Clin path Flashcards
osmolarity vs osmolality
Both: Concentration of a solute
Osmolarity
* Moles per liter (per volume)
* Calculated: Na, K, Glu, Urea
* 2(Na +K) + glu/18 + BUN/2.8
Osmolality
* Moles per kilogram (per weight)
* Measured: Osmometer
Osmo gap
Osmo Gap = Osmolality (measured) – Osmolarity (calculated)
normal gap: -5 - 15
increased osmo gap causes
Ethylene glycol
Propylene glycol
Ethanol
Mannitol
Radiographic contrast
An osmotic agent not accounted for in the osmolarity formula
response to hyperosmolality
thirst center stim> promote water intake
ADH released> promotes kidneys to absorb water
response to hypoosmolality
decreased water intake
increased water secretion
hypovolemia is detected by:
kidneys (Juxtagolmerular cells)
* activate renin-angiotensin-aldosterone
* reabsorb Na+, water, secrete K+
carotid sinus baroreceptors
* detect hypovolemia, and ADH > vasoconstriction
hypernatremia and hyperchloremia
dehydration
* inadequate water intake
* pure water loss (diabetes insipidus)
* osmotic diuresis (diabetes mellitus)
* hyperaldosteronism
* excess intake (salt poisoning)
glucocorticoids, endotoxins, hypercalcemia
acquired diabetes insipidus
dehydration due to water loss > hypernatremia and hyperchloremia
can be caused by glucocorticoids, endotoxins, hypercalcemia
Hyponatremia & Hypochloremia
Sodium & chloride loss (anywhere you can lose water)
* GI tract (diarrhea, diuresis)
* Kidneys
* Skin (sweat)
Excess water (heart failure)
Sodium & chloride shifting
* Cell lysis (K+ Leaks out, Na+/Cl- leaks into cell)
* Cavitary (3rd) space (uroabdomen)
* diabetes mellitus
selective hypochloremia
vomiting
metabolic alkalosis
selective hyperchloremia
Secretional metabolic acidosis
diarrhea
aka hyperchloremic metabolic acidosis
hyperkalemia
increased potassium
Increased intake
* IV fluids
decreased renal excretion
* renal failure (anuric or oliguric)
* hypoadrenocorticism (Addisons)
* urinary tract obstruction
postassium shifting
* Metabolic acidosis
* Cell lysis
* Cavitary (3rd) space (uroabdomen)
decreased Na:K ratio
less than 27 (decreased Na, increased K)
diseases:
* Hypoadrenocorticism (Addison’s disease, less than 22)
* Renal failure
* Urinary tract obstruction
* Uroabdomen
* Rhabdomyolysis
* Diabetic ketoacidosis
* Diarrhea
biologically active form of Ca
free Ca
not bound to protein or anions
Major factors affecting Ca
Age: puppies have higher Ca
intestinal absorption: require vit D
resorption from bone
resorption from tubular fluid
Major factors affecting serum P levels
renal clearance
intestinal absorption
resorption from bone
shifting from ECF/ICF
Age (younger=higher)
PTH
activated by decreased serum Ca levels
causes:
* bone: increase resorption of Ca and P from bone
* increased absorption of Ca and P from intestine
* Kidney: increased resorption of Ca, excretion of P
Net effect: Increase Ca, decrease P
Vitamin D
net effect: Increase Ca and P
calcitonin
net effect: decrease Ca and P
Hypocalcemia
Hypoalbuminemia
Primary hypoparathyroidism
Milk fever
Renal secondary hyperparathyroidism
Nutritional secondary hyperparathyroidism
others
Primary hypoparathyroidism
Uncommon
Damage to the gland by trauma, inflammation, surgical removal
* No response to hypocalcemia
* Decreased resorption from bone, decreased intestinal absorption
* Hyperphosphatemia develops and inhibits vitamin D activation > worsening of hypocalcemia
Milk fever (parturient hypocalcemia)
Most common in dairy cattle
High calcium diet during the dry period leads to suppression of the parathyroid gland
Sudden demand for Ca in the milk > decrease in serum Ca
Parathyroid gland secretes PTH, but its effects are too slow to mobilize sufficient Ca in time
Continued loss of Ca into milk > severe hypocalcemia and clinical signs
* Recumbency, bradycardia, arrhythmias
Mildly decreased P, mildly increased Mg, and mildly increased glucose also common
Similar conditions can occur in dogs, ewes, and mares
Renal secondary hyperparathyroidism
↓Ca
* Decreased renal reabsorption of calcium
* Decreased hydroxylation (activation) of vitamin D
* Increase in P > complexing with Ca (metastatic mineralization)
Parathyroid hyperplasia > increased PTH
↑P due to decreased renal excretion of P
Nutritional secondary hyperparathyroidism
Diets with ↓Ca:P
* All meat diets in carnivores
* Excessive grain diets in horses
* High grain/nut diets or lack of UVB source in reptiles
Serum Ca is often WRI, but may be decreased
Decreased Ca stimulated PTH secretion
* Resorption from bone > “rubber jaw”
Serum P may be increased if due to high P diet, but won’t be increased as much as is seen with renal secondary hyperparathyroidism
hypercalcemia causes
Young, growing animals
Hyperparathyroidism
Humoral hypercalcemia of malignancy
Vitamin D toxicity
others
Primary hyperparathyroidism
Parathyroid adenoma secretes PTH
increased Ca
P may be decreased or WRI
Humoral hypercalcemia of malignancy (HHM)
Secretion of PTH-like hormone, PTHrP
Increased Ca
P may be decreased or WRI
Most common neoplasms are lymphoma and apocrine gland anal sac adenocarcinoma (AGASACA)
Others also possible
Vitamin D toxicity
rodenticides, supplements, some plants
Vit D: Increase serum Ca and P
mineralization of tissues > death
* if Ca x P >80 mineralization
Hyperphosphatemia
Hypoparathyroidism
Decreased GFR for any reason
Vitamin D toxicosis
Shift of PO4 from ICF to ECF
Hypophosphatemia
Equine renal failure
Prolonged anorexia
Milk fever
Major factors affecting serum Mg
Serum protein concentration
GI absorption
* Rumen in ruminants
* Distal SI and colon in monogastrics
* Enhanced by Vit D
* Inhibited by dietary Ca and PO4
Excretion
* Fecal
* Kidneys
* Mammary gland
Hypermagnesemia
Decreased urinary excretion
* Renal failure and other causes of decreased GFR (herbivores)
Shift from ICF to ECF
* In vivo hemolysis or delayed RBC separation from serum (except cattle)
Increased PTH: Milk fever
Hypomagnesemia
Hypoproteinemia
Inadequate GI absorption
* Prolonged anorexia
* Calves on whole milk diet
* Grass tetany
Grass tetany
Lush pasture with low Mg
Mg needed for PTH function
↓Mg and ↓PTH
May lead to hypocalcemia
Hypocalcemia may not respond to treatment until hypomagnesemia is corrected
Hypothalamic-pituitary-adrenal axis (HPAA)
Hyperadrenocorticism in dogs
Clinical signs: PU/PD, Polyphagia, Muscle weakness, pendulous abdomen, Alopecia, thin skin, Hepatomegaly, Panting
Clin path abnormalities:
* Elevated ALP (dogs)
* Stress leukogram
* Isosthenuria/hyposthenuria
* Hypercholesterolemia
* Recurring urinary and skin infections
* Hyperglycemia/concurrent DM
Cushings
Types of Hyperadrenocorticism in dogs
Pituitary dependent (secondary HAC)
* 80% of canine HAC
* Pituitary microadenoma
Adrenal dependent (primary HAC)
* 20% of canine HAC
* Adrenocortical adenoma or adenocarcinoma
* May produce cortisol precursors (17-hydroxyprogesterone) instead of cortisol
Iatrogenic
* Exogenous glucocorticoid administration
Pituitary dependent (secondary HAC)
80% of canine HAC
Pituitary microadenoma
Adrenal dependent (primary HAC)
20% of canine HAC
Adrenocortical adenoma or adenocarcinoma
May produce cortisol precursors (17-hydroxyprogesterone) instead of cortisol
Iatrogenic Hyperadrenocorticism in dogs
Exogenous glucocorticoid administration
hyperadrenocorticism screening tests
Urine cortisol-creatinine ratio (UCCR)
Low-dose dexamethasone suppression test (LDDST)
ACTH stimulation test
hyperadrenocorticism Confirmatory/differentiating tests
Endogenous ACTH (eACTH)
Low-dose dexamethasone suppression test LDDST
High-dose dexamethasone suppression test (HDDST)
Abdominal ultrasound
Head and abdominal CT/MRI
Urine cortisol-creatinine ratio (UCCR)
Collect urine in the morning at home and measure cortisol and creatinine
Positives
* Very sensitive
* 90% of dogs with HAC will have elevated UCCR
* Easy and inexpensive
* Owners can collect urine at home = less stress to patient
Negatives
* Poor specificity
* 20% specificity
* 80% false positive rate
* Use primarily in patients with only a few signs of HAC
* Use to rule HAC OUT, DO NOT USE to rule HAC in
Low-dose dexamethasone suppression test (LDDST)
Baseline cortisol measured, dexamethasone administered, cortisol measured again at 4h and 8h
* Use the 8h value to rule in/out HAC
* Use the 4h value to differentiate PDH from AT
Positives:
* Cheaper than ACTH stimulation test
* May differentiate PDH from AT
* High sensitivity
Negatives:
* Lower specificity than ACTH stim test
* High false positive rate
* Best to use with patients who have classic clinical and CBC/chem features of HAC
ACTH stimulation test
Measure baseline cortisol, give ACTH, measure cortisol again in 1-2h
Positives
* Highest specificity (low false positive rate)
* Does not require all-day hospitalization (test done in 1-2h)
* May be less stressful to patient
* Can identify iatrogenic HAC
Negatives
* Less sensitive than LDDST
* More expensive than LDDST
Use to screen patients that are not the classic presentation
* Less likely to get false positive than with LDDST
Also used to monitor therapy
Key points Comparing the screening tests (UCCR vs ACTH stim vs LDDST)
UCCR
* High sensitivity
* High negative predictive value
* Poor specificity
ACTH stimulation test
* Most specific test
* High positive predictive value
* Not as sensitive as the others
LDDST
* High sensitivity
* High negative predictive value
* Reliable if clinical signs and clin path data are supportive of HAC
* Specificity is poor if there is non-adrenal illness
High-dose dexamethasone suppression test (HDDST)
Used to help differentiate PDH from ADH
Only about 14% of the dogs with PDH that don’t suppress at 8h on the LDDST will suppress at 8h on the HDDST
dont really use
High-dose dexamethasone suppression test (HDDST)
Used to help differentiate PDH from ADH
Only about 14% of the dogs with PDH that don’t suppress at 8h on the LDDST will suppress at 8h on the HDDST
dont really use
Endogenous ACTH (eACTH)
Single time-point measurement of ACTH
Very sensitive to specimen handling, consult lab for best procedure
Positives
* Good at differentiating PDH from AT
Negatives
* ACTH is very unstable > prone to pre-analytical error and falsely decreased values
* Some assays have a poor detection limit
* Misclassification of HAC type in 15-25% of cases
Use to differentiate PDH from AT ONLY after HAC is ruled in
Do NOT use to screen for HAC
Hypoadrenocorticism causes and clinical signs
Addisons
Cause:
* >90% Primary: lymphocytic adrenalitis > destruction of all three layers of adrenal cortex > lack of aldosterone and cortisol; “atypical Addison’s disease” is a lack of cortisol only
* Secondary: lack of ACTH > lack of cortisol
* Iatrogenic: chronic corticosteroid treatment > atrophy of pituitary and adrenal glands
Clinical signs:
* Occurs most commonly in** young to middle-aged dogs;** rare in cats
* Lethargy, weakness, vomiting, diarrhea, abdominal pain, anorexia; often intermittent
* Bradycardia, collapse, shock, hypovolemia
Hypoadrenocorticism causes and clinical signs
Addisons
Cause:
* >90% Primary: lymphocytic adrenalitis > destruction of all three layers of adrenal cortex > lack of aldosterone and cortisol; “atypical Addison’s disease” is a lack of cortisol only
* Secondary: lack of ACTH > lack of cortisol
* Iatrogenic: chronic corticosteroid treatment > atrophy of pituitary and adrenal glands
Clinical signs:
* Occurs most commonly in** young to middle-aged dogs;** rare in cats
* Lethargy, weakness, vomiting, diarrhea, abdominal pain, anorexia; often intermittent
* Bradycardia, collapse, shock, hypovolemia
Hypoadrenocorticism clin path abnormalities
Azotemia, hyperphosphatemia, inadequately concentrated urine
Hyponatremia, hyperkalemia, Na:K ratio <27
Absence of stress leukogram
+/- hypoglycemia, anemia, hypercalcemia
Tests for hypoadrenocorticism
Baseline cortisol
* Use to rule OUT hypoadrenocorticism
* Use when there is less suspicion of Addison’s
* A normal baseline cortisol rules out Addison’s
* Decreased baseline cortisol does NOT confirm hypoadrenocorticism
ACTH stimulation test
* Confirmatory test
* Use when there is high suspicion of Addison’s
* Addisonian animals will have a flat ACTH response
Normal thyroid pathway
- TRH stims release of TSH from pituitary
- TSH stims thyroid to secrete T4 (and some T3)
- T4 has negative feedback on hypothalamus and pituitary
tests for hyper/hypothyroid
hyperthyroid: TT4, fT4
hypo: TT4, fT4, TSH
Hyperthyroidism in cats
Cause: Thyroid adenoma (primary hyperthyroidism)
Generally occurs in middle-aged to older cats
Clinical signs:
* Hyperactivity
* weight loss despite normal appetite or polyphagia
* +/- PU/PD, tachycardia, vomiting, patchy alopecia, unkempt haircoat,
Clin path abnormalities:
* mild to moderate increase in ALP, mild increases in ALT, AST
* hypocalcemia and hyperphosphatemia
* +/- azotemia, mild polycythemia, stress leukogram
TT4
total T4
Increased TT4 = hyperthyroidism
* TT4 in upper half of the reference interval > gray zone (10% of hyperthyroid cats will fall in this area)
* TT4 secretion is pulsatile, can be variable in hyperthyroid cats
* Non-thyroidal illness can falsely decrease values
Use as a screening test to rule out hypothyroidism
* 95% hypothyroid dogs will have ↓TT4
* 20% dogs without hypothyroidism may have ↓TT4 – “euthyroid sick” (false positives for hypothyroid)
* Rarely, autoantibodies may falsely increase TT4
fT4
free T4
Use when there is clinical suspicion of hyperthyroidism, but TT4 is in the upper half of the reference interval
Non-thyroidal illness can cause false increases
DO NOT USE fT4 ALONE FOR DIAGNOSIS OF HYPERTHYROIDISM
Use equilibrium dialysis fT4 test > not affected by non-thyroidal illness
Hypothyroidism in dogs
Cause:
* 95% Primary: lymphocytic thyroiditis > follicular destruction
* ≤5% Secondary: structural or biochemical lesion in the pituitary: pituitary tumor/cyst, pituitary hypoplasia, TSH deficiency in giant schnauzers
Clinical signs
* Weight gain without increase in food intake
* Lethargy
* Cold intolerance, heat-seeking behavior
* Dull haircoat, alopecia, hyperpigmentation – without pruritus
* +/- secondary skin disorders: seborrhea, dry coat, pyoderma
Clin path abnormalities
* Hypercholesterolemia (80%) and hypertriglyceridemia
* Mild non-regenerative anemia (30%) or hct in low end of RI
* +/- Increased liver enzymes, increased CK
Lymphocytic thyroiditis
Hypothyroidism in dogs
Clinical signs develop gradually over years
Lymphocytes and plasma cells produce antibodies directed at thyroglobulin (most common), colloid, TT3, TT4
TSH test
Theoretically, dogs with primary hypoparathyroidism should have elevated TSH
Only about 2/3 hypothyroid dogs have elevated TSH
Some of these may have secondary hypothyroidism (↓TSH> ↓T4)
Diabetes mellitus
Clinical signs:
* PU/PD
* Weight loss despite normal or increased appetite
* Decreased appetite
* +/- diabetic cataracts (dogs), recurring skin and urinary infections
Clin path abnormalities
* Dehydration: erythrocytosis, increased Pi, azotemia
* Isosthenuric or minimally concentrated urine, glucosuria, ketonuria
* Hyponatremia, hypochloremia, +/- hypokalemia, +/- hypophosphatemia
* Hypercholesterolemia, hypertriglyceridemia
* Acidosis, increased anion gap (ketoacidosis)
* Hyperosmolality
* Increased hepatic and pancreatic enzyme activities
Diagnosis of Diabetes Mellitus
Differentiate from other causes of hyperglycemia
Severity of hyperglycemia
* DM typically >250 mg/dL
* Stress/excitement in cats can be >300 mg/dL
* Fast small animals for 12h before blood collection
Urine glucose/ketones
* Glucosuria expected with DM
* Glucosuria possible but unlikely with transient increases
* Ketonuria may be present with DM, but is not expected with stress/excitement
Fructosamine
* Estimate of glucose concentrations over the previous 2-3 weeks
* Will not be increased with stress/excitement
Fructosamine
Monitoring of insulin therapy
Marked elevation with poor control
Mild elevation with good control
Considerable variability regardless of control
Single blood draw – easier on owner and patient than glucose curve
Glucose curve
Monitor glucose concentration over an 8, 12, or 24h period – document time and dose of insulin administration and meals
Will detect Somoygi effect with insulin overdosing
Time-consuming, difficult for owner to do, stressful for patients in-hospital > accuracy?
Hypoglycemia causes
- Insulin overdose
- Extreme exertion – hunting dogs, endurance horses
- Glycogen storage diseases – rare
- Hepatic insufficiency – should see hypoalbuminemia, decrased BUN, and increased serum bile acids
- Neonatal (all species)/juvenile (toy breed puppies <6 mo) – fasting or other stressors
- Bovine ketosis/lactational hypoglycemia
- Pregnancy – dogs and sheep
- Sepsis
- Xylitol toxicosis in dogs
- Insulinoma – dogs, cats, ferrets
Somoygi effect
insulin overdosing with rebound hyperglycemia
Insulinoma
Beta cell tumor > secretes insulin > hypoglycemia
Patients with insulinomas may be euglycemic
Measure serum insulin at a time when patient is hypoglycemic
Increased insulin or insulin WRI with concurrent hypoglycemia > insulinoma
Hypokalemia is also frequently associated with hyperinsulinism
