Weighing in at around 3 pounds, the liver is the body’s second largest organ; only the skin is larger and heavier. The liver performs many essential functions related to digestion, metabolism, immunity, and the storage of nutrients within the body. These functions make the liver a vital organ without which the tissues of the body would quickly die from lack of energy and nutrients. Fortunately, the liver has an incredible capacity for regeneration of dead or damaged tissues; it is capable of growing as quic
Human Anatomy & Physiology of the Liver
Weighing in at around 3 pounds, the liver is the body’s second largest organ; only the skin is larger and heavier. The liver performs many essential functions related to digestion, metabolism, immunity, and the storage of nutrients within the body. These functions make the liver a vital organ without which the tissues of the body would quickly die from lack of energy and nutrients. Fortunately, the liver has an incredible capacity for regeneration of dead or damaged tissues; it is capable of growing as quickly as a cancerous tumor to restore its normal size and function.
Anatomy of the Liver
The liver is a roughly triangular organ that extends across the entire abdominal cavity just inferior to the diaphragm. Most of the liver’s mass is located on the right side of the body where it descends inferiorly toward the right kidney. The liver is made of very soft, pinkish-brown tissues encapsulated by a connective tissue capsule. This capsule is further covered and reinforced by the peritoneum of the abdominal cavity, which protects the liver and holds it in place within the abdomen.
The peritoneum connects the liver in 4 locations: the coronary ligament, the left and right triangular ligaments, and the falciform ligament. These connections are not true ligaments in the anatomical sense; rather, they are condensed regions of peritoneal membrane that support the liver.
- The wide coronary ligament connects the central superior portion of the liver to the diaphragm.
- Located on the lateral borders of the left and right lobes, respectively, the left and right triangular ligaments connect the superior ends of the liver to the diaphragm.
- The falciform ligament runs inferiorly from the diaphragm across the anterior edge of the liver to its inferior border. At the inferior end of the liver, the falciform ligament forms the round ligament (ligamentum teres) of the liver and connects the liver to the umbilicus. The round ligament is a remnant of the umbilical vein that carries blood into the body during fetal development.
The liver consists of 4 distinct lobes – the left, right, caudate, and quadrate lobes.
- The left and right lobes are the largest lobes and are separated by the falciform ligament. The right lobe is about 5 to 6 times larger than the tapered left lobe.
- The small caudate lobe extends from the posterior side of the right lobe and wraps around the inferior vena cava.
- The small quadrate lobe is inferior to the caudate lobe and extends from the posterior side of the right lobe and wraps around the gallbladder.
The tubes that carry bile through the liver and gallbladder are known as bile ducts and form a branched structure known as the biliary tree. Bile produced by liver cells drains into microscopic canals known as bile canaliculi. The countless bile canaliculi join together into many larger bile ducts found throughout the liver.
These bile ducts next join to form the larger left and right hepatic ducts, which carry bile from the left and right lobes of the liver. Those two hepatic ducts join to form the common hepatic duct that drains all bile away from the liver. The common hepatic duct finally joins with the cystic duct from the gallbladder to form the common bile duct, carrying bile to the duodenum of the small intestine. Most of the bile produced by the liver is pushed back up the cystic duct by peristalsis to arrive in the gallbladder for storage, until it is needed for digestion.
The blood supply of the liver is unique among all organs of the body due to the hepatic portal vein system. Blood traveling to the spleen, stomach, pancreas, gallbladder, and intestines passes through capillaries in these organs and is collected into the hepatic portal vein. The hepatic portal vein then delivers this blood to the tissues of the liver where the contents of the blood are divided up into smaller vessels and processed before being passed on to the rest of the body. Blood leaving the tissues of the liver collects into the hepatic veins that lead to the vena cava and return to the heart. The liver also has its own system of arteries and arterioles that provide oxygenated blood to its tissues just like any other organ.
The internal structure of the liver is made of around 100,000 small hexagonal functional units known as lobules. Each lobule consists of a central vein surrounded by 6 hepatic portal veins and 6 hepatic arteries. These blood vessels are connected by many capillary-like tubes called sinusoids, which extend from the portal veins and arteries to meet the central vein like spokes on a wheel.
Each sinusoid passes through liver tissue containing 2 main cell types: Kupffer cells and hepatocytes.
- Kupffer cells are a type of macrophage that capture and break down old, worn out red blood cells passing through the sinusoids.
- Hepatocytes are cuboidal epithelial cells that line the sinusoids and make up the majority of cells in the liver. Hepatocytes perform most of the liver’s functions – metabolism, storage, digestion, and bile production. Tiny bile collection vessels known as bile canaliculi run parallel to the sinusoids on the other side of the hepatocytes and drain into the bile ducts of the liver.
Physiology of the Liver
The liver plays an active role in the process of digestion through the production of bile. Bile is a mixture of water, bile salts, cholesterol, and the pigment bilirubin. Hepatocytes in the liver produce bile, which then passes through the bile ducts to be stored in the gallbladder. When food containing fats reaches the duodenum, the cells of the duodenum release the hormone cholecystokinin to stimulate the gallbladder to release bile. Bile travels through the bile ducts and is released into the duodenum where it emulsifies large masses of fat. The emulsification of fats by bile turns the large clumps of fat into smaller pieces that have more surface area and are therefore easier for the body to digest.
Bilirubin present in bile is a product of the liver’s digestion of worn out red blood cells. Kupffer cells in the liver catch and destroy old, worn out red blood cells and pass their components on to hepatocytes. Hepatocytes metabolize hemoglobin, the red oxygen-carrying pigment of red blood cells, into the components heme and globin. Globin protein is further broken down and used as an energy source for the body. The iron-containing heme group cannot be recycled by the body and is converted into the pigment bilirubin and added to bile to be excreted from the body. Bilirubin gives bile its distinctive greenish color. Intestinal bacteria further convert bilirubin into the brown pigment stercobilin, which gives feces their brown color.
The hepatocytes of the liver are tasked with many of the important metabolic jobs that support the cells of the body. Because all of the blood leaving the digestive system passes through the hepatic portal vein, the liver is responsible for metabolizing carbohydrate, lipids, and proteins into biologically useful materials.
Our digestive system breaks down carbohydrates into the monosaccharide glucose, which cells use as a primary energy source. Blood entering the liver through the hepatic portal vein is extremely rich in glucose from digested food. Hepatocytes absorb much of this glucose and store it as the macromolecule glycogen, a branched polysaccharide that allows the hepatocytes to pack away large amounts of glucose and quickly release glucose between meals. The absorption and release of glucose by the hepatocytes helps to maintain homeostasis and protects the rest of the body from dangerous spikes and drops in the blood glucose level. (See more about glucose in the body.)
Fatty acids in the blood passing through the liver are absorbed by hepatocytes and metabolized to produce energy in the form of ATP. Glycerol, another lipid component, is converted into glucose by hepatocytes through the process of gluconeogenesis. Hepatocytes can also produce lipids like cholesterol, phospholipids, and lipoproteins that are used by other cells throughout the body. Much of the cholesterol produced by hepatocytes gets excreted from the body as a component of bile.
Dietary proteins are broken down into their component amino acids by the digestive system before being passed on to the hepatic portal vein. Amino acids entering the liver require metabolic processing before they can be used as an energy source. Hepatocytes first remove the amine groups of the amino acids and convert them into ammonia and eventually urea. Urea is less toxic than ammonia and can be excreted in urine as a waste product of digestion. The remaining parts of the amino acids can be broken down into ATP or converted into new glucose molecules through the process of gluconeogenesis.
As blood from the digestive organs passes through the hepatic portal circulation, the hepatocytes of the liver monitor the contents of the blood and remove many potentially toxic substances before they can reach the rest of the body. Enzymes in hepatocytes metabolize many of these toxins such as alcohol and drugs into their inactive metabolites. And in order to keep hormone levels within homeostatic limits, the liver also metabolizes and removes from circulation hormones produced by the body’s own glands.
The liver provides storage of many essential nutrients, vitamins, and minerals obtained from blood passing through the hepatic portal system. Glucose is transported into hepatocytes under the influence of the hormone insulin and stored as the polysaccharide glycogen. Hepatocytes also absorb and store fatty acids from digested triglycerides. The storage of these nutrients allows the liver to maintain the homeostasis of blood glucose. Our liver also stores vitamins and minerals - such as vitamins A, D, E, K, and B12, and the minerals iron and copper - in order to provide a constant supply of these essential substances to the tissues of the body.
The liver is responsible for the production of several vital protein components of blood plasma: prothrombin, fibrinogen, and albumins. Prothrombin and fibrinogen proteins are coagulation factors involved in the formation of blood clots. Albumins are proteins that maintain the isotonic environment of the blood so that cells of the body do not gain or lose water in the presence of body fluids.
The liver functions as an organ of the immune system through the function of the Kupffer cells that line the sinusoids. Kupffer cells are a type of fixed macrophage that form part of the mononuclear phagocyte system along with macrophages in the spleen and lymph nodes. Kupffer cells play an important role by capturing and digesting bacteria, fungi, parasites, worn-out blood cells, and cellular debris. The large volume of blood passing through the hepatic portal system and the liver allows Kupffer cells to clean large volumes of blood very quickly.
|The Liver is an organ on the right side of the body weighing about 1.5Kg. It is distinctly the largest and a key organ of a human body, characterized by its muddy red colour. It is strategically the first port of entry from the process of digestion before nutrients leave for the rest of the body. It is the only organ in the human body that can regenerate unless struck by disease.|
|Essential Functions of the Liver are || |
- Using Food to make chemicals for essential functions of the body
- Processing drugs to modified forms that are easily absorbed
- Manufacturing essential substances
- Storage of nutrients for various processes
- Detoxification and excretion of substances that are no longer needed by the body
|The liver's key role as a member of the human body || |
- Production of Energy instantly
- Making proteins for body building and tissue repair
- Storing vitamins, minerals, and sugars for various functions
- Regulating fat transport across the body
- Regulating Blood clotting activities
- Regulating levels of chemicals and drugs in the blood
- Regulating hormone balance
- Helping in digestion by production of bile
- Helping to eliminate excess cholesterol levels
- Neutralizing poisonous substances
- Metabolism of alcohol
- A vital organ in blood formation before birth
- Helping to resist infection
- Regenerating its own damaged tissue
- Resisting infections by helping to remove bacteria from blood
- Cleansing Blood by discharging waste products
|Anatomy and physiology of the liver related to blood flow and biochemistry || |
|The Liver and Blood Flow|
|Systemic circulation: Oxygenated blood that has returned from the lungs to the left ventricle of the heart is pumped to all of the tissues of the body.|
|Pulmonary circulation: After reaching the tissues, blood is returned to the right side of the heart, from where it is pumped to the lungs and then returned to the left side of the heart after taking up oxygen and giving off carbon dioxide.|
|Portal circulation: Blood from the gut and spleen flow to and through the liver before returning to the right side of the heart. The large vein through which blood is brought to the liver is called the portal vein. After passing through the liver, blood flows into the hepatic vein, which leads into the inferior vena cava to the right side of the heart. The liver also receives some blood directly from the heart via the hepatic artery. In the esophagus, stomach, small intestine and rectum, the portal circulation and veins of the systemic circulation are connected. Under normal conditions, there is little to no back flow from the portal circulation into the systemic circulation. |
|The Liver and Biochemical Functions|
The liver performs many biochemical functions. Blood clotting factors are synthesized in the liver. Albumin, the major protein in the blood, is also synthesized in and secreted from the liver. The modification and/or synthesis of bile components also takes place in the liver. Many of the body's metabolic functions occur primarily in the liver including the metabolism of cholesterol and the conversion of proteins and fats into glucose. The liver is also where most drugs and toxins, including alcohol, are metabolized.
|Bilirubin Secretion |
|The liver is the site of bile formation. Bile contains bile salts, fatty acids, cholesterol, bilirubin and other compounds. The components of bile are synthesized and modified in hepatocytes (the predominant cell type in the liver) and secreted into small bile ducts within the liver itself. These small bile ducts form a branching network of progressively larger ducts that ultimately become the common bile duct that takes bile to the small intestine. Bilirubin is a yellow pigment that derives primarily from old red blood cells. Bilirubin is taken up by hepatocytes from the blood, modified in the hepatocytes to a water soluble form and secreted into the bile.|
Liver disease is an acute or chronic damage to the liver, usually caused by infection which can be viral or non-viral, abnormal changes seen through growth of tumors or tumor-like processes, changes or abnormalities in the metabolic process or naturally through a congenital process.
Diseases of the liver can also be categorized by the effect. Hepatitis is inflammation of the liver, cirrhosis involves scarring and progressive cell death, stones develop and form blockages, fatty liver and cancer are modification effects from causes that could be related to genetic defects, lifestyle, environment, or other diseases. All these prevent vital functions of the liver and may cause a build-up of damaging substances to the liver itself that could even be a threat to life. Liver diseases can be acute (usually for a short duration) or chronic (commonly lifelong)
|Liver disease is often discovered during routine testing. Having no symptoms at all is not uncommon.|
|Acute liver diseases present themselves with symptoms such as high bilirubin-counts (bilirubin is a by-product that is derived from the breakdown of red blood cells), jaundice (yellowing of the skin and eyes), dark yellow/orange coloured urine, or light, clay –coloured stools. A loss of appetite, nausea, vomiting, and diarrhea are not uncommon symptoms either. |
|Chronic liver disease can present themselves with jaundice (yellowing of the skin and eyes), dark yellow/orange coloured urine, abdominal swelling due to ascites (accumulation of fluid), pruritusunexplained weight loss or gain, (itching), and abdominal pain. Many of these symptoms may not be present until the disease has reached an advanced stage.|
|Diagnosis of a liver disease considers the patient’s history, symptoms if experienced, a physical examination, laboratory tests, often a radiological study and a biopsy are conducted. A hepatologist would be the expert to make the most reliable diagnosis and recommendations.|
Patients with liver diseases often have questions about their various results while trying to understand their importance. Our attempt is to explain some of the commonly prescribed tests for liver diseases that could be abnormal in individual patients. Please do bear in mind that abnormalities of these tests do not mean a diagnosis of a specific disease. Only a qualified physician who is aware of the entire case is able to give the best diagnosis.
| What laboratory tests are used to detect a problem with the liver?|| |
|Three types of tests are often used to detect liver disease; these tests measure the levels of specific enzymes, bilirubin, or protein present as part of assessing the liver function. A test sample is usually a blood sample. This sample is extracted from the body using a syringe.|
Enzymes: are proteins that help cells do their work. When cells are injured, enzymes tend to leak into the blood stream to produce higher-than-normal levels. All liver enzymes are measured by the amounts in the serum (blood), which is why they may be referred to as Serum ALT, AST, ALP. Three common enzymes used to detect liver diseases are:
- Alanine aminotransferase (ALT) – an enzyme found mainly in liver cells. Raised ALT levels can be due to damage or death of a liver cell causing its leakage in the blood stream. All forms of hepatitis cause damage to liver cells where a raised ALT level can lead the physician to suspect a liver disease. Its severity, however, will be subject to other tests as part of confirmation.
- Aspartate aminotransferase (AST) – another enzyme found in the liver and a few other places, particularly the heart and other muscles. It is less specific for liver disease alone as a raised AST could also be one early indication for a heart attack. Usually where the liver is inflamed, raised ALT and AST levels are in the ratio of 1:1. However, in specific diseases such as alcoholic hepatitis or liver shock, AST levels could be higher than blood ALT levels.
- Alkaline phosphatase (ALP) – an enzyme related to the bile ducts; often increased when they are blocked. Alkaline phosphatase is also produced by the kidneys, intestine, placenta and bone. Increased levels of ALP in the presence of normal or moderately elevated AST and ALT are suggestive of an obstruction in the bile duct or a bile duct disease such as primary biliary cirrhosis or primary sclerosing cholangitis. ALP elevated can also be an indication of a bone disorder as it is also produced in bones.
- Gamma-glutamyltranspeptidase (GGT) - another enzyme produced in the bile ducts which may be elevated in the blood alongside ALP in patients with bile duct diseases. GGT is an extremely sensitive test. There are also chances of increased GGT due to drugs and alcohol, particularly in heavy drinkers with no liver damage or inflammation.
|Bilirubin is a waste product made from destruction of old red blood cells. It is a yellow compound that causes the jaundice and dark yellow coloured urine when present in increased amounts. Bilirubin is removed from the blood by the liver that chemically modifies it by a process called conjugation and secretes as bile. Tests for bilirubin are |
- Total bilirubin measures all the bilirubin in the blood (direct + indirect)
- Conjugated or direct bilirubin - measures a form produced in the liver
- Un-conjugated or indirect bilirubin- measures an indirect form of bilirubin that was not converted to the conjugated form in the liver.
|A Variation in the ratios of direct and indirect bilirubin may be an indication for a liver disease that could be due to|
- increased production
- decreased uptake by the liver
- decreased conjugation
- decreased secretion from the liver
- due to blockage in the bile duct
|Albumin - tell how well the liver is synthesizing this protein. Low albumin levels are suggestive of poor liver function. Chronic liver diseases that are compensated may show normal albumin levels. Decreased levels of albumin are common in cirrhosis or where significant liver damage is present. Low levels of albumin can also be indications for other diseases such as malnutrition and certain kidney disorders.|
|Serum Protein electrophoresis is a test where the major proteins in the serum are separated in an electric field to determine concentrations. The four major types of serum proteins are albumin, alpha-globulins, beta-globulins and gamma-globulins. Serum protein electrophoresis is a useful test for patients with liver diseases as it can give the physician several diagnostic possibilities. For instance: in cirrhosis the albumin can be decreased but the gamma-globulin level may be elevated. High gamma-globulin levels may also be found in types of autoimmune hepatitis whereas a low alpha-globulin level could suggest a metabolic disease such as alpha-1-antitrypsis deficiency.|
|Prothrombin time (PT)- Factors needed for blood clotting are made in the liver. In cases where the liver function is abnormal, the synthesis and secretion of these factors into the blood is lowered. The PT is a test where clotting time becomes prolonged if factors made by the liver are found to be low in the blood. In compensated chronic liver diseases, clotting factors are not low until the liver reaches the stage of cirrhosis or significant damage. An elevated PT can also be seen in acute liver diseases where there may be severe liver damage which becomes normal once the patient recovers. PT time can also be prolonged in cases of vitamin K deficiency and from drugs such as warfarin (which is used as an anti-coagulant) and in other non-liver diseases.|
|Platelet count- These are the smallest units of blood cells that are involved in clotting. In certain individuals with a liver disease, the spleen becomes enlarged as the blood flow to the liver is impaired. Platelet counts fall following development of cirrhosis, however, platelet counts could be abnormal in disorders other than liver diseases.|
| What types of imaging are used to detect the severity of a liver disease ?|| |
|Imaging is important for making an accurate diagnosis on various biliary tract diseases and for diagnosing focal liver lesions such as tumours. In diagnosing diffuse hepatic diseases such as cirrhosis or hepatitis, it is limited.|
Transabdominal Ultrasound- is traditionally performed across the abdomen. Preparation for an ultrasound may require a period of fasting. It is the least expensive, safest and fairly sensitive for imaging the biliary system especially the gall-bladder. Often it is selected as the procedure of choice for screening biliary tract abnormalities and making a difference between a intrahepatic (that which occurs within liver cells and can be managed medically) and extrahepatic (that which occurs within a duct and can be managed surgically) causes of jaundice as well as detecting liver masses. The kidney, pancreas and blood vessels can also be seen on such ultrasounds. Usually presence of intestinal gas or obesity can obscure visibility.
Transabdominal ultrasound can detect focused liver lesions (> 1 cm in diameter) more accurately than diffuse diseases (eg, fatty liver, cirrhosis). Generally, cysts are echo-free; solid lesions (eg, tumors, abscesses) which are echogenic (can reflect high-frequency sound waves that allows imaging by ultrasound techniques).
Endoscopic Retrograde Cholangiopancreatography (ERCP) combines endoscopy through the second portion of the duodenum with contrast imaging of the biliary and pancreatic ducts. An endoscope is placed in the descending duodenum, then where the Papilla of Vater is cannulated (a procedure involving adding a tube so that fluids are drained to maximize the effect of the procedure) Meanwhile the pancreatic and biliary ducts are injected with contrast. ERCP is the procedure of choice when bile duct stones are suspected but have not been found on less invasive tests. The test is especially valuable for diagnosing correctable biliary tract lesions causing persistent jaundice (eg, stone, stricture, sphincter of Oddi dysfunction). Besides providing excellent images of the biliary tract and pancreas, ERCP reveals some of the upper GI tract. This procedure allows biopsies and other interventional procedures to be performed such as biliary stone extraction.
|Carcinoma (cancers) also appear as nonspecific solid mass. Ultrasound has been used to screen for hepatocellular carcinoma in patients at high risk (those with chronic hepatitis B). This ability to localize focal lesions can permits ultrasound-guided aspiration and biopsy.|
|Doppler ultrasound is a noninvasive method that assesses direction of blood flow and patency (extent of any obstruction) of key blood vessels around the liver. These are the portal vein and hepatic artery.70% of the blood and nutrients are supplied to the liver is through the portal vein and 30% through the hepatic artery. Doppler ultrasound can reveal evidence of portal hypertension with collateral flow, assess the patency (obstruction) of liver shunts (eg, surgical portocaval, percutaneous transhepatic), and reveal hepatic artery thrombosis after a liver transplantation. It also can detect any unusual vascular structures. Most patients with cirrhosis are recommended a Doppler ultrasound.|
|Computerized Tomography (CT) is commonly used to identify hepatic masses, particularly small metastases. It has an accuracy of about 80%. A CT with an intravenous (IV) contrast is accurate for diagnosing carvenous (deep-set) hemangiomas of the liver as well as distinguishing them from other abdominal masses. Unlike an ultrasound, neither obesity nor intestinal gas can cloud a CT image. CT can detect fatty liver and increased hepatic density possibly associated with iron overload. However, a CT is less helpful than ultrasound in diagnosing biliary obstruction.|
|Magnetic Resonance Imaging (MRI) consists of imaging blood vessels (without using a contrast dye) and hepatic tissues. It is an expensive technique where its indications are still evolving. MRI is superior to CT and ultrasound for diagnosing diffuse liver diseases such as fatty liver and hemochromatosis and for clarifying some focal defects such as hemangiomas. MRI can reveal blood flow and complements doppler ultrasound and CT angiography in diagnosing any vascular abnormalities and in performing vascular mapping before a liver transplantation.|
|Magnetic Resonance Cholangiopancreatography (MRCP). MRCP is more sensitive than CT or ultrasound in diagnosing common bile duct abnormalities, particularly stones. Its images are comparable to those from an ERCP and percutaneous transhepatic cholangiography, which are more invasive. MRCP is a useful screening tool where biliary obstruction is suspected and a usual step before proceeding to therapeutic ERCP.|
Percutaneous transhepatic cholangiography (PTC): PTC involves puncture of the liver with a needle under fluoroscopic or ultrasound guidance to cannulate (a procedure involving adding a tube so that fluids are drained to maximize the effect of the procedure) the peripheral intrahepatic bile duct system which is just above the common hepatic duct where contrast material is injected. PTC is highly diagnostic for biliary disease and can be therapeutic such as during decompression of the biliary system. However, ERCP is generally preferred because PTC causes complications such as sepsis, bleeding, bile leaks).
Liver biopsy can provide a tissue of the liver, which is then mounted on a slide and studied for changes due to disease. A small core of tissue is obtained that is representative even with focal lesions. Ultrasound- or CT-guided biopsies definitely improve the yield. A biopsy is valuable in detecting tuberculosis (TB) or other infiltrations and help to clarifying the underlying cause of the liver inflammation such as ischemic injury, rejection after liver transplantation, biliary tract disease, or viral hepatitis. Serial biopsies are commonly performed over years, may be necessary for monitoring disease progression.
| What invasive diagnostic procedures are used to confirm the severity of a liver disease?|| |
Gross examination and histopathology are often definitive. Cytology, frozen section, and culture are useful processes in selected cases. Metal content can be measured in the biopsy specimen: copper in suspected Wilson's disease and iron in hemochromatosis.
Limitations of liver biopsy include a sampling error and occasional errors or uncertainty in cases of cholestasis.
Indications for Liver Biopsy
- Unexplained liver enzyme abnormalities
- Alcoholic liver disease or nonalcoholic steatosis (diagnose and stage)
- Chronic hepatitis (diagnose and stage)
- Suspected rejection after liver transplantation that cannot be diagnosed by less invasive methods
- Hepatosplenomegaly of unknown cause
- Unexplained intrahepatic cholestasis
- Suspected malignancy (focal lesions)
- Unexplained systemic illness–eg, fever of unknown origin, inflammatory or granulomatous diseases (culture is performed with biopsy)
An endoscope as used in the field of gastroenterology is a thin flexible tube which uses a lens or miniature camera to view various areas of the gastrointestinal tract. When the procedure is performed to examine certain organs such as the bile ducts or pancreas, the organs are not viewed directly, but rather indirectly through the injection of x-ray dye into the bile duct.
The performance of an exam using an endoscope is referred by the general term endoscopy. Diagnosis through biopsies or other means and therapeutic procedures can be done with these instruments.
Extracorporeal shock-wave lithotripsy (ESWL)
This is a technique that uses high-pressure waves similar to sound waves that can be "focused" on a very small area, thereby fracturing small solid objects such as gallstones, kidney stones, etc. The small fragments can pass more easily and harmlessly into the intestine or can be dissolved with medications.
The Hepatic Venous Pressure Gradient (HVPG)
The HVPG represents the gradient between portal vein and intra-abdominal vena cava pressure. HVPG measurement is done after an overnight fast, under conscious sedation and monitoring for vital signs (This includes heart rate, arterial blood pressures, digital oxygen saturation, and ECG).
Under local anesthesia, central vein (for pressure monitoring) is punctured using the Seldinger technique. There are four steps to the Seldinger technique
- Venepuncture is performed with a introducer needle or trocar (a sharp hollow needle)
- A soft tipped guide wire is passed through the needle and the needle removed
- A cannula or dilator is passed over the guide wire
- Cannula or dilator is removed and catheter is passed over wire using fluoroscopy to establish its position- The guidewire is then removed
The Seldinger technique has been refined to help reduce complications such as infection, haemorrhage and accidental perforation during intervention into a vein. The advantage of this procedure is a possibility of a biopsy alongside measurement of the pressure in the portal vein. Use of doppler ultrasound helps to minimize complications such as leakage, hematoma, and rarely, reaction in the vein, rupture of venous trocar, or arteriovenous puncture causing a fistula. The key measurement of a HVPG procedure are the Free Hepatic Venous Pressure and the Wedge Hepatic Venous Pressure. The difference between the two measurements will provide the pressure gradient in the liver to ascertain severity of portal hypertension.
Grading of pressure
Persons with normal portal pressure measure between 1-5mmHg.
Persons with portal pressure above 5mmHg are graded as subclinical portal hypertension.
Persons with portal pressure equal and over 10mmHg are assessed to be clinically significant portal hypertension.
Persons with a portal pressure over 12mmHg are at risk for a varaceal rupture.
What are some common liver disease symptoms?
When diagnosing liver disease, the physician looks at the patient's symptoms and conducts a physical examination. In addition, the physician may request a liver biopsy, liver function tests, an ultrasound, or a CT scan (computerized tomography scan).
Some common liver disease symptoms include the following, each of which are described briefly below:
- liver enlargement
- portal hypertension
- liver encephalopathy
- liver failure
What is jaundice?
Jaundice is a yellow discoloration of the skin and eye whites due to abnormally high levels of bilirubin (bile pigment) in the bloodstream. Urine is usually dark because of the bilirubin excreted through the kidneys. High levels of bilirubin may be attributed to inflammation or other abnormalities of the liver cells or blockage of the bile ducts. Sometimes jaundice is caused by the breakdown of a large number of red blood cells, which can occur in newborns. Jaundice is usually the first sign, and sometimes the only sign, of liver disease.
What is cholestasis?
Cholestasis is reduced or stopped bile flow. Bile flow may be blocked inside or outside the liver. Symptoms may include:
- dark urine
- pale stool
- bone loss
- easy bleeding
- small, spider-like blood vessels visible in the skin
- enlarged spleen
- fluid in the abdominal cavity
- pain from the biliary tract or pancrea
- enlarged gallbladder
- Some causes of cholestasis include:
- primary biliary cirrhosis
- drug effects
- hormonal changes during pregnancy
- a stone in the bile duct
- bile duct narrowing
- bile duct cancer
- pancreatic cancer
- inflammation of the pancreas
What is liver enlargement?
Liver enlargement is usually an indicator of liver disease, although there are usually no symptoms associated with a slightly enlarged liver (hepatomegaly). Symptoms of a grossly enlarged liver include abdominal discomfort or "feeling full."
What is portal hypertension?
The portal vein carries about 1500 ml/min of blood from the small and large bowel, spleen, and stomach to the liver at a pressure of about 5 mmHg. Any obstruction or increased resistance to flow or due to pathological increases in portal blood flow could lead to portal hypertension with portal pressures over 12 mm Hg. Although the differential diagnosis is extensive, alcoholic and viral cirrhosis are the leading causes of portal hypertension in Western countries, whereas liver disease due to schistosomiasis is the main cause in other areas of the world (caused by a parasitic worm). Portal vein thrombosis is the commonest cause in children. In India and Japan non-cirrhotic portal fibrosis is a known cause of portal hypertension seen in lower-social groups and low hygiene.
Portal hypertension is abnormal high blood pressure in the portal vein, which supplies the liver with blood from the intestine. Portal hypertension may be due to increased blood pressure in the portal blood vessels or resistance to blood flow through the liver. Portal hypertension can lead to the growth of collateral vessels that connect to the general circulation, bypassing the liver. When this occurs, substances that are normally removed by the liver pass into the general circulation. Symptoms of portal hypertension may include:
- a distended abdominal cavity (ascites)
- bleeding of the varicose veins at the lower end of the esophagus and in the stomach lining
What is gastric bleeding?
Increases in portal pressure disturb the portal systemic circulation. These factors are partly responsible for the important complications of chronic liver disease, including variceal bleeding, hepatic encephalopathy, ascites, hepatorenal syndrome, recurrent infection, and abnormalities in coagulation. Variceal or gastric bleeding is the most serious complication and is an important cause of death in patients with cirrhotic liver disease.
Patients with varices have a 30% lifetime risk of gastric bleeding, and a third of those who bleed will die. Patients who have bled once from oesophageal varices have a 70% chance of bleeding again and about a third of further bleeding episodes are fatal.
What is ascites?
Ascites is fluid build-up in the abdominal cavity, caused by fluid leaks from the surface of the liver and intestine. Ascites due to liver disease usually accompanies other liver disease characteristics such as portal hypertension. Symptoms of ascites may include a distended abdominal cavity, which causes discomfort and shortness of breath. Causes of ascites may include:
- liver cirrhosis (especially cirrhosis caused by alcoholism)
- alcoholic hepatitis
- chronic hepatitis
- obstruction of the hepatic vein
- Ascites can also be caused by non-liver disorders.
What is Cirrhosis?
Cirrhosis is characterized anatomically by widespread nodules in the liver combined with fibrosis. The fibrosis and nodule formation causes distortion of the normal liver architecture which interferes with blood flow through the liver. Cirrhosis can also lead to an inability of the liver to perform its biochemical functions.
The journey of what goes wrong in Cirrhosis
- Cirrhosis results from damage to liver cells from toxins, inflammation, metabolic derangements and other causes. In cryptogenic liver disease, the cause is unknown.
- Damaged and dead liver cells are replaced by fibrous tissue leads to fibrosis (scarring). Liver cells begin to regenerate in an abnormal pattern primarily forming nodules that are surrounded by fibrous tissue
- Grossly abnormal liver architecture leads to decreased blood flow to and through the liver. There is decreased blood flow to the liver and blood back up in the portal vein and portal circulation leads to some of the serious complications of cirrhosis. Blood can back up in the spleen causing it to enlarge and sequester blood cells.
- Most often, the platelet count falls because of splenic sequestration (withholding of the blood) leading to abnormal bleeding. If the pressure in the portal circulation increases because of cirrhosis and blood withheld, blood can flow backwards from the portal circulation to the systemic circulation where they are connected. This can lead to varicose veins in the stomach and esophagus (gastric and esophageal varices) and rectum (hemorrhoids). Gastric and esophageal varices can rupture, bleed massively and even cause death.
- Hypertension in the portal circulation, along with other hormonal, metabolic and kidney abnormalities in cirrhosis, can also lead to fluid accumulation the abdomen (ascites) and the peripheral tissue (peripheral edema).
- Decreased bilirubin secretion from hepatocytes in cirrhosis leads to the back up of bilirubin in the blood. This leads to jaundice, the yellow discoloration of the skin and eyes. As the water-soluble form of bilirubin also backs up in the blood, bilirubin can also spill into the urine giving it a bright yellow to dark brown color.
- Abnormal biochemical function of the liver in cirrhosis can lead to several complications. The serum albumin concentration falls which can lead to aggravation of ascites and edema. The metabolism of drugs can change requiring dose adjustments.
- In men, breast enlargement (gynecomastia) sometimes occurs because metabolism of estrogen in the liver is decreased.
- Decreased production of blood clotting factors can lead to bleeding complications.
- Derangements in the metabolism of triglycerides, cholesterol and sugar can occur.
- In earlier stages, cirrhosis frequently can cause insulin resistance and diabetes mellitus.
- In later stages or in severe liver failure, blood glucose may be low because it cannot be synthesized from fats or proteins.
- Cirrhosis, especially in advanced cases, can cause profound abnormalities in the brain. In cirrhosis, some blood leaving the gut bypasses the liver as blood flow through the liver is decreased.
- Metabolism of components absorbed in the gut can also be decreased as liver cell function deteriorates.
Both of these derangements can lead to hepatic encephalopathy as toxic metabolites, normally removed from the blood by the liver, can reach the brain.
- In its early stages, subtle mental changes such as poor concentration or the inability to construct simple objects occurs.
In severe cases, hepatic encephalopathy can lead to stupor, coma, brain swelling and death.
- Cirrhosis can lead to immune system dysfunction causing an increased risk of infection. Ascites fluid in the abdomen often becomes infected with bacteria normally present in the gut (spontaneous bacterial peritonitis).
- Cirrhosis can also lead to kidney dysfunction and failure.
- End-stage cirrhosis, can trigger kidney dysfunction called hepatorenal syndrome can occur. This is fatal unless a liver transplant takes place.
Clinical Symptoms and Diagnosis of Cirrhosis
Cirrhosis is usually an easy diagnosis to make when any or all of the above abnormalities and complications are present. This is especially true when the underlying liver disease can be identified. The underlying liver disease is identified in most patients, however, sometimes it will not be discovered despite recommending specific diagnostic tests. Such cases are called "cryptogenic" cirrhosis.
Some patients with cirrhosis, especially early in the course of the disease, will have no overt clinical signs or symptoms. Some may have only subtle physical changes such as
- Red palms or red spots that blanch on their upper body (spider angiomata)
- Hypertrophy of the parotid glands
- Gynecomastia or fibrosis of tendons in the palms.Some patients may only have subtle abnormalities on blood tests, and in some cases, all blood tests may be normal.
- Radiological and nuclear medicine tests may give clues as to the presence of cirrhosis
- The diagnosis of cirrhosis can often be made by an ultrasound
- The diagnosis of the liver architecture can only be made by a biopsy.
Cirrhosis of the liver is irreversible but treatment of the underlying liver disease may slow or stop the progression. Such treatment depends upon the underlying etiology. In cryptogenic cirrhosis, since the cause is unknown, supportive therapy directed at alleviating symptoms due to progression and its complications is the only answer.
- Bleeding esophageal varices can be treated with endoscopic sclerotherapy or rubber band ligation.
- Ascites and edema are often responsive to a low sodium diet and such a diet must be emphasized in patients with these symptoms. More advanced ascites and edema can respond to diuretic therapy.
- A low protein diet and agents such as lactulose may help hepatic encephalopathy.
Infections such as spontaneous bacterial peritonitis must be rapidly treated with appropriate antibiotics.
- Drugs metabolized in the liver must be given with caution.
- Coagulation disorders will sometimes respond to vitamin K.
- Liver transplantation is highly effective for the treatment of end-stage cirrhosis. Transplantation is usually needed when complications such as encephalopathy, ascites or bleeding varices are uncontrollable or when biochemical function is severely depressed.
What is liver encephalopathy?
Liver encephalopathy is the deterioration of brain function due to toxic substances building up in the blood, which are normally removed by the liver. Liver encephalopathy is also called portal-systemic encephalopathy, hepatic encephalopathy, or hepatic coma. Symptoms may include:
- impaired consciousness
- changes in logical thinking, personality, and behavior
- mood changes
- impaired judgement
- sluggish speech and movement
- loss of consciousness
What is liver failure?
Liver failure is severe deterioration of liver function. Liver failure occurs when a large portion of the liver is damaged due to any type of liver disorder. Symptoms may include:
- tendency to bruise or bleed easily
- impaired brain function
- general failing health
- loss of appetite
Supportive Treatments in management of characteristics of Liver Disease
In sclerotherapy a sclerosant solution (ethanolamine oleate or sodium tetradecyl sulphate) is injected into the bleeding varix or the overlying submucosa. Injection into the varix obliterates the lumen by thrombosis whereas injection into the submucosa produces inflammation followed by fibrosis. The first injection controls bleeding in 80% of cases. If bleeding recurs, the injection is repeated. Complications are related to toxicity of the sclerosant and include transient fever, dysphagia and chest pain, ulceration, stricture, and (rarely) perforation.
Band ligation is achieved by a banding device attached to the tip of the endoscope. The varix is aspirated into the banding chamber, and a trip wire dislodges a rubber band carried on the banding chamber, ligating the entrapped varix. One to three bands are applied to each varix, resulting in thrombosis. Band ligation eradicates oesophageal varices with fewer treatment sessions and complications than sclerotherapy.
Balloon tube tamponade
The balloon tube tamponade may be life saving in patients with active variceal bleeding if emergency sclerotherapy or banding is unavailable or not technically possible because visibility is obscured. In patients with active bleeding, an endotracheal tube is inserted to protect the airway before attempting to place the oesophageal balloon tube.
A Minnesota balloon tube has four entry points
- 1for gastric aspiration
- 2 to inflate the gastric and oesophageal balloons
- 1 above the oesophageal balloon for suction of secretions to prevent aspiration.
The tube is inserted through the mouth, and correct positioning in the stomach is checked by auscultation while injecting air through the gastric lumen. The gastric balloon is then inflated with 200 ml of air. Once fully inflated, the gastric balloon is pulled up against the oesophagogastric junction, compressing the submucosal varices. The tension is maintained by strapping a split tennis ball to the tube at the patient's mouth.
An oesophageal balloon is rarely required. Complications could be
gastric and oesophageal ulceration Continued bleeding during balloon tamponade indicates an incorrectly positioned tube or bleeding from another source. After resuscitation, and within 12 hours, the tube is removed and endoscopic treatment repeated.
- oesophageal perforation.
Transjugular intrahepatic portosystemic shunt (TIPS)
Transjugular intrahepatic portosystemic shunt is the best procedure for patients whose bleeding is not controlled by endoscopy. It is effective only in portal hypertension of hepatic origin (caused by fibrosis of the liver for example). The procedure is performed via the internal jugular vein under local anaesthesia with sedation. The hepatic vein is cannulated and a tract created through the liver from the hepatic to the portal vein, with a needle under ultrasonographic and fluoroscopic guidance. The tract is dilated and an expandable metal stent inserted to create an intrahepatic portosystemic shunt. The success rate is excellent. Haemodynamic effects are similar to those found with surgical shunts, with a lower procedural morbidity and mortality. The process lasts one to three hours, but you should expect to stay in the hospital overnight after the procedure.
Transjugular intrahepatic portosystemic shunting is an effective salvage procedure for stopping acute variceal haemorrhage, controlling bleeding from gastric varices, and congestive gastropathy after failure of medical and endoscopic treatment.
What Tests Are Required Before the TIPS?
Before receiving either of these procedures, the following tests may be performed to determine the extent and severity of your condition:
- Evaluation of your medical history
- A physical examination
- Blood tests
- Angiogram (an X-ray test that takes pictures of the blood flow within a particular artery)
- Before either the TIPS procedure, your doctor may ask you to have other preoperative tests, which may include an electrocardiogram (EKG) (a test that records the electrical activity of your heart), chest X-ray, or additional blood tests. If your doctor thinks you will need additional blood products they will be ordered at this time.
How Successful Is the TIPS Procedure?
The TIPS procedure controls bleeding immediately in more than 90% of patients. However, in about 20% of patients, the shunt may narrow, causing varices to re-bleed at a later time.
What Complications Are Associated With TIPS?
Shunt narrowing or occlusion (blockage) can occur within the first year after the procedure. Follow-up ultrasound examinations are performed frequently after the TIPS procedure to detect these complications. The signs of occlusion include increased ascites (accumulation of fluid in the abdomen) and re-bleeding. This condition can be treated by a radiologist who re-expands the shunt with a balloon or repeats the procedure to place a new stent.
Encephalopathy, or abnormal functioning of the brain, can occur with severe liver disease. Hepatic encephalopathy can become worse when blood flow to the liver is reduced by TIPS, which may result in toxic substances reaching the brain without being metabolized first by the liver. This condition can be treated with medications, diet, or by occluding the shunt (making the shunt inaccessible).
What is the Distal splenorenal shunt (DSRS) Procedure?
The DSRS is a surgical procedure during which the vein from the spleen (called the splenic vein) is detached from the portal vein and attached to the left kidney (renal) vein. This surgery selectively reduces the pressure in the varices and controls the bleeding. It is usually performed only in patients with good liver function. General anesthesia is given before the surgery, which lasts about four hours. You should expect to stay in the hospital from seven to 10 days.
How Successful Is the DSRS Surgery?
DSRS controls bleeding in more than 90% of patients, with the highest risk of any re-bleeding occurring in the first month. The DSRS procedure provides good long-term control of bleeding.
What Complications Are Associated With DSRS Surgery?
Ascites, an accumulation of fluid in the abdomen, can occur. This can be treated with diuretics and restricted sodium intake.
Follow-Up Care Following TIPS or DSRS Procedures
DSRS controls bleeding in more than 90% of patients, with the highest risk of any re-bleeding occurring in the first month. The DSRS procedure provides good long-term control of bleeding.
- Ten days after hospital discharge, meet with your surgeon or hepatologist (liver specialist) to evaluate your progress. Lab work will be done at this time.
- Six weeks after the TIPS procedure (and again three months after the procedure), have an ultrasound so your doctor can check that the shunt is functioning properly. You will have an angiogram (an x-ray of blood vessels) only if the ultrasound indicates that there is a problem. You will also have lab work done at these times.
- Six weeks after the DSRS procedure (and again three months after the procedure), meet with the surgeon to evaluate your progress. Lab work will be done at this time.
- Six months after either the TIPS or DSRS procedure, have an ultrasound to make sure the shunt is working properly. Also, visit the surgeon or hepatologist.
- Twelve months after either procedure, have another ultrasound of the shunt. Also, you may have an angiogram so that your doctor can check the pressure within your veins across the shunt.
- If the shunt is working well, every six months after the first year of follow-up appointments, have an ultrasound, lab work, and visit with your doctor.
- More frequent follow-up visits may be necessary, depending on your condition.
- Attend all follow-up appointments as scheduled to ensure that the shunt is functioning properly. Be sure to follow the dietary recommendations that your healthcare providers give you.
Long term management
After the acute variceal haemorrhage has been controlled, treatment should be initiated to prevent rebleeding, which occurs in most patients.
Repeated endoscopic treatment
Repeated endoscopic treatment eradicates oesophageal varices in most patients, and provided that follow up is adequate serious recurrent variceal bleeding is uncommon. Because the underlying portal hypertension persists, patients remain at risk of developing recurrent varices and therefore require lifelong regular surveillance endoscopy.
Long term drug treatment
The use of beta blockers after variceal bleeding has been shown to reduce portal blood pressures and lower the risk of further variceal bleeding. Patients would be recommended beta blockers unless they have contraindications. Best results are obtained when portal blood pressure is reduced by more than 20% of baseline or to below 12 mm Hg.
Surgical management of varices
Patients with good liver function in whom endoscopic management fails or who live far from centres where endoscopic sclerotherapy services are available are candidates for surgical shunt procedures. A successful portosystemic shunt prevents recurrent variceal bleeding but is a major operation that may cause further impairment of liver function.
Partial portacaval shunts with 8 mm interposition grafts are equally effective to other shunts in preventing rebleeding and have a low rate of encephalopathy. Oesophageal transection and gastric devascularisation are now rarely performed but have a role in patients with portaland splenic vein thrombosis who are unsuitable for shunt procedures
and continue to have serious variceal bleeding despite endoscopic and drug treatment. Liver transplantation is the treatment of choice in advanced liver disease. Hepatic decompensation is the ultimate decompressive shunt for portal hypertension and also restores liver function. Transplantation treats other complications of portal hypertension and has one year and five year survival rates of 80% and 60% respectively.
Most patients with portal hypertension never bleed, and it is difficult to predict who will. Attempts at identifying patients at high risk of variceal haemorrhage by measuring the size or appearance of varices have been largely unsuccessful. Beta blockers have been shown to reduce the risk of bleeding, and all patients with varices should take them unless contraindicated.
Hypertensive portal gastropathy
Gastric varices and portal hypertensive gastropathy
Gastric varices are the source of bleeding in 5.10% of patients with variceal haemorrhage. Higher rates are reported in patients with left sided portal hypertension due to thrombosis of the splenic vein. Endoscopic control of gastric varices is difficult unless they are located on the proximal lesser curve in continuation with oesophageal varices. Endoscopic administration of cyanoacrylate monomer (superglue) is useful for gastric varices. The transjugular intrahepatic portosystemic shunt is increasingly used to control bleeding in this group. Bleeding from portal hypertensive gastropathy accounts for 2.3% of bleeding episodes in cirrhosis. When bleeding occurs its diffuse nature precludes the use of endoscopic treatment. Optimal management is with a combination of terlipressin and beta blockers.