Everything You Need To Know About Liver

The liver is the second largest organ system found in the human body weighing in at approximately 3 lbs. In terms of importance for life, the liver ranks fourth behind the brain, heart, and lungs.

Chronic liver dysfunction can pose a serious threat for health and wellbeing. It has been estimated in the US that liver disease is the second leading cause of death amongst digestive disorders.[1]  Approximately 30 million Americans have some form of liver disease including 20% of Americans with non-alcoholic fatty liver disease (NAFLD). The latter is most problematic due to the strong link between NAFLD and the onset of metabolic syndrome.[2]

The liver is involved with about 500 different processes in the human body.

A collection of diseases including heart disease, type II diabetes, and cancer, metabolic syndrome affects about one-third of the US population among all adults with prevalence reaching 50% in adults 60 years of age or older.[3] Unfortunately, those figures are only rising.

The progression of NAFLD is related to the many digestive and metabolic functions the liver performs. The largest gland in the body, the liver serves a variety of purposes including roles in metabolism, detoxification, digestion, and immunity.[4]  Complications from NAFLD include liver cirrhosis and primary liver cancer which both have grim prognoses. Each year it is estimated that 21,000 new cases of primary liver cancer are diagnosed with approximately 15,000 deaths.[5]

The liver can process 1.4 liters of blood every minute.

The link between liver health and overall health is unquestioned. Understanding the everyday health practices that affect the liver will allow one to maintain a higher quality of life. Here are some interesting facts about the liver:

Interesting Facts

• The liver is the largest internal organ,[6] second only to skin in terms of size.
• The liver is classified as a gland and is the largest gland in the human body. The liver secretes a variety of enzymes and metabolic modifiers important for life.
• The liver is the most metabolically active tissue in the human body accounting for 27% of basal metabolic rate (BMR).[7] The BMR accounts for all the energy consumed by a tissue. The liver tops the heart (≈ 60 beats/min), the lungs, and brain, all of which are highly active body tissue.
• The liver is involved with about 500 different processes in the human body. [6] Human metabolism, which accounts for all of the chemical reactions that occur in the body on a moment-to-moment basis, largely takes place in the liver.
• At any given moment, approximately 10% of blood volume is found in the liver. [6] Blood from both general circulation and portal circulation (digestive system) are processed by the liver.
• The liver can process 1.4 liters of blood every minute. [6] That is three-quarters of a standard bottle of soda every minute.
• The liver is capable of regeneration and therefore can be transplanted.⁵ The health of the individual receiving the liver transplant will affect the regenerative process.

Liver Anatomy

The liver is located in the upper right quadrant of the abdominal cavity just below the diaphragm, and sits on top of the stomach, right kidney, and intestine.[8] The liver is shaped like a cone and can be broken up into segments. Typically, the liver is separated into right and left lobes delineated by connective tissue called the falciform ligament. However, the liver can be further separated into segments when distinguishing the path of blood through the tissue.

At any given moment, approximately 10% of blood volume is found in the liver.

The liver contains a large amount of blood vessels which both supply the tissue with oxygenated blood and input blood from other systems such as the digestive system for processing. The major blood vessels that enter and exit the liver are:

• The hepatic artery (supplies oxygenated blood to the liver)
• The inferior vena cava (IVC) [Returns blood leaving the liver and the lower extremities (legs) to the heart for oxygenation and circulation]
• The portal vein, which carries the blood from the digestive system that collects any accumulated nutrients from the diet.

Each branch of the major blood vessels entering the liver correspond with a different lobe, which is the preferred segmentation of the liver for surgeons. The major blood vessels entering the liver spread deep into the tissue and intersect at specialized blood vessels called sinusoids. Any nutrient or non-nutrient entity that is sent to the liver for processing is pooled in the sinusoid vessels and are emptied into the IVC.[9] The cellular level of the liver is organized into functional units called lobules. [9]

Functions of the Liver

The functions of the liver are diverse and are dependent on cell type and a phenomenon in the liver called zonation which has been linked to the level of oxygen the cells in each zone receive. [9]

The most abundant cells of the liver are the hepatocytes, which account for 75-80% of the total cell count.[10] Hepatocytes can perform a variety functions including energy nutrient balance, energy nutrient metabolism, digestion support, and detoxification of potentially harmful substances such as drugs and alcohol. [10]

The liver is the first stop for most of our ingested nutrients. The portal vein is a direct link between the gastro-intestinal (GI) tract and the liver. Absorbed nutrients are transported directly to the liver for processing before entering the general circulation.

The liver is capable of regeneration and therefore can be transplanted!

Accompanying the nutrients are many substances that can be harmful to the body. The liver hepatocytes can perform a variety of chemical reactions to eliminate threats, such as environmental toxins, then shuttle the product to the kidneys to be removed via urine. All the energy nutrients (carbohydrate, fats, and proteins) are synthesized in the liver.

The liver plays a role in blood sugar dynamics. The liver can store glucose and can produce new glucose from various metabolic precursors. In response to the hormone glucagon, which signals low blood glucose concentrations, the liver can secrete glucose into the blood to reestablish normal values.

The liver also can regulate fats by the synthesis of both fatty acids and cholesterol. The fate of new fats are regulated by the livers interaction with lipoproteins, a variety of which are produced for the transport of fats around the body. The name lipoprotein is indicative of the function each type performs (lipo=fatty acids + protein). Fats create the ball-like structure of lipoproteins while the protein portion gives information to the body’s cell types on what to do with the cargo. Each type of lipoprotein is distinguished by size, density (ratio of fat to protein), and cargo (primarily fats).

Human metabolism, which accounts for all of the chemical reactions that occur in the body on a moment-to-moment basis, largely takes place in the liver.

The most notable varieties of lipoproteins are LDL and HDL (low-density lipoprotein and high-density lipoprotein), often referred to as “bad” and “good” cholesterol. The primary function of LDL and HDL is to transport cholesterol to and from the liver which has been linked to the progression of heart disease.

Proteins are both made and metabolized in the liver. Hepatocytes contain a large amount of rough endoplasmic reticulum (rER) and ribosomes. Both rER and ribosomes are important cell organelles that allow the cell to take genetic information from the nucleus, translate that code, and build a protein. The liver can also perform a process called deamination, which allows for protein utilization as an energy source, important during periods of low energy intake.

Many non-energy nutrients are activated by the liver. For example, vitamin D, which can be provided by the diet and be made from cholesterol in the skin after exposure to UV light (sun exposure), must be completely activated by the liver before it can help maintain calcium balance and bone health.

The liver is also involved in immune functioning. Specialized macrophages (immune cells) called Kupffer cells are located in the liver.[8]  Kupffer cells engage any microorganisms that may have passed through the border created by the cells of the small intestine during nutrient absorption.

One final vital function of the liver is the storage of valuable nutrients such as vitamin A, vitamin K, and iron.

Common Liver Diseases

The most common liver diseases most associated with the United States can all be traced to a specific initiating event called fatty liver. Development of fatty liver can be traced to two events: excessive alcohol consumption and excessive processed carbohydrate consumption.[1]  The latter is more problematic and is often called non-alcoholic fatty liver disease (NAFLD). The incidence of NAFLD is rising in both adult populations and children.[11]  The more severe version of NAFLD is referred to as NASH (nonalcohol steatohepatitis) and is prevalent in 2-3% of the population. The most afflicted are the morbidly obese. [11]

If NAFLD is not treated, many life-threatening complications can occur. First and foremost is liver fibrosis, which is characterized by increased scar tissue formation by Kupffer cells. Chronic liver fibrosis leads to liver cirrhosis which usually requires a liver transplant. NAFLD is a precursor for metabolic syndrome which can lead to insulin resistance (type II diabetes) and heart disease, two of the most prominent causes of death in the US.

The progression of NAFLD can also lead to primary liver cancer. The formation of cancer in the liver is most often associated with cells forming in other tissues and metastasizing to the liver. However, a type of primary cancer called hepatocellular carcinoma (HCC) is commonly associated with NAFLD. The prognosis for HCC is very poor. Most are given 3-6 months to live.[12]

The other common liver disease is the hepatitis virus. Viral hepatitis is caused by 5 different viruses with strains B and C accounting for the majority of cases. Both can lead to liver cancer and cirrhosis if not treated.[13]

Liver Health

Liver health is easily traced to overall health habits. The progression of fatty liver requires the environmental trigger to occur; therefore, quality health habits are most associated with prevention of NAFLD.

There has been a strong link between energy dense processed foods and NAFLD. Most notably are the roles of processed sugars and starches such as sugar, wheat flour, and high fructose corn syrup.

The latter, high fructose corn syrup, is a common ingredient used to sweeten overly processed foods because of the cost to profit ratio it allows producers to obtain. High fructose corn syrup is used in many processed foods including candy and soda. While all “free” carbohydrates (extracted, easily absorbed, ex. sugar and flour ) are risky with respect to NAFLD, high fructose corn syrup seems to be more dangerous.

A recent study compared a control diet with a high fructose diet of similar macronutrient composition in an animal model. The results showed a significant trend towards increased fat accumulation and increased markers of inflammation in the animals fed the high fructose diet.[14]

Exercise can greatly reduce the risk of NAFLD, as well as reverse the effects, provided permanent damage has not over-accumulated. High-frequency exercise has been shown to reduce incidence of NAFLD by 16% and improved recovery from NAFLD by 40%.[15]  The type of exercise has little effect on the outcome, with both endurance-based (cardio) and resistance-based (weight training) programs serving equally.[16]

Overall, regular activity and diets low in processed, energy dense foods are the best option for liver health. Some foods that have a positive effect on liver health include citrus fruits, apples, avocados, beets, garlic, and green tea.[17]

Another factor affecting liver health is the health of the GI tract. Avoiding processed foods and using probiotic foods such as kombucha (a fermented tea drink), can reduce gut permeability and prevent the liver from overexposure to potentially harmful materials accumulated in the portal vein. Other foods that are considered probiotic include kefir (fermented dairy) and kimchee (fermented cabbage).

To avoid infection from the hepatitis virus it is best to avoid direct contact with blood or body fluids from infected individuals. This includes unprotected sex, a common route for hepatitis C.