticonvulsants (if liver disease) • Acetaminophen • Antineoplastics (if liver disease) • Increased albumin: • Long term high dose corticosteroids The most common causes of albumin <2.0 g/dl are liver failure and PLE PLE and/or GI hemorrhage are possible even when owners think stools are normal

  38. Serum Proteins Look at serum proteins together! • Very high globulins and mild hypoalbuminemia (>2 g/dl) • Work up hyperglobulinemia first • Low albumin and low globulin – panhypoproteinemia Non-selective protein loss • External hemorrhage (including GI loss) – also low PCV • Exudate skin wounds • Protein losing enteropathy (PLE) • Hemodilution – aggressive IV fluid therapy • Low albumin and normal globulin • Selective loss or sequestration of albumin – effusions, vasculitis • Poor albumin production

  39. Serum Proteins Look at serum proteins together! • Low globulins and normal to increased albumin • Immunodeficiency – congenital or acquired • Congenital immunodeficincies result in neonatal death which is difficult to definitively diagnose • Acquired immunodeficiencies often due to lymphoproliferative disease or cancer chemotherapy • High albumin and globulin – nonselective hyperproteinemia • dehydration • Hyperglobulinemia • Acute phase protein increase – mild elevation • Chronic antigenic stimulation – plasma cells in LN & BM • Paraproteinemia – neoplasia

  40. Serum Proteins Acute Phase Proteins – alpha & beta globulins • indications • Need specific information about inflammation or coagulation • Examples: • Fibrinogen (Cornell) • Haptoglobin (Kansas State U) • C-reactive protein (TAMU GI Lab) • Complement c3a • Serum amyloid A • Hemolysis and lipemia can interfere • Negative acute phase proteins decrease w/ inflammation • Albumin and transferrin (KSU) • Alpha-1-acid glycoprotein • Alpha-1 antiprotease • Alpha-2 macroglobulin • Ceruloplasmin (KSU)

  41. Serum Proteins Acute Phase Proteins – alpha & beta globulins • High Fibrinogen • indicates acute inflammation • In house meters are available • Low Fibrinogen • consumptive coagulopathy such as DIC • Rare congenital deficiencies

  42. Summary PowerPoint – Proteins, Sugars, Fats • .pptx • .pdfs – 1 and 6 slides per page Vet Articles • Flash Glucose Monitoring Device • Guidelines for Glucometers Video – application of Flash Device Video – removal of Flash Device

  43. Summary Vet Handouts • Baycom – HbA1c Literature • Blount – • Bicarbonate Administration • Hyperlipidemia • IV Potassium Chart • F&N – Algorithm for Interpreting Glucose Curves • Willard – Algorithm for Dx of Hyperlipidemia • Willard – Algorithm for Dx of Hypoalbuminemia

  44. Summary Client Handout • Home Glucose Testing, Ear Prick, Lip Prick • Hyperlipidemia • Hypoglycemia Laboratory Information • Cornell – Blood Collection Guidelines, Payment Form, Price List, Sample Labels, Shipping Guidelines, Submission Form, Subm Guidelines • Kansas – Submission Form • TAMU GI Lab – Submission Form

  45. Acknowledgements • Richard Nelson. Small Animal Clinical Diagnosis by Laboratory Methods, 5th Edition. Ch 8 – Endocrine, Metabolic and Lipid Disorders. Eds. Michael Willard, Harold Tvedten. • Mark C Johnson. Small Animal Clinical Diagnosis by Laboratory Methods, 5th Edition. Ch 12 – Immunologic and Plasma Protein Disorders. Eds. Michael Willard, Harold Tvedten.

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