Clin path Flashcards

1
Q

osmolarity vs osmolality

A

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

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2
Q

Osmo gap

A

Osmo Gap = Osmolality (measured) – Osmolarity (calculated)
normal gap: -5 - 15

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3
Q

increased osmo gap causes

A

Ethylene glycol
Propylene glycol
Ethanol
Mannitol
Radiographic contrast

An osmotic agent not accounted for in the osmolarity formula

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4
Q

response to hyperosmolality

A

thirst center stim> promote water intake
ADH released> promotes kidneys to absorb water

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5
Q

response to hypoosmolality

A

decreased water intake
increased water secretion

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6
Q

hypovolemia is detected by:

A

kidneys (Juxtagolmerular cells)
* activate renin-angiotensin-aldosterone
* reabsorb Na+, water, secrete K+

carotid sinus baroreceptors
* detect hypovolemia, and ADH > vasoconstriction

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7
Q

hypernatremia and hyperchloremia

A

dehydration
* inadequate water intake
* pure water loss (diabetes insipidus)
* osmotic diuresis (diabetes mellitus)
* hyperaldosteronism
* excess intake (salt poisoning)

glucocorticoids, endotoxins, hypercalcemia

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8
Q

acquired diabetes insipidus

A

dehydration due to water loss > hypernatremia and hyperchloremia
can be caused by glucocorticoids, endotoxins, hypercalcemia

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9
Q

Hyponatremia & Hypochloremia

A

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

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10
Q

selective hypochloremia

A

vomiting
metabolic alkalosis

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11
Q

selective hyperchloremia

A

Secretional metabolic acidosis
diarrhea
aka hyperchloremic metabolic acidosis

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12
Q

hyperkalemia

A

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)

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13
Q

decreased Na:K ratio

A

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

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14
Q

biologically active form of Ca

A

free Ca
not bound to protein or anions

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15
Q

Major factors affecting Ca

A

Age: puppies have higher Ca
intestinal absorption: require vit D
resorption from bone
resorption from tubular fluid

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16
Q

Major factors affecting serum P levels

A

renal clearance
intestinal absorption
resorption from bone
shifting from ECF/ICF
Age (younger=higher)

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17
Q

PTH

A

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

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18
Q

Vitamin D

A

net effect: Increase Ca and P

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19
Q

calcitonin

A

net effect: decrease Ca and P

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20
Q

Hypocalcemia

A

Hypoalbuminemia
Primary hypoparathyroidism
Milk fever
Renal secondary hyperparathyroidism
Nutritional secondary hyperparathyroidism
others

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21
Q

Primary hypoparathyroidism

A

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

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22
Q

Milk fever (parturient hypocalcemia)

A

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

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23
Q

Renal secondary hyperparathyroidism

A

↓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

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24
Q

Nutritional secondary hyperparathyroidism

A

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

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25
hypercalcemia causes
Young, growing animals Hyperparathyroidism Humoral hypercalcemia of malignancy Vitamin D toxicity others
26
Primary hyperparathyroidism
Parathyroid adenoma **secretes PTH** **increased Ca** **P may be decreased or WRI**
27
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
28
Vitamin D toxicity
rodenticides, supplements, some plants Vit D: **Increase serum Ca and P** mineralization of tissues > death * if Ca x P >80 mineralization
29
Hyperphosphatemia
Hypoparathyroidism Decreased GFR for any reason Vitamin D toxicosis Shift of PO4 from ICF to ECF
30
Hypophosphatemia
Equine renal failure Prolonged anorexia Milk fever
31
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
32
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**
33
Hypomagnesemia
Hypoproteinemia Inadequate GI absorption * Prolonged anorexia * Calves on whole milk diet * **Grass tetany**
34
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
35
Hypothalamic-pituitary-adrenal axis (HPAA)
36
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
37
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
38
Pituitary dependent (secondary HAC)
80% of canine HAC Pituitary microadenoma
39
Adrenal dependent (primary HAC)
20% of canine HAC Adrenocortical adenoma or adenocarcinoma May produce cortisol precursors (17-hydroxyprogesterone) instead of cortisol
40
Iatrogenic Hyperadrenocorticism in dogs
Exogenous glucocorticoid administration
41
hyperadrenocorticism screening tests
Urine cortisol-creatinine ratio (UCCR) Low-dose dexamethasone suppression test (LDDST) ACTH stimulation test
42
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
43
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**
44
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
45
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
46
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
47
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
48
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
49
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
50
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
50
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
51
Hypoadrenocorticism clin path abnormalities
**Azotemia**, hyperphosphatemia, inadequately concentrated urine Hyponatremia, hyperkalemia, **Na:K ratio <27** Absence of stress leukogram +/- hypoglycemia, anemia, hypercalcemia
52
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
53
Normal thyroid pathway
1. TRH stims release of TSH from pituitary 2. TSH stims thyroid to secrete T4 (and some T3) 3. T4 has negative feedback on hypothalamus and pituitary
54
tests for hyper/hypothyroid
hyperthyroid: TT4, fT4 hypo: TT4, fT4, TSH
55
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
56
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
57
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
58
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
59
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
60
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)
61
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
62
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 * **Glucosuri**a 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
63
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
64
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?
65
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
66
Somoygi effect
insulin overdosing with rebound hyperglycemia
67
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