Phosphate Flashcards
Hypophosphataemia - Causes
Causes alcohol excess acute liver failure diabetic ketoacidosis refeeding syndrome primary hyperparathyroidism osteomalacia Fanconi Syndrome
Hypophosphataemia - Consequences
Consequences red blood cell haemolysis white blood cell and platelet dysfunction muscle weakness and rhabdomyolysis central nervous system dysfunction
Low Phosphate and Refeeding Syndrome - Example Question
A 49-year-old man with a history of alcoholism has been admitted to the ward for a detoxification program. He was brought to the hospital by police in an intoxicated state. He has been treated with B vitamin replacement therapy and has now begun re-feeding. You are asked to see him because of acute shortness of breath and generalised muscle weakness. On examination his blood pressure is 100/80 mmHg, pulse is 86 beats per minute and regular. He has bilateral crackles on auscultation of his chest consistent with heart failure, and global 4/5 power weakness.
Which of the following is the most likely cause of his symptoms?
Low thiamine > Low phosphate Low potassium Low folate Low magnesium
Globalised muscle weakness coupled with symptoms of heart failure is consistent with re-feeding syndrome. This occurs because of intra-cellular movement of phosphate, thought to be related to be related to hyperinsulinaemia because of carbohydrate loading. Heart failure and muscle weakness can be avoided by ensuring that any feeds used contain adequate phosphate when used in the treatment of patients at risk of re-feeding syndrome, such as those with alcoholism and / or eating disorders.
Low thiamine results in Wernicke-Korsakoff syndrome. Although low potassium can result in muscle weakness and is seen in reactive hyperinsulinaemia, feeds normally contain adequate potassium to avoid this, hence it’s less likely than hypophosphataemia in this situation. Folate deficiency is manifest by anaemia, glossitis, and neuropathy, and magnesium deficiency presents with similar symptoms to hypocalcaemia.
Refeeding Syndrome
Refeeding syndrome
Refeeding syndrome describes the metabolic abnormalities which occur on feeding a person following a period of starvation. The metabolic consequences include: hypophosphataemia hypokalaemia hypomagnesaemia abnormal fluid balance
These abnormalities can lead to organ failure.
Prevention
NICE produced guidelines in 2006 on nutritional support. Refeeding syndrome may avoided by identifying patients at a high-risk of developing refeeding syndrome:
Patients are considered high-risk if one or more of the following:
BMI < 16 kg/m2
unintentional weight loss >15% over 3-6 months
little nutritional intake > 10 days
hypokalaemia, hypophosphataemia or hypomagnesaemia prior to feeding (unless high)
If two or more of the following:
BMI < 18.5 kg/m2
unintentional weight loss > 10% over 3-6 months
little nutritional intake > 5 days
history of: alcohol abuse, drug therapy including insulin, chemotherapy, diuretics and antacids
NICE recommend that if a patient hasn’t eaten for > 5 days, aim to re-feed at no more than 50% of requirements for the first 2 days.
Fanconi’s Syndrome
Fanconi syndrome
Fanconi syndrome describes a generalised disorder of renal tubular transport in the proximal convoluted tubule resulting in: type 2 (proximal) renal tubular acidosis polyuria aminoaciduria glycosuria phosphaturia osteomalacia
Causes cystinosis (most common cause in children) Sjogren's syndrome multiple myeloma MGUS nephrotic syndrome Wilson's disease
Fanconi syndrome is a generalised disorder of proximal renal tubular function. Reabsorption of filtered solutes is impaired and as a result, large quantities of bicarbonate, potassium, phosphate, glucose, uric acid and amino acids are lost in the urine. It is also associated with the development of type 2 (proximal) renal tubular acidosis.
Example Set of Blood Results: K+ 2.9 mmol/l LOW Phosphate 0.38 mmol/l LOW Urine dip Glucose ++ Protein ++ Sodium nitroprusside test Positive (due to aminoaciduria) Cl- 115 mmol/l ELEVATED Bicarbonate 18 mmol/l LOW
Fanconi’s Syndrome - Example Question
A 66-year-old gentleman is reviewed in the General Medical Clinic with a 4-week history of polyuria, polydipsia, and generalised muscle weakness. He denies weight loss but does describe the presence of deep aching pains in his arms, legs, and lower back.
His past medical history is remarkable for hypertension, treated with amlodipine 5mg once daily and ramipril 7.5mg once daily. He also tells you that he has an ‘antibody disorder’ that requires no specific treatment but necessitates yearly follow-up at the Haematology Clinic.
Examination reveals a well-looking gentleman. His pulse is 74 bpm and his blood pressure is 132/63mmHg. There is no conjunctival pallor and his chest is clear to auscultation. His abdomen is soft and non-tender.
A series of investigations are requested:
Hb 132 g/l Na+ 136 mmol/l Bilirubin 17 µmol/l Platelets 278 * 109/l K+ 2.9 mmol/l ALP 172 u/l WBC 6.5 * 109/l Cl- 115 mmol/l ALT 35 u/l Neuts 3.8 * 109/l Urea 5.2 mmol/l γGT 39 u/l Lymphs 1.8 * 109/l Creatinine 87 µmol/l Total Protein 92 g/l Eosin 0.01 * 109/l Albumin 40 g/l
Calcium 2.24 mmol/l Adj. Calcium 2.24 mmol/l Phosphate 0.38 mmol/l Bicarbonate 18 mmol/l Fasting glucose 4.9 mmol/l
Urine dip Glucose ++ Protein ++
Sodium nitroprusside test Positive
What is the most likely diagnosis?
Multiple myeloma > Fanconi syndrome Diabetes mellitus Cystinuria Pseudohypoaldosteronism
A difficult question: the patient has presented with fairly non-specific symptoms and a raft of metabolic abnormalities. The easiest approach is to consider each of the diagnoses in turn.
The history of bone pain combined with the presence of an underlying ‘antibody disorder’ could point you toward a diagnosis multiple myeloma. This is supported by the large discrepancy between the total protein and albumin, indicating that the patient’s globulins are grossly elevated. However, the blood tests also reveal the presence of normal haemoglobin, calcium, and renal function. Taken together, these abnormalities point instead to a diagnosis of monoclonal gammopathy of uncertain significance (MGUS).
Diabetes mellitus would explain the polyuria, polydipsia, and glycosuria, however, the normal fasting glucose makes this unlikely.
Pseudohypoaldosteronism is due to aldosterone resistance and leads to renal salt wasting and hyperkalaemia. This is inconsistent with the biochemistry in the vignette.
Fanconi syndrome is a generalised disorder of proximal renal tubular function. Reabsorption of filtered solutes is impaired and as a result, large quantities of bicarbonate, potassium, phosphate, glucose, uric acid and amino acids are lost in the urine. It is associated with the development of type 2 (proximal) renal tubular acidosis, as indicated by the elevated chloride and low bicarbonate in the patient’s blood results. The remaining metabolic abnormalities can all be explained by the loss of these solutes in the urine, which in turn explain the presence of glucose and protein on urine dipstick.
A number of congenital and acquired conditions can lead to the development of Fanconi syndrome. although onset in later life suggests an acquired cause. In this case, MGUS is likely to be the predisposing factor.
The clinical features that cause patients to seek treatment are usually polydipsia and polyuria secondary to the osmotic effect of the urinary solute load. Bone pain due to osteomalacia and muscle weakness due to hypophosphataemia may also occur. Hypokalaemia may cause palpitations and can occasionally result in sudden death due to cardiac arrhythmia.
Cystinuria causes recurrent renal calculi that typically present in the first decades of life. The diagnosis was historically made by the sodium nitroprusside test, which is included here as a red herring and is positive due to the generalised aminoaciduria associated with Fanconi syndrome.
