Hypocalcemia

Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Patients can exhibit symptoms from neuromuscular irritability (tetany, Chvostek sign, Trousseau sign) to cardiovascular dysfunction (arrhythmia). Confirmation of hypocalcemia is required with correction of the value depending on albumin level or ionized calcium (the metabolically active form), followed by PTH level, and determination of the underlying cause. Correction of calcium is dictated by the degree of severity of hypocalcemia. In severe cases, IV calcium administration is required. Treatment of the underlying cause is recommended.

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Calcium Homeostasis

Calcium

Calcium is the most abundant mineral in the human body; 99% is found in bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones. Calcium in the blood exists in 3 forms:

  • 15% is bound to small anions (citrate, phosphate).
  • 45% is protein-bound calcium (mostly with albumin).
  • 40% is ionized or free calcium (metabolically active or able to be transported into cells).

Levels:

  • Normal serum total calcium: 8.5–10.5 mg/dL (2.12–2.62 mmol/L)
  • Normal ionized calcium: 4.65–5.25 mg/dL (1.16–1.31 mmol/L)

Importance of calcium:

  • Bone mineralization
  • Cofactor of enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
  • Cardiac and nerve function
  • Muscle contraction
  • Regulation of clotting mechanisms
  • Effective intracellular messenger for a variety of substances (e.g., insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin)

Calcium regulation

Bone, intestine, and kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys are involved in homeostasis.

Key elements of calcium regulation:

  • Parathyroid hormone (PTH) (from parathyroid glands Parathyroid glands The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands):
    • ↑ Vitamin D production in the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys, ↑ reabsorption of calcium in distal tubule
    • ↑ Calcium absorption in the intestines
    • ↑ Bone resorption (release of calcium and phosphate from the bones)
  • Vitamin D:
    • With sunlight exposure, 7-dehydrocholesterol is converted into cholecalciferol (vitamin D3) in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin
    • Vitamin D3 is converted into 25-hydroxyvitamin D (calcidiol) in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
    • Calcidiol goes to the kidney and is converted into 1,25-dihydroxyvitamin D (calcitriol), which is the active form.
    • Effects:
      • Activation of osteoclasts to release calcium and phosphorus
      • Intestinal calcium and phosphate absorption
  • pH: 
    • ↑ pH (alkalosis) will ↑ the binding of calcium to albumin = ↓ ionized calcium
    • ↓ pH (acidosis) will ↓ the binding of calcium to albumin = ↑ ionized calcium
  • Albumin:
    • ↓ Serum protein/albumin (i.e., nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome) = ↓ serum calcium (pseudohypocalcemia)
    • ↑ Serum protein/albumin (i.e., multiple myeloma Multiple myeloma Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma) = ↑ serum calcium (pseudohypercalcemia)
    • In the above cases, ionized calcium is normal.
    • For every ↓ in albumin by 1 g/dL → ↓ in calcium by 0.8 mg/dL
    • Corrected Ca²+ (mg/dL) = measured total Ca²+ (mg/dL) + [0.8 x (4.0 – albumin concentration in g/dL)]
  • Other factors:
    • Calcitonin from the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland (opposes PTH → ↓ calcium)
    • Hyperphosphatemia (↑ phosphate binding, ↓ ionized calcium)
    • Hypomagnesemia (↓ PTH release → ↓ calcium)
Calcium metabolism

Schematic diagram of calcium regulation:
Low plasma calcium stimulates the release of parathyroid hormone (PTH), which increases calcium and phosphate release from bones, calcium absorption in the GI tract, and vitamin D production in the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys. In turn, active vitamin D increases calcium release from bones and calcium absorption in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine.

Image by Lecturio.

Etiology

Associated with ↑ PTH:

  • Vitamin D deficiency:
    • Malabsorption Malabsorption Malabsorption involves many disorders in which there is an inability of the gut to absorb nutrients from dietary intake, potentially including water and/or electrolytes. A closely related term, maldigestion is the inability to break down large molecules of food into their smaller constituents. Malabsorption and maldigestion can affect macronutrients (fats, proteins, and carbohydrates), micronutrients (vitamins and minerals), or both. Malabsorption and Maldigestion
    • Reduced exposure to sunlight
    • Renal failure
    • Liver failure
  • Hyperphosphatemia:
    • Tumor lysis syndrome Tumor lysis syndrome Tumor lysis syndrome is a potentially lethal group of metabolic disturbances that occurs when large numbers of cancer cells are killed rapidly. The lysed cells release their intracellular contents into the bloodstream, resulting in the development of hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. Tumor Lysis Syndrome
    • Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis
  • PTH resistance:
    • Altered postreceptor PTH signaling pathway
    • Effect: Target organ is unresponsive to PTH.
  • Acute pancreatitis Acute pancreatitis Acute pancreatitis is an inflammatory disease of the pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients typically present with epigastric pain radiating to the back. Acute Pancreatitis: Calcium binds free fatty acids (released by pancreatic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes).
  • Osteoblastic metastasis (i.e., breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer): Calcium is deposited in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones around the tumor.

Hypoparathyroidism (↓ PTH):

  • Complication of thyroid/parathyroidectomy, or neck surgery/trauma/radiation
  • Congenital causes (e.g., DiGeorge syndrome DiGeorge syndrome DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). DiGeorge Syndrome, familial hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism)
  • Autoimmune hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism ( antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to calcium-sensing receptors)
  • Parathyroid gland infiltration

Drug induced:

  • Loop diuretics Loop diuretics Loop diuretics are a group of diuretic medications primarily used to treat fluid overload in edematous conditions such as heart failure and cirrhosis. Loop diuretics also treat hypertension, but not as a 1st-line agent. Loop Diuretics
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
  • Calcitonin
  • Chemotherapy
  • Bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix "-dronate" or "-dronic acid" (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates
  • Fluoride poisoning

Others:

  • Multiple blood transfusions (high concentrations of citric acid, which bind to serum calcium)
  • Inadequate oral intake of calcium
  • Hypomagnesemia
  • Alkalosis
  • Hungry bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones syndrome

Clinical Presentation

Manifestations depend on the level and onset of hypocalcemia:

  • Mild disease is asymptomatic, but serum total calcium of < 7.0–7.5 mg/dL will produce symptoms.
  • Acute decline hypocalcemia produces more symptoms than gradual onset hypocalcemia.

Symptoms:

  • Increased neuromuscular excitability:
    • Tetany:
      • Sensory: perioral and acral paresthesias
      • Motor: carpopedal spasms, muscle cramps, spasm of the respiratory muscle and glottis
      • Autonomic: biliary colic, diaphoresis, bronchospasm
    • Classic physical findings of tetany:
      • Chvostek sign: Tapping on the facial nerve in the area of the cheek results in ipsilateral twitching of the lip and facial musculature.
      • Trousseau sign: Carpal spasms (“claw hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand”) are induced by inflation of the blood pressure cuff above the systolic pressure for 3 minutes.
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures:
    • Generalized tonic-clonic
    • Focal
    • Generalized absence
  • Papilledema ± increased intracranial pressure Increased Intracranial Pressure Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP) (severe hypocalcemia)
  • Neuropsychiatric symptoms (reversible):
    • Depression
    • Psychotic disorders
    • Anxiety
  • Cardiovascular:
    • Myocardial dysfunction → hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure
    • ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Normal Electrocardiogram (ECG) changes: long QT interval with risk of torsades de pointes
  • Chronic changes:
    • Hypoparathyroidism: cataracts, dental abnormalities, dementia
    • Vitamin D deficiency: osteomalacia Osteomalacia Rickets and osteomalacia are disorders of decreased bone mineralization. Osteomalacia affects the sites of bone turnover in children and adults. Although most cases are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Osteomalacia and Rickets, osteopenia, hypotonia, stunted growth in children

Diagnosis

  • Review clinical history and manifestation.
  • Laboratory tests:
    • Serum calcium concentration  
    • Confirm true hypocalcemia:
      • Repeat test.
      • Obtain serum albumin and calculate corrected Ca2+ (mg/dL). 
      • Ionized calcium level
    • Serum PTH levels:
      • ↓ PTH indicates hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism.
      • ↑ PTH indicates kidney disease, vitamin D deficiency, or pseudohypoparathyroidism.
    • Serum phosphate levels: 
      • Decreased or normal in vitamin D deficiency
      • Elevated in hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism, pseudohypoparathyroidism, or chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
    • Serum magnesium levels: Hypocalcemia from ↓ magnesium resolves with correction of low magnesium.
    • Serum vitamin D levels: 
      • Measure calcidiol or 25(OH)D.
      • Hypocalcemia increases PTH, which increases renal production of 1,25-dihydroxyvitamin D (appears normal or high).
    • Comprehensive metabolic panel to exclude any renal or hepatic diseases
  • Others:
    • Alkaline phosphatase: ↑ in osteomalacia Osteomalacia Rickets and osteomalacia are disorders of decreased bone mineralization. Osteomalacia affects the sites of bone turnover in children and adults. Although most cases are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Osteomalacia and Rickets from severe vitamin D deficiency
    • Amylase: if pancreatitis suspected
    • Urinary calcium: low in vitamin D deficiency or hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism
    • ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Normal Electrocardiogram (ECG): prolonged QT interval, possible ventricular arrhythmias
Table: Laboratory findings in hypocalcemia
Diagnosis Hypoparathyroidism Vitamin D deficiency Magnesium deficiency Chronic kidney disease
PTH Low High Normal/low High
Phos High Low Normal High
25(OH)D Normal Low* Normal Normal/low
1,25(OH)2D Normal/low Normal/high* Normal Low
Mg Normal Normal Low Normal/high
Clinical clues
  • Neck surgery
  • Autoimmune disease
  • Bone tenderness
  • Osteomalacia
  • Alcohol use
  • Diuretics
  • Associated with hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia
Abnormal creatinine
PTH: parathyroid hormone
Phos: phosphate
25(OH)D: 25-hydroxyvitamin D/calcidiol
1,25(OH)2D: 1,25-dihydroxyvitamin D/calcitriol
Mg: magnesium
*25(OH)D is a better measurement for vitamin D deficiency because 1,25(OH)2D increases with low calcium, triggering ↑ PTH → ↑ renal production of calcitriol

Management

Management depends on the underlying cause and severity.

Mild hypocalcemia

Approach for:

  • Asymptomatic patients
  • Patients with mild symptoms (i.e., oral paresthesia)
  • Patients with chronic hypocalcemia

Treatment:

  • Oral replacement with 1,500–2,000 mg of elemental calcium/day
  • Either calcium citrate or calcium carbonate

Severe hypocalcemia/acute hypocalcemia

Approach for:

  • Patients with tetany, carpopedal spasm, or seizures
  • Patients with prolonged QT
  • Patients with acute decline to ≤ 7.5 mg/dL (i.e., post head or neck surgery)

Treatment:

  • IV calcium gluconate, OR
  • IV calcium chloride

Additional considerations

  • Hypomagnesemia:
    • Correct deficient magnesium.
    • IV magnesium sulfate
  • Chronic kidney disease (individualized treatment): 
    • Oral calcium is given as a phosphate binder.
    • Vitamin D replacement may be needed in some patients.
  • Vitamin D deficiency: vitamin D supplementation
  • Chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease: Calcidiol is given because it does not require 25-hydroxylation in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver.

Clinical Relevance

The following are conditions related to hypocalcemia:

  • Vitamin D deficiency: vitamin D is a fat-soluble, substance vitamin essential for proper function of the human body, especially for skeletal health. Demineralization of the bones leads to osteomalacia Osteomalacia Rickets and osteomalacia are disorders of decreased bone mineralization. Osteomalacia affects the sites of bone turnover in children and adults. Although most cases are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Osteomalacia and Rickets in adults and rickets with osteomalacia Osteomalacia Rickets and osteomalacia are disorders of decreased bone mineralization. Osteomalacia affects the sites of bone turnover in children and adults. Although most cases are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Osteomalacia and Rickets in children. Other manifestations include bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones tenderness, muscle weakness, and fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures(s). Deficiency is determined by obtaining a 25-hydroxyvitamin D (calcidiol) concentration. Management includes vitamin D replenishment.
  • Osteomalacia and rickets: softening of the bones due to bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones demineralization, mostly related to deficiency of vitamin D. Rickets Rickets Rickets and osteomalacia are disorders of decreased bone mineralization. Rickets affects the cartilage of the epiphyseal growth plates in children. Although most cases of rickets are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Rickets commonly presents with skeletal deformities and growth abnormalities. Osteomalacia and Rickets presents in children, who have open and growing epiphyseal growth plates. Osteomalacia presents commonly in adults, whose growth plates generally have already closed.  Rickets Rickets Rickets and osteomalacia are disorders of decreased bone mineralization. Rickets affects the cartilage of the epiphyseal growth plates in children. Although most cases of rickets are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Rickets commonly presents with skeletal deformities and growth abnormalities. Osteomalacia and Rickets manifests with skeletal deformities and growth abnormalities. Osteomalacia patients exhibit bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and pathologic fractures. Diagnosis is made based on a combination of clinical findings, laboratory tests, and imaging. Treatment includes vitamin D, calcium, and phosphorus supplementation.
  • Acute pancreatitis Acute pancreatitis Acute pancreatitis is an inflammatory disease of the pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients typically present with epigastric pain radiating to the back. Acute Pancreatitis: an inflammatory disease of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients present with epigastric pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain radiating to the back. Diagnosis requires 2 of 3 criteria, including characteristic abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, serum amylase, and lipase 3x the upper limit of normal, or characteristic radiology findings. Low calcium is a Ranson criteria factor and commonly used to assess severity. Management includes aggressive IV hydration, analgesia, nutrition support, and treatment of the underlying cause.
  • Chronic kidney disease ( CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease): kidney impairment lasting for at least 3 months, which implies CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease is irreversible. Hypertension and diabetes are the most common causes; however, a multitude of other diseases can also be the etiology. One of the complications of CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease (especially in the later stages) is secondary hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism (mineral and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones disorder). Increased phosphate overwhelms the regulatory system, and calcium binding with phosphate lowers the ionized calcium, leading to symptomatic hypocalcemia.
  • Cirrhosis: a late stage of hepatic necrosis and scarring. Chronic cellular damage causes extensive distortion of the normal hepatic architecture, which can lead to impairment of normal blood flow through the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver. Common causes are chronic, excessive alcohol use, viral hepatitis, and nonalcoholic steatohepatitis (NASH). Chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease leads to impaired vitamin D production. Calcidiol, which does not require hepatic 25-hydroxylation, can be given to patients with hypocalcemia.
  • Hypoparathyroidism: reduced PTH levels due to poor function of the parathyroid glands Parathyroid glands The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands. The cause of hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism is most commonly iatrogenic, following neck surgery. Parathyroid hormone deficiency results in low serum calcium levels, causing increased neuromuscular excitability. Acute onset (usually postsurgical) is treated with emergent IV administration of calcium gluconate. Chronic hypoparathroidism requires long-term calcium and vitamin D supplementation and monitoring.
  • DiGeorge syndrome DiGeorge syndrome DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). DiGeorge Syndrome: a condition caused by a microdeletion at location q11.2 of chromosome 22. DiGeorge syndrome DiGeorge syndrome DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). DiGeorge Syndrome is also known as 22q11.2 syndrome. A defective development of the 3rd and 4th pharyngeal pouches leads to thymic and parathyroid hypoplasia, causing T cell immunodeficiency and hypocalcemia, respectively. Diagnosis is made with clinical findings, laboratory tests (low calcium), echocardiogram, and genetic analysis. Treatment can include calcium supplementation, surgery (for heart defects and palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Oral Cavity: Palate abnormalities), and thymus or hematopoietic cell transplantation.
  • Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis: a condition characterized by muscle necrosis and the release of myoglobin, which has nephrotoxic effects. Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis may be caused by trauma or direct muscle compression; or, rhabdomyolysis can be nontraumatic (e.g., intense exertional activity). Creatine kinase elevation with presentation of myalgias and dark urine are highly suggestive of the diagnosis. Hyperphosphatemia results from necrotic muscles, which leads to hypocalcemia. The formation of calcium phosphate salts contribute to renal failure. Management is with IV fluid resuscitation.

References

  1. Dawson-Hughes, B. (2021). Vitamin D deficiency in adults. UpToDate. Retrieved May 7, 2021, from https://www.uptodate.com/contents/vitamin-d-deficiency-in-adults-definition-clinical-manifestations-and-treatment
  2. Goltzman, D. (2021). Clinical manifestations of hypocalcemia. UpToDate. Retrieved May 7, 2021, from https://www.uptodate.com/contents/clinical-manifestations-of-hypocalcemia
  3. Goltzman, D. (2021). Diagnostic approach to hypocalcemia. UpToDate. Retrieved May 7, 2021, from https://www.uptodate.com/contents/diagnostic-approach-to-hypocalcemia
  4. Goltzman, D. (2021). Etiology of hypocalcemia in adults. UpToDate. Retrieved May 7, 2021, from https://www.uptodate.com/contents/etiology-of-hypocalcemia-in-adults
  5. Gotlzman, D. (2021). Treatment of hypocalcemia. UpToDate. Retrieved May 7, 2021, from https://www.uptodate.com/contents/treatment-of-hypocalcemia
  6. Goyal A, Singh S. (2020). Hypocalcemia. StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK430912/

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