P

P

Parathyroid Hormone

DEFINITION

Hormone produced by parathyroid glands in response to low blood calcium levels; important in the rapid and precise regulation of calcium

SYNONYMS

Parathormone, PTH

TYPICAL NORMAL RANGE

Dogs and cats: 2-13 pmol/L. Results may vary among laboratories; established reference ranges for the laboratory should be used for exact interpretation of results.

PHYSIOLOGY

Parathyroid hormone (PTH) acts directly on bone and kidney and indirectly on the gastrointestinal (GI) tract to increase serum calcium levels. PTH acts on the kidney to increase renal excretion of phosphate, increase tubular resorption of calcium, and convert vitamin D precursors to active vitamin D (which along with PTH increases calcium absorption from the GI tract). PTH acts on bone to mobilize calcium and phosphate. Ultimately, these actions result in elevation of blood calcium and hypophosphatemia.

CLINICAL APPLICATIONS

CAUSES OF ABNORMALLY HIGH LEVELS: Hyperparathyroidism: primary hyperparathyroidism (parathyroid adenoma/hyperplasia), multiple endocrine neoplasia, chronic kidney disease (renal secondary hyperparathyroidism), pseudohyperparathyroidism (decreased PTH-receptor receptiveness). Rare: nutritional secondary hyperparathyroidism.

NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH: Serum ionized calcium, CBC, serum chemistry profile, urinalysis, high-resolution cervical ultrasound (radiologist), thoracic and abdominal imaging of other endocrine organs

CAUSES OF ABNORMALLY LOW LEVELS: Parathyroid inflammation and degeneration (lymphocytic parathyroiditis), inadvertent surgical removal of parathyroid (thyroidectomy in cats), decreased PTH production due to inhibition (hypervitaminosis D, hypercalcemic disorders except primary hyperparathyroidism)

NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS LOW: Same as for elevated PTH

SPECIMEN AND PROCESSING CONSIDERATIONS

LAB ARTIFACTS THAT MAY INTERFERE: Prolonged storage (>2 months) or thawing of sample may cause artificial results, either increased or decreased. Lipemia and hemolysis falsely decrease measurement. EDTA plasma samples have higher values.

SPECIMEN: Serum (red-top tube without additive; do not use serum separator tube) is used for the assay. Samples should be centrifuged immediately after clotting, frozen, and shipped frozen for analysis as soon as possible.

RELATIVE COST: $$

• It is important to know both serum ionized calcium and PTH levels to correctly correlate laboratory results. Ionized hypercalcemia should cause PTH levels to be low or undetectable.

• Renal disease and secondary hyperparathyroidism will typically produce increased ionized calcium and normal to decreased PTH.

• PTH levels in the mid- or high-normal range (or higher) with concurrently elevated ionized calcium suggest primary hyperparathyroidism. With normal parathyroid gland function, ionized hypercalcemia should cause feedback inhibition and very low PTH levels.

AUTHOR: DEBORAH G. DAVIS

Parathyroid Hormone-Related Protein

DEFINITION

Humoral factor with a molecular structure similar to parathyroid hormone (PTH); can bind to PTH receptors. It plays an important role in humoral hypercalcemia of malignancy.

SYNONYM

TYPICAL NORMAL RANGE

Not normally found circulating in the blood. Dogs: <2 pmol/L.

PHYSIOLOGY

Important endocrine and paracrine hormone in the fetus. Produced in minimal amounts in tissues of normal adults and functions in a paracrine manner. In humoral hypercalcemia of malignancy, neoplastic cells secrete excess amounts of PTHrP and other cytokines. PTHrP binds to the PTH receptors in bone and kidney and mimics the effects of PTH. It results in osteoclastic bone resorption, increased renal resorption of calcium, and decreased renal resorption of phosphate. Malignancies associated with increased levels of PTHrP are T-cell lymphoma, thymoma, and apocrine gland adenocarcinoma of the anal sac. Sporadic cases of humoral hypercalcemia of malignancy have been seen with other carcinomas as well.

CLINICAL APPLICATIONS

CAUSES OF ABNORMALLY HIGH LEVELS: Humoral hypercalcemia of malignancy.

NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH: Review physical exam, including rectal palpation in all dogs (apocrine gland adenocarcinoma, sublumbar lymphadenopathy). Measure serum ionized calcium, serum phosphorus, serum PTH. Humoral hypercalcemia of malignancy usually causes elevated ionized calcium level, low-normal or low PTH level, and low phosphorus level. CBC, serum biochemistry profile, urinalysis, and diagnostic imaging to identify and define extent of neoplastic disease.

SPECIMEN AND PROCESSING CONSIDERATIONS

LAB ARTIFACTS THAT MAY INTERFERE: Repeated thawing causes degradation of the protein and interferes with validity of results (either falsely increasing or decreasing). Proteases in serum can degrade PTHrP and cause false-negative results.

SPECIMEN: Contact laboratory for specifics. If serum is sent, immediately spin the sample after it clots, separate serum, transfer to plastic tube, and freeze. Ship frozen. If plasma is used, EDTA (lavender-top tube) with a protease inhibitor (apoprotinin or leupeptin) should be added. Plasma should be separated from the erythrocytes, transferred to a plastic tube, and shipped frozen.

RELATIVE COST: $$$

PEARLS

Three mechanisms can cause cancer-associated hypercalcemia: humoral hypercalcemia of malignancy, local bone resorption induced by hematologic neoplasms growing into the bone marrow (e.g., multiple myeloma), and local bone resorption induced by metastatic bone lesions.

AUTHOR: DEBORAH G. DAVIS

Pelger Huët

DEFINITION

A congenital defect in nuclear lobulation of leukocytes that is rarely reported in dogs and cats. The characteristic appearance of a hyposegmented nucleus is most evident in neutrophils but also occurs in eosinophils, basophils, monocytes, and megakaryocytes. The nuclear shape of affected neutrophils can be bilobed (“pince nez” cell), band, round, or oval, similar to neutrophilic precursors, but the nuclear chromatin of affected neutrophils is coarsely condensed, similar to mature neutrophils.

SYNONYMS

Pelger Huët anomaly or syndrome, pseudo-Pelger Huët

PHYSIOLOGY

Segmented neutrophils in dogs and cats typically have 3-5 nuclear lobes. In the congenital form of Pelger-Huët, hetero-zygotes are most common, and they exhibit hyposegmented neutrophils, many of which resemble band neutrophils. The heterozygous condition is considered benign because affected animals have no ill effects, and neutrophil function tests are not significantly altered. The low incidence of homozygotes is attributed to embryonic death. Rarely, during the course of severe inflammatory disease in unaffected animals, hyposegmentation of neutrophils will occur as a transient reversible condition (“pseudo” Pelger Huët).

SPECIMEN AND PROCESSING CONSIDERATIONS

SPECIMEN: EDTA whole blood (lavender-top tube) and freshly prepared blood smear for laboratory to stain

PEARLS

• When an otherwise unremarkable CBC report has a substantial left shift in an apparently healthy dog or cat, consider the likelihood of Pelger Huët anomaly.

• Pelger Huët is essentially an incidental finding in dogs, with no clinical adverse effect.

AUTHOR: STEPHEN D. GAUNT

Phenobarbital Serum Level

DEFINITION

Used for monitoring patients receiving phenobarbital for treating seizures and for determining whether therapeutic or potentially toxic levels have been reached

SYNONYMS

TYPICAL NORMAL RANGE

Therapeutic range: 15-40 mg/mL

PHYSIOLOGY

The elimination half-life of orally administered phenobarbital in dogs ranges widely, from 12-125 hours (average approximately 48 hours). Peak levels occur 4-8 hours after administration. Pharmacokinetics can be altered by chronic administration, concurrent disease (especially liver disease), age, and concurrent administration of other drugs. For this reason, monitoring of serum drug levels at steady state (14-16 days after starting treatment) is recommended. Peak and trough levels, which were previously recommended, are not considered necessary for making therapeutic decisions.

CLINICAL APPLICATIONS

CAUSES OF ABNORMALLY HIGH LEVELS: >45 mg/mL considered toxic

NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH: Correlate levels with clinical signs (i.e., presence or absence of seizures). Consider effect of concurrently administered drugs or concurrent disease on pharmacokinetics. Evaluate a liver profile. Whether liver disease, other disease, or drugs are present, high levels should prompt the consideration of dose reduction, with institution of a second antiseizure drug if needed.

CAUSES OF ABNORMALLY LOW LEVELS: Serum levels <10 mg/mL are subtherapeutic.

NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS LOW: Correlate drug levels with clinical signs (seizures) to decide whether to increase dose, replace with other antiseizure drug, or discontinue.

SPECIMEN AND PROCESSING CONSIDERATIONS

DRUG EFFECTS ON LEVELS: Concurrent administration of many other drugs, such as certain antibiotics (e.g., doxycycline, chloramphenicol, metronidazole), anticoagulants (warfarin), cardiopulmonary drugs (e.g., aminophylline/theophylline, certain β-blockers, quinidine), glucocorticoids (prednisone, others) and many others, may increase or decrease levels of phenobarbital. Consult a pharmacology textbook or pharmacist for information regarding specific drug interactions.

LAB ARTIFACTS THAT MAY INTERFERE: Collection of blood in a serum separator tube can falsely decrease levels. Moderate to marked lipemia or icterus may artifactually increase reported drug levels.

SPECIMEN: 1 mL of serum (red-top tube; do not use serum separator tube)

RELATIVE COST: $$

PEARLS

Phenobarbital is involved in many drug interactions; consult a pharmacology textbook or pharmacist if multiple medications.

AUTHOR: SHERRY J. MORGAN

Phosphorus

DEFINITION

Inorganic form of phosphate; the major intracellular anion; primarily located in bone (as hydroxyapatite), with the remainder in soft tissues and in circulation

SYNONYMS

Phosphate, Po₄ ²⁻

TYPICAL NORMAL RANGE

Dogs: 3.2-8.1 mg/dL (1.03-2.61 mmol/L). Cats: 3.2-6.5 mg/dL (1.03-2.09 mmol/L).

PHYSIOLOGY

Clinical assays measure only the total inorganic phosphorus, although both organic and inorganic phosphorus are present (depending on pH). Blood levels are affected by intestinal absorption, shifting between intracellular and extracellular compartments, renal clearance, and animal age. Parathyroid hormone (PTH) triggers phosphaturia.

CLINICAL APPLICATIONS

CAUSES OF ABNORMALLY HIGH LEVELS: Decreased glomerular filtration rate (decreased renal excretion due to renal failure, prerenal or postrenal azotemia), hypoparathyroidism, acromegaly, increased intestinal absorption (phosphate enema, increased vitamin D, ischemic intestinal lesions), myopathies, hyperthyroidism in cats, osteolytic bone lesions, normal bone growth.

PEARLS

• Healthy animals <1 year of age may normally have elevated serum phosphorus levels.

• Acute hypophosphatemia (e.g., during initial management of diabetic ketoacidosis) carries the risk of causing severe hemolytic anemia.

AUTHOR: DEBORAH G. DAVIS

Platelets

DEFINITION

• Thrombocytopenia: decreased platelet count

• Thrombocytosis: increased platelet count

• Thrombopathia: abnormal platelet function

TYPICAL NORMAL RANGE

• Dogs: 150,000-500,000/mcL

• Cats: 150,000-400,000/mcL

• 7-15 platelets per 100× field (blood film) associated with adequate platelet numbers

PHYSIOLOGY

Platelets form from megakaryocytes in bone marrow, spleen, and lung. Platelets are discoid, anucleate, 5- to 7-mcm cytoplasmic fragments important in primary hemostasis. They adhere to subendothelium by the binding of von Willebrand factor (vWF) to platelet glycoprotein Ib (GPIb). Aggregation occurs through binding of platelet membrane a^IIbβ³ with fibrinogen or vWF. Activated platelets release granule contents (fibrinogen, factor V, ADP, ATP, plasminogen), thromboxane A2, and arachidonic acid. Mediator release and reactions with leukocytes are important in inflammation and wound healing.

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Tags: Clinical Veterinary Advisor Dogs and Cats

Jul 24, 2016 | Posted by admin in SMALL ANIMAL | Comments Off

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