Exam 3 Flashcards
Plasma Proteins V Serum Proteins
Plasma • Measured by refractometer • Albumin • Globulins • Clotting factors • Fibrinogen
Serum • Measured by biochemistry analyzer • Albumin • Globulins • NO Fibrinogen
Albumin
o (-) Charge o smaller than globulins o made by liver o 75-80% of oncotic pressure o Carrier protein o Half-life 1 to 3 weeks
Globulins; basics & 3 types
o (+) charge
o Larger than albumin
o Made by plasma cells and liver
o Abs, enzymes, protein carriers, etc
Three types
• α- produced in the liver
• β- mainly liver, some lymphoid tissue
• γ- lymphoid tissue (antibodies)
Fibrinogen
o Type of globulin
o Clotting factor and indicator of inflammation
o Synthesized in liver
o Measured in plasma
Hyperfibrinogenemia
• Early Inflammation (large animals)
• Dehydration (way less common)
Hypofibrinogenemia
• Usually not detected, but may be present in DIC
• Congenital – rare
Acute Phase Proteins
Positive • Increase w/ acute inflammation • Fibrinogen (large animals) • C-reactive protein (good for dogs) • Haptoglobin • Serum Amyloid A (SSA) (good for horses) • α1-acid glycoprotein (good for cats)
Negative
• Decrease w/ acute inflammation
• Albumin & transferrin
Hyperproteinemia
Hyperalbuminemia
• Hemoconcentration
• NEVER increase production!!!
Hyperglobulinemia
• Inflammation (APP and immunoglobulins also elevated)
• B-lymphocyte neoplasia
Serum protein electrophoresis
o normal looks like hang loose hand
polyclonal response
• broad peak in gamma region = inflammation
• rise in multiple serum protein & Abs (hills above)
monoclonal response • narrow peak in gamma region = • Plasma cell neoplasia (multiple myeloma) • B cell lymphoma • Lymphocytic leukemia
Hypoalbumenia
Loss
• Renal dz
• GI dz
• Hemorrhage
Decreased production
• Liver failure
• Inflammation
Hemodilution
• Excess IV fluids
• Edema
Panhypoproteinemia
- hypoalbuminemia & hypoglobulinemia
- Hemorrhage
- Protein losing enteropathy
- Severe exudation or effusion
- Hemodilution (uncommon)
- Intestinal parasitism
Hypoglobulinemia
- Failure of passive transfer
* Acquired immune deficiency
Triglycerides & Cholesterol
Triglycerides
o From diet or synthesized in hepatocytes, adipocytes
o Major lipid in adipose tissue: serves as energy source
o Circulating levels depend on fat in diet and insulin
Cholesterol
o From diet or synthesized in liver
o cell membrane structure & steroid synthesis
o Catabolized by liver
4 Important Lipases
Pancreatic Lipase
• intestines
• degrades dietary fat -> chylomicron
Lipoprotein Lipase
• Vascular endothelium
• Activated by insulin, glucagon and thyroid hormones
• Breaks down TG to FFA + glycerol that gets to adipocytes and muscle
• Remnants (VLDL) goes to liver
Hepatic Lipase
• Liver
• hydrolyzes phospholipids and removes TG from LDL from circulation
Hormone-sensitive triglyceride lipase • Inside adipocytes • Responsible for lipolysis • Stimulated by catecholamines, glucagon, growth hormone • Inhibited by insulin
Lipemia V Hyperlipidemia
Lipemia • Gross milky appearance • VLDL and/or chylomicrons • can induce hemolysis • can interfere with spectrophotometry
Hyperlipidemia
• Serum may be milky OR clear
• Increased lipids in the blood
Physiologic Hyperlipidemia Vs Pathologic lipemia/hyperlipidemia
Physiologic Hyperlipidemia o Postprandial • increased chylomicrons • Hypertriglyceridemia • +/- Hypercholesterolemia • Fast 12h should eliminate
Pathologic Lipemia / Hyperlipidemia
o Due to abnormal synthesis or abnormal clearance
o Primary or secondary
Primary causes of hyperlipidemia
o Less common
o Hyperlipoproteinemia mini schnauzer etc (LPL deficiency)
o Hyperchylomicronemia in cats (LPL deficiency)
o Idiopathic hypercholesterolemia (unknown mech)
Secondary Causes of Hyperlipidemia
o abnormal synthesis, lipolysis, and/or clearance
Endocrine Dz
• Diabetes Mellitus = decrease LPL activity, high fat mobilization
• Hypothyroidism (unknown mech)
• Hyperadrenocorticism = Corticosteroids stimulate VLDL synthesis, antagonize insulin, decrease LPL activity
Nephrotic syndrome & Pancreatitis
• Defective lipid metabolism
Cholestasis
• Reduced biliary excretion of cholesterol
glucocorticoids
• antagonize insulin
Hypertriglyceridemia in Ponies, Donkeys and Horses
o mobilization of fatty acids from adipose tissue -> formation of TG and VLDL in liver
o secondary to negative energy balance
Hypocholesterolemia
Hepatic insufficiency:
• decreased production
GI disease:
• decrease absorption
Hypoadrenocorticism:
• cortisol influences on lipoprotein metabolism (decreased function)
Severe malnutrition
Acute hemorrhage
Inherited
• Holstein calves (rare)
Non-esterified fatty acids (NEFA) in ruminants; physiologic Vs pathologic increase
o Excessive (-) energy balance does not cause triglyceride or cholesterol abnormalities o NEFA formed from triglycerides
Physiologic increase
• exercise -> release catecholamines & ACTH -> hydrolytic activity of hormone-sensitive lipase -> fat mobilization to meet excess energy requirements.
Pathologic increase
• Due to (-) energy balance in dairy
Insulin, Glucagon, & Blood Glucose
Fall in blood glucose
• secretion of glucagon -> glycogen to glucose -> glucose to blood
Rise in blood glucose
• Insulin secretion -> uptake of glucose -> glucose to glycogen/fat -> decrease glucose in blood
Other hormonal regulation of glucose
Glucocorticoids
• Stimulate hepatic gluconeogenesis
• Creates state of insulin resistance by stimulating adipocyte specific LPL
• Increases glycogen stores in liver
Catecholamines • Free fatty acid + glycerol • Inhibits insulin secretion • Stimulates growth hormone release (favors insulin resistance) • Stimulates hepatic glycogenolysis
Growth Hormone
• Inhibits actions of insulin (favors insulin resistance)
Hypoglycemia
Hyperinsulinism
• β-cell tumors (insulinomas)
• Therapeutic insulin overdose
Decreased insulin antagonists
• Hypoadrenocorticism (low corticosteroids)
Decreased glucose production
• Hepatic insufficiency
• Neonatal/juvenile hypoglycemia:
• severe starvation (rare)
Increased utilization (in vitro, most common)
• Exogenous utilization by RBCs or leukocytes
• Extreme leukocytosis
Physiologic
• Extreme exertion
• Pregnancy/lactation (negative energy balance)
Others
• Sepsis
• Neoplasia
• Decreased glycogenolysis (genetic)
Test useful for evaluating hypoglycemia
Serum Insulin
• hypoglycemia is present (<60 mg/dl) and insulin levels are normal to increased = Insulinoma is likely
Physiologic causes of Hyperglycemia
Chronic stress
• Increased blood glucocorticoid levels Promotes gluconeogenesis and insulin resistance
Excitement/pain/fear
• Increased catecholamines
Postprandial
• 2-4 hours post meal in animals with simple stomach
Pathologic Causes of Hyperglycemia
Deficiency of insulin
• Diabetes mellitus Type I
Insulin resistance • Diabetes mellitus Type II • Hyperadrenocorticism • Acromegaly (excess Grown Hormone) • Endotoxemia
Glucagon producing tumors (rare)
Excess catecholamines
• pheochromocytomas (tumor)
Drugs:
• glucocorticoids, megestrol acetate, xylazine, glucose administration, ketamine, others
Tests useful for evaluating hyperglycemia
Urinalysis
• renal capacity exceeded -> glucose “spill-over” into urine
• Stress/excitement hyperglycemia usually not high enough to cause glucosuria (occurs more often with cats)
• Proximal tubular abnormalities (Fanconi’s syndrome)
• persistent hyperglycemia & glucosuria = likely Diabetes mellitus (check for ketone bodies!)
Fructosamine
• Indicates of blood glucose average over 2-3 weeks
• Glucose combines with amine groups of albumin and other proteins
• Must have Hyperglycemia present >4 days
• Can differentiate Diabetes mellitus from excitement
Ketone Bodies
Ketone Bodies; why are they produced? types, detection, common causes
- Often results in titrational metabolic acidosis
- detected in urine prior to blood
- urine dipsticks may not detect β hydroxybutyrate
negative energy balance
• Decreased carb metabolism (low insulin)
• Decreased carb availability
• Increased lipolysis
Types of Ketone bodies
• Acetoacetate**, β-hydroxybutyrate, acetone
Common causes • Diabetes Mellitus (also hyperglycemia) • Bovine ketosis • Pregnancy toxemia in ewes • Hepatic lipidosis • Severe starvation • Prolonged Anorexia
Regulation of Ca & P
Calcitonin • Produced by thyroid • Increase Ca & P deposition in bone • Decreases uptake Ca & P in kindey • Down Ca & P
PTH • Produced by parathyroid gland • Stimulate release from bone • Increase Ca uptake & decrease P uptake in kidney • Up Ca down P
Vit D
• Increase P & Ca uptake in GI
• Up Ca & P
Free Ionized Ca
o iCa is most accurate assessment of Ca++ conc
o If tCa is decreased, need iCa to determine significance
o iCa can change w/ change in pH so need to run w/in 30 mins
Basics of Hypercalcemia & clinical signs
Imbalance of: • Ca2+ release from bone • Ca2+ excretion by kidneys • Increased Vitamin D activity • Hormones
Clinical signs are often variable:
• PU/PD → Diabetes insipidus (Ca2+ inhibits ADH function)
• Lethargy, anorexia, vomiting, constipation/weakness
• Mineralization of soft tissues if iP x Ca > 70 mg/dL
Hypercalcemia due to Increased PTH
Humoral hypercalcemia of malignancy (high PTHrp)
• most common cause of hypercalcemia in dogs
• Lymphosarcoma (mostly T cell)
• Anal sac apocrine gland adenocarcinoma
• Multiple myeloma, other carcinomas
Primary hyperparathyroidism
• Increase in PTH caused by tumor (usually an adenoma)
• increased iCa2+, decreased iP (if GFR is normal), and increased PTH
Diseases that cause Hypercalcemia due to decreased urinary excretion
Renal disease
• Common with equine CKD
• Less common in other species
Hypoadrenocorticism (Addison’s disease)
• Mechanism is poorly understood
• Typically a mild elevation
• iCa2+ is typically normal but can be increased
Causes of Hypercalcemia due to increased Vit D Activity
Vitamin D toxicosis
• Over-supplementation
• Cholecalciferol containing rodenticides
• Some plants
Granulomatous disease
• Vit D like metabolites production by epithelioid macrophages
Neoplasia
• Ca2+ and iP are increased and PTH is normal to decreased with hypervitaminosis D
Hypercalcemia due to Excess Release from Bone
Osteolytic bone lesions
• Inflammation (bacterial, fungal, etc)
• Neoplasia (osteosarcoma, multiple myeloma)
• Degenerative bone disease
Young, growing animals
• very mild
Acronym for Hypercalcemia
GOSH DARNIT G ranulomatous (over production of Vit D) O steolysis (inflammation, cancer, degenerative diseases) S peudo H yperparathyroidism (too much PTH)
D too much Vitamin D A ddison’s (we don’t know mechanism, mild increases) R enal (CKD, most common in horses) N eoplasia (lymphoma, anal sac adenocarcinoma, others) I diopathic (most common in cats) T emperature (hypothermia can cause but not common)
Assessment when you have hypercalcemia
o good history (diet, toxin exposure, etc)
o physical exam
o Palpate lymph nodes, check anal sacs (dogs)
o Radiography/ultrasound (abdomen, PTH glands)
o CBC, chemistry profile, UA (look at your basics!)
o Rule out artifact!! (i.e., lipemia may increase Ca2+)
o Measure iCa2+ if needed!!
o Measure PTH/PTHrp along with iCa2+ (if clinically indicated)
Clinical Signs of Hypocalcemia (short acronym)
o C convulsions
o A Arrhythmias
o T tetany
o S spasms & stridor
Most common cause of Mild hypocalcemia
o Decreased in protein bound fraction
o Due to hypoalbuminemia
o Corrected Ca = (3.5-[albuin]) + tCa
Hypocalcemia due to drecreased PTH producton/activity
Primary hypoparathyroidism • parathyroid glands are damaged by neoplasia, trauma, surgery, inflammation • Ca2+ is low • iP is high, • PTH is low
Hypomagnesemia
• May result in decreased PTH activity because secretion relies on Mg2+
Pseudohypoparathyroidism
• Defective PTH receptor or pathways (rare)
4 reasons for Hypocalcemia
Renal (CKD) 2nd Hyperparathyroidism
• Retention of iP and decreased Vit D
Nutritional 2nd Hyperparathyroidism
• Bone disorder caused by excess PTH
• due to diet with excess Pi or low Ca
Hypovitaminosis D in camelids
EPI or any malabsorption condition
• Low Vit D, Ca2+, and Albumin
Hypocalcemia due to increased Use
Pregnancy/parturition, lactation
• Demand greater than intake/ability to respond
• Milk fever in cattle
• Eclampsia in dogs, mares
• Very good response if treated promptly with Ca2+
Random Causes of Hypocalcemia
Deposition • Tissue necrosis • Saponification of fat with acute pancreatitis • Ethylene glycol toxicity • Blister beetle toxicosis
Hyperphosphatemia
Decreased excretion from kidneys
• Decreased GFR is the most common cause!!
Increased intestinal absorption
• High concentrations in diet
• Hypervitaminosis D
• Overt supplementation
Release from bone or cells • Massive tissue damage • Young growing animal • Osteolytic bone lesion • Hemolysis (massive)
Hypophosphatemia
Increased excretion in kidneys
• Increased PTH or PTHrp
• Prolonged diuresis
• Tubular genetic defects (rare)
Decreased intestinal absorption
• Low iP diet or anorexia
• Malnutrition or malabsorption
• Hypovitaminosis D (see mostly in camelids)
High insulin
Excessive utilization (milk fever, eclampsia)
Hypomagnesemia
Redistribution
• Hypoalbuminemia
Decreased intake
• Poor diet
• Grass tetany = Lush green pasture high in K and low in Mg
Increased loss
• Kidneys- diuresis
• hypercalcemia (inhibits Mg
reabsorption)
• GI tract-malabsorption
Hypermagnesemia
o Decreased GFR
o iatrogenic
Hemorrhagic Effusion
o Platelets = contamination
o Erythrophagocytosis, hemosiderin, hematoidin = hemorrhage
Caused by • trauma, • surgery, • neoplasia, • hemostatic defects
Chylous Effusion
o Small mature lymphocytes
o May become mixed (lymphocytes, neutrophils, macrophages)
o Fluid triglycerides > serum triglycerides
Causes: • neoplasia, • cardiac dz, • trauma to lymphatic vessels, • lung torsion
Neoplastic Effusion
o Common cause of abdominal & thoracic effusion
o Usually not inflammatory but may have blood & inflammation
o Lymphoma or carcinoma
o Diagnostic cells may not be present in effusion
Feline Infectious Peritonitis (FIP)
o Very high protein in serum & fluid
o Usually low TNCC
o Mix of neutrophils & macrophages
Caused by
• Inflammation
• Vasculitis
Bilous Effusion
o Bile (dark green pigment) in peritoneal fluid
o Neutrophilic or mixed inflammation
o Bilirubin in fluid > serum
Cause
• Gall bladder or common bile duct rupture
Epithelial Cell Neoplasia
o Large round/oval or polygonal cells in tight clusters
o Neuroendocrine tumors
Mesenchymal Cell Neoplasia
o Few spindle shaped cells seen
o Poorly define cytoplasmic border
o Large elongated nuclei
Round Cell Neoplasia
o Discrete individual small-medium round cells o FNA smears are very cellular o Histiocytoma o Lymphosarcoma o Plasma cell tumor o Mast cell tumor o Transmissible venereal tumor
