Phosphate Disorders Hypophosphatemia Flashcards
What is hypophosphatemia defined as?
Serum phosphorus level [Pi] < 2.5 mg/dL
What are the highest and lowest serum phosphorus levels observed during the day in individuals with normal kidney function?
Highest in the early morning hours, lowest in the late morning hours
What condition develops in patients receiving mannitol?
Pseudohypophosphatemia
What causes pseudohypophosphatemia in patients receiving mannitol?
Binding of mannitol to the molybdate used to determine the serum [Pi]
What are the classifications of hypophosphatemia based on serum [Pi] levels?
- Severe: [Pi] < 1.0 mg/dL
- Moderate: [Pi] 1.0–1.9 mg/dL
- Mild: [Pi] 2.0–2.5 mg/dL
In which patients is hypophosphatemia commonly seen?
Hospitalized patients with sepsis, chronic alcoholism, COPD, and trauma
What are the four categories of causes of hypophosphatemia?
- Shift from extracellular to intracellular compartment
- Decreased intestinal absorption
- Increased kidney loss
- Drugs
What is one mechanism that causes hypophosphatemia due to a shift from extracellular to intracellular compartment?
Glucose-induced transcellular distribution
What role do phosphate binders play in hypophosphatemia?
They bind phosphate in the gut, decreasing intestinal absorption
Which vitamin deficiency is associated with decreased intestinal absorption leading to hypophosphatemia?
Vitamin D deficiency
What is the effect of primary and secondary hyperparathyroidism on kidney phosphate absorption?
Decreases kidney absorption by inhibiting phosphate transporters
What is the most common hypophosphatemic disorder?
X-Linked Hypophosphatemia
What gene is mutated in X-Linked Hypophosphatemia?
PHEX gene
What are the clinical features of X-Linked Hypophosphatemia?
- Hypophosphatemia
- Phosphaturia
- Short stature
- Rickets and osteomalacia
- Dental abscesses
What is the treatment for X-Linked Hypophosphatemia?
Oral calcitriol and phosphate
What causes Autosomal Dominant Hypophosphatemic Rickets (ADHR)?
Activating mutations in the FGF-23 gene
What are common symptoms of ADHR?
- Hypophosphatemia
- Lower extremity deformities
- Bone pain
- Weakness
- Phosphaturia
What is the treatment for Autosomal Recessive Hypophosphatemic Rickets (ARHR)?
Calcitriol and phosphate
What is Tumor-Induced Osteomalacia (TIO)?
An acquired paraneoplastic syndrome associated with mesenchymal tumors
What are the biochemical findings in Tumor-Induced Osteomalacia?
- Phosphaturia
- Elevated FGF-23
- Normal Ca²⁺ and PTH levels
What is the treatment strategy for Tumor-Induced Osteomalacia?
Identification and resection of the tumor, calcitriol, and phosphate
What characterizes Hereditary Hypophosphatemic Rickets with Hypercalciuria due to Type IIc mutations?
Mutations in the Na/Pi-type IIc cotransporter gene
What is the predominant treatment for Hereditary Hypophosphatemic Rickets with Hypercalciuria?
Phosphate supplementation
What is the genetic cause of Hereditary Hypophosphatemic Rickets with Hypercalciuria due to Type IIa mutations?
Heterozygous mutations in the SLC34A1 gene
What is the role of Na/H Exchanger Regulatory Factor (NHERF)1 in phosphate transport?
Maintains stability of Na/Pi-IIc cotransporter at the apical membrane
What is the effect of mutations in the NHERF1 gene?
Causes hypophosphatemia, phosphate wasting, and increased risk for kidney stones
What are common treatments for various hypophosphatemic conditions?
- Calcitriol
- Phosphate supplementation
True or False: Hypophosphatemia is common in the general population.
False
What is the genetic mutation associated with X-linked hypophosphatemia (XLH)?
PHEX gene mutation
XLH is characterized by elevated FGF-23 levels and low phosphate levels.
What is the effect of FGF-23 in hypophosphatemic disorders?
Increased phosphate excretion and decreased serum phosphate
FGF-23 plays a key role in phosphate regulation.
Which disorder is associated with a mutation in the DMP1 gene?
Autosomal recessive hypophosphatemic rickets type 1 (ARHR1)
ARHR1 shows increased FGF-23 and decreased phosphate levels.
What is the most common electrolyte abnormality observed in refeeding syndrome (RFS)?
Hypophosphatemia
RFS occurs in malnourished individuals after nutrition is restarted.
What are the mechanisms contributing to hypophosphatemia in refeeding syndrome?
High carbohydrate meals, increased glycolysis, depleted phosphate stores, phosphate consumption for ATP
Each mechanism contributes to the shift and depletion of phosphate.
True or False: Hypophosphatemia can lead to sudden deaths in refeeding syndrome.
True
High caloric diets can exacerbate hypophosphatemia, leading to organ failure.
What is the typical serum phosphate level in acute severe symptomatic hypophosphatemia?
<1.0 mg/dL
This condition requires careful monitoring and treatment.
What is the recommended initial treatment for severe hypophosphatemia?
IV phosphate administration
Oral phosphate is preferred when symptoms are absent.
List the main clinical manifestations of severe hypophosphatemia.
- Neurologic: confusion, seizures
- Cardiovascular: cardiomyopathy
- Skeletal muscle: weakness, rhabdomyolysis
- Bone: pain, rickets
- Hematologic: hemolysis
- Respiratory: muscle weakness, hypoxia
These manifestations result from ATP depletion and altered cellular function.
What is the role of cinacalcet in kidney transplantation?
Improves PTH levels and phosphate wasting
This treatment addresses secondary hyperparathyroidism post-transplant.
What laboratory findings are indicative of kidney phosphate wasting?
FEₚₒ₄ >5%
This indicates that the kidneys are losing phosphate and not absorbing it.
What is the normal range for TmP/GFR in adults?
0.8–1.35 mmol/L
Values <0.8 indicate kidney phosphate wasting.
What is the first step in diagnosing hypophosphatemia?
Establish the cause through history and physical examination
This involves looking for signs and symptoms as well as dietary and medication history.
Fill in the blank: The presence of _______ can indicate chronic alcoholism in a patient with hypophosphatemia.
Hepatomegaly
This can be a sign of underlying causes contributing to phosphate deficiency.
What are the potential risks of IV phosphate administration?
Hypocalcemia and fluid overload
Patients with heart failure are particularly at risk.
What is a common cause of hypophosphatemia in critically ill patients?
Use of glucose-containing solutions
This can lead to shifts in phosphate levels.
What is the relationship between ATP depletion and hypophosphatemia?
Depletion of ATP leads to altered cellular function and hypoxia
ATP is critical for energy metabolism and cellular functions.
What should be monitored in patients receiving IV phosphate repletion?
Serum phosphate levels
Frequent monitoring is crucial to avoid complications.
What is the biochemical abnormality associated with decreased 2,3-diphosphoglycerate in hypophosphatemia?
Increased oxygen affinity of hemoglobin
This can lead to reduced oxygen delivery to tissues.
Name a treatment for hypophosphatemia that can be given orally.
Neutra-phos
This is a common oral phosphate preparation.
What is the serum phosphate level range for moderate hypophosphatemia?
0.58–0.7 mmol/L (1.8–2.2 mg/dL)
What complications are associated with IV phosphate administration?
Hypocalcemia and hyperphosphatemia
When is IV phosphate administration generally not required?
In moderate hypophosphatemia unless symptoms warrant IV therapy
What is the management approach for chronic hypophosphatemia?
Depends on the underlying cause; oral therapy is indicated
What can long-term oral therapy for hypophosphatemia suppress?
1,25(OH)₂D₃ levels and raise PTH and FGF-23 levels
What is suggested to suppress PTH levels in chronic hypophosphatemia?
Concomitant administration of calcitriol
What dietary change may improve hypophosphatemia in kidney transplant patients?
Increase in dietary phosphate
What is a major concern when using oral phosphate therapy in severe hypophosphatemia?
Hyperphosphatemia
Which drug does NOT cause hypophosphatemia?
Calcitriol
What is the serum phosphate level for severe hypophosphatemia?
<1.0 mg/dL
Which metabolic abnormality is NOT related to severe hypophosphatemia?
Metabolic alkalosis
What is a complication of low serum phosphate levels?
Rhabdomyolysis
What treatment is indicated for asymptomatic moderate hypophosphatemia?
Oral phosphate repletion
What is the treatment for hyperalimentation-induced severe hypophosphatemia?
Aggressive intravenous (IV) treatment with 1 mmol/kg over 10 h
What does transcellular distribution of phosphate occur after?
Carbohydrate load or glucose infusion
Which human phosphate wasting disease is associated with high levels of active vitamin D?
Primary hyperparathyroidism
What is the serum phosphate status in Autosomal Dominant Hypophosphatemic Rickets (ADHR)?
↓
What is the serum calcium status in Autosomal Recessive Hypophosphatemic Rickets (ARHR)?
N
What is the serum 1,25(OH)₂D₃ level in X-linked hypophosphatemia (XLH)?
↓/N
What is the PTH status in tumor-induced osteomalacia (TIO)?
N
Match the serum values with the patient history: A 45-year-old woman with hilar adenopathy
A
Match the serum values with the patient history: A 30-year-old obese female with short-bowl resection
B
Match the serum values with the patient history: A 60-year-old man with a lung mass
C
Match the serum values with the patient history: A 24-year-old female with flank pain and UTIs
D
Match the serum values with the patient history: A 50-year-old housewife with joint pain and nocturia
E
What is hypophosphatemia defined as?
A serum phosphorus level [Pi] < 2.5 mg/dL
When are the highest serum phosphorus levels typically observed?
In the early morning hours
What condition can develop in patients receiving mannitol?
Pseudohypophosphatemia
What causes pseudohypophosphatemia in patients receiving mannitol?
Binding of mannitol to the molybdate used to determine serum [Pi]
What leukocyte count can cause pseudohypophosphatemia?
Leukocyte count >310,000/μL
How can pseudohypophosphatemia be corrected?
Filtration of serum deproteinizes
What are the three classifications of hypophosphatemia based on severity?
- Severe: serum [Pi] < 1.0 mg/dL
- Moderate: serum [Pi] 1.0–1.9 mg/dL
- Mild: serum [Pi] 2.0–2.5 mg/dL
What can cause severe hypophosphatemia?
Prolonged use of antacids such as aluminum hydroxide, magnesium hydroxide, or calcium carbonate/acetate
Is moderate hypophosphatemia typically symptomatic or asymptomatic?
May be symptomatic or asymptomatic
Is hypophosphatemia common in the general population?
No, it is rather uncommon
What conditions have a high incidence of hypophosphatemia in hospitalized patients?
- Sepsis
- Chronic alcoholism
- Chronic obstructive pulmonary disease (COPD)
What type of patients also have a high incidence of hypophosphatemia?
Patients with trauma
What is one cause of hypophosphatemia related to the shift of phosphate?
Shift from extracellular to intracellular compartment
This includes factors such as glucose, insulin, catecholamines, and respiratory alkalosis.
What mechanism does insulin use to contribute to hypophosphatemia?
Transcellular distribution
Insulin facilitates the movement of phosphate from the extracellular to the intracellular compartment.
What is refeeding syndrome in relation to hypophosphatemia?
Glucose and insulin-induced transcellular distribution, consumption during glucose metabolism, and ATP production
This condition can lead to significant phosphate depletion.
What is one cause of hypophosphatemia due to decreased intestinal absorption?
Malabsorption
This results in reduced intestinal absorption of phosphate.
What do phosphate binders do?
Bind phosphate in the gut
Examples include calcium acetate, aluminum hydroxide, and magnesium salts.
What is Tenapanor’s role in hypophosphatemia?
Na/H exchanger isoform 3 inhibitor, which reduces paracellular transport of phosphate in the intestine
It helps in managing phosphate levels by affecting intestinal absorption.
What is a consequence of vitamin D deficiency in relation to hypophosphatemia?
Decreased intestinal absorption
Vitamin D is crucial for phosphate absorption in the intestines.
What can lead to increased kidney loss of phosphate?
Primary and secondary hyperparathyroidism
These conditions inhibit phosphate transporters in the proximal tubule.
What genetic condition is associated with mutations in the PHEX gene?
X-linked hypophosphatemia
This inherited disorder results in phosphate wasting.
What is one drug that can cause hypophosphatemia?
Osmotic diuretics
These decrease kidney reabsorption and increase phosphaturia.
What effect do corticosteroids have on phosphate levels?
Decrease intestinal phosphate absorption and increase phosphaturia
This can contribute to hypophosphatemia.
Fill in the blank: Alcoholism can lead to hypophosphatemia due to _______.
Poor intake, frequent use of phosphate binders, vitamin D deficiency
Alcoholism can significantly impact phosphate levels through various mechanisms.
What is the effect of diabetic ketoacidosis on phosphate levels?
Decreased total body phosphate due to osmotic diuresis
Hypophosphatemia can occur after insulin administration.
True or False: Metabolic acidosis decreases Na/Pi-IIa cotransporter activity.
True
This can result in lower phosphate reabsorption in the kidneys.
What is a potential consequence of toxic shock syndrome related to phosphate?
Cellular uptake probably due to respiratory alkalosis
This condition can lead to hypophosphatemia through altered cellular mechanisms.
What is the most common hypophosphatemic disorder?
X-Linked Hypophosphatemia
Inherited as an autosomal dominant disease
What gene is associated with X-Linked Hypophosphatemia?
PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome)
Inactivating mutations in this gene cause the disorder
At what age does X-Linked Hypophosphatemia typically present?
Within 2 years of age
List the key characteristics of X-Linked Hypophosphatemia.
- Hypophosphatemia
- Phosphaturia
- Short stature
- Rickets and osteomalacia
- Dental abscesses
What are the effects of X-Linked Hypophosphatemia on calcium and phosphate absorption?
Decreased intestinal Ca²⁺ and phosphate absorption, and decreased kidney phosphate absorption
What is the role of FGF-23 in X-Linked Hypophosphatemia?
It is produced due to inactivating mutations of PHEX
What are the biochemical characteristics of X-Linked Hypophosphatemia?
- Elevated FGF-23 levels
- Normal serum Ca²⁺ levels
- Normal parathyroid hormone (PTH) levels
- Low 1,25(OH)₂D₃ levels
How does high FGF-23 activity affect vitamin D levels in X-Linked Hypophosphatemia?
It leads to low 1,25(OH)₂D₃ levels
What treatment options are available for X-Linked Hypophosphatemia?
- Oral calcitriol
- Phosphate
- Burosumab (human anti-FGF23 monoclonal antibody)
True or False: Treatment with oral calcitriol and phosphate reduces phosphaturia.
False
What is the effectiveness of burosumab in treating X-Linked Hypophosphatemia?
It appears to be effective in children 1 year and older
What is the most common hypophosphatemic disorder?
X-Linked Hypophosphatemia
Inherited as an autosomal dominant disease
What gene is associated with X-Linked Hypophosphatemia?
PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome)
Inactivating mutations in this gene cause the disorder
At what age does X-Linked Hypophosphatemia typically present?
Within 2 years of age
List the key characteristics of X-Linked Hypophosphatemia.
- Hypophosphatemia
- Phosphaturia
- Short stature
- Rickets and osteomalacia
- Dental abscesses
What are the effects of X-Linked Hypophosphatemia on calcium and phosphate absorption?
Decreased intestinal Ca²⁺ and phosphate absorption, and decreased kidney phosphate absorption
What is the role of FGF-23 in X-Linked Hypophosphatemia?
It is produced due to inactivating mutations of PHEX
What are the biochemical characteristics of X-Linked Hypophosphatemia?
- Elevated FGF-23 levels
- Normal serum Ca²⁺ levels
- Normal parathyroid hormone (PTH) levels
- Low 1,25(OH)₂D₃ levels
How does high FGF-23 activity affect vitamin D levels in X-Linked Hypophosphatemia?
It leads to low 1,25(OH)₂D₃ levels
What treatment options are available for X-Linked Hypophosphatemia?
- Oral calcitriol
- Phosphate
- Burosumab (human anti-FGF23 monoclonal antibody)
True or False: Treatment with oral calcitriol and phosphate reduces phosphaturia.
False
What is the effectiveness of burosumab in treating X-Linked Hypophosphatemia?
It appears to be effective in children 1 year and older
What is Autosomal Dominant Hypophosphatemic Rickets (ADHR)?
ADHR is a rare disorder caused by activating mutations in the FGF-23 gene, preventing proteolytic cleavage of FGF-23 and increasing circulating levels of this hormone.
What is the phenotype of ADHR similar to?
The phenotype is similar to that of X-linked hypophosphatemia.
What is the clinical onset variability in ADHR due to?
Incomplete penetrance.
How does ADHR typically present in childhood?
Hypophosphatemia and lower extremity deformities.
What symptoms may develop in adolescence or adulthood for individuals with ADHR?
Bone pain, weakness, and phosphaturia.
What may happen to phosphaturia in some ADHR patients after puberty?
It may improve.
What is the treatment for ADHR?
Calcitriol and phosphate.
What causes Autosomal Recessive Hypophosphatemic Rickets type 1 (ARHR1)?
Inactivating mutations in the DMP (dentin matrix protein) 1 gene.
What role does DMP 1 play in the body?
Participates in bone mineralization of extracellular matrix.
What is the clinical manifestation of DMP 1 deficiency similar to?
Similar to that of ADHR.
What causes Autosomal Recessive Hypophosphatemic Rickets type 2 (ARHR2)?
Inactivating mutation in the ENPPI (endonucleotide pyrophosphatase/phosphodiesterase I) gene.
What is the treatment for both ARHR1 and ARHR2?
Calcitriol and phosphate.
What does TIO stand for?
Tumor-Induced Osteomalacia
What type of tumors are typically associated with TIO?
Mesenchymal tumors
During which decade of life does TIO usually occur?
6th decade of life
Name one phosphaturic factor associated with TIO.
FGF-23
List three other phosphaturic factors identified with TIO.
- sFRP-4 (frizzled-related protein-4)
- MEPE (matrix extracellular phosphoryloprotein)
- FGF-7
What are the biochemical findings in TIO similar to?
ADHR
What are the biochemical markers associated with TIO?
- Phosphaturia
- Elevated FGF-23
- Normal Ca²⁺ levels
- Normal PTH levels
What is the first step in the treatment of TIO?
Identification of the tumor
What treatments are included for TIO?
- Resection or chemotherapy
- Calcitriol
- Phosphate
What is Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) caused by?
Mutations in the gene that encodes Na/Pi-type IIc cotransporter
It is a rare autosomal recessive disorder.
At what age does HHRH typically occur?
In the first 2 years of life.
What are the main clinical features of HHRH?
- Growth retardation
- Rickets
- Increased kidney phosphate and Ca²⁺ excretion
How does HHRH differ from other hypophosphatemic rickets?
HHRH is characterized by elevated levels of 1,25(OH)₂D₃, leading to hypercalciuria and hypercalcemia.
What is the recommended treatment for HHRH?
Phosphate supplementation.
Is calcitriol recommended for treating HHRH?
No, it is not recommended due to the risk of hypercalcemia and kidney stone formation.
What gene is associated with Type IIa mutations in hereditary hypophosphatemic rickets?
SLC34A1 gene (Na/Pi-IIa protein).
What biochemical abnormalities were reported in patients with Type IIa mutations?
- Hypophosphatemia
- Phosphate wasting
- Elevated 1,25(OH)₂D₃ levels
What was discovered in the study of siblings with Type IIa mutations after 20 years?
Persistent Fanconi syndrome, phosphate wasting, bone mineral deficiency, and decreased glomerular filtration rates.
What is the role of Na/H Exchanger Regulatory Factor (NHERF)1 in phosphate transport?
It maintains the stability of the Na/Pi-II₆ cotransporter at the apical membrane.
What condition was found in individuals with loss-of-function mutations in the NHERF1 gene?
Hypophosphatemia and phosphate wasting with higher risk for kidney stones and bone demineralization.
What did Schlingmann et al. report regarding SCL34A1 mutations?
Loss-of-function mutations in SCL34A1 in infants with idiopathic infantile hypercalcemia and nephrolithiasis.
What were the clinical features of the case of hypophosphatemic rickets in a 13-month-old girl with Klotho mutation?
- Poor linear growth
- Large head
- Poor response to vitamin D₂ therapy
What genetic abnormality was found in the girl with hypophosphatemic rickets related to Klotho?
A de novo translocation of the α-Klotho gene.
How did the girl’s condition improve?
With vitamin D₂ and phosphate treatment.
What was the result of the girl’s treatment by age 7?
She developed hypercalcemia, requiring parathyroidectomy.
What gene is associated with X-linked hypophosphatemia (XLH)?
PHEX
XLH is characterized by elevated FGF-23 and decreased phosphate (Pi) levels.
What is the FGF-23 level in autosomal dominant hypophosphatemic rickets (ADHR)?
↑
ADHR is associated with the FGF-23 gene.
In what disorder is DMP1 the associated gene?
ARHR1
ARHR1 features elevated FGF-23 and decreased phosphate levels.
What gene is linked to ARHR2?
ENPP1
Similar to ARHR1, ARHR2 also has elevated FGF-23 and decreased phosphate.
What is the calcitriol level in hereditary hypophosphatemic rickets with hypercalciuria (HHRH) associated with SLC34A3?
↑
This form of HHRH shows decreased phosphate levels and increased calcium excretion.
Which gene is associated with the HHRH condition that has N for FGF-23?
SLC34A1
This variant of HHRH shows increased phosphate and calcium excretion.
What is the phosphate excretion level in NHERF1 disorder?
N
NHERF1 shows elevated calcitriol and increased calcium excretion.
What is the calcium level in Klotho disorder?
↓
Klotho disorder features elevated FGF-23 and PTH levels.
Fill in the blank: The phosphate (Pi) level in XLH is _______.
↓
XLH is characterized by elevated FGF-23 and normal PTH levels.
True or False: In HHRH with SLC34A3, the phosphate excretion is decreased.
False
HHRH with SLC34A3 shows increased phosphate excretion.
What is the PTH level in ARHR1?
N
ARHR1 features elevated FGF-23 and decreased phosphate levels.
What is Refeeding Syndrome (RFS)?
RFS occurs in malnourished individuals following administration of oral, enteral, or parenteral nutrition.
Commonly seen in hospitalized patients who are malnourished due to poor oral intake, starvation, anorexia nervosa, or systemic illness such as malignancy.
What is the most commonly observed electrolyte abnormality induced by RFS?
Hypophosphatemia.
This condition is characterized by low levels of phosphate in the blood.
What are some mechanisms that contribute to hypophosphatemia in RFS?
- High carbohydrate meal causing intracellular shift of phosphate
- Increased consumption of phosphate during glycolysis
- Depleted body stores of phosphate during poor oral intake
- Consumption of phosphate for formation of ATP and increased production of products such as creatine kinase and 2,3-diphosphoglycerate.
These mechanisms lead to a rapid decrease in phosphate availability in the body.
What severe consequence can occur following RFS with a high caloric diet?
Sudden deaths due to hypophosphatemia, leading to almost all organ systems failing.
This highlights the critical nature of managing caloric intake in at-risk patients.
How can hypophosphatemia be prevented in patients at risk for RFS?
Feeding should consist of low calories with gradual increase to maintain the target caloric intake.
This approach helps to mitigate the risk of electrolyte imbalances.
What other electrolyte abnormalities can occur along with hypophosphatemia due to high glucose?
- Hypokalemia
- Hypomagnesemia.
These conditions further complicate the management of patients experiencing RFS.
What supplementation can help prevent RFS?
Supplementation of K⁺, Mg²⁺, and phosphate along with nutrition.
This strategy helps to correct electrolyte imbalances and supports patient recovery.
What percentage of kidney transplantation patients develop mild to moderate hypophosphatemia?
About 90%.
This condition may last for months to years post-transplant.
What are some causes of hypophosphatemia following kidney transplantation?
- Tertiary hyperparathyroidism
- Elevated FGF-23 levels
- Vitamin D deficiency.
These factors contribute to phosphate wasting in transplanted patients.
What treatment improves both PTH levels and phosphate wasting in kidney transplant patients?
Cinacalcet.
This medication is used to manage hyperparathyroidism and its effects on phosphate metabolism.
What electrolyte disorder is frequently observed in critically ill patients?
Hypophosphatemia.
It is a common electrolyte disorder during ICU stays.
What are common causes of hypophosphatemia in critical care units?
- Glucose-containing solutions
- Insulin administration
- Starvation
- Refeeding
- Sepsis
- Shock
- Trauma
- Postoperative state
- Respiratory alkalosis
- Metabolic acidosis
- Medications such as catecholamines and diuretics
- Kidney replacement therapies.
These causes highlight the multifactorial nature of electrolyte disturbances in critically ill patients.
What is the first step in diagnosing hypophosphatemia?
Establish the cause from history, physical examination, and clinical setting.
What should be inquired about during the history taking for hypophosphatemia?
Signs and symptoms, history of alcoholism, medications, dietary intake, IV fluids, and diagnosis.
Which system should be focused on during the physical examination for hypophosphatemia?
Musculoskeletal system.
What are signs of rhabdomyolysis in hypophosphatemia?
Muscle tenderness and pain.
What indicates rickets in children during physical examination?
Pathologic or pseudofractures and skeletal deformities.
What features indicate chronic hypophosphatemia in adults?
Rachitic features.
What is indicated by short stature with increased upper to lower body ratio?
Previous childhood rickets.
What condition is associated with sinus tumors in the context of hypophosphatemia?
Tumor-induced osteomalacia (TIO).
What might hepatomegaly suggest in a patient with hypophosphatemia?
Chronic alcoholism or tumors.
What physical examination finding suggests X-linked hypophosphatemia in adults?
Limited spine, joint, and hip motion.
What serum electrolytes should be measured in the evaluation of hypophosphatemia?
Ca²⁺, phosphate, Mg²⁺, alkaline phosphatase, and GFR.
What urine tests are relevant in diagnosing hypophosphatemia?
Urine phosphate, phosphate, creatinine, and pH.
What does a fractional excretion of phosphate (FEₚₒ₄) <5% suggest?
Nonkidney loss of phosphate.
What does a fractional excretion of phosphate (FEₚₒ₄) >5% suggest?
Kidney origin of hypophosphatemia.
What is the formula for calculating tubular reabsorption of phosphate (TRP)?
TRP = 1 - FEₚₒ₄.
What is the normal range for TmP/GFR in adults?
0.8–1.35 mmol/L.
What does TmP/GFR <0.8 indicate?
Kidney phosphate wasting.
Which serum and urine levels are helpful in diagnosing various causes of hypophosphatemia?
Ca²⁺, PTH, 25(OH)D₃, 1,25(OH)₂D₃, and FGF-23.
What do increased alkaline phosphatase and PTH levels suggest?
Primary or secondary hyperparathyroidism and FGF-23-mediated hypophosphatemia.
In which conditions are serum FGF-23 levels elevated?
X-linked hypophosphatemia, ADHR, ARHR, TIO, and after kidney transplantation.
What imaging studies are useful for chronic hypophosphatemia?
- Plain radiographs for fractures and skeletal abnormalities
- Dual-energy x-ray absorptiometry scan for bone density and osteomalacia
- Bone scan for increased uptake of technetium in osteomalacia
- CT, MRI, PET for TIO.
What is the primary goal in the treatment of hypophosphatemia?
Removing the causes such as medications or dietary deficiency whenever possible.
What is considered severe hypophosphatemia in mg/dL?
<1.0 mg/dL
What is the treatment for acute severe symptomatic hypophosphatemia?
IV administration of either sodium or potassium phosphate with frequent monitoring of serum [Pi].
What is the infusion rate for phosphorus in hyperalimentation-induced hypophosphatemic patients?
Not exceeding 7.5 mmol/h.
What percentage of severe hypophosphatemic patients benefited from tailored IV phosphorus regimens according to Taylor et al.?
63%
What percentage of moderately hypophosphatemic patients benefited from tailored IV phosphorus regimens according to Taylor et al.?
78%
Fill in the blank: In surgical intensive care patients, sodium or potassium phosphate is dissolved in 250 mL of ______ and infused over 6 hours.
D5W
What are the two types of phosphate preparations listed in Table 21.4?
Intravenous and Oral
What is the phosphate content of Neutral Na/K PO₄ preparation?
1.1 mmol/mL
What is the phosphate content of Neutra-phos oral preparation?
250 mg/packet
What is the phosphate repletion protocol for a serum phosphate level of <0.32 mmol/L for a patient weighing 61-80 kg?
40 mmol
True or False: IV phosphate administration is associated with hypocalcemia and hyperphosphatemia.
True
What is suggested to suppress PTH levels during oral therapy for chronic hypophosphatemia?
Concomitant administration of calcitriol.
What may improve hypophosphatemia in kidney transplant patients?
An increase in dietary phosphate.
What is the primary treatment for chronic hypophosphatemia?
Oral therapy.
Fill in the blank: Long-term oral therapy may suppress 1,25(OH)₂D₃ levels and raise ______ and FGF-23 levels.
PTH
What is the phosphate content of K-phos original preparation?
150 mg/capsule
What is the phosphate content of potassium PO₄ preparation?
3 mmol/mL
