Do you have too much ammonia in your blood? Let's learn about the dangerous condition of hyperammonemia!

There are so many things going on inside our bodies, right? Sometimes, when these processes go a little out of whack, big problems can arise. For example, hyperammonemia is a serious condition that occurs when a waste product called ammonia increases in our blood. It is very important to be aware of this because it can have a big impact on your life if not taken care of properly.

What is Hyperammonemia?

Simply put, hyperammonemia is when your blood ammonia levels are abnormally high. Ammonia, or NH3, is a waste product produced in our intestines when we digest the proteins we eat. Normally, this ammonia goes to our liver and is processed there. We call this process the urea cycle . Through this cycle, ammonia is converted into a less harmful substance called urea and excreted in the urine. However, if something goes wrong with this urea cycle, or if the liver is unable to process this ammonia properly, ammonia starts to accumulate in the blood. This increase in ammonia in the blood is very toxic to our Central Nervous System (CNS) , which is the brain and spinal cord. That is why hyperammonemia is a condition that requires immediate medical attention and can even be life-threatening .

Who can develop this the most?

This condition, called hyperammonemia, can affect newborns, young children, and adults.

• Among adults, about 90% of those who suffer from this condition are those with cirrhosis of the liver .
• Newborn babies can develop this because they are born with a defect in the urea cycle (congenital urea cycle disorder) . These are genetic conditions.
• Also, severe liver failure and inherited metabolic diseases can cause hyperammonemia in young children.

It's hard to say exactly how common this is, as it can be caused by a variety of factors. But researchers estimate that urea cycle disorders, one of the causes, affect one in 250,000 babies born in the United States and one in 440,000 babies born internationally.

What are the causes of hyperammonemia?

There can be several reasons for this. These reasons can change with age. But in general, two of the main causes are liver problems and urea cycle disorders (UCDs) .

Due to liver problems

Our liver is the main organ that converts ammonia into urea. So if the liver is damaged or diseased, it cannot process ammonia properly. This is when ammonia builds up in the blood. Here are some liver-related conditions that can cause hyperammonemia:

• Liver disease : When the liver is damaged , its ability to process ammonia is limited. This is more common in severe liver disease, but even in people with stable liver disease, ammonia levels can sometimes suddenly rise, for example, if something happens in the stomach or intestines (gastrointestinal bleeding ) or if there is an electrolyte imbalance . This is the main cause of high ammonia levels in adults and children.
• Hepatic encephalopathy : This occurs when the liver is damaged and cannot process ammonia properly. Ammonia builds up in the blood and travels to the brain. This can cause confusion, disorientation , and even coma. It can sometimes be fatal.
• Cirrhosis of the liver: Cirrhosis is the replacement of healthy liver tissue with scar tissue. This can cause the liver to not function properly and can lead to hyperammonemia. Cirrhosis is a chronic liver disease.
• Acute liver failure: This is when the liver suddenly stops working. It can be caused by a variety of diseases and conditions. For example, drug-induced liver injury caused by certain medications, such as acetaminophen , accounts for 50% of all cases of acute liver failure in the United States. It accounts for 64% of cases of hyperammonemia in children.
• Decreased blood flow to your liver: If blood doesn't flow properly to your liver, the body can't send ammonia to the liver to be processed. Even then, ammonia builds up in the blood.
• Reye's syndrome:This is a very rare condition. It affects the blood, brain, and liver. It usually causes elevated blood ammonia levels and low blood glucose levels. It most commonly affects young children and adolescents who are recovering from viral infections such as chickenpox or the flu/influenza and who have taken aspirin for those symptoms. The exact cause of Reye's syndrome is not known. However, because of this risk, aspirin should not be given to young children and adolescents unless specifically recommended by a doctor.

Due to Urea Cycle Disorders (UCDs)

As we've discussed before, the urea cycle is the process by which toxic ammonia is converted into urea and excreted in the urine. This cycle has several steps, each of which requires a different type of enzyme. These enzymes are:

• N-acetyl-glutamate synthase (NAGS)
• Carbamoyl phosphate synthetase (CPS)
• Ornithine transcarbamylase (OTC)
• Argininosuccinate synthetase (AS)
• Argininosuccinic acid lyase (ASL)
• Arginase (ARG1)

If one of these enzymes is deficient, the urea cycle does not work properly. Ammonia builds up in the blood. This type of enzyme deficiency is called a urea cycle disorder (UCD). UCDs can cause hyperammonemia, which can be acute or chronic. UCDs are congenital conditions. Newborns with a complete deficiency of a urea cycle enzyme usually develop acute hyperammonemia within 24 to 72 hours of birth. Whether the enzyme deficiency is mild or partial, ammonia buildup can occur at any time in life, during illness, stress, or other stressful events. These UCDs account for 23% of cases of acute hyperammonemia in critically ill young children.

Other reasons

Apart from this, there may be several other reasons:

• Kidney (renal) failure: If the kidneys are unable to properly excrete urea due to kidney failure, it can cause ammonia to accumulate in the blood.
• Certain blood disorders: Hyperammonemia can also be caused by blood disorders such as multiple myeloma and acute leukemia.
• Certain infections: urease-producing organisms such as Proteus mirabilis , Escherichia coli (E. coli) and KlebsiellaBacterial infections such as streptococci, especially in children with congenital urinary tract defects and in older adults with urinary retention due to urinary tract infections (UTIs), can cause severe hyperammonemia.

What are the symptoms of Hyperammonemia?

Symptoms can vary greatly depending on how mild or severe the condition is, as well as the age at which it develops.

Mild symptoms common to children and adults

• Nausea and vomiting
• Stomach pain
• Frequent irritability
• Headache (headache)
• Difficulty with balance, coordination, and speech (ataxia)
• Behavioral changes

Additional mild symptoms that only affect children

• Failure to thrive
• Muscle weakness (hypotonia)
• Neurodevelopmental delays

Severe symptoms in children and adults

These are very dangerous symptoms. If you have any of these, you should seek medical advice immediately.

• Confusion and disorientation
• Mood swings
• Excessive sleepiness
• Changes in consciousness
• Seizures
• Rapid breathing (Hyperventilation)
• Coma

Warning: If you or someone close to you has these symptoms, please call 911 immediately, or go to the emergency department of your nearest hospital. Elevated blood ammonia levels are life-threatening and require immediate medical attention!

Symptoms in newborn babies

If a newborn baby is affected by hyperammonemia, the following symptoms usually appear within 24 to 72 hours of birth:

• Frequent irritability, frequent crying
• Vomiting
• Lethargy
• Seizures
• Grunting when breathing
• Rapid breathing (Hyperventilation)

Important: If your baby shows these symptoms, call the doctor immediately if you are still in the hospital. If you are at home, call 911 immediately, or take them to the nearest hospital. This is not something to delay.

How do doctors diagnose this?

Doctors usually suspect hyperammonemia by testing ammonia levels in the blood.

• For babies up to one month old, if the ammonia level in the blood is greater than 80 micromol/liter (80 micromol/L).
• For older children, if it is greater than 55 micromol/liter (55 micromol/L).
• In adults, if it is greater than 30 micromol/liter (30 micromol/L).

This unit of measurement (micromol/L) is a way of measuring the amount of ammonia in the blood.

What tests are done to detect this?

The main test is a blood test that measures the level of ammonia in your blood. If your ammonia level is high, your doctor may do other tests to find the cause. For example, blood tests to check your liver function and kidney function , as well as a urinalysis . Because hyperammonemia can damage the central nervous system and be life-threatening, your doctor may also do imaging tests, such as a CT (computed tomography) scan or MRI (magnetic resonance imaging) scan, to check for complications affecting the brain.

What are the treatments for hyperammonemia?

Treatment depends on the cause. For example, in an adult, it is due to liver disease or hepatic encephalopathy, or in a newborn, it is due to a urea cycle disorder (UCD). In acute hyperammonemia, the main goal is to reduce the level of ammonia in the blood and control specific complications such as cerebral edema and increased pressure around the brain (intracranial hypertension).

• If a newborn baby has hyperammonemia, doctors will stop giving them protein (because ammonia is produced when protein is digested) and instead give them glucose, a sugar solution, to provide calories. They will also use a procedure called hemodialysis . This involves cleaning the baby's blood and removing ammonia through a dialysis machine and a special filter (like an artificial kidney).
• People with partial urea cycle enzyme deficiency (UCD) who develop hyperammonemia due to stress, such as stress-induced hyperammonemia, are also given protein withdrawal and glucose as calories. Hemodialysis is only performed if their ammonia levels do not decrease within a few hours of initial treatment.
• The treatment for hepatic encephalopathy is to reduce the production of ammonia in the intestines. The first-line treatment is oral medications containing lactulose and lactitol . These sugars reduce the production and absorption of ammonia in the intestines.

Doctors may recommend dietary supplements such as these to help people with urea cycle disorders reduce the frequency of their symptoms:

• L-carnitine
• L-ornithine-L-aspartate
• Arginine

Are there ways to avoid this situation?

Because there are many causes of hyperammonemia, not all conditions can be prevented. However, you can take steps to prevent some types of liver disease, especially those related to your diet and lifestyle. If you are at risk for liver disease, your doctor may recommend making these lifestyle changes:

• It is okay to avoid or limit alcohol consumption.
• Avoid foods and drinks that contain trans fats or high-fructose corn syrup.
• To avoid liver damage, be very careful when using prescription and over-the-counter medications.
• Exercising regularly .
• Limiting the consumption of red meat.

To prevent Reye's syndrome, a condition that causes hyperammonemia in children and young adults, do not give aspirin to children for symptoms of a viral infection (such as the flu or chickenpox) unless specifically recommended by a doctor. Urea cycle defects (UCDs) are rare, but there are genetic tests to see if you have the genes that cause them. Talk to your doctor about this.

What is the prognosis for this condition?

The outlook for hyperammonemia, that is, the ability to recover, depends on several factors:

• How high your ammonia levels are.
• How long the ammonia level has been elevated.
• What causes hyperammonemia?

In general, the outlook for hyperammonemia is poor. If left untreated or treated late, irreversible brain swelling is associated with a high mortality rate. Unfortunately, no matter how quickly or aggressively a newborn is treated with severe hyperammonemia, there is no guarantee that the outcome will be good. In the United States, the 11-year survival rate for people with urea cycle defects (UCDs) who develop hyperammonemia early in life is about 35%. For those who develop hyperammonemia later in life, the survival rate is about 87%. The one-year and three-year survival rates of patients with severe hepatic encephalopathy due to hyperammonemia have been reported to be 42% and 23%, respectively.

What are the possible complications of hyperammonemia?

If this condition is not treated promptly, elevated ammonia levels can damage the central nervous system and lead to life-threatening complications. Such complications include:

• Cerebral edema
• Increased pressure around the brain (Intracranial hypertension)
• Brain herniation – This is most often caused by swelling of the brain and increased pressure around the brain.
• Coma
• Death

If someone has chronic mild hyperammonemia for a long time, they may develop intellectual disability and permanent behavioral and psychiatric problems.

When should we see a doctor?

If you or someone you care about has symptoms of hyperammonemia, call 911 immediately or go to the nearest hospital. This is not something to delay. If you have liver disease or partial urea cycle enzyme deficiency, it is very important to see your doctor regularly to manage your condition and monitor your ammonia levels.

Hyperammonemia is a serious condition that can be caused by several things. If you, your child, or your baby have these symptoms, seek help right away. If you have liver disease, or if someone in your family has urea cycle disorders (UCDs), talk to your doctor about your risk of developing hyperammonemia. They are there to help you.

Finally, remember this.

Okay, so here are some of the most important things you need to remember from what we've talked about:

• Hyperammonemia is a dangerously high level of ammonia in the blood. This is very harmful to our brain and nervous system.
• There can be several reasons for this. Liver problems and urea cycle disorders (UCDs) are the main causes.
• Symptoms vary depending on the severity of the condition and age. They can range from mild symptoms such as nausea, vomiting, and headache to more severe symptoms such as confusion, seizures, and coma. Newborns should also be especially concerned about their symptoms.
• If you have severe symptoms, you should seek medical advice without delay. This can be a life-or-death situation.
• Treatment depends on the cause. Prompt treatment can reduce ammonia levels and control complications.
• While some causes cannot be prevented, some risks can be reduced by maintaining a healthy lifestyle and taking care of your liver .
• Whether you have liver disease or someone in your family has UCDs, it's important to have regular medical checkups.

Don't forget, you know your health best. If you feel anything different or unusual, don't be afraid to talk to a doctor. Hyperammonemia, ammonia, liver, urea cycle, brain, symptoms, treatment