[05.02a] CMD - Calcium and Metabolic Bone Disorders Part 1 V2.pdf

99%

What percentage of the body's total calcium and phosphorus is stored in bone?

1%

What percentage of total body calcium is metabolically active and available for physiological processes like muscle contraction?

45%

What proportion of metabolically active plasma calcium is bound to plasma proteins, primarily albumin?

15%

What percentage of plasma calcium is complexed or bound to non-protein anions like phosphate and citrate?

40%

What percentage of serum calcium exists in the free or ionized state?

Corrected for albumin

When using serum total calcium to assess calcium status, what correction must always be made to accurately reflect physiologically active calcium?

21 days

What is the approximate half-life of albumin, making its serum levels relatively stable over three weeks?

Increased binding of calcium to albumin, causing a decrease in ionized calcium

How does an increase in serum pH (alkalosis) affect ionized calcium levels?

Acute respiratory alkalosis or hyperventilation syndrome

What acute acid-base disorder can lead to symptomatic hypocalcemia due to rapid increased binding of calcium to albumin?

Cramps, paresthesia, tetany, and seizures

What clinical symptoms can develop from acute hypocalcemia during severe hyperventilation or alkalosis?

Decreased binding of calcium to albumin, causing an increase in ionized calcium

How does a decrease in serum pH (acidosis) affect ionized calcium levels?

Elevation in ionized calcium concentration

Pathophysiologically, true hypercalcemia is fundamentally caused by an elevation in which form of serum calcium?

Corrected Ca = Measured total Ca +

0.8 x (4.0 - Albumin)

What is the mathematical equation used to correct serum total calcium for a low albumin level (< 4.0 g/dL)?

Corrected Ca = Measured total Ca +

0.8 x (Albumin - 4.0)

What is the mathematical equation used to correct serum total calcium for a high albumin level (> 4.0 g/dL)?

0.8 mg/dL

For every 1 g/dL shift in serum albumin above or below 4.0 g/dL, by how much does total serum calcium change in the same direction?

8.5 to 10.5 mg/dL

What is the standard normal reference range for total serum calcium in adults?

Parathyroid Hormone (PTH)

Which polypeptide hormone controls the minute-to-minute level of ionized calcium in the blood and extracellular fluid?

84 amino acids

How many amino acids make up the single-chain polypeptide hormone PTH?

Chief cells

Which specific cells of the parathyroid gland synthesize and secrete PTH?

4 minutes

What is the approximate biological half-life of intact PTH in circulation?

Concentration of ionized calcium in the blood

What is the primary physiological regulator of PTH synthesis and secretion?

Four

How many parathyroid glands are typically present in normal anatomy behind the thyroid gland?

2 to 17 glands

What is the reported range of parathyroid gland numbers that can be found in human anatomy due to developmental variations?

Neck to mediastinum

Along what anatomical spectrum can ectopic parathyroid glands be located due to embryological migration?

Calcium-sensing receptor (CaSR)

Which G-protein coupled cell surface receptor on chief cells senses extracellular ionized calcium concentration?

Inhibition of PTH secretion

What effect does high extracellular ionized calcium binding to the CaSR have on PTH secretion?

Release / secretion of PTH

What occurs to PTH secretion when extracellular calcium drops and does not occupy the CaSR?

Low serum calcium (hypocalcemia)

What is the main humoral stimulus for PTH secretion?

Stimulates bone resorption by osteoclasts

How does PTH act on bone to elevate serum calcium and phosphorus?

Stimulates calcium reabsorption in the renal tubules

How does PTH affect renal calcium handling to conserve calcium?

Activates renal 1-alpha-hydroxylase to produce calcitriol (active Vitamin D)

How does PTH indirectly promote calcium absorption in the small intestine?

Basic Multicellular Unit (BMU)

What anatomical team of osteoclasts and osteoblasts carries out the continuous process of bone remodeling?

Osteoclasts chew up / resorb bone; Osteoblasts build / form bone

What are the fundamental physiological roles of osteoclasts versus osteoblasts in bone remodeling?

Basic Multicellular Units tunnel through the tissue

How do basic multicellular units advance during bone remodeling within cortical bone?

Basic Multicellular Units move across the trabecular surface

How do basic multicellular units advance during bone remodeling within cancellous/trabecular bone?

Contraction of lining cells and recruitment/fusion of osteoclast precursors

What cellular events initiate the activation phase of bone remodeling?

Acidification and proteolytic digestion

By what biochemical mechanisms do active multinucleated osteoclasts dissolve bone matrix during resorption?

Secretion of osteoid matrix, which subsequently undergoes mineralization

How do osteoblasts form new bone following osteoclastic excavation?

Osteoid

What unmineralized organic matrix is secreted by osteoblasts during bone formation?

Lining cells

After osteoid mineralization is complete, what do flattened osteoblasts become on the surface of new bone?

Bone turnover

What term describes the overall rate of bone remodeling in the skeleton?

Fast / elevated bone turnover

What effect does a persistently high level of PTH have on the rate of bone turnover?

Fat-soluble vitamin (along with A, E, and K)

To what solubility class of vitamins does Vitamin D belong?

Dermal synthesis via sunlight / UV exposure

What is the major natural source of Vitamin D in humans, making dietary supplementation unnecessary under adequate conditions?

Melanin pigment protects against UV rays, reducing dermal Vitamin D synthesis

Why do individuals with darker skin pigmentation synthesize less Vitamin D for a given amount of sun exposure?

10 to 15 minutes of hands, arms, and face exposure 2-3 times per week between 10 AM and 2 PM

What recommended duration, frequency, and time window of sunlight exposure supports adequate Vitamin D synthesis?

Clothing, sunscreen, window glass, and air pollution

What environmental and lifestyle factors reduce dermal synthesis of Vitamin D from sunlight?

Liver

In which organ does the first enzymatic hydroxylation of Vitamin D take place?

CYP27A1 (sterol 27-hydroxylase)

Which liver microsomal enzyme converts Vitamin D into 25-hydroxyvitamin D

?

25-hydroxyvitamin D

25(OH)D

What is the major circulating, biologically inactive form of Vitamin D measured to assess body stores?

Kidney

In which organ does the second enzymatic hydroxylation occur to generate active Vitamin D?

CYP27B1 (25-hydroxyvitamin D-1-alpha-hydroxylase)

Which renal tubular enzyme converts 25(OH)D into active 1,25-dihydroxyvitamin D

?

1,25-dihydroxyvitamin D

1,25(OH)2D

or Calcitriol

What is the fully active hormone form of Vitamin D that regulates mineral ion homeostasis?

Major steroid hormone regulating mineral ion homeostasis

What endocrine classification best describes the active hormone calcitriol?

3 out of 5 Filipinos

According to 2013 data cited in the lecture, what proportion of Filipinos suffer from Vitamin D deficiency?

Ergocalciferol (D2) or Cholecalciferol (D3)

Which specific inactive precursor forms should be used for routine Vitamin D replacement in patients with intact PTH and functioning kidneys?

Calcium entry into circulation exceeds urinary excretion or bone deposition

What fundamental physiological imbalance leads to hypercalcemia?

Primary hyperparathyroidism and Malignancy

What are the two most common overall causes of hypercalcemia in outpatient and inpatient settings?

Asymptomatic

What is the most common clinical presentation of patients with mild or moderate hypercalcemia?

Moans, Groans, Stones, and Psychotic Overtones

What classic mnemonic summarizes the clinical manifestations of symptomatic hypercalcemia?

Bone and joint pain, bone weakening, and muscle weakness or aches

What specific musculoskeletal manifestations fall under 'Moans' in hypercalcemia?

Abdominal pain, nausea, vomiting, constipation, peptic ulcers, and pancreatitis

What specific gastrointestinal manifestations fall under 'Groans' in hypercalcemia?

Kidney stones (nephrolithiasis), polyuria/frequent urination, and chronic kidney disease

What specific renal manifestations fall under 'Stones' in hypercalcemia?

Fatigue, depression, irritability, impaired short-term memory, loss of concentration, and brain fog

What specific neurological and psychiatric manifestations fall under 'Psychotic Overtones' in hypercalcemia?

Hyperparathyroidism, Malignancy, Immobilization, Hyperthyroidism, and Cushing's syndrome

What underlying conditions cause hypercalcemia primarily through accelerated osteoclastic bone resorption?

Immobilization causes loss of mechanical load on bone, stopping calcium deposition while resorption continues

Why can stroke patients or immobilized individuals develop hypercalcemia?

Granulomatous diseases (Sarcoidosis, Tuberculosis) and Vitamin D intoxication

What conditions cause hypercalcemia primarily through excessive gastrointestinal calcium absorption?

Granulomas express extrarenal 1-alpha-hydroxylase, autonomously converting 25(OH)D to active calcitriol

How do granulomatous diseases like sarcoidosis and tuberculosis cause hypercalcemia?

Familial Hypocalciuric Hypercalcemia (FHH) and Thiazide diuretics

What two conditions cause hypercalcemia primarily through decreased renal excretion of calcium?

Parathyroid adenoma, Pituitary tumors, and Enteropancreatic tumors

What classic triad of endocrine tumors defines Multiple Endocrine Neoplasia type 1 (MEN 1)?

Medullary Thyroid Carcinoma, Pheochromocytoma, and Parathyroid Hyperplasia

What triad of endocrine diseases defines Multiple Endocrine Neoplasia type 2A (MEN 2A)?

Parathyroid Hormone-related Protein (PTHrP)

Which humoral factor secreted by solid tumors causes humoral hypercalcemia of malignancy by mimicking PTH?

Osteolytic bone metastases and local cytokine release

By what local skeletal mechanism do breast cancer and multiple myeloma cause hypercalcemia of malignancy?

Thiazide diuretics, Lithium, Teriparatide, excessive Vitamin A, and Theophylline toxicity

What medications are recognized causes of PTH-independent hypercalcemia?

Hyperthyroidism, Acromegaly, and Pheochromocytoma

What non-parathyroid endocrine disorders can present with PTH-independent hypercalcemia?

Milk-alkali syndrome

What syndrome of hypercalcemia, metabolic alkalosis, and renal insufficiency results from excessive intake of calcium and absorbable alkali?

Confirm elevated serum calcium on repeat measurement (corrected for albumin or ionized calcium)

What is the mandatory first step in evaluating a patient with suspected hypercalcemia?

Water is allowed during fasting to prevent dehydration from falsely elevating calcium and creatinine levels

What specific fasting fluid instruction must be given to patients prior to repeat calcium testing, and why?

Measure intact Parathyroid Hormone (PTH)

What primary laboratory test differentiates PTH-mediated hypercalcemia from non-PTH-mediated hypercalcemia?

PTH is mid-to-upper normal or minimally elevated (inappropriately normal)

What pattern of intact PTH is characteristic of Familial Hypocalciuric Hypercalcemia (FHH)?

24-hour urine calcium

What diagnostic test is required when FHH is suspected due to hypercalcemia with normal or minimally elevated PTH?

24-hour urine calcium < 100 mg / 24 hours (or urine calcium to creatinine ratio < 0.01)

What 24-hour urine calcium value confirms the diagnosis of FHH over primary hyperparathyroidism?

Primary Hyperparathyroidism

Which type of hyperparathyroidism is characterized by autonomous parathyroid hyperfunction resulting in elevated PTH and high serum calcium?

Parathyroid adenoma

What is the most common single lesion underlying primary hyperparathyroidism?

Secondary Hyperparathyroidism

Which type of hyperparathyroidism represents a compensatory physiological response to hypocalcemia, presenting with elevated PTH and low/normal calcium?

Tertiary Hyperparathyroidism

Which type of hyperparathyroidism results from prolonged secondary HPT leading to autonomous parathyroid hyperfunction and hypercalcemia?

Primary and Tertiary hyperparathyroidism

In which two types of hyperparathyroidism is serum calcium consistently elevated?

Secondary hyperparathyroidism

In which type of hyperparathyroidism is serum calcium characteristically low or low-normal?

Single benign parathyroid adenoma (~80% of cases)

What underlying tissue abnormality accounts for approximately 80% of primary hyperparathyroidism cases?

Multiple gland hyperplasia or multiple adenomas (15-20% of cases)

What tissue abnormality accounts for 15-20% of primary hyperparathyroidism cases?

Asymptomatic hypercalcemia discovered incidentally on routine biochemical screening

What is the most common clinical presentation of primary hyperparathyroidism today?

Symptomatic phenotype (1930s-1970s)

Which historic phenotype of primary hyperparathyroidism presented with overt skeletal lesions, severe kidney stones, and proximal muscle weakness?

Asymptomatic phenotype (1970s-present)

Which phenotype of primary hyperparathyroidism emerged with widespread automated blood chemistry screening?

Normocalcemic primary hyperparathyroidism

Which phenotype presents with persistently elevated PTH but consistently normal serum calcium levels?