2. Dr. Abrar Ali Katpar
Nephrology Department
King Khalid Hospital-Hail
3. Phosphate is most abundant intracellular anion & is essential in All cells for:
Membrane structure,
Energy storage, &
Transport
It produces ATP, which provides energy for nearly all cell functions.
Is an essential component of DNA & RNA.
Is also necessary in RBCs for production of 2,3-diphosphoglycerate (2,3-DPG),
which facilitates release of O2 from Hb.
85% phosphorus is in bone as hydroxyapatite,
15% is present 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 explains the
systemic nature of injury caused by phosphate deficiency.
Normal range = 2.5-4.5 mg/dL or 0.81-1.45 mmol/L
Dr Abrar Ali Katpar
5/17/2013
3
4. Hypophosphatemia is defined as:
Mild
Moderate
Severe
2-2.5 mg/dL,
1-2 mg/dL,
< 1 mg/dL,
or 0.65-0.81 mmol/L
or 0.32-0.65 mmol/L
or 0.32 mmol/L
Mild to moderately severe hypophosphatemia is usually
asymptomatic.
Major clinical sequelae occurs in severe
hypophosphatemia.
As in the case of other intracellular ions (eg, K, Mag), a
decrease in the level of serum phosphate should be
distinguished from a decrease in total body storage of
phosphate (phosphate deficiency).
Dr Abrar Ali Katpar
5/17/2013
4
5. Phosphorus homeostasis is complex and regulated by the actions
of several hormones.
PTH causes phosphate to be released from bone and inhibits
renal reabsorption of phosphorus, resulting in phosphaturia.
Vitamin 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 shown to be important in phosphatewasting diseases, such as :
oncogenic osteomalacia,
X-linked hypophosphatemic rickets,
autosomal dominant hypophosphatemic rickets,
autosomal recessive hypophosphatemia, and
tumoral calcinosis.
Dr Abrar Ali Katpar
5/17/2013
5
6. Hypophosphatemia is caused by:
Intracellular shift of phosphate from serum,
2. Increased urinary excretion of phosphate,
3. Decreased intestinal absorption of phosphate,
4. Decreased dietary intake.
1.
Hypophosphatemia may be transient, reflecting
intracellular shift with minimal clinical consequences.
The disease also may reflect a deeper state of total
body phosphate depletion with significant sequelae.
Dr Abrar Ali Katpar
5/17/2013
6
7. Respiratory alkalosis moves phosphate into cells by
activating phosphofructokinase, which stimulates
intracellular glycolysis.
Glycolysis leads 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 alkalosis is one of the most common
causes of hypophosphatemia, discovery of
hypophosphatemia should prompt a search for the serious
causes of hyperventilation, when clinically appropriate.
Dr Abrar Ali Katpar
5/17/2013
7
8. 1. Intracellular shift
Administering carbohydrate lowers serum phosphate
by stimulating the release 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
into cells and cell products.
Dr Abrar Ali Katpar
5/17/2013
8
10. 1. Intracellular shift
DK is also an important cause of hypophosphatemia.
Metabolic acidosis and insulin deficiency will mobilize
intracellular phosphate stores, causing them to shift to the
extracellular space and leading to urinary losses.
Treatment of DKA with insulin causes phosphate to move
back into cells resulting in a decrease of serum phosphate
levels.
Routine replacement of phosphate in the setting of DKA is
not proven to decrease morbidity or mortality.
However, because patients in DKA are often hypokalemic
and hypophosphatemic, some clinicians replete these
losses with potassium phosphate salts.
Dr Abrar Ali Katpar
5/17/2013
10
11. 1. Intracellular shift
Catecholamines and beta-receptor agonists also
stimulate phosphate uptake into cells.
Certain rapidly growing malignancies (eg, acute
leukemia, lymphomas) may consume phosphate
preferentially, leading to hypophosphatemia.
In most cases of intracellular phosphate shift, serum
phosphate normalizes once the precipitating cause is
removed.
Dr Abrar Ali Katpar
5/17/2013
11
12. 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 seen in hyperosmolar hyperglycemic syndrome
(HHS), also produces increased urinary excretion of phosphorus.
Diuretics, including loop diuretics, thiazides, and carbonic anhydrase
inhibitors (eg, acetazolamide) interfere with the ability of the proximal tubule
to reabsorb phosphorus, thus producing hyperphosphaturia and potentially
leading to hypophosphatemia. Patients with transplanted kidneys, congenital
defects (X-linked hypophosphatemia [XLH] and autosomal dominant
hypophosphatemic rickets [ADHR]), or Fanconi syndrome (proximal tubule
dysfunction) also may excrete excess urinary phosphate.
There is also evidence that shows estrogen to be a downregulator of a renal
sodium phosphate cotransporter, causing significant hypophosphatemia in
patients.
Dr Abrar Ali Katpar
5/17/2013
12
13. 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 aluminum
hydroxide, aluminum carbonate, and calcium
carbonate).
Also, the intestine "senses" luminal concentrations of
phosphate and regulates the excretion of phosphate in
the kidney by elaborating novel factors that alter renal
phosphate reabsorption.
Dr Abrar Ali Katpar
5/17/2013
13
14. Decreased dietary intake of phosphate is a rare cause
of hypophosphatemia because of the ubiquity of
phosphate in foods.
Dietary sources of phosphate include fruits,
vegetables, meats, and dairy products.
Vitamin D enhances the absorption of both phosphate
and calcium.
Certain conditions such as anorexia nervosa or chronic
alcoholism may lead to hypophosphatemia in part due
to this mechanism, as well as increased renal
excretion.
Dr Abrar Ali Katpar
5/17/2013
14
15. Weakness of skeletal or smooth muscle.
It can involve any muscle group, alone or in combination, ranging from
ophthalmoplegia to proximal myopathy to dysphagia or ileus.
Rhabdomyolysis via ATP depletion and the consequent inability of
muscle cells to maintain membrane integrity.
Acute alcohol withdrawal= vulnerable to rhabdomyolysis secondary to
hypophosphatemia, which is caused by the rapid uptake of phosphate
into muscle cells.
Rarely rhabdomyolysis in DKA or being refed after starvation.
Respiratory insufficiency = with severe hypophosphatemia, particularly
in malnourishment.
Impaired cardiac contractility = occurs, leading to myocardial
depression.
BP and stroke volume have been shown to improve when serum
phosphorus is corrected.
The hypophosphatemic myocardium also has a reduced threshold for
ventricular arrhythmias.
Dr Abrar Ali Katpar
5/17/2013
15
16. Phosphate deficiency = impairs neurologic function, which may
be manifested by
confusion, seizures, and coma.
Peripheral neuropathy and ascending motor paralysis, similar to GB
syndrome.
Extrapontine myelinolysis also reported.
Hematologic function may be impaired.
The hemolytic anemia associated with severe hypophosphatemia
has been attributed to the inability of erythrocytes to maintain
integrity of cell membranes in the face of ATP depletion, leading to
their destruction in the spleen.
Compromises O2 delivery to the tissues due to decreases in
erythrocyte 2,3-DPG and the resulting leftward shift in the oxygenhemoglobin dissociation curve.
Leukocyte function is affected, which results in impaired
chemotaxis and phagocytosis.
Dr Abrar Ali Katpar
5/17/2013
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18. Frequency
United States
2-3% of hospitalized patients
30% of patients admitted to ICUs.
17% HIV-positive patients
38.5%, falciparum malaria,
Fortunately, severe hypophosphatemia is rare, occurring in
no more than 0.5% of hospitalized patients.
Sex
No predilection is known.
Age
In All ages.
Dr Abrar Ali Katpar
5/17/2013
18
19. Weakness is the most common symptom and may
involve any muscular system to any extent.
Diplopia
Dysarthria
Dysphagia
Weakness of trunk or extremities, particularly large
muscle groups
Symptoms of respiratory insufficiency or myocardial
depression may indicate hypophosphatemia.
Neurologic symptoms may vary, ranging from simple
paresthesias to profound alterations in mental status.
Dr Abrar Ali Katpar
5/17/2013
19
20. Muscle weakness = most common physical finding;
careful assessment of motor strength on neurologic examination is
critical.
Weakness may be subtle or profound and may involve any muscle
group.
Diminished respiratory rate & tidal volume;
Tachypnea may be present, an important clue to one of the most
common etiologies (respiratory alkalosis).
Hypotension & cardiac compromise.
Pale skin & conjunctivae secondary to the hemolytic anemia.
Signs of rhabdomyolysis.
Mental status abnormalities.
Dr Abrar Ali Katpar
5/17/2013
20
21. Patients withdrawing from alcohol.
Patients undergoing treatment for DKA.
Other risk factors
Chronic alcoholism
Chronic ingestion of phosphate-binding antacids
Total parenteral nutrition (TPN) with inadequate phosphate
supplementation
Refeeding after prolonged starvation (eg, anorexia nervosa)
Hypophosphatemia may also occur in the setting of
thyrotoxic periodic paralysis (TPP).
If considering this diagnosis, the presence of
hypophosphatemia suggests TPP rather than spontaneous
periodic paralysis, in which phosphorus levels are likely to be
normal.
Dr Abrar Ali Katpar
5/17/2013
21
24. Serum phosphate level
Normal range 2.5-4.5 mg/dL.
Hypophosphatemia
Mild =
Moderate =
Severe =
2-2.5 mg/dL
1-2 mg/dL
< 1 mg/dL
Since the serum phosphate level may not accurately reflect the level of
intracellular phosphate, always correlate serum phosphate levels with
clinical findings, especially before embarking upon aggressive
replacement therapy.
Abnormalities in serum magnesium, calcium, and potassium levels
may occur.
Hypomagnesemia often is associated with the shift of phosphate into
cells.
Hypercalcemia is common in primary hyperparathyroidism.
Derangements in serum K may occur with certain hypophosphatemia
causes, such as DKA and alcoholism.
Dr Abrar Ali Katpar
5/17/2013
24
25. Treatment is twofold.
Correct any precipitating causes.
Replace total body phosphates.
Depending on the clinical situation, replacement
options include:
Dietary phosphate,
Oral phosphate preparations, &
IV phosphate.
Dr Abrar Ali Katpar
5/17/2013
25
26. Hypophosphatemia and hypokalemia can coexist in certain disorders like DK &
alcoholism, so replacement with K salt is most appropriate.
Mild to moderately severe, asymptomatic hypophosphatemia
Spontaneously normalizes over several days when factors inducing are
corrected.
May require oral phosphate replacement.
In minimal symptoms or moderate hypophosphatemia, providing oral
phosphate replacement may be desirable.
The average adult consumes 1 gram of phosphorus daily.
A quart of cow's milk provides this amount of phosphorus (1 mg phosphorus/mL).
Dairy products have an additional advantage of supplying absorbable calcium, which
can help avoid the hypocalcemia that may result with more aggressive replacement
regimens.
Phosphorus preparations with Na & K are available, but they have
disadvantages, including causing osmotic diarrhea, volume overload, or
hyperkalemia.
Usual starting doses are 2-3 grams of elemental phosphorus in divided doses.
Dr Abrar Ali Katpar
5/17/2013
26
27. 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 makes interpreting a
low serum phosphate level difficult & predicting the amount
required to replenish cellular stores nearly impossible.
Accordingly, recommendations for IV phosphate in the
literature are varied & based on therapeutic experiences with
limited numbers of patients.
Avoid hyperphosphatemia when replacing phosphorus
intravenously, as this can lead to hypocalcemia (leading to
tetany) and calcium-phosphate deposition in tissues (eye,
heart, kidney, lung).
Dr Abrar Ali Katpar
5/17/2013
27
28. Class Summary
These agents are used to increase serum phosphorus to
normal physiologic levels.
Potassium phosphate/sodium acid phosphate
IV preparations are available as
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.
Dr Abrar Ali Katpar
5/17/2013
28
29. One Canadian group recently reported:
30 mmol of potassium phosphate via central line over 3
h for severe hypophosphatemia
15 mmol of potassium phosphate via central line over 3 h
for moderate hypophosphatemia.
Another study reported safely administering IV
phosphate at a rate of:
14.5 mmol of phosphate ions over 1 h.
Dr Abrar Ali Katpar
5/17/2013
29
30.
Tablet of = 250mg/298mg
852 mg dibasic potassium phosphate/155 mg monobasic Adverse Effects
potassium phosphate/130 mg sodium phosphate per
tablet yields 250 mg phosphorus/298 mg (13 mEq)
Frequency Not Defined
1. Headache
sodium /45 mg (1.1mEq) potassium
1.
Hypophosphatemia=
1-2 tablets PO QID
2.
Increase Urinary Phosphate=
1-2 tablets PO QID
Other Information
Take with a full glass of water
Avoid antacids containing aluminum, magnesium or
calcium
May precipitate passing of existing kidney stones
Other Indications & Uses
Lowers urinary calcium level in idiopathic hypercalcuria
Rickets may benefit from phosphate therapy, but high
serum phosphate may increase incidence of extra-skeletal
calcification.
Dr Abrar Ali Katpar
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Dizziness
Confusion
Weakness or heaviness of legs
Numbness or tingling
Tachycardia
Shortness of breath
Gastrointestinal upset
Mild laxative effect
Lower extremity swelling
Weight gain
Low urine output
Thirst
5/17/2013
30
31. Severe or symptomatic = admission for IV
replacement.
Equilibration of IV with intracellular phosphate
usually leads to recurrence of 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 level every 6 hours to
guide further treatment.
Dr Abrar Ali Katpar
5/17/2013
31
32. Complications of IV phosphate replacement,
including:
hypocalcemia (tetany) and hyperphosphatemia.
Avoid hyperphosphatemia because it can cause crystal
deposition in various tissues (eg, blood vessels, eye, lung,
heart, kidney).
Always administer IV phosphate cautiously in patients
with renal failure.
Dr Abrar Ali Katpar
5/17/2013
32
33. Consultations
Based on any underlying or suspected etiologies.
Patient Education
Patients and their families should be taught that 1 quart
of cow's milk provides the amount of phosphate
consumed by the average person/day.
Dr Abrar Ali Katpar
5/17/2013
33
