Endocrine System: Calcium, Phosphorus, Parathyroid Flashcards
What are the major functions of calcium?
- formation of bone and teeth
- enzyme co-factor (coagulation cascade)
- signal transduction
- neurotransmitter release
- muscle contraction
What are the major functions of phosphorus? What controls its renal excretion?
- generates ATP
- component of DNA, enzymes, and hormones
- buffers to maintain blood pH
- part of the bone matrix
PTH —> promotes loss in urine
Where is magnesium found? What functions does it have?
intracellular cation
- cofactor in many enzymatic reactions creating ATP
- required for protein and nucleic acid synthesis
- nerve conduction
What regulates magnesium concentrations? How is its concentration in serum balanced?
intestinal absorption and renal excretion influenced by PTH and vitamin D
dietary intake and excretion
- most lost in feces
- ingestion of milk
What receptors regulate calcium concentrations? How?
calcium-sensing receptors (CaSR) regulate the response of parathyroid chief cells, C-cells of the thyroid, and renal epithelial cells
stimulation due to increased calcium decreases NaCl, calcium, and magnesium reabsorption in the PT of the kidneys
What ion is necessary for calcium-sensing receptors (CaSR) function? What happens when this ion is deficient?
magnesium
hypomagnesemia = decreased PTH secretion
What 3 hormones are responsible for regulating calcium and phosphorus homeostasis? Organs?
- parathyroid hormone - increases Ca, decreases P
- vitamin D, calcidiol, calcitriol - increases Ca, increases P
- calcitonin - decreases Ca
intestine (absorption), kidney (reabsorption), bone (storage, resorption)
How should calcium and phosphorus levels be interpreted on biochemistry?
TOGETHER - controlled by the same hormones and concentrations affect each other
What produces parathyroid hormone? What 2 functions does it have?
chief cells
- increases plasma iCa for minute-to-minute regulation
- decrease plasma P
When is PTH secretion stimulated? Inhibited?
low plasma calcium concentrations
low plasma phosphorus
How does PTH affect calcium and phosphorus concentration?
increases serum calcium by stimulating calcium resorption from bone, reabsorption from kidney, and calcium absorption from the intestine, and forming active vitamin D in the kindey
decreases phosphorus resorption by the kidney by increasing secretion in the urine
What produces calcitonin? What 4 net effects does it have?
parafollicular (C) cells in the thyroid (in response to hypercalcemia)
- decreases serum calcium
- decreases bone resorption (inhibits osteoclasts)
- decreases calcium absorption in the GIT
- decreases calcium reabsorption in the kidneys
What effect does calcitonin have on phosphorus?
increased excretion by the kidneys
What is the metabolically active form of vitamin D? What 2 net effects does it have?
1,25-dihydroxycholecalciferol
increased serum calcium* and phosphorus:
- increased absorption in the GIT
- facilitates PTH on bone, causing resorption
In what 3 ways is calcium found in plasma?
- 50-55% ionized (active)
- 35-45% protein bound - 80% to albumin
- 5-10% complexes with other ions, like bicarb, lactate, citrate, and phosphate
In what 2 ways is plasma calcium measured?
- total calcium on the biochem panel - ionized, protein-bound, complexed
- ionized calcium - specialty calcium panels and point-of-care instruments
How does albumin concentration affect calcium?
hypoalbuminemia = apparent hypocalcemia
(calcium is transported mostly by albumin)
What is the active form of calcium? How is its concentration within tCa affected by pH?
iCa
- ACIDOSIS = increased iCa due to release from albumin
- ALKALOSIS = decreased iCa due to increased binding
What are the main 2 ways iCa is measured? What machines do this?
- serum
- heparinized plasma
- ion-sensitive electrodes (direct potentiometry)
- blood gas analyzers
- point-of-care analyzers
How can true hypocalcemia and apparent hypocalcemia be differentiated?
apparent = hypoalbuminemia
- iCa remains within RI = hypoalnuminemic hypocalcemia
- iCa under RI = true hypocalcemia
What are the main DDx for hypercalcemia?
DRAGON SHIT
- vitamin D toxicity
- Renal failure
- Addison’s disease
- Granulomatous disease
- Osteolytic lesions
- Neoplasia
- Spurious
- Hyperparathyroidism
- Idiopathic (cats)
- Toxins
What are 10 clinical signs of hypercalcemia?
- shivering
- lethargy
- depression
- inappetence
- muscle weakness
- constipation
- bradycardia
- arrhythmias
- PU/PD
- vomiting/diarrhea
What are the main causes of hyperparathyroidism? How does it affect calcium and phosphorus levels?
- functional (PTH-secreting) parathyroid adenomas
- hyperplasia
increased PTH = increased tCa, increased iCa, and decreased phosphorus
What is Addison’s disease? How does it affect calcium levels?
hypoadrenocorticism —> hypercalcemia in about 30% of Addisonian dogs
(unknown mechanism)
In what animals does renal disease most commonly affect calcium levels?
horses —> hypercalcemia
What are 4 causes of vitamin D toxicity? What 2 effects does it have on calcium and phosphorus levels?
- cholecalciferol-containing rodenticides
- excessive supplementation
- vitamin D glycoside-containing plants
- vitamin D-containing creams or medications
- decreased PTH = increased tCa, iCa, and P
- increased PTHrp = normal to decreased PTH, increased tCa and iCa, normal to decreased P (neoplastic)
How does granulomatous disease cause hypercalcemia?
macrophages produce a vitamin D-like molecule during active inflammation
What is the most common cause of hypercalcemia in dogs? How does this work?
neoplasia —> hypercalcemia of malignancy
tumors often produce parathyroid hormone-related peptide (PTHrp):
- lymphoma
- apocrine gland adenocarcinoma of the anal sac
- multiple myeloma
How does humoral hypercalcemia of malignancy affect biochemistry results?
- PTHrp increased
- PTH decreased
- P decreased (may be increased with renal damage)
rule out NEOPLASIA in any animal with HYPERCALCEMIA
How are iCa, P, PTH, PTHrp levels affected by primary hyperparathyroidism, hypercalcemia of malignancy, and renal hyperparathyroidism?
What are 7 causes of hypocalcemia?
- hypoalbuminemia (decreased tCa, normal iCa)
- chronic renal failure
- critical illness and sepsis
- alkalosis
- grass/hypomagnesemic tetany
- milk fever (parturient paresis) in cattle
- intestinal malabsorption
How does primary hypoparathyroidism affect calcium levels?
decreased PTH = decreased tCa and iCa, and increased P
What are the 2 types of secondary hyperparathyroidism?
- NUTRITIONAL = diets with decreased Ca/vitamin D = increased PTH
- RENAL = decreased calcitriol production = decreased iCa and increased P = increased PTH
How does acute pancreatitis cause hypocalcemia?
saponification of fat and formation of calcium soaps
What 2 toxins cause hypocalcemia?
- blister beetle (cantharidin) - horses
- ethylene glycol
What are 6 signs of hypocalcemia?
- muscle tremors
- convulsions/seizures
- ataxia
- flaccid paralysis
- weakness
- tetany
What is the top cause of hyperphosphatemia? What is it also secondary to?
azotemia/decreased GFR
disturbances in calcium metabolism: primary hypoparathyroidism (low PTH), vitamin D toxicity
What are 5 additional causes of hyperphosphatemia?
- bone growth in young animals
- osteolysis
- in vitro hemolysis (artifact)
- muscle damage
- tumor lysis syndrome
How does tumor lysis affect biochemistry results?
- increased P
- increased K
- decreased Ca
What is the major cause of hypophosphatemia?
disorder of calcium metabolism
- primary hyperparathyroidism
- hypercalcemia of malignancy
What are 5 additional causes of hypophosphatemia?
- decreased GI absorption due to deficiencies, vomiting, diarrhea, or malabsorption
- milk fever and eclampsia
- equine renal failure
- insulin administration/excess causes P to shift from ECF to ICF
- EDTA
What are 4 clinical signs of hypophosphatemia?
- ileus of GIT
- cardiomyopathy
- metabolic acidosis due to impaired bicarb absorption and calciuria
- seizures, coma, ataxia
What are 2 causes of hypermagnesemia?
- renal failure - any reason for azotemia
- administration of antacids or magnesium cathartics to renal failure patients
In what animals is hypomagnesemia most common? What causes this? What happens if this occurs with hypocalcemia?
ruminants
inadequate magnesium intake (grass tetany)
hypocalcemia may be refractory to treatment until hypomagnesemia is corrected
What are 5 additional causes of hypomagnesemia?
- hypoparathyroidism
- DM
- lactation tetany
- PLE
- critical illness or sepsis
What are the 2 major diseases tested on chemistry panels and endocrine testing?
- primary hyperparathyroidism —> increased PTH = increased Ca and decreased P
- hypoparathyroidism —> decreased PTH = decreased Ca and increased P
(chemistry = tCa, iCa, P; endocrine testine = PTH)
What is the most common cause of hyperparathyroidism in dogs and cats? What are 4 diagnostic characteristics?
unilateral parathyroid adenoma that produces excessive PTH
- persistent hypercalcemia (tCa AND iCa)
- decreased phosphorus
- normal to subtle increase in PTH
- undetectable PTHrp
What are 4 clinical signs of hyperparathyroidism? How can a physical exam aid in diagnosis?
(due to hypercalcemia)
- PU/PD secondary to nephrogenic DI = poorly concentrated urine
- dysuria, urolithiasis
- GI = vomiting, diarrhea
- muscle weakness and lethargy
parathyroid enlargement upon palpation and US
What 2 lesions cause hypoparathyroidism?
- lymphocytic plasmacytic destruction of parathyroid tissue progresses to fibrosis, decreasing the amount of parathyroid cells
- iatrogenic - surgical removal
What are the 3 diagnostic features of hypoparathyroidism? What can appear in severe cases?
- persistent hypocalcemia (tCa AND iCa)
- mildly decreased P
- normal to subtle decreased PTH
hyperglycemia due to inability to produce insulin
What signalment commonly presents with hypoparathyroidism? What are 5 possible clinical signs?
young to middle-aged, FS dogs (sometimes cats)
due to hypocalcemia:
- panting
- tremors/shaking
- agitation
- facial rubbing
- seizures
CASE: 13 y/o FS cross-breed dog presented due to chronic lethargy. PE revealed a patient in lateral recumbency, mild tachycardia, and presence of a perianal mass.
- DDx for hypercalcemia?
- Based on history and biochem, what is the cause of hypercalcemia?
- Why is PTH decreased?
- Why is there hypophosphatemia?
- What further tests are required?
DRAGON SHIT - Addison’s, neoplasia, hyperparathyroidism
perianal mass with hypercalcemia and increased PTHrp = paraneoplastic hypercalcemia
PTHrp is produced by neoplastic cells, which induces hypercalcemia leading to a suppression to PTH secretion
hypercalcemia of malignancy depressed P retention
FNA of perianal mass
CASE: 6 y/o MN Labrador Retriever presented due to a change in temperament in the last few months and constipation in the last few days.
- How would the initial high calcium be explained?
- What additional tests would you do?
increased mobilization from bone or absorption in intestine (primary hyperparathyroidism), increased vitamin D (hypervitaminosis D), decreased urinary excretion (renal failure), idiopathic
PTH to identify primary hyperparathyroidism, frequently caused by adenomas that increase PTH secretion
PTHrp to exclude hypercalcemia of malignancy, although there is no evidence of neoplasia in history
CASE: 6 y/o MN Labrador Retriever presented due to a change in temperament in the last few months and constipation in the last few days. Increased calcium was initially seen on biochem, then is decreased below RI. ADDITIONALLY: small mass was found on ventral neck during US examination. Sx excised parathyroid.
- What is your suspicion?
- How would the reduced calcium after a few days be explained?
high Ca, low P, high PTH indicative of primary hyperparathyroidism
dog developed hypocalcemia after Sx to remove the adenoma —> parathyroid adenomas commonly suppress the other gland
- Ca was stabilized after infusions of calcium gluconate, high calcium diets, and vitamin D
CASE: 9 y/o intact male dog. History of one seizure and occasional tremors. Physical exams showed physical abnormalities and patient underwent a seizure during the exam.
Analyze hematology results. What is this presentation typical for?
- mature neutrophilia
- lymphopenia
- monocytosis
STRESS LEUKOGRAM
CASE: 9 y/o intact male dog. History of one seizure and occasional tremors. Physical exams showed physical abnormalities and patient underwent a seizure during the exam.
Analyze biochemical panel results. What is likely the cause?
- increased serum glucose concentration is typical for glucocorticoid-induced hyperglycemia —> likely due to stress, especially in light of the leukogram
- decreased serum creatinine concentration is not important in most case (may result from diuresis)
- hypocalcemia and hyperphosphatemia: renal failure, pancreatitis, azotemia, excessive phosphorus diet, hypoparathyroidism
- norma BUN and decreased creatinine indicates normal renal function
- clinical signs not typical of pancreatitis, no evidence of prerenal azotemia, unknown diet —> hypoparathyroidism
CASE: 9 y/o intact male dog. History of one seizure and occasional tremors. Physical exams showed physical abnormalities and patient underwent a seizure during the exam. Suspected hypoparathyroidism.
What could explain the normal PTH concentration?
other causes of hypocalcemia
- hypoalbuminemia
- renal failure
- pancreatitis with prerenal azotemia
- diet high in phosphorus
