Hypophosphatemia

Background
• Phosphat is most abundant intracellular & is essential in
all cells for :
- Memberane structure
- Energy storage
- Transport
• It produce ATP, which provides energy for nearly all
cells functions.
• Is an essential component of DNA and RNA
• It produce ATP, which provides energy for nearly all cells
functions.
• It also necessary in RBSs for production of 2,3
diphosphoglycerate (2,3-DPG) which facilitates release
of O2 from Hb.
- 85% phophorus is in bone as hydroxyapatite
- 15% is presen in soft tissue.
- Only 0.1% present in extracellular fluid, and it is this fraction that is
measured with a S.Phos level.
• Reducing available phosphate may compromise any
organ system, alone or in combination
• The critical role phosphate plays in every cell tissue,
and organ cells systemic nature of injury caused by
phosphate deficiency (normal range 2.5-4.5 mg/dl)
Definition
Hyphophosphatemia is defined as:
- Mild : 2-2.5 mg/dl atau 0.65-0.81mmol/L
- Moderate: 1-2 mg/dl atau 0.32-0.65 mmol/L
- Severe : <1 mg/dl atau 0.32 mmol/L

Mild to moderately ssevere hyphophosphatemia

is usually asymptomatic

Major clinical sequele occurs in severe

hypophosphatemia

As in the case of other intracellular ions (eg K,

Mg), a decrease in th level serum of phosphate
should be distinguished from a decrease in total
body storage of phosphate (phosphate deficiency)
 Pathophysiology
Do you know • Phsosphorus homeostatis is complex and regulated by the action
about of several hormones
phosphate ?
• PTH causes phosphate to be released from bone and inhibits
renal reabsorption of phosphorus, resulting in phosphaturia.

• Vitamine D aids in intestinal reabsorption of phosphorus

• Thyroid hormone and growth hormone act to increase renal

reabsorption of phosphate.

• Finally, a new class of phosphate-regulating factors, the so-called

phosphatonins, have been show to be important in phosphate-
wasting disease, such as:
• Oncogenic osteomalacia,
• X-linked hypophosphatemic rickets,
• Autosomal dominant hypophoshatemic rickets,
• Autosomal recessive hypophosphatemia, and tumoral
calcinosis.
 Pathophysiology
Do you know
• Hypophosphatemia is caused by:
about
• Intracellular shift of phosphate from serum,
phosphate ?
• Increased urinary excreation of phosphate,
• Decreased intestinal absorption of phosphate,
• Decrease dietary intake.

• Hypophosphatemia may be transient, reflecting intracellular

shift with minimal clinical consequences.

• The disease also may reflect a deeper state of tota; body

phosphate depletion with significant sequelae.
 Phatophysiology
1. Intracellular shift
• Respiratory alkalosis moves phosphate into cells by activating
phosphofructokinase, which stimulates intracellular glycolysis

• Glycolysis lead to phosphate consumption as phosphorylated glucose

precursors are produced.

• Any cause of hyperventilation (eg. Sepsis, anxiety, pain, heatstroke,

alcohol withdrawal, DKA, Hepatic encephalopathy, salicylate toxicity) can
precipitate hypophosphatemia.

• Since respiratory alkolosis is one of the most common causes of

hypophosphatemia, discovery of hypophosphatemia.

• Administering carbohydrate lowers serum phosphate by stimulating the

relase of insulin, which moves phosphate and glucose into cells.

• This so-called refeeding syndrome occurs when starving or chronically

malnourished patients are refed or given intravenous (IV) glucose, and
typically produces a hypophosphatemic state by treatment day 3 or 4.

• In addition, during refeeding, cells switch to an anabolic state, resulting in

further phosphate depletion as this essential substrate is incorporated inti
cells and cell product.
 Phatophysiology
1. Intracellular shift
• DK is also an important cause of hypophosphatemia.

• Metabolic acidosis and insulin deficiency will mobilize intracellular phosphate

store, causing them to shift to the extracellular space and leading to urinary
losses.

• Treatment of DKA with insulin causes phosphate to move back into celss
resulting in a decrease of serum phosphate.

• Routine replacement of phosphate in the setting od DKA is not proven to

decrease morbidity or mortality.

• However, because patient in DKA are often hypokalemic and hypophosphatemic,

some clinicians replete these losses with potassium phosphate salts.

• Cathecolamins and beta-receptor agonists also stimulate phosphate uptake into

cells.

• Certain rapidly growing malignancies (eg, acute leukemia,lymphomas) may

cnsume phosphate prefentially, leading to hypophosphatemia.

• In the cases of intracellular phosphate shift, serum phosphate normalize once

the precipitating cause is removed.
 Phatophysiology
2. Increase urinary excreation
• Since pTH stimulates the kidneys to excrete phosphate, hypophosphatemia is a
common sequela of primary and secondary hyperparathyroidism.

• Urinary loss of phosphate also occurs with acute volume expansion due to a
dilution of serum calcium, which, in turn, triggers an increase in the release of
PTH.

• Osmotic diuresis, such as seecn in hyperosmolar hyperglycemic syndrome

(HHS), also produces increased urinary excretion of phosphorus.

• Diuretic, including loops diuretic, thiazides, and carbonic anhydrase inhibitors

(eg, acetazolamide) interfere with the ability of the proximal tubules to reabsorb
phosphorus, thus producing hyperphosphaturia and potentially leading to
hypophosphatemia. Patients with transplanted kidneys, congenital defect (X-
linked hypophosphatemia (XLH) and autosomal dominant hyperphosphatemic
rickets (ADHR), or Fanconi syndromes (proximal tubules dysfunction) also may
excrete excess urinary phosphate.

• There is also evidence that show esterogen to be a downregulator of a renal

sodium phosphate cotransporter, causing significant hypophosphatemia in
patients.
 Phatophysiology
3. Decreased intestinal absorption
• Phosphate may be lost via the gut, as in chronic diarrhea,
malabsorption syndromes, severe vomiting, or NG suctioning.

• Phosphate may also be bound in the gut, thereby preventing

absorption (eg, chronic use of sucralfate, or phosphate-binding
antacids, including aluminium hydroxide, aluminium carbonate, and
calcium carbonate.

• Also, the intestine “sense” luminal concetrations of phosphate and

regulates the excretion of phosphate in the kidney by elaborating
novel factors the alter renal phosphate reabsorption.
 Phatophysiology
3. Decreased dietary intake
• Decreaseddietary intake of phosphate is a rare cause of
hypophosphatemia because of ubiquity of phosphate in foods.

• Dietary sources of phosphate include fruits, vegetable, meats, and

dairy product.

• Vitamin D enhances the reabsorption of both phosphate and

calcium.

• Certain condition such as anorexa nervosa or chronic alcohilsm

may lead to hyphosphatemia in part due to this mechanism, as well
as increased renal excretion.
 Manifestation
of
phosphate deficiency
• Weakness of skeletal or smooth muscle

• Rhabdomyolisis via ATP depletion and the

consequent inability of muscle cells to maintain
membrane integrity

• Respiratory insufficiency = with severe

hypophosphatemia, particularly in malnousrishment.

• Impaired cardiac contractility = occurs, leading to

myocardial depression

• Impairs neurologic function (eg, confussion, seizure,

and coma, peripheral neurophaty, extrapontine
myelinolysis).

• Impaired hematologic function (eg, hemolytic anemia,

impaired leukocyte function)
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 Epidemiology

No prediction is know

Frequency Sex Age

United States: In all ages

• 2-3% of hospitalized
patients
• 30% of patients
admitted to ICUs.
• 17% HIV-positive
patients
• 38.5% falciparum
malaria
• 0.5% severe
hypophosphatemia
 Causes
Patient undergoing treatment for Patient withdrawing from alcohol
DKA

Other risk factor:

• Chronic alcoholism
• Chronic ingestion of phosphate-binding
Thyrotoxic Periodic Paralysis (TPP)
antacids • If considering the diagnosis, the presence
• Total parenteral nutrition (TPN) with of hypophosphatemia suggest TPP rather
inadequate phosphate supplementation than spontaneous periodic paralysis, in
• Refeeding after prolonged starvation which phosphorus levels are likely to be
(eg, anorexia nervosa) normal
 Differential
Diagnose

• Alcoholic ketoacidosis

• Anxiety

• CBRNE – Botulism

• Diabetic ketoacidosis

• Guillain – Barre Syndrome

• Hyperparathyroidism

• Hyperventilation Syndrome
 Laboratory
Studies

• Normal range : 2.5-4.5 mg/dL

• Hypophosphatemia
• Mild : 2-2.5 mg/dl atau 0.65-0.81mmol/L
• Moderate: 1-2 mg/dl atau 0.32-0.65
mmol/L
• Severe : <1 mg/dl atau 0.32 mmol/L
• Correlate serum phosphate level with clinical
finding
• Abnormalities in serum magnesium, calcium,
and potassium levels may occurs
• Hypomagnesemia often is associated
with the shift of phosphate into cells
• Hypercalcemia is common in primary
hyperparathyroidism
• Derangement in serum K may occur
with certain hypophosphatemia causes,
such as DKA and alcoholism.
 Treatment
• Treatmend is two fold.
• Correct any precipitating causes.
• Replace total body phosphates.
• Depending on the clinical situation,
replacement option include:
• Dietary phosphate,
• Oral phosphate preparation • Mild to moderately severe, asymptomatic
• IV phosphate hypophosphatemia
• Hypophosphatemia and hypokalemia can • Spontaneously normalize over several days
coexist in certain disorders like DKA, when factors including are corrected.
• May require oral phosphate replacement
alcoholism, so replacement with K salt is
• In minimal symptoms or moderate
most appropriate.
hypophosphatemia, providing oral phosphate
replacement may be desirable
• The average adult consumes 1 gram of
phosphorus daily
• Phosphorus preparation with Na & K are available,
but they have disadvantage, including causing
osmotic diarrhea, volume overload, or hyeperklemia
• Usual starting doses are 2-3 grams of elemental
phosphorus in divided doses.
 Emergency
Treatment
• Severe/symptomatic hypophosphatemia
• Patients with symptoms of hypophosphatemia or with
serum phosphate levels <1 mg/dL require IV phosphate
replacement.

• The intracellular nature of phosphate level difficult &

predicting the amount required to replenish cellular
store nearly impossible.

• Accordingly, recomendtation for IV phosphate in the

literature are varied & baes on therapeutic experiences
with limited numbers of patients

• Avoid hyperphosphatemia when replacing phosphorus

intraveneously, as this can lo hypocalcemia (leading to
tetany) and calcium-phosphate deposition in tissues
(eye, heart, kidney, lung)
 Medication

Electrolyte supplement
• Potassium phosphate/sodium acid phosphate
• IV preparation (eg, sodium phosphate (Na2
HPO4 and NAH2 PO4)
• Potassium phosphate (K2 HPO4 and KH2
PO4)
• Response to IV phosphorus supplementation
varies widely and may be associated with
hyperphosphatemia and hypocalcemia
• Rate of infusion and choice of initial dosage should
be based on severity of hypophosphatemia and
presence of symptoms.
• When treating hypophosphatemia with potassium
phosphate, potassium level may limit amount of
phosphate that can be given safely
Further inpatient care
• Severe or symptomatic = admission for IV replacement

• Equilibration of IV tiwh intracellular phosphate usually

leads to recurrence f hypophosphatemia monitoring &
replacement is necessary over 2-3 days.

• A rational approach to IV replacement is to administer a

predefined amount of phosphate, then reevaluate the
resulting serum phosphate every 6 hours to guide further
treatment.
Complications
• Complication of IV phosphate
replacement:
• Hypocalcemia (tetany) and
hyprphosphatemia.
• Always administer IV
phosphate cautiously in
patients with renal failure.
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