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High Urea Levels in the Blood (Azotemia, Uremia)

What is urea?

Urea is the organic compound high in nitrogen that is formed in the body during protein and ammonia breakdown. It is fairly harmless but large quantities can be dangerous and urea is constantly passed out by the kidneys in urine.

Proteins are broken down into simpler substances known as amino acids which are then metabolized further in a process known as deamination. This provides energy for the body or the amino acids can be converted into carbohydrates or fats as the body requires. Most of the deamination occurs in the liver with small quantities being processed in other tissues like the kidneys.

During the process, several compounds are formed as byproducts. Urea is one of these products along with ammonia. Urea does not affect the pH of the body fluids and is fairly harmless in low to moderate levels. Ammonia on the other hand can alter the pH of the blood and disrupt homeostasis. Apart from being a byproduct of protein breakdown, the bacteria in the gut may also manufacture ammonia which is then absorbed into the blood stream. The body converts any ammonia into urea.

Excess Urea in the Blood

Urea is not the only nitrogenous waste product in the blood. Several waste products become highly toxic to the body if it persists in the blood stream for longer than it should or accumulates to higher than normal levels. Despite the fact that a host of toxins are responsible for the clinical syndrome, it is urea and creatinine, a compound associated with muscle breakdown, that are mainly implicated.

There are two terms associated with high levels of urea in the blood. The first is azotemia which means an elevated level of nitrogenous wastes in the blood – blood urea nitrogen and creatinine. The second term is uremia which refers to the clinical signs and symptoms as well as the other biochemical abnormalities seen with elevated urea levels.

Azotemia is either prerenal or postrenal. In prerenal azotemia there is a disorder with blood flow to the kidney so nitrogenous waste products cannot be filtered out. With postrenal azotemia the blockage of the urinary tract beyond the kidney that prevents the excretion of urea and other wastes.

What is uremia?

Uremia is an accumulation of urea and other nitrogenous waste products in the blood which are usually excreted by the kidneys into the urine. With uremia, the clinical signs and symptoms of this underlying problem becomes evident due to the impact of nitrogenous waste products on other systems and disruption of other metabolic process. Depending on the severity of the waste accumulation, the condition can vary from being asymptomatic or even lead to death.

Causes of Uremia

Uremia is seen primarily with chronic kidney disease particularly end-stage renal disease (ESRD). The inability of the kidney to efficiently filter the blood of toxic products allows it to accumulate in the blood stream. This may be seen with a range of systemic and renal diseases including :

  • Glomerulonephritis
  • Urinary stones
  • Polycystic kidney disease
  • IgA nephropathy
  • Hypertension
  • Diabetes mellitus – diabetic nephropathy
  • Systemic lupus erythematosus (SLE)
  • Goodpasture syndrome

Signs and symptoms

The syndrome of uremia is not only associated with the nitrogenous waste products like urea. By affecting multiple symptoms and metabolic processes, other compounds, electrolytes and even hormones disrupt homeostasis. Some of the signs and symptoms seen with uremia are unrelated to nitrogenous waste products or its effects on other systems but rather arise from the primary disorder often being kidney failure.

These signs and symptoms are not specific to uremia but rather to chronic kidney disease.

  • Nausea and vomitng
  • Fluid retention (edema)
  • Dehydration
  • Pale to yellow sickly appearances of the skin (sallow not jaundice)
  • Itching of the skin (pruritis) and skin rashes (dermatitis)
  • Difficulty breathing
  • Pulmonary edema (fluid in the lungs)
  • High blood pressure
  • Inflammation of the gut, particularly the upper and lower portions – esophagitis, gastritis and colitis
  • Metabolic acidosis
  • Anemia
  • Congestive heart failure
  • Cardiomyopathy (enlarged heart)
  • Bleeding disorders
  • High potassium levels (hyperkalemia)
  • High phosphate levels (hyperphosphatemia)
  • Low calcium levels (hypocalcemia)
  • Peripheral neuropathy
  • Myopathy
  • Encephalopathy