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Questions and Answers
In most species, how many pairs of parathyroid glands are typically present?
In most species, how many pairs of parathyroid glands are typically present?
- Two pairs (correct)
- One pair
- Four pairs
- Three pairs
Which of the following chemical types best describes parathyroid hormone (PTH)?
Which of the following chemical types best describes parathyroid hormone (PTH)?
- Fatty acid derivative
- Steroid hormone
- Protein/peptide hormone (correct)
- Amine hormone
What are the primary cell types found within the parathyroid gland?
What are the primary cell types found within the parathyroid gland?
- Follicular and parafollicular cells
- Basophils and acidophils
- Chief and oxyphil cells (correct)
- Alpha and beta cells
What stimulates the release of parathyroid hormone (PTH)?
What stimulates the release of parathyroid hormone (PTH)?
What is the primary effect of parathyroid hormone (PTH) on phosphate levels in the blood?
What is the primary effect of parathyroid hormone (PTH) on phosphate levels in the blood?
What is the effect of increased plasma phosphate concentration on ionized calcium?
What is the effect of increased plasma phosphate concentration on ionized calcium?
Which three organs are primarily involved in the regulation of calcium levels?
Which three organs are primarily involved in the regulation of calcium levels?
What is the role of osteocytes in response to PTH?
What is the role of osteocytes in response to PTH?
In the kidneys, what effect does parathyroid hormone (PTH) have on phosphate reabsorption?
In the kidneys, what effect does parathyroid hormone (PTH) have on phosphate reabsorption?
Which enzyme does parathyroid hormone (PTH) stimulate in the kidneys to activate Vitamin D?
Which enzyme does parathyroid hormone (PTH) stimulate in the kidneys to activate Vitamin D?
What is the function of calcitonin?
What is the function of calcitonin?
What stimulates the release of calcitonin?
What stimulates the release of calcitonin?
Which cells produce calcitonin?
Which cells produce calcitonin?
What is the primary effect of calcitonin on phosphate?
What is the primary effect of calcitonin on phosphate?
Which of the following is a typical finding in primary hyperparathyroidism?
Which of the following is a typical finding in primary hyperparathyroidism?
Which of the following most accurately describes the synthesis pathway of PTH?
Which of the following most accurately describes the synthesis pathway of PTH?
What is the primary mechanism by which PTH increases serum calcium levels?
What is the primary mechanism by which PTH increases serum calcium levels?
What is the significance of ionized calcium (iCa) in the blood?
What is the significance of ionized calcium (iCa) in the blood?
What is the effect of PTH on osteoblasts?
What is the effect of PTH on osteoblasts?
Which of the following best describes the condition known as nutritional secondary hyperparathyroidism (NSHP)?
Which of the following best describes the condition known as nutritional secondary hyperparathyroidism (NSHP)?
In hindgut fermenters, how intestinal calcium absorption regulated differently than in other animals?
In hindgut fermenters, how intestinal calcium absorption regulated differently than in other animals?
What is the expected urinalysis result of a hindgut fermenter (such as a horse) that is regulating blood Calcium with their urinary loss system?
What is the expected urinalysis result of a hindgut fermenter (such as a horse) that is regulating blood Calcium with their urinary loss system?
Why is it important to consider calcium homeostasis when internal parasites are suspected as the cause of a prolapse in reptiles?
Why is it important to consider calcium homeostasis when internal parasites are suspected as the cause of a prolapse in reptiles?
Prolonged deficiency of calcium or vitamin D3 is implicated in nutritional secondary hyperparathyroidism due to
Prolonged deficiency of calcium or vitamin D3 is implicated in nutritional secondary hyperparathyroidism due to
Which of the following is a key difference between the actions of calcitonin and parathyroid hormone (PTH)?
Which of the following is a key difference between the actions of calcitonin and parathyroid hormone (PTH)?
For a dog with hypoparathyroidism, which clinical sign would be the most unexpected?
For a dog with hypoparathyroidism, which clinical sign would be the most unexpected?
Which of the following statements best describes the role of G-protein coupled receptors in PTH synthesis?
Which of the following statements best describes the role of G-protein coupled receptors in PTH synthesis?
What is the underlying cause of the cardiac arrhythmias (bradycardia) that can be caused by hypercalcemia during hyperparathyroidism?
What is the underlying cause of the cardiac arrhythmias (bradycardia) that can be caused by hypercalcemia during hyperparathyroidism?
Why might a patient with advanced kidney disease experience secondary hyperparathyroidism?
Why might a patient with advanced kidney disease experience secondary hyperparathyroidism?
Which statement describes an appropriate action to maintain calcium/phosphate homeostasis?
Which statement describes an appropriate action to maintain calcium/phosphate homeostasis?
After secretion of PTH, what is its half-life?
After secretion of PTH, what is its half-life?
Which of the following is a symptom of hypoparathyroidism?
Which of the following is a symptom of hypoparathyroidism?
Which of the following is NOT a typical symptom of primary hyperparathyroidism?
Which of the following is NOT a typical symptom of primary hyperparathyroidism?
What is the role of phosphate in the body?
What is the role of phosphate in the body?
What is the percentage of calcium found in the bone?
What is the percentage of calcium found in the bone?
What causes Nutritional Secondary hyperparathyroidism?
What causes Nutritional Secondary hyperparathyroidism?
What are the predisposing factors in Nutritional Secondary hyperparathyroidism?
What are the predisposing factors in Nutritional Secondary hyperparathyroidism?
In a patient with hypoparathyroidism, which of the following would be seen during diagnosis? Choose the BEST answer
In a patient with hypoparathyroidism, which of the following would be seen during diagnosis? Choose the BEST answer
Which factor would cause Gl hormones to stimulate secretion of calcitonin?
Which factor would cause Gl hormones to stimulate secretion of calcitonin?
Which factor is important to know when thinking about the calcium to phosphate ratio in blood?
Which factor is important to know when thinking about the calcium to phosphate ratio in blood?
Which statement about the parathyroid gland is FALSE?
Which statement about the parathyroid gland is FALSE?
When blood calcium decreases, which of the following does not occur?
When blood calcium decreases, which of the following does not occur?
In a scenario where a patient is experiencing increased blood calcium, and a parathyroidectomy is performed, what would be MOST important to monitor immediately post-op?
In a scenario where a patient is experiencing increased blood calcium, and a parathyroidectomy is performed, what would be MOST important to monitor immediately post-op?
Flashcards
Parathyroid Glands
Parathyroid Glands
Glands located near the thyroid that produce parathyroid hormone (PTH).
Parathyroid Anatomy
Parathyroid Anatomy
Most species have two pairs of parathyroid glands, but pigs and rats typically have only one pair. The location varies among species.
Parathyroid Cell Types
Parathyroid Cell Types
The two types of parathyroid cells, responsible for hormone production and cellular function, within the glandular tissue.
PTH Secretion
PTH Secretion
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Parathyroid Function
Parathyroid Function
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Calcium's Roles
Calcium's Roles
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Ionized Calcium (iCa)
Ionized Calcium (iCa)
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Calcium Regulation
Calcium Regulation
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PTH Actions
PTH Actions
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Osteoblasts
Osteoblasts
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Osteocytes
Osteocytes
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PTH on Bone Cells
PTH on Bone Cells
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PTH and Osteoclasts
PTH and Osteoclasts
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PTH on Kidneys
PTH on Kidneys
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PTH and Phosphate
PTH and Phosphate
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PTH and Vitamin D
PTH and Vitamin D
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PTH on Kidneys
PTH on Kidneys
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Calcitriol Function
Calcitriol Function
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PTH Control
PTH Control
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Calcitonin
Calcitonin
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Calcitonin Release
Calcitonin Release
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Calcitonin Actions
Calcitonin Actions
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Calcitonin Effects
Calcitonin Effects
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Calcitonin Regulation
Calcitonin Regulation
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Hyperparathyroidism
Hyperparathyroidism
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Hyperparathyroidism Symptoms
Hyperparathyroidism Symptoms
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Nutritional Hyperparathyroidism
Nutritional Hyperparathyroidism
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NSHP Factors
NSHP Factors
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Hypoparathyroidism
Hypoparathyroidism
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Hypoparathyroidism Symptoms
Hypoparathyroidism Symptoms
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Study Notes
Learning Objectives
- Locate the parathyroid glands and describe their macro and microanatomy
- Understand the relevance of calcium and phosphate to maintain body homeostasis
- Understand the synthesis, regulation, and transport of PTH
- Describe the effects of parathyroid hormones on target tissues/organs
- Understand the role of PTH on calcitriol activation and its importance on calcium metabolism
- Understand the relationship between PTH and calcitonin and their effects on calcium and phosphate homeostasis
- Understand the symptoms of the main pathologies related to parathyroid hormones, including hyperparathyroidism/secondary nutritional hyperparathyroidism, and hypoparathyroidism
Terminology and Abbreviations
- AMP stands for Adenosine Monophosphate
- ATP stands for Adenosine Triphosphate.
- ECF refers to extra cellular fluid
- GI refers to gastrointestinal
- iCa is Ionized calcium
- PTH stands for parathyroid hormone
Parathyroid Gland - Anatomy
- Most species have two pairs of parathyroid glands
- Pigs and rats have only one pair of parathyroid glands
- The location of parathyroid glands varies between species
- Parathyroid glands are usually at the poles of the two lobes of the thyroid glands
Chemical Structure of Hormones: Protein and Peptide Hormones
- Protein and peptide hormones comprise the majority of hormones
- Examples of protein and peptide hormones include insulin, ACTH, PTH, CCK, LH, FSH, and TSH
- Protein and peptide hormones are synthesized as inactive molecules in the ER, known as pre-prohormones
- They are cleaved in the Golgi apparatus to form prohormones
- The hormones are packaged into secretory granules awaiting secretion
Parathyroid Gland Cell Types
- There are two types of parathyroid cells in the glandular tissue: chief cells and oxyphil cells
- Chief cells produce PTH (Parathormone or Parathyroid hormone)
- The function of oxyphil cells is unknown; these cells are larger than chief cells and possess oxidative and hydrolytic enzyme activity
PTH Synthesis
- Parathyroid cells are very sensitive to a decline in blood ionized calcium [iCa]
- Calcium-sensing receptors on the gland membrane surface are involved in PTH synthesis
- G-Protein coupled receptors (cAMP-PKA-gene transcription)
- A decrease in blood [iCa] (hypocalcemia) stimulates PTH release
- Normal or increased [iCa] in blood (hypercalcemia) inhibits PTH release
- Prepro-PTH is synthesized in rER and then cleaved to pro-PTH
- The "pro" portion is removed in the Golgi apparatus, and the resulting PTH is secreted by exocytosis
- PTH is metabolized by the liver and the kidneys with a half-life of 5-10 minutes
Parathyroid Gland – Calcium and Phosphate
- The main gland involved in the Calcium (Ca2+) & Phosphate (PO4) homeostasis
- Calcium and phosphate ions play a major role in physiological homeostasis
- Phosphate (PO4) acts as a buffer system
- Phosphate is a composition of the cell membrane and intracellular components, nucleic acid, Adenosine Triphosphate (ATP), and Adenosine Monophosphate (AMP)
- 85% of phosphate is found in bones, 14% intracellularly, and 1% in ECF
- Calcium is required for muscle contraction and nerve cell activity
- Calcium facilitates the release of hormones by exocytosis and enables the activation of several enzymes
- Calcium is involved in blood coagulation
- Calcium ensures the maintenance of membrane stability
- Calcium provides structural integrity to bones and teeth
- 99% of calcium is found in bones, less than 1% intracellularly, and 0.1% in ECF
Pool of Calcium
- 99% of calcium is found in bones in the form of hydroxyapatite crystals, which contain calcium, phosphate, and water
- Less than 1% of calcium is intracellular and bound to proteins within the ER or mitochondria, and increased intracellular calcium concentrations indicate increased cell activity
- 0.1% of calcium is found in ECF, which is the interstitial fluid and blood
- 50% of calcium is ionized (iCa), which is biologically active and precisely regulated
- 40% of calcium is bound to proteins, mainly albumin
- 10% of calcium is combined with other anions
- iCa is the most important pool for physiological control of calcium concentrations in the blood
Calcium: Phosphate Ratio
- High levels of plasma phosphate concentration means a rise in the fraction of Ca2+ that is complexed (bound) increases which decreases the ionized Ca2+ concentration
- If the plasma phosphate concentration decreases -> the complexed Ca2+ decreases ionized Ca2+ increases
- Maintaining the blood Ca:P ratio is essential for homeostasis
Calcium-Phosphate Metabolism
- Calcium level regulation involves controlling the movement of calcium between the extracellular fluid (ECF) and three organs:
- Bones
- Kidneys
- GI tract
- Three hormones are involved in this process:
- PTH (parathyroid hormone)
- Active Vitamin D (Calcitriol – steroid-like molecule)
- Calcitonin (thyroid hormone – parafollicular cells/C-cells)
PTH Actions
- The net effect of PTH is to increase calcium and decrease phosphate concentrations in ECFs
- PTH has a direct effect on bone and kidney metabolism of calcium
- PTH has an indirect effect on GI metabolism of calcium (absorption)
- This indirect effect is conducted via calcitriol
Bones
- Osteoblasts are responsible for the formation of new bone tissue, which entails bone developing and remodeling
- Osteocytes enable biomineralization (local mineral deposition at the bone matrix) and are differentiated from osteoblasts (mesenchymal stem cells)
- Osteoclasts degrade bone tissue and are differentiated from monocytes (hematopoietic stem cells)
PTH Actions – Two Direct Effects on Bone
- PTH promotes the transfer of iCa across the osteoblast-osteocyte membrane
- Osteocytes pump iCa from the fluids within bone canaliculi into the extracellular fluid, then into the blood
- PTH binds to receptors on bone osteoblast cells and stimulates the production of osteoclast-activating factor
- PTH causes activation of nearby osteoclasts
- PTH moves toward the bone and begins to digest the organic matrix, resulting in bone resorption
- PTH releases iCa and PO43- into the blood
PTH Actions - Direct Effects on Kidneys
- PTH acts on the distal convoluted tubules, increasing reabsorption of calcium
- PTH acts on the proximal convoluted tubules, decreasing renal reabsorption of phosphate
- PTH acts on Vitamin D activation by the kidneys
- Vitamin D must be transformed by the liver and kidneys to become biologically activated
- PTH stimulates the kidney enzyme 1-alfa-hydroxylase, which converts calcidiol 25(OH)D to calcitriol 1,25(OH)2D
- Vitamin D becomes an active hormone under PTH action on renal cells
- Calcitriol increases absorption of calcium by the GI tract and enhances the effects of PTH on bone metabolism of calcium
Vitamin D Metabolism
- In the presence of UV light, Vitamin D3 (Cholecalciferol) is made in the skin
- Vitamin D3 can be found in oily fish, egg yolks, and fortified food
- Vitamin D2 (Ergocalciferol) is found in fortified foods, salmon, mushrooms, and egg yolks
- The liver converts Vitamin D3 and D2 to 25-hydroxyvitamin D (Calcidiol)
- The kidney converts 25-hydroxyvitamin D to 1,25 dihydroxyvitamin D (Calcitriol) via 1-alfa-hydroxylase
- The product is the biologically active form.
- Due to its lipid nature, calcitriol is carried in plasma by transcalciferin, which is produced in the liver
PTH Actions - Indirect Effect on GI
- Calcitriol stimulates the active transport of dietary calcium across the intestinal epithelium
- Without calcitriol, most animals cannot acquire enough calcium from their diet to support normal bone structure
- An animal can regulate iCa entering the blood from its diet by regulating calcitriol
- However, hindgut fermenters (horses and rabbits) are exceptions to this rule
- These animals have intestinal mechanisms to absorb calcium all the time
- Furthermore, they regulate blood Ca2+ by increasing/decreasing urinary loss
- These animals can present chalky white-colored urine
PTH Regulation
- PTH secretion is mainly controlled by free (ionized) calcium concentration in the blood
- A decrease in [iCa] stimulates PTH secretion
- An increase in [iCa] inhibits PTH secretion
Calcitonin
- Calcitonin is produced by parafollicular cells or C-cells in the thyroid gland
- These cells are scattered throughout the body of the thyroid gland, among the follicles
- Calcitonin is synthesized as a protein hormone
- An increase in blood [iCa] stimulates calcitonin release
- Calcitonin counterbalances the effects of PTH
Calcitonin Actions
- Calcitonin reduces the movement of calcium from the bone to the ECF
- It moves against the bone calcium pool (decreasing the action of osteocytes behind the osteoblast-osteocyte barrier)
- Calcitonin decreases bone resorption through a direct inhibitory effect on osteoclasts
- Calcitonin increases movement of phosphate from ECF into bone
- Calcitonin increases renal excretion of calcium and phosphate
Calcitonin Regulation
- Calcitonin secretion is regulated by calcium concentration in the blood
- Increased [iCa] stimulates calcitonin secretion
- GI hormones also stimulate the secretion of calcitonin
Calcium Metabolism
- PTH increases reabsorption in the kidneys, increases absorption in the GI tract, and increases mobilization from the bones
- Calcitonin increases excretion in the kidneys and the storage from the bones
Hyperparathyroidism
- Primary Hyperparathyroidism entails excessive synthesis and secretion of parathyroid hormone (PTH) by abnormal chief cells of the parathyroid gland, or parathyroid adenoma
- It leads to persistent hypercalcemia, which means negative feedback control is lost, then secretion of PTH is not suppressed by high calcium levels
- Symptoms related to hypercalcemia mainly affect the kidneys, GI tract, and neuromuscular system
- These symptoms can include Polydipsia and Polyuria, which decreases the ability of the kidneys to respond to antidiuretic hormone (ADH)
- Calciuria can result in urolithiasis and secondary urinary tract infection (UTI)
- Hyperparathyroidism depresses the excitability of the central and peripheral nervous systems, decreases GI smooth muscle excitability, and decreases cell membrane permeability of muscles
- Cardiac arrhythmias (bradycardia) can be caused by hypercalcemia
- A diagnosis can be determined via urinalysis (crystalluria – calcium crystals) and serum biochemistry, which will indicate both total and ionized calcium levels are elevated
- Secondary hyperparathyroidism in horses (Nutritional secondary hyperparathyroidism (NSH), also known big-head disease), is caused by excessive mobilization of calcium from the skeleton under the influence of parathyroid hormone
- The condition occurs due to:
- a dietary calcium deficiency
- excess levels of phosphorus
- an inverted calcium-to-phosphorus ratio in the total diet
- high levels of oxalates in forages, which interfere with digestion and absorption of calcium
- Nutritional metabolic bone disease in reptiles and amphibians (NMBD) includes: Nutritional secondary hyperparathyroidism (NSHP)
- NSHP predisposing factors:
- low dietary calcium and vitamin D3
- inverted Ca:P ratio
- lack of UV-B light exposure
- inappropriate temperature gradient
- This can be caused by unappropriated diet and excessive production of parathyroid hormone (PTH) from the parathyroid gland in response to hypocalcemia
- Secondary hyperparathyroidism also occurs because of dietary and/or husbandry mismanagement, with the most implicated factors being prolonged deficiency of dietary calcium or vitamin D3, imbalance of the calcium-phosphorus ratio in the diet (usually an excess of phosphorus), and inadequate exposure to ultraviolet (UVB) radiation in diurnal animals
Hypoparathyroidism
- Hypoparathyroidism is an absolute or relative deficiency of parathyroid hormone (PTH)
- It can be idiopathic, which is most common, and caused by autoimmune destruction of the parathyroid or other causes, like trauma, agenesis, or surgical destruction of PT gland
- Inappropriately low levels of PTH classically result in hypocalcemia, decreased calcitriol, and hyperphosphatemia
- Symptoms may range from mild to severe, and are related to calcium deficiency, including muscle weakness, cramps, seizures, neuromuscular and neurologic signs, hypotension, decreased heart contractility, and skeletal deformities
- Diagnosis occurs via serum biochemistry: low total and ionized calcium, undetectable PTH concentrations, and hyperphosphatemia is common
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