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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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Practical Clinical PathologyProteins, 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 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
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
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
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
Continuous Glucose Monitoring (CGM) Systems (Flash) Dr. Greg Matt, Houston TX
Continuous Glucose Monitoring (CGM) Systems (Flash) Dr. Greg Matt, Houston TX
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
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
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
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 )
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)
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
DDx Fasting Hypoglycemia • Toxicity • Xylitol • alpha lipoic acid • Insulin or oral hypoglycemics • Beta blockers – propranolol, atenolol • Ethylene glycol
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
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
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
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
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
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
Pattern Recognition Hypoglycemia • DDx Hypoglycemia Geriatric dogs or cats • hepatobiliary disease • Beta cell neoplasia (insulinoma) • Extrapancreatic neoplasia • Hypoadrenocorticism • Sepsis
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
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
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
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
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)
Hypercholesterolemia DDx high cholesterol • Hypothyroidism • Hyperadrenocorticism • Diabetes mellitus • Liver Disease • Protein losing nephropathy • Drugs – corticosteroids, methimazole, phenytoin, thiazide diuretics, phenothiazines
Hypocholesterolemia DDx low cholesterol • Liver Disease – portacaval shunt, cirrhosis • Lymphangiectasia • Selected neoplasias • Starvation • Drug therapy • L-asparaginase, azathioprine • Colchicine • Cholestyramine • Oral aminoglycosides
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
Serum Proteins DDx increased Albumin • Dehydration • Falsely increased ( refractometer) • Lipemia • severe hyperglycemia • Azotemia • Hyperchloridemia, hypernatremia • Severe hyperbilirubinemia
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
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
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
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
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
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
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)
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
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
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
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
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.