Exam 3 Flashcards
(136 cards)
1
Q
Plasma Proteins V Serum Proteins
A
Plasma • Measured by refractometer • Albumin • Globulins • Clotting factors • Fibrinogen
Serum • Measured by biochemistry analyzer • Albumin • Globulins • NO Fibrinogen
2
Q
Albumin
A
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
3
Q
Globulins; basics & 3 types
A
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)
4
Q
Fibrinogen
A
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
5
Q
Acute Phase Proteins
A
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
6
Q
Hyperproteinemia
A
Hyperalbuminemia
• Hemoconcentration
• NEVER increase production!!!
Hyperglobulinemia
• Inflammation (APP and immunoglobulins also elevated)
• B-lymphocyte neoplasia
7
Q
Serum protein electrophoresis
A
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
8
Q
Hypoalbumenia
A
Loss
• Renal dz
• GI dz
• Hemorrhage
Decreased production
• Liver failure
• Inflammation
Hemodilution
• Excess IV fluids
• Edema
9
Q
Panhypoproteinemia
A
- hypoalbuminemia & hypoglobulinemia
- Hemorrhage
- Protein losing enteropathy
- Severe exudation or effusion
- Hemodilution (uncommon)
- Intestinal parasitism
10
Q
Hypoglobulinemia
A
- Failure of passive transfer
* Acquired immune deficiency
11
Q
Triglycerides & Cholesterol
A
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
12
Q
4 Important Lipases
A
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
13
Q
Lipemia V Hyperlipidemia
A
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
14
Q
Physiologic Hyperlipidemia Vs Pathologic lipemia/hyperlipidemia
A
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
15
Q
Primary causes of hyperlipidemia
A
o Less common
o Hyperlipoproteinemia mini schnauzer etc (LPL deficiency)
o Hyperchylomicronemia in cats (LPL deficiency)
o Idiopathic hypercholesterolemia (unknown mech)
16
Q
Secondary Causes of Hyperlipidemia
A
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
17
Q
Hypertriglyceridemia in Ponies, Donkeys and Horses
A
o mobilization of fatty acids from adipose tissue -> formation of TG and VLDL in liver
o secondary to negative energy balance
18
Q
Hypocholesterolemia
A
Hepatic insufficiency:
• decreased production
GI disease:
• decrease absorption
Hypoadrenocorticism:
• cortisol influences on lipoprotein metabolism (decreased function)
Severe malnutrition
Acute hemorrhage
Inherited
• Holstein calves (rare)
19
Q
Non-esterified fatty acids (NEFA) in ruminants; physiologic Vs pathologic increase
A
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
20
Q
Insulin, Glucagon, & Blood Glucose
A
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
21
Q
Other hormonal regulation of glucose
A
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)
22
Q
Hypoglycemia
A
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)
23
Q
Test useful for evaluating hypoglycemia
A
Serum Insulin
• hypoglycemia is present (<60 mg/dl) and insulin levels are normal to increased = Insulinoma is likely
24
Q
Physiologic causes of Hyperglycemia
A
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
25
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
26
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
27
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
```
28
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
29
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
30
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
31
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
32
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
33
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
34
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
35
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)
```
36
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)
37
Clinical Signs of Hypocalcemia (short acronym)
o C convulsions
o A Arrhythmias
o T tetany
o S spasms & stridor
38
Most common cause of Mild hypocalcemia
o Decreased in protein bound fraction
o Due to hypoalbuminemia
o Corrected Ca = (3.5-[albuin]) + tCa
39
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)
40
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
41
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+
42
Random Causes of Hypocalcemia
```
Deposition
• Tissue necrosis
• Saponification of fat with acute pancreatitis
• Ethylene glycol toxicity
• Blister beetle toxicosis
```
43
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)
```
44
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)
45
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
46
Hypermagnesemia
o Decreased GFR
| o iatrogenic
47
Hemorrhagic Effusion
o Platelets = contamination
o Erythrophagocytosis, hemosiderin, hematoidin = hemorrhage
```
Caused by
• trauma,
• surgery,
• neoplasia,
• hemostatic defects
```
48
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
```
49
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
50
Feline Infectious Peritonitis (FIP)
o Very high protein in serum & fluid
o Usually low TNCC
o Mix of neutrophils & macrophages
Caused by
• Inflammation
• Vasculitis
51
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
52
Epithelial Cell Neoplasia
o Large round/oval or polygonal cells in tight clusters
| o Neuroendocrine tumors
53
Mesenchymal Cell Neoplasia
o Few spindle shaped cells seen
o Poorly define cytoplasmic border
o Large elongated nuclei
54
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
```
55
Cytologic Criteria for Malignant Neoplasia
* Anisocytosis
* Pleomorphism
* Basophilia
* Vacuolization
* Poorly defined cell margins
56
Nuclear Criteria for Malignant Neoplasia
* More important than cytoplasmic
* Macrokaryosis
* Anisokaryosis
* Increased mitotic figures
* Multinucleation
* “Coarse” nuclear chromatin
* Macronucleoli
* Nuclear molding
* Angular nucleoli
* Abnormal mitosis
57
When to collect bone marrow
```
▪ Hard to explain peripheral Cytopenias
▪ Further evaluation of suspect cells in blood (e.g., leukemia)
▪ Staging of lymphoma
▪ Suspect marrow toxicity
▪ Myelophthisic process
```
58
Most important thing to remember when looking at bone marrow
ALWAYS have a concurrent CBC from the same time & day
59
Blood Group Ags Vs Abs
Blood Group Antigens
o Glycolipids or glycoproteins on RBCs
o Species specific
Blood Group Antibodies
o Naturally occurring Abs against some RBC Ags early in life
o Other abs form when the RBC Ag is transfused into recipient
60
Canine Blood Groups
DEA 1
• 2nd Most common
• no naturally occurring Abs
• acute hemolytic reaction
DEA 3
• Naturally occurring Abs
DEA 4
• Most common
• No naturally occurring Abs
DEA 5
• Naturally occurring Abs
DEA 7
• Naturally occurring Abs
Dal & Kai
• New blood groups
61
Transfusion Reactions in dogs
o DEA 1 (+) blood given to sensitized, DEA 1 (-) -> immune-mediated severe acute hemolytic transfusion reaction.
o most common naturally occurring ab in dogs is against DEA 7
62
Universal Dog Donor
o must be DEA 4(+) and DEA 1,3,5,7 (-)
o Labs cannot test for 3, Dal, Kai
63
Feline Blood Groups
```
o different neuraminic acid residues on a ceramide-dihexose on the RBC
o Type A – glycolyl-neuraminic acid
o Type B – acetylneuraminic acid
o Type AB – no naturally occurring ABs
o Type B often occurs in exotic cats
```
64
Feline Blood Type B
o have strong, naturally occurring anti-A antibodies.
o first time transfusion of type A blood into type B recipient -> DEATH!
o Type A kittens born to type B queens can die after suckling anti-A Abs
65
Feline Blood Genotype Testing
o Genetic test from UC Davis
o Identifies type B or non type B & carriers of B
o ALL cats should be blood typed before even the first transfusion
66
Neonatal Isoerythrolysis
o usually from passive transfer of Abs against Qa and Aa blood types
o Mare and sire have different blood types
->
o Foal inherits a blood type from sire that mare lacks
->
o Mare builds Abs against it
->
o First foal usually not affected ->
o second foal suckles Ab in colostrum and develops hemolytic anemia
67
Blood Typing Vs Cross matching
Blood Typing
o Identifying RBC Ags by reacting RBC with Ab or reagent
Crossmatching
o Identifying serologic incompatibility between donor and recipient
68
Blood Typing Cards
o Commercially available
o Contain antisera or reagent dried on cards
o Use drop of whole EDTA blood from patient
o Agglutination is a positive response
o Canine cards type for DEA 1
o Feline cards type for A, B, and AB
69
Blood Typing w/ Alvedia
Dogs & cats
• Test for DEA1 & A ,B
• Use one drop of EDTA blood
• 2 minutes
Horses
• Tests Ca blood type
70
Major Vs Minor Crossmatch
Major
• Donor RBC (Ag) + recipient plasma/serum (Ab)
Minor
• Donor plasma/serum (Ab) + recipient RBC (Ag)
71
Procedure for Crossmatching
o Washed RBCs (Ag) + plasma or serum (Ab) ->
o Incubate ->
o Check for hemolysis ->
o Centrifuge ->
o Check for agglutination or hemolysis ->
o Check for agglutination under microscope
72
Alvedia Crossmatch Test Method
o Mix donor RBCs & patient plasma or serum
o Incubate 10 mins
o Add coomb’s reagent strip
o (+) line at site of reagent = incompatibility
73
What does a compatible crossmatch mean?
o Abs against red blood cells cannot be detected.
o Does not indicate that donor & recipient have same blood type
o Does not detect Ab against platelets, WBCs or proteins
o Sensitization may still occur
74
What to do in the case of a hemolytic transfusion reaction
```
o Repeat crossmatch, retype
o Check PCV
o Check for hemoglobinemia/uria
o Check for bilirubinemia/uria
o Coombs’ test
```
75
Basics of the thyroid gland & functions
o Located around trachea
o follicles filled with colloid containing thyroglobulin
Thyroglobulin
• glycoprotein precursor to thyroid hormone
Functions
o Converts iodid to iodine
o Form thyronine (T3) & thyroxine (T4)
76
Basics of Thyroid Hormones
```
o T3 & 4 bound to plasma proteins
o Umbound T3 & T4 enter cells & bind to nuclear receptor
o Abundance of T4
o T3 more active
o T4 can be converted to T3 in tissue
o rT3 is inactive
```
77
Functions of thyroid hormones
```
o Increase transcription of genes
o Maintain metabolism
o Regulate temp
o Growth & maturation
o Stimulate HR, CO & blood flow
```
78
Control of Thyroid hormone synthesis & secretion
o Hypothalamus & anterior pituitary stimulate synthesis of T3 & 4
o Thyroid glands secrete T3 & T4
o Negative feedback loop
79
Serum Total T4 Test
o diagnosis of hypo/hyperthyroidism.
o measure protein bound + “free” T4.
o RIA or chemiluminescent immunoassays are used.
o Young animals have higher values.
o Extrathyroidal disease can decrease values!
(euthyroid sick syndrome)
80
Serum Free T4 Test
o T4 not bound to protein (0.1% of total T4)
o Less affected by non-thyroidal factors.
o More sensitive and specific test for hypothyroidism than total T4.
o Measured by equilibrium dialysis technique (send out test).
81
Serum Total T3 Test
o Part of thyroid panel
| o Low total T3 w/ normal T4 is questionable
82
Serum Endogenous TSH Test
o Help diagnose hypothyroidism
o Species specific assay
o Increases in about 75% of hypothyroid dogs
o Best used with free T4
83
Autoantibodies Thyroid Test
o Meausres serum Abs against T4, T3, and thyroglobulin
o indicative of thyroid destruction associated with lymphocytic thyroiditis.
o Abs to T4/T3 interfere w/ RIA measurement
o Thyroglobulin autoantibody can be positive in hypothyroid dogs
84
TSH Stimulation Test
o thyroid response to exogenous TSH.
o differentiate hypothyroidism from euthyroid sick
o Bovine TSH used, but not always easy to obtain.
o rhTSH has been used more recently.
o Want a response at least 2 ug/dl above baseline
85
TRH Stimulation Test
o Not commonly used
| o differentiate hypothyroidism from euthyroid sick
86
T3 Suppression Test
```
o check for hyperthyroidism
o Measure baseline T4 and T3 ->
o give dose of T3
->
o Measure serum T4 and T3 ->
o If T4 decreased to less than 1.5 ug/dl or greater than 50% suppression of baseline, then euthyroid
o If T4 the same then hyperthyroidism
```
87
Hypothyroidism; species, cause, clinical signs
o Most common endocrinopathy in the dogs
o Result of lymphocytic thyroiditis or thyroid atrophy.
```
Clinical Signs
• Weight gain
• Lethargy
• heat seeking
• truncal alopecia
• Hypercholesterolemia
• Persistent lipemia (hyperlipidemia)
• Mild anemia
• Increased CK if myopathy present
```
88
Diagnosing Hypothyroidism
* Test TT4 or free T4 and TSH
* If total T4 in mid to upper range = unlikely hypothyroidism
* If T4 low or low normal -> measure free T4 by equilibrium dialysis. TSH can also be measured.
* 10% of euthyroid sick dogs will have low free T4,
* 25% of hypothyroid dogs will have normal TSH
89
Euthyroid Sick Syndrome
o Nonthyroidal illness
o lower serum total T4 and T3.
o Multifactorial mechanism
o Some drugs, such as glucocorticoids, can also affect thyroid hormone concentrations.
90
How to monitor thyroid replacement therapy
o Administer T4 for 4 weeks ->
o Draw sample 4-8 hours post pill ->
o Serum T4 should be 30-60 nmol/L (2.3-4.6 mcg/dL)
91
Hyperthryroidism; species, cause, clinical signs
o Most common endocrine disorder of cats.
o Bilateral thyroid adenomatous hyperplasia or adenoma is most common cause
o Can have hyperthyroidism AND euthyroid sick = normal T4
```
Clinical Signs
• Weight loss
• Polypahgia
• Vomiting & Ds
• Enlarged thyroid
• Thin
• Cardiovascular signs
• Mild increase in ALT & AP
```
92
Diagnosing hyperthyroidism
* High total T4
* If high-normal ->
* Repeat total T4 OR
* Run free T4 OR
* Do T3 suppression test OR
* Run cTSH assay (undetectable suggests hyperthyroid)
93
Cells of the pancreas
Exocrine acinar cells
```
Islets of langherhans
• Alpha cells—glucagon
• Beta cells—insulin
• Delta cells—somatostatin
• F cells—pancreatic polypeptide
```
94
Insulin
o Secreted by b cells of pancreatic islets
o response to hyperglycemia
o Lowers blood glucose
o Promotes glucose uptake by liver, skeletal muscle, and fat
o Inhibits gluconeogenesis in liver
o Promotes liver glycogen formation and storage
95
Glucagon
o Secreted by alpha cells of pancreatic islets
o response to hypoglycemia
o Binds to glucagon receptor on cells
o Increases blood glucose
o Stimulates hepatic gluconeogenesis & glycolysis
o Inhibits cellular insulin receptor affinity
o Inhibits insulin action intracellularly
96
Glucose Test
o Persistent changes indicate islet cell disorders
o glucose can increase or decrease with nonpancreatic disorders
o Transient physiologic hyperglycemia is common in cats
97
Fructosamine & Glycosylated Hemoglobin Test
o Glycated proteins
o Markers of mean glucose concentration over the lifespan of the protein
o used to monitor glucose control in diabetics
Serum fructosamine
• glucose concentration over previous 2-3 weeks
Glycosylated hemoglobin
• glucose concentration over previous 2-3 months (hemoglobin A1C).
98
Serum Insulin Test
o Not used for diabetics
o Used to diagnose insulinoma
o Used to diagnose equine metabolic syndrome
99
2 Insulin Secretory Response Tests
IV glucose or glucagon tolerance test
• Baseline glucose and/or insulin –>
• IV dextrose or IV glucagon –>
• Serial glucose and insulin samples
Oral glucose tolerance test
• Baseline glucose and/or insulin –>
• Oral dextrose
–>
• Serial glucose and insulin samples
100
Blood Glucose Curve
o Assess response to insulin therapy
o Measure blood glucose every 2 hrs
o 80-150mg/dl glucose should occur halfway through curve
101
Diabetes Mellitus Type I
* Loss of Beta cells
* Absolute deficiency of
insulin
* No increase in serum insulin after glucose or glucagon administration
* Insulin dependent (IDDM)
* Most common type in dogs
102
Diabetes Mellitus Type II
* Gradual loss or dysfunction of beta cells or insulin interference/resistance (target cells do not respond to insulin)
* Non-insulin-dependent (NIDDM)
* can become insulin dependent (IDDM)
* cats: a result of impaired insulin secretion, insulin resistance, and/or amyloid deposition in islets
* Not easy to tell type I from II in animals
103
Clinical Signs of Diabetes Mellitus
* fasting, persistent hyperglycemia
* PU/PD, polyphagia, weight loss
* Liver enzymes often increased
* Glucosuria—may be associated with evidence of cystitis
* Hypercholesterolemia and hypertriglyceridemia
104
What causes insulin resistance?
```
o Drugs—glucocorticoids
o Progesterone
o Obesity
o Infections
o Pancreatitis
o Growth hormone--acromegaly
o Neoplasia
```
105
Feline Acromegaly/Hypersomatotropism
o chronic, excessive secretion of growth hormone (GH)
o older (8-14 yr) cats
o Caused by pituitary adenoma
o Leads to diabetes mellitus & abnormal bone growth
o Stimulates secretion of insulin-like growth factor (IGF-1) by liver.
o IGF-1 used to help diagnose
106
Diabetic Ketoacidosis
o Metabolic acidosis
o Ketosis and ketonuria occur initially
o High anion gap
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Ketones
o Acetoacetate, b-hydroxybutyrate, acetone
o Formed due to increased mobilization of lipids
o Excessive β oxidation of fatty acids generates acetyl CoA, which stimulates hepatic ketogenesis
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Monitoring Diabetes w/ Portable Blood Glucose Meters
o Easy to use, inexpensive, many different models
o Can overestimate or underestimate blood glucose
o whole blood glucose ~ 10% less than plasma glucose
o Point of care instruments such as the iSTAT can also be used and are quite accurate.
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Continuous Glucose Monitoring Systems
o FreeStyle Libre Flash Glucose Monitoring System (FGMS)
o measures interstitial glucose and relays recorded measurements to transmitter.
o Once attached, can generate 14 days of glucose readings while patient is at home.
o Less invasive than serial venipunctures
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Insulinoma
o Neoplasm of pancreatic islet cells.
o profound hypoglycemia.
o If suspected, evaluate serum insulin while animal is hypoglycemic. ->
o Serum insulin >20 microU/ml + blood glucose <60 mg/dl is diagnostic
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Equine Metabolic Syndrome
o Syndrome in horses with risk factors for laminitis.
o disturbance in relationship among insulin, glucose, and lipids.
o young to middle-aged horses with regional or general fat deposits.
o Hyperinsulinemia
o Serum glucose can be normal.
o excessive hyperinsulinemic response to oral or IV carbohydrate challenge
o hypertriglyceridemia
o May see increased leptin
o Must differentiate from PPID
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Chemicals Produced by the Adrenal-Pituitary Axis
CRH
• Corticotropin releasing hormone
• polypeptide secreted by neurons in anterior hypothalamus
ACTH
• Adrenocorticotropic hormone
• polypeptide produced by pituitary gland
Cortisol
• Made from cholesterol
• actions on glucose, blood cells, other endocrine systems
Aldosterone
• synthesized in zona glomerulosa of adrenal cortex.
• retention of Na+ and excretion of K+.
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ACTH Stim Test; what does it tests for, method, results
* Very specific
* Screen for hyperadrenocorticism or hypoadrenocorticism.
* monitor therapy for hyperadrenocorticism
* Preferred test for iatrogenic hyperadrenocorticism.
Method
• Take baseline sample for cortisol ->
• inject ACTH ->
• take another sample for cortisol 1-2 hours later.
Results
• Normal: Cortisol increase 2-3 times
• Pituitary dependent hyperadrenocorticism: large increase outside of normal
• Adrenal dependent hyperadrenocorticism: may or may not respond.
• iatrogenic hyperadrenocorticism: No/little response
• hypoadrenocorticism: no response
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Low Dose Dexamethasone Suppression Test; what does it tests for, method, results
* Very sensitive
* screen for hyperadrenocorticism.
* Used in dogs, cats, and horses (higher dose for cats)
Method
• Take baseline sample for cortisol ->
• inject dexamethasone ->
• take another sample for cortisol at 4 hours and at 8 hours (18-20 hours later in horses).
Results
• Normal: Cortisol will decrease to <1.0 ug/dl by 8hrs
• Pituitary & adrenal dependent hyperadrenocorticism: no suppression
• Pituitary dependent hyperadrenocorticism: may see suppression at 4hrs but not at 8
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Urine Cortisol:Creatinine Ratio
* Very sensitive but not specific
* Cortisol concentrations in urine = plasma cortisol concentrations.
* Reference values for MSU Endocrinology Lab are 8-24 in dogs.
* normal test rules out hyperadrenocorticism
* abnormal result is not diagnostic
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High Dose Dexamethasone Suppression Test; what does it tests for, method, results
* differentiate ADH from PDH
* used as a screening test in cats.
* Not used so much currently
Method
• Take baseline sample for cortisol ->
• inject high dose of
dexamethasone ->
• take another sample for cortisol at 8 hours.
Results
• PDH: Cortisol decrease to less than 50% of baseline by 8hrs
• 20-30% dogs w/ PDH fail to suppress
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Endogenous Plasma ACTH; what does it tests for, results
* differentiate Adrenal Hyperadrenocorticism from PDH
* Sometimes used as screening test in horses
* Variable reliability due to instability of test
* Can be used alone or after TRH administration for diagnosis of pituitary pars intermedia dysfunction (PPID) in horses.
Results
• PDH: Plasma ACTH is normal to increased
• ADH: Plasma ACTH decreased
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Hormones Used to Assess Adrenal Function
* Androstenedione
* Estradiol
* 17 OH Progesterone
* Ald
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What to do with an animal showing signs of hyperadrenocorticcism but testing (-)
* If animal shows signs but tests are (-)
* Do a different test
* Test again in 1-3 months
* Use sex hormone profile (especially in ferrets)
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Hyperadrenocorticcism; causes & clinical signs
• Cushing’s
Causes
• pituitary or adrenal neoplasia
• drugs
```
Clinical Signs
• PU/PD
• Abdominal enlargement
• Lethargy
• Alopecia
• Muscle wasting
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Hyperadrenocorticcism; Expected Lab Values
* “Stress” leukogram
* Thrombocytosis--mild
* Increased ALP (dogs)
* Mild increase ALT
* Hyperglycemia
* Hypercholesterolemia, hypertriglyceridemia
* Proteinuria—mild
* Low USG
* Abnormal adrenal tests
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Hypoadrenocorticcism; basics & 3 types
* Addison’s
* failure of adrenal to secrete cortisol aldosterone
* ACTH Stim is best test
Idiopathic primary
• immune-mediated?
• May be a genetic basis in some dogs.
Iatrogenic primary
• from treatment with o,p-DDD
OR
• abrupt cessation of exogenous glucocorticoid therapy
Secondary
• pituitary or hypothalamic disease
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Hypoadrenocorticcism; Clinical Signs & Lab Values
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Clinical Signs
• Weak pulse
• Bradycardia
• GI signs
• Weight loss
• PU/PD
```
```
Lab Values
• Lack of “Stress” leukogram
• lymphocytosis and/or eosinophilia
• Normocytic, normochromic anemia
• hyponatremia,
hyperkalemia, hypochloremia
• Mild hypercalcemia
• Azotemia
• Variable metabolic acidosis, hypoglycemia, hypoalbuminemia
```
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Equine Hyperadrenocorticism; basics, cause, diagnosis
* pituitary pars intermedia dysfunction (PPID)
* older horses
* hirsutism (excessive hair growth), PU/PD, chronic laminitis
* younger horses - equine metabolic syndrome mimics PPID
Cause
• hyperplasia or benign neoplasia of pars intermedia of anterior pituitary
Diagnosis
• resting or post TRH endogenous ACTH
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Hyperaldosteronism
* hypokalemia and hypernatremia.
* often caused by adrenal neoplasia in cats.
* Increased plasma aldosterone concentrations will occur at baseline and post ACTH stimulation.
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Pros & Cons of Cytology
```
Pros
• Non-invasive
• Quick
• Inexpensive
• No anesthesia needed
```
```
Cons
• Susceptible to sampling bias
• No tissue architecture
• Malignancy overlaps w/ hyperplasia
• Possible transplant of tumor cells
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Pros & Cons of Histopathology
Pros
• Definitive
• Tissue architecture
• Able to evaluate metastasis
```
Cons
• Invasive
• Slower
• Costly
• Anesthesia required
```
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Fine Needle Aspirate (FNA)
```
o Low sample contamination
o Minimally invasive sample of organs
o Best for fluids
o 22-25 gauge needle
o can’t use for bloody samples
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Impression smears, scraping, and swabs are used for...
Impression Smears
o exudative cutaneous lesions
o cytologic prep of biopsy samples
Scraping
o Fibrotic lesions that can’t be FNA’d
o Must have blood in sample for proper fixation
Swab
o When anatomy does not allow for FNA
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Types of Slide Prep
Squash
• Best for cytology
Linear
• Poorly cellular sample
Smear
• Blood
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How to evaluate cytology sample microscopically
o Giemsa/Wrights stain or Diff-quick
o Keep away from formalin!!
o Scan w/ 4x to10x entire slide & look for cell distribution/features
o ZigZag, Up/Down
o When you find a good area, look at on 100x
Avoid areas w/
• too little stain
• too thick sample
• most cells broken
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Degenerated Neutrophils
* Found in tissue (not in blood)
* came in contact w/bacteria (septic)
* have much lighter color nuclei
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4 Types of Inflammation
Mixed or Pyogranulomatous inflammation
• Macrophages, neutrophils, lymphocytes (chronic process)
• Pyogrnaulomatous is mixed W/ multinucleated giant cells, epithelioid macrophages
Lymphocytic
• Increased # mature/small lymphocytes
Lymphoplasmacytic
• Mix of lymphocytes & plasma cells
Eosinophilic
• Greater than 10% eosinophils
• Allergy, parasitism, paraneoplastic
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Body Fluid Analysis; normal Vs Abnormal
Normal
• Small amount of fluid protects organs
• Ultra-filtrate of blood (low protein/low cell)
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Abnormal/evaluated
• Effusions
• Synovial fluid
• Transtracheal wash
• Bronco alveolar lavage
• Cerebrospinal fluid
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Fluid Collection for cytology & parameters to evaluate body fluid
Fluid Collection
o Purple top – cell evaluation
o Red top – biochemical and/or microbiological evaluation
o Fresh, unstained, refrigerated slides
Evaluate body fluids
Physical
• Volume, color, turbidity, specific gravity
Cellular
• Total nucleated cell count, morphology, PCV/RBC
Chemical
• Tprotein, glucose, lactate, creatinine, amylase, CK, cholesterol
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3 Classifications of effusions
Transudate
• due to hypoalbuminemia -> decreased oncotic pressure
• protein < 2.5 g/dL
• TNCC < 1,000/uL,
• very few mononuclear cells (most are macrophage)
Modified transudate
• many causes
• Usually increased hydrostatic pressure or increased permeability in capillaries and/or lymphatic vessels
• Protein > 2.5
• TNCC < 5,000
• Mix of macrophages, lymphocytes, neutrophils
Exudate
• increased vascular permeability due to inflammation
• Can be septic (usually bacteria) OR nonseptic (irritants, necrosis, etc)
• Protein > 2.5
• TNCC > 5,000
• Many neutrophils
