70. Metabolic disorders and organ dysfunctions in uraemia

Last updated on January 24, 2019 at 23:10


Uraemia means “urine in the blood”. Chronic renal failure is the underlying pathological disease that causes uraemia. Uraemia is the clinical condition people with chronic renal failure have and is what causes most of the symptoms related to it. Uraemia and chronic renal failure are sometimes used interchangeably.

By definition is uraemia the condition where the normal excretory functions are disturbed, which leads to accumulation in the blood of all substances that should be excreted in urine, like:

  • Nitrogen-containing waste products, like urea and creatinine
  • H+ (proton)
  • PO43- (phosphate)
  • SO42- (sulphate)
  • Aluminium
  • Na+ (sodium)
  • K+ (potassium)
  • Hormones like insulin, glucagon, gastrin and prolactin
  • Other uraemic toxins (see below)

In addition to abnormal excretion will reabsorption be deficient as well, meaning that the plasma concentration of these substances can fall:

  • Bicarbonate
  • Calcium
  • Iron
  • Protein

BUN (blood urea nitrogen) measures the amount of nitrogen as part of the urea molecule in the blood, instead of measuring the amount of urea itself. It’s really silly and is mostly in use in USA and America-influenced countries. However, you can and should think of BUN as the same as the urea content in the blood. In Norway at least, we use the urea level instead of BUN.

The urea level in the blood is called blood urea nitrogen (BUN). It’s normally between 6 and 20 mg/dL. The condition where there is high BUN (but no uraemia (yet)) is called azotaemia. Symptoms of uraemia start to appear when the BUN reaches around 80 mg/dL.

It’s difficult to pinpoint exactly at which phase of chronic renal failure uraemia occurs. Urea and creatinine levels in the serum have noticeable increase when GFR is below 50% of normal. However, phase I and II are often asymptomatic for the patient, even though they already have some degree of uraemia at phase II. Uraemia is most characteristic in end-stage renal failure.


From topic 64. Recall that end-stage renal failure occurs when GFR is less than 15% than normal. At this point will the excretory functions be so impaired that phosphate and protons are retained.

Not just one substance causes the problems in uraemia, but rather many. Uraemic toxins are substances that are normally present in very small amounts in the blood but are toxic when present in high concentration. The most important are:

  • Urea
  • Creatinine
  • Guanidino compounds (Includes three molecules: MG, GSA, GAA)
    • When urea accumulates will the urea cycle slow down, causing accumulation of arginine and ornithine. These amino acids will enter other pathways that form these guanidino compounds.
  • PTH
  • Ammonia
  • Uric acid

These substances are toxic by the following mechanisms:

  • They slow down cell metabolism by inhibiting enzymes non-specifically
  • They increase membrane permeability
  • They damage the neural, immune, haematopoietic and cardiovascular systems
  • They demyelinate nerves
  • They inhibit AVP (ADH) secretion
Consequences of uraemia
  • Cardiovascular
    • Hypertension (explained in topic 69)
    • High cardiac output (to compensate for anaemia)
    • Myocardial impairment (due to acidosis, hyperkalaemia, hypertension, anaemia)
    • Dilatative cardiomyopathy (due to uraemic toxins)
    • Rhythm abnormalities (due to electrolyte imbalance)
    • Fibrinous pericarditis
    • Widespread bleeding and oedema
  • Haematologic
    • Anaemia (explained in topic 69)
    • Decreased granulocyte number and function (due to uraemic toxins)
  • Respiratory
    • Pleuritis
    • Pulmonary oedema
  • Gastrointestinal
    • Especially in end-stage renal failure
    • Anorexia
    • Ulceration (due to hyperacidity due to increased gastrin)
    • Nausea, vomiting
  • Metabolic
    • Hypometabolism (due to enzyme inhibition)
    • Glucose utilization decreases -> Hyperglycaemia
    • Metabolic acidosis (due to increased H+ retention)
    • Cells lose K+ and gain Na+, Ca2+ and water, causing swelling
    • Enhanced protein catabolism, which increases production of urea
    • Bone deformities (explained in topic 69)
  • Neuromuscular
    • Enhanced neuromuscular excitability (due to hypocalcaemia)
    • Muscle atrophy (due to protein deficiency)
    • Uraemic encephalopathy (see topic 71)
    • Sensory, motor and autonomic problems
  • Symptoms
    • Itching
    • Fatigue
    • Nausea

Because of hyposthenuria is the failing kidney unable to deal with salt or water loads (increased salt or water intakes). Any of these will cause a quick rise in plasma volume (overfilling), leading to fast development of oedema, not only in the periphery but in the lung and brain also. The rise in plasma volume also causes a rise in the blood pressure. Salt and water intake must therefore be monitored closely.

Excess water intake may lead to hypotonicity.

Also because of hyposthenuria is the kidney unable to regulate salt reabsorption, meaning that the serum sodium level is almost completely dependent on the salt intake. This means that salt intake is also majorly affects the blood pressure and the tonicity. Excess salt intake will lead to hypertonicity.

Uraemia also has a macroscopical finding. Uraemic frost is a description for what looks like frost on the affected persons head. It occurs when the BUN level is above 200 mg/dL (not important), but is very uncommon nowadays as most people with renal failure are treated (mostly by dialysis), so that the BUN level never gets that high. The person’s sweat contains urea, and when the sweat evaporates will urea crystallize.


Black man with dandruff? No, it’s uraemic frost.

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69. Chronic renal failure. Causes, characteristics and progression

Next page:
71. Uremic coma

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