Urea

Do you know how urine is produced? What about what is inside urine? As strange as it may sound, within the next minute, 1.2 litres of blood will pass through your kidneys, where urea and other waste products are filtered out, forming urine. One of the main compounds in urine is urea, a waste product in the metabolism of nitrogen-containing substances such as proteins. In this article, we will learn more about urea, its definition, functions, what causes high urea in urine and its side effects, and even some common uses of urea! 

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    What is the Definition of Urea?

    Our body contains a lot of protein, constantly being made and broken down in different tissues. Proteins are amino acids with the general chemical formula of R-CH(NH2)-COOH, where R is a side chain.

    As you may notice, there is at least one amine group -NH2 in all amino acids.

    After a meal, digested food molecules such as amino acids are absorbed into the blood in the small intestine. The blood then carries them to the liver via the portal circulation. Most times, there is a surplus of amino acids absorbed; instead, the body needs other molecules such as fatty acids or different types of amino acids. Liver cells break down excess amino acids in the body that cannot be stored into intermediate compounds that can be used for making other amino acids, sugars, or fatty acids.

    Enzymes in the liver, such as transaminases, split up the surplus of amino acid molecules, removing the amine group from the amino acids. The part of the molecule which contains carbon can then be used for making other types of amino acids. Alternatively, it can be converted to glucose and stored as glycogen in the liver or converted to fatty acids and stored in fatty tissues.

    The amine group, which contains nitrogen, is turned into ammonia, which is highly toxic. So, it is immediately converted into urea, an inorganic molecule with the chemical formula of CO(NH2)2, in a cycle of reactions called the urea cycle.

    Urea is considered a waste product, and high levels of it in the blood can be harmful. Therefore, most urea must be filtered out of the blood. Most of the blood urea is filtered out in the kidneys, with a small amount excreted in sweat.

    Urea is a by-product of amino acid breakdown in the liver that is filtered out of the blood in the kidneys, with some also excreted in sweat.

    The Functions of Urea

    During the catabolism of amino acids, the amine group that is released becomes ammonia. Free ammonia is very toxic to cells, particularly nerve cells in the brain. The liver rapidly converts ammonia to urea in a series of reactions knowns as the urea cycle.

    Urea is a lot less toxic than ammonia, and it is eventually excreted in the urine.

    Production of urea allows the blood ammonia levels to be maintained at a low and safe concentration.

    Urea is also one of the big players in the corticomedullary gradient in the kidneys. As it gets deeper into the kidneys, the concentration of urea increases. The fluid that is collected is high in waste products, but it also contains a lot of water molecules. Water moves from an area of low osmolarity to high osmolarity. As the fluid moves, the osmolarity outside becomes more significant than inside. So water leaves. The corticomedullary gradient ensures that throughout the path of the collecting duct, the osmolarity outside the duct is greater than the osmolarity inside. Therefore, water constantly moves out of the duct, producing concentrated urine.

    The corticomedullary osmotic gradient is the osmolarity gradient in the fluid between kidney cells.

    Sodium ions and urea are the primary solutes in this gradient, and their concentration increases as it gets deeper into the kidneys.

    Osmolarity is a term that describes the number of particles of solute in a solution.

    Causes of High Urea in Urine

    The kidneys are vital homeostatic organs located in the back of the abdomen that filter out excess water, ions, and urea from roughly 150 litres of blood daily to produce about 2 litres of urine.

    You can consider your kidneys to be your body's waste treatment facilities!

    In addition to filtering blood, the kidneys regulate the water content of our blood and synthesise important hormones such as erythropoietin and activated vitamin D.

    The medulla and cortex are the two primary sections of the kidney. The cortex is the lighter portion found outside, while the medulla is in the middle, connecting to the renal pelvis and ureter.

    Each kidney has around a million functioning filtering units called nephrons. Each nephron stretches from the cortex to the medulla and comprises many components, each with a specific role.

    Blood pressure is slightly higher in the glomerulus, a collection of capillaries with walls like a sieve. Tiny molecules such as water, glucose, urea, and ions can pass through the sieve, but larger molecules, such as proteins and blood cells, remain in the glomerulus and are returned to blood circulation.

    The collection of tiny molecules and filtered water runs down a series of nephrons and enters the collecting duct. The nephrons play an essential role in creating an osmotic gradient, called the corticomedullary gradient, that increases as it goes deeper into the medulla. Later, this gradient allows more water to be reabsorbed in the collecting duct. The end product is highly concentrated urine with high amounts of waste products that eventually flow into the bladder via the ureters.

    An osmotic gradient refers to the differences in concentration between two solutions on different sides of a semipermeable membrane.

    As we explained earlier, urea is a by-product of protein metabolism. Therefore, if for any reason protein metabolism is increased in the body, more urea will be produced and excreted in the urine.

    For example, high amounts of protein in the diet can lead to higher protein breakdown and the production of more urea.

    Alternatively, when the body is dehydrated and needs to preserve its water content, more water is reabsorbed from the urine in the kidneys. This increases the concentration of urea in the urine.

    What Are the Side Effects of Urea?

    Even though urea is less toxic than ammonia, high urea levels in the blood can have serious consequences. The term uraemia is used to describe elevated urea concentrations in the blood.

    Typical amounts of urea in the blood range from 2.5 - 7.8 mmol/L.

    • Seizures,

    • coma,

    • cardiac arrest,

    • and death

    Are a few severe side effects of untreated uraemia.

    In addition, high urea levels can accelerate platelet removal and impair their ability to bind to damaged sites along blood vessels. Platelets are the primary agents that initiate the cascade for clot formation. As a result, untreated uraemia can lead to spontaneous bleeding. This can occur in the gut or brain, leading to further complications.

    Urea is filtered out of the blood by the kidneys. If the kidneys stop filtering the blood adequately, urea will accumulate in the blood. Kidney problems can be classified into two groups: acute kidney injury (AKI) and chronic kidney disease (CKD).

    • AKI is when the kidneys suddenly stop working correctly, typically because of another severe disease.
    • CKD is a long-term disorder in which the kidneys do not function as well as they should.

    AKI and CKD can lead to the build-up of waste products in the blood. But CKD leads to uraemia more often than AKI.

    Common Uses of Urea

    Urea became the first organic molecule that could be synthetically made. It is a compound with many applications in medical and non-medical fields.

    Agriculture

    Urea is an ideal soil fertiliser since it has more nitrogen content ratio than all solid nitrogen-carrying fertilisers. Once added to the soil, urea is broken down into ammonia and carbon dioxide. The bacteria in the ground then convert the ammonia to nitrate, which is then absorbed by the plant roots.

    The plant uses nitrate for making organic nitrogen-containing compounds such as amino acids and nucleotides.

    Car Industry

    Urea is used in catalytic converters of cars to reduce the omission of the dangerous nitrogen oxide compounds (NOx) in exhaust gases. In these catalytic converters, urea is injected into the exhaust system, where urea is broken down into ammonia and carbon dioxide. Ammonia then reacts with NOx gases and produces nitrogen gas and water, which are non-toxic compounds.

    Medical Applications

    A urea breath test is a tool that uses urea tagged with carbon-14 to check for the presence of Helicobacter pylori (H. pylori) in the stomach. H. pylori bacterial infection is associated with stomach and small intestine ulcers. This bacterium has an enzyme called urease that catalyses the breaks down of urea to ammonia and carbon dioxide. Ammonia in solution is basic, and it reacts with the acid in the stomach to ensure the environment is less acidic and more suitable for the bacteria to grow.

    There are two isotopes of carbon: carbon-13 and carbon-14.

    Carbon-13 is the stable isotope and one that is more commonly found, making carbon-14 rarer.

    In the urea breath test, the person being tested is given carbon-14 tagged urea to drink. If a person has H. pylori in their stomach, the bacteria convert the urea to ammonia and carbon dioxide. Therefore, the person would have higher amounts of carbon dioxide with carbon-14 in the air they exhale.

    Urea - Key takeaways

    • Proteins are constantly being made and broken down in the body. Proteins are made of amino acids, and during protein metabolism, the amine groups of amino acids are removed and converted to urea, which is eventually excreted in the urine.

    • Kidneys are vital organs that remove the excess water, ions, and urea from the blood.

    • In chronic kidney disease and acute kidney injury, the kidney is impaired and does not filter the blood as well as it should. This leads to the build-up of waste products such as urea in the blood.

    • High levels of urea in the blood can be toxic and lead to seizures, coma and eventually death.

    • Outside the body, urea is used for various applications. These include being used as fertiliser in agriculture, catalytic converters of automobiles, and urea breath tests.


    1. NHS Bristol Trust, Urea, https://www.nbt.nhs.uk/severn-pathology/requesting/test-information/urea#:~:text=Reference%20range%3A%202.5%20%2D%207.8%20mmol%2FL.
    Frequently Asked Questions about Urea

    What is urea's normal range?

    The normal range of urea in the blood is from 2.5 - 7.8 mmol/L.

    Is urea harmful to humans?

    High levels or urea can be harmful to humans. Even though urea is less toxic than ammonia, high levels of urea in the blood can have some serious consequences. Seizures, coma, cardiac arrest, and death are a few severe effects of untreated elevated blood urea levels. 

    What is Urea used for?

    Urea is a compound with many applications. Urea is used as fertilizer in agriculture, in catalytic converters of automobiles, as well in urea breath test. 

    Does urea come from urine?

    Urea is abundantly found in the urine of animals. 

    Urea is also commercially produced for industrial applications. This is done by reacting ammonia and carbon dioxide at very high temperatures.

    For industrial applications, 

    What are the functions of urea?

    The function of urea is to carry the amine group removed from amino acids during protein metabolism in the body. This is because urea is less toxic than ammonia. Furthermore, urea has many medical and nonmedical applications.  

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