Puddle sign In gastroenterology, the puddle sign is a physical examination maneuver that can be used to detect the presence of ascites. It is useful for detecting small amounts of ascites -- as small as 120 mL; shifting dullness and bulging flanks typically require 500 mL. The steps are outlined as follows: 1. Patient lies prone for 5 minutes 2. Patient then rises onto elbows and knees 3. Apply stethoscope diaphragm to most dependent abdomen 4. Examiner repeatedly flicks near flank with finger. Continue to flick at same spot on abdomen 5. Move stethoscope across abdomen away from examiner 6. Sound loudness increases at farther edge of puddle 7. Sound transmission does not change when patient sits In relation to auscultatory percussion, the puddle sign is more specific, but less sensitive. Rovsing's sign Rovsing's sign, named after the Danish surgeon Niels Thorkild Rovsing, is a sign of appendicitis. If palpation of the left lower quadrant of a person's abdomen results in more pain in the right lower quadrant, the patient is said to have a positive Rovsing's sign and may have appendicitis. In acute appendicitis, palpation in the left iliac fossa may produce pain in the right iliac fossa. Most practitioners push on the left lower quadrant to see where the patient complains of pain. If pain is felt in the right lower quadrant, then there may be an inflamed organ or piece of tissue in the right lower quadrant. The appendix is generally the prime suspect, although other pathology can also give a "positive" Rovsing's sign. If left lower quadrant pressure by the examiner leads only to left-sided pain or pain on both the left and right sides, then there may be some other pathologic etiology. This may include causes relating to the bladder, uterus, ascending (right) colon, fallopian tubes, ovaries, or other structures. McBurney's sign It is the name given to the tenderness over the point over the right side of the abdomen that is one-third of the distance from the ASIS (anterior superior iliac spine) to the umbilicus (the belly button). This point roughly corresponds to the most common location of the base of the appendix where it is attached to the cecum. The anterior cutaneous branch of iliohypogastric nerve is found near McBurney's point. Cullen's sign Cullen's sign is superficial edema and bruising in the subcutaneous fatty tissue around the umbilicus. This sign takes 24-48 hours to appear and can predict acute pancreatitis, with mortality rising from 8-10% to 40%. It may be accompanied by Grey Turner's sign (bruising of the flank), which may then be indicative of pancreatic necrosis with retroperitoneal or intraabdominal bleeding. Causes Causes include: acute pancreatitis, where methemalbumin formed from digested blood tracks around the abdomen from the inflamed pancreas bleeding from blunt abdominal trauma bleeding from ruptured abdominal aortic aneurysm bleeding from ruptured ectopic pregnancy Importance of the sign is on a decline since better diagnostic modalities are now availabl Vomiting Exams and Tests: The polyps develop mainly in the small intestine, but also in the colon. A colonoscopy will show colon polyps. The small intestine is evaluated with either a barium x-ray (small bowel series) or a small camera that is swallowed and then take multiple pictures as it travels through the small bowel (capsule endoscopy). Additional exams may show: Intussusception (part of the intestine folded in on itself) Noncancerous tumors in the ear (exostoses) Management: Surgery may be needed to remove polyps that cause long-term problems. Iron supplements help counteract blood loss. Persons with this condition should be monitored by a health care provider and be checked periodically for cancerous polyp changes. Prognosis: There may be a significant risk of these polyps becoming cancerous. Some studies link PJS and cancers of the gastrointestinal tract, lung, breast, uterus, and ovaries. Virchow's node Malignancies of the internal organs can reach an advanced stage before giving symptoms. Stomach cancer, for example, can remain symptomless while metastatizing. One of the first visible spots where these tumors metastatise is the left supraclavicular lymph node. The left supraclavicular node is the classical Virchow's node because it is on the left side of the neck where the lymphatic drainage of most of the body (from the thoracic duct) enters the venous circulation via the left subclavian vein.The metastasis blocks the thoracic duct leading to regurgitation into the surrounding nodes ie. virchow's node. Another concept is that one of the supraclavicular nodes corresponds to the end node along the thoracic duct and hence the enlargement. Differential diagnosis of an enlarged Virchow's node includes lymphoma, various intra-abdominal malignancies, breast cancer, and infection (e.g. of the arm). Similarly, an enlarged right supraclavicular lymph node tends to drain thoracic malignancies such as lung and esophageal cancer, as well as Hodgkin's lymphoma. Mallory–Weiss syndrome Mallory–Weiss syndrome or gastro-esophageal laceration syndrome refers to bleeding from tears (a Mallory-Weiss tear) in the mucosa at the junction of the stomach and esophagus, usually caused by severe retching, coughing, or vomiting. Causes: It is often associated with alcoholism[1] and eating disorders and there is some evidence that presence of a hiatal hernia is a predisposing condition. Clinical Presentation: Mallory–Weiss syndrome often presents as an episode of vomiting up blood (hematemesis) after violent retching or vomiting, but may also be noticed as old blood in the stool (melena), and a history of retching may be absent. In most cases, the bleeding stops spontaneously after 24–48 hours, but endoscopic or surgical treatment is sometimes required and rarely the condition is fatal. Diagnosis: Definitive diagnosis is by endoscopy. General Management: The blood transfusions and intravenous fluids will help restore the fluid and electrolyte balance. Most of the time, esophageal bleeding stops spontaneously. Treatment is usually supportive as persistent bleeding is uncommon. However cauterization or injection of epinephrine[2] to stop the bleeding may be undertaken during the index endoscopy procedure. Very rarely embolization of the arteries supplying the region may be required to stop the bleeding. If all other methods fail, high gastrostomy can be used to ligate the bleeding vessel. Mallory-Weiss syndrome can be treated. The doctor will stabilize the patient with blood transfusions and intravenous fluids. If bleeding does not stop, patients are treated with an injection of epinephrine (adrenaline) and/or the bleeding artery is cauterized with heat. In some cases, surgery is performed to stop the bleeding. Plummer-Vinson syndrome Plummer-Vinson syndrome (PVS), also called Paterson-Brown-Kelly syndrome or sideropenic dysphagia presents as a triad of dysphagia (due to esophageal webs), glossitis, and iron deficiency anemia.[1] It most usually occurs in postmenopausal women. Clinical Presentation: PVS sufferers often complain of a burning sensation with the tongue and oral mucosa, and atrophy of lingual papillae produces a smooth, shiny red tongue dorsum. Symptoms include: Dysphagia (difficulty in swallowing) Pain Weakness Odynophagia (Painful swallowing) Atrophic glossitis Angular stomatitis Increased risk of carcinoma Serial contrasted gastrointestinal radiography or upper gastrointestinal endoscopy may reveal the web in the esophagus. Blood tests show a hypochromic microcytic anemia that is consistent with an iron-deficiency anemia. Biopsy of involved mucosa typically reveals epithelial atrophy (shrinking) and varying amounts of submucosal chronic inflammation. Epithelial atypia or dysplasia may be present. Causes and associated conditions: The cause of PVS is unknown; however, genetic factors and nutritional deficiencies may play a role. Male to female ratio is 3:1, particularly in middle age. Peak age over 50 years. In these patients, esophageal squamous cell carcinoma risk is increased;[1] therefore, it is considered a premalignant process. The condition is associated with koilonychia, glossitis, cheilitis, and splenomegaly Management: Treatment is primarily aimed at correcting the iron-deficiency anemia. Patients with PVS should receive iron supplementation in their diet. This may improve dysphagia and pain. If not, the web can be dilated during upper endoscopy to allow normal swallowing and passage of food. Prognosis: Patients generally respond well to treatment. Iron supplementation usually resolves the anemia, and corrects the glossodynia (tongue pain). Complications: There is risk of perforation of the esophagus with the use of dilators for treatment. Furthermore it is one of the risk factors for developing squamous cell carcinoma of the oral cavity, esophagus and hypopharynx. Prevention: Good nutrition with adequate intake of iron may prevent this disorder Asperger's Syndrome Asperger's syndrome is a developmental disorder. It is classified as an autism spectrum disorder, one of a distinct group of neurological conditions characterized by a greater or lesser degree of impairment in language and communication skills, as well as repetitive or restrictive patterns of thought and behavior. Unlike children with autism, children with Asperger's syndrome retain their early language skills. Asperger's syndrome affects far more boys than girls. Symptoms of Asperger's Syndrome: The most common symptom of Asperger's syndrome is a child’s obsessive interest in a single object or topic to the exclusion of any other. Children with Asperger's syndrome want to know everything about their topic of interest and their conversations with others will be about little else. Their expertise, high level of vocabulary, and formal speech patterns make them seem like little professors. Other symptoms of of Asperger's syndrome include: repetitive routines or rituals peculiarities in speech and language socially and emotionally inappropriate behavior and the inability to interact successfully with peers problems with non-verbal communication clumsy and uncoordinated motor movements Children with Asperger's syndrome are often are isolated because of their poor social skills and narrow interests. Children with Asperger's syndrome usually have a history of developmental delays in motor skills such as pedaling a bike, catching a ball, or climbing outdoor play equipment. They are often awkward and poorly coordinated with a walk that can appear either stilted or bouncy. Causes: The exact cause of Asperger's syndrome is unknown. Management: Treatments address the three core symptoms of Asperger's syndrome: poor communication skills, obsessive or repetitive routines, and physical clumsiness. Foot Syndrome Burning foot syndrome is a common complaint among many groups of people, most commonly in the older group over 50 years of age. Symptoms of Burning Foot Syndrome The most common symptom of burning foot syndrome are burning, stinging, redness and swelling. Most times, the only symptoms present are burning and stinging feet. Causes of Burning Foot Syndrome Some common causes of burning foot syndrome are: Ingestion of alcohol over a long period of time Irritating fabrics Fungal infections Poorly fitted shoes Blood disorders Nerve damage Kidney failure Liver damage Thyroid dysfunction Gastric restriction in morbid obesity DiGeorge Syndrome DiGeorge syndrome is a rare congenital disease characterized a history of recurrent infection, heart defects and unique facial features. DiGeorge syndrome is caused by a large deletion from chromosome 22. The deletion is a result of an an error in recombination at meiosis. Several genes from chromosome 22 are not present in DiGeorge syndrome patients. Symptoms of DiGeorge Syndrome: The symptoms of DiGeorge syndrome vary greatly between individuals. Researches believe that the variation in the symptoms is related to the amount of genetic material lost in the chromosomal deletion. The more genetic material is lost, the greater the amount of symptoms. Some common symptoms of DiGeorge syndrome are: Speech impairments. Immune deficiency Learning disabilities Hypocalcemia Recurrent infections Underdeveloped thymus gland Hypoparathyroidism Lack of T-cells Congenital heart disease Heart murmur Heart failure Underdeveloped parathyroid glands Underdeveloped chin Downward slanting eyes Convulsions Treatment Options for DiGeorge Syndrome: The damaged chromosome cannot be repaired. Treatments are aimed to reduce symptoms and complications. Some common treatments are surgery for heart problems, and thymus cell transplants to restore the immune system Fragile X Syndrome Fragile X syndrome is a genetic condition involving changes in the long arm of the X chromosome. Fragile X syndrome is characterized by mental retardation. Fragile X syndrome is the most common form of inherited mental retardation in males and a significant cause in females. Boys are affected more severely than girls because boys only have one X chromosome and girls have two X chromosomes. Fragile X syndrome is also called Fragile X. It appears in families of every ethnic group and income level. A person inherits Fragile X syndrome from their parents. Symptoms of Fragile X Syndrome: The most common symptoms of Fragile X syndrome are: Mental retardation Large testicles Family history of fragile X syndrome Tendency to avoid eye contact Hyperactive behavior Large forehead and/or ears with a prominent jaw Fragile X syndrome is also associated with problems with sensation, emotion, and behavior. Management: Unfortunately, there is no specific treatment for Fragile X syndrome. However, with training and education, children with Fragile X syndrome can function at as high a level as is possible. Complications of Fragile X Syndrome Complications vary depending on the type and severity of symptoms. Prevention: Genetic counseling may help prospective parents with a family history of Fragile X syndrome can help determine the level of risk of having a child with Fragile X syndrome. Guillain-Barré Syndrome Guillain-Barré (Ghee-yan Bah-ray) syndrome is an inflammatory disorder of the peripheral nerves. Peripheral nerves are nerves outside the brain and spinal cord. In this disorder, the body's immune system attacks part of the nervous system. Clinical Features: Guillain-Barré syndrome is characterized by the rapid onset of weakness and often, paralysis of the legs, arms, breathing muscles and face. Guillain-Barré Syndrome can develop over the course of hours or days, or it may take up to 3 to 4 weeks. Most people reach the stage of greatest weakness within the first 2 weeks after symptoms appear. Abnormal sensations also occur. Guillain-Barré syndrome, is also called Acute Inflammatory Demyelinating Polyneuropathy and Landry's Ascending Paralysis. There are many symptoms of Guillain-Barré syndrome. Varying degrees of weakness or tingling sensations in the legs is usually the first symptom. In most instances the weakness and abnormal sensations spread to the arms and upper body. These symptoms can increase in intensity until the muscles cannot be used at all, and the patient is almost totally paralyzed. Cause: The exact cause of Guillain-Barré syndrome is not known. About 50% of cases occur shortly after a viral or bacterial infection such as a sore throat or diarrhea. A lot of cases developed in people who received the 1976 swine flu vaccine. Management: Currently, there is no cure for Guillain-Barré syndrome. However, some of the symptoms can be treated. There are therapies available that can lessen the severity of the symptoms and accelerate the recovery in most patients. Guillain-Barre syndrome is a very serious disease that requires immediate hospitalization. It requires immediate hospitalization because it can worsen rapidly. Most newly diagnosed patients are hospitalized and usually placed in an intensive care unit to monitor breathing and other body functions. Gilbert's Syndrome Gilbert's syndrome is a disorder that affects the way the liver processes bilirubin. Bilirubin results from the normal breakdown of red blood cells. Gilbert's syndrome is a common cause of elevated blood levels of bilirubin in people with no other signs or symptoms of liver disease. In some cases, Gilbert's syndrome may cause jaundice. Clinical Features: Usually there are no symptoms for Gilbert's syndrome. When symptoms do occur, the most common symptoms of are: Jaundice Abdominal pain Loss of appetite Fatigue Weakness after suffering an infection Causes: The exact cause of Gilbert's syndrome is unknown. However, researchers believe that Gilbert's syndrome may be caused by reduced activity of a particular enzyme. The reduced activity of the enzyme makes the liver less capable of processing bilirubin. Researchers do not know what causes the enzyme to function poorly. Gilbert's syndrome is caused by a 70%-80% reduction in the glucuronidation activity of the enzyme Uridine-diphosphate-glucuronosyltransferase isoform 1A1 (UDPglucuronosyltransferase 1A1). The enzyme is produced from a gene named UGT1A1, located on human chromosome 2. A normal UGT1A1 gene has a promoter region TATA box containing the genetic subsequence A(TA6)TAA. The allele polymorphism is referred to as UGT1A1*28. Gilbert's syndrome is most commonly associated with homozygous A(TA7)TAA alleles. In 94% of GS cases, mutations in two of the other glucoronyltransferase variations UGT1A6 (rendered 50% inactive) and UGT1A7 (rendered 83% ineffective) are also present. Because of its effects on drug and bilirubin breakdown and because of its genetic inheritance, Gilbert's syndrome can be classed as a minor inborn error of metabolism. Diagnosis: Examination of the blood sample for an increase in unconjugated bilirubin. People with GS show predominantly elevated unconjugated bilirubin, while conjugated is usually within normal ranges and form less than 20% of the total. Levels of bilirubin in GS patients is reported to be from 20 μM to 90 μM (1.2 to 5.3 mg/dL) compared to the normal amount of < 20 μM. GS patients will have a ratio of unconjugated/conjugated (indirect/direct) bilirubin that is commensurately higher than those without GS. The level of total bilirubin is often increased if the blood sample is taken after fasting for two days, and a fast can therefore be useful diagnostically. If the total bilirubin does in fact increase while fasting, the patient can then be given low doses of phenobarbital when fasting has ended, and following samples should show a decrease in total bilirubin toward normal levels. Also a mutation detection DNS test of UGT1A1 with Polymerase chain reaction and DNS fragment sequencing. Management: Gilbert's syndrome usually isn't serious and needs no treatment. Goodpasture's Syndrome Goodpasture's syndrome is a rare disease, autoimmune disease that can affect the lungs and kidneys. An autoimmune disease is a condition in which the body's own defense system reacts against some part of the body itself. When the immune system is working normally, it creates antibodies to fight off germs. In Goodpasture's syndrome, the immune system makes antibodies that attack the lungs and kidneys. Why this happens is uncertain. A combination of factors has been implicated, among them the presence of an inherited component and exposure to certain chemicals. Symptoms of Goodpasture's Syndrome The most common symptoms of Goodpasture's syndrome are: Fatigue Nausea Difficulty breathing Extreme or unnatural paleness Blood in the urine Protein in the urine Goodpasture's syndrome can also cause people to cough up blood or feel a burning sensation when urinating. Diagnosis: A blood test and/or a kidney biopsy diagnose Goodpasture's syndrome. Management: Goodpasture's syndrome is treated with oral immunosuppressive drugs to keep the immune system from making antibodies. Corticosteroid drugs may be given intravenously to control bleeding in the lungs. A process called plasmapheresis may be helpful and necessary to remove the harmful antibodies from the blood; this is usually done in combination with the immunosuppressive drug treatment. Mirizzi's Syndrome Mirizzi's syndrome is a condition characterized by stricture of the common hepatic duct. The common hepatic duct is the duct formed by the junction of the right hepatic duct (which drains bile from the right half of the liver) and the left hepatic duct (which drains bile from the left half of the liver). Mirizzi's syndrome may be mistaken for pancreatic cancer or cholangiocarcinoma. Causes: Mirizzi's syndrome is caused by chronic cholecystitis and large gallstones resulting in constriction of the common bile duct. cholecystitis is an inflammation of the gallbladder that causes severe abdominal pain. In some cases, the gallstone erodes into the common hepatic duct and produces a cholecystocholedochal fistula. Symptoms of Mirizzi's syndrome: The most common symptoms of Mirizzi's syndrome are: Jaundice Fever Recurrent cholangitis Right upper quadrant pain Elevated bilirubin Pancreatitis Cholecystitis Diagnosis: Doctors usually diagnose Mirizzi's syndrome via CT scan or ultrasonography. Management: Mirizzi's syndrome can be treated. Common treatments include surgical removal of the gallbladder and reconstruction of the common bile duct and the hepatic duct Sjögren's syndrome Sjögren's syndrome, also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva. Nine out of ten Sjögren's patients are women and the average age of onset is late 40s, although Sjögren's occurs in all age groups in both women and men. Causes: Sjögren's syndrome can exist as a disorder in its own right (Primary Sjögren's syndrome) or it may develop years after the onset of an associated rheumatic disorder such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, primary biliary cirrhosis etc. (Secondary Sjögren's syndrome). An autoantigen is alpha-Fodrin. Diagnosis: Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as anti-nuclear antibody (ANA) and rheumatoid factor (because SS frequently occurs secondary to rheumatoid arthritis), which are associated with autoimmune diseases. Typical Sjögren's syndrome ANA patterns are SSA/Ro and SSB/La, of which SSB/La is far more specific; SSA/Ro is associated with numerous other autoimmune conditions but are often present in Sjögren's. The Schirmer test measures the production of tears: a strip of filter paper is held inside the lower eyelid for five minutes, and its wetness is then measured with a ruler. Producing less than five millimeters of liquid is usually indicative of Sjögren's syndrome. However, lacrimal function declines with age or may be impaired from other medical conditions. An alternative test is nonstimulated whole saliva flow collection, in which the patient spits into a test tube every minute for 15 minutes. A resultant collection of less than 1.5 mL is considered a positive result. It takes longer time to perform than a Schirmer test, but does not require specific equipment. A slit-lamp examination is done to look for dryness on the surface of the eye. Salivary gland function can be tested by collecting saliva and determining the amount produced in a five minute period. A lip biopsy can reveal lymphocytes clustered around salivary glands, and damage to these glands due to inflammation. Peutz-Jeghers syndrome Peutz-Jeghers syndrome (PJS) is a disorder often passed down through families (inherited) in which the person develops intestinal polyps and is at a significantly higher risk for developing certain cancers. Causes: It is unknown how many people are affected by PJS. However, the National Institutes of Health estimates that it affects about 1 in 25,000 to 300,000 births. There are two types of PJS: Familial PJS is due to a mutation in a gene called STK11. The genetic defect is passed down (inherited) through families as an autosomal dominant trait. That means if one of your parents has this type of PJS, you have a 50:50 chance of inheriting the bad gene and having the disease. Sporadic PJS is not passed down through families and appears unrelated to the STK11 gene mutation. Symptoms: Brownish or bluish-gray pigmented spots on the lips, gums, inner lining of the mouth, and skin Clubbed fingers or toes Cramping pain in the belly area Dark freckles on and around the lips of a newborn Blood in the stool that can be seen with the naked eye (occasionally) Nephrotic syndrome Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein (proteinuria at least 3.5 grams per day per 1.73m2 body surface area) from the blood into the urine. Kidneys affected by nephrotic syndrome have small pores in the podocytes, large enough to permit proteinuria (and subsequently hypoalbuminemia, because some of the protein albumin has gone from the blood to the urine) but not large enough to allow cells through (hence no hematuria). By contrast, in nephritic syndrome, RBCs pass through the pores, causing hematuria Causes: Nephrotic syndrome has many causes and may either be the result of a disease limited to the kidney, called primary nephrotic syndrome, or a condition that affects the kidney and other parts of the body, called secondary nephrotic syndrome. Primary Primary causes of nephrotic syndrome are usually described by the histology, i.e. minimal change disease (MCD) like minimal change nephropathy which is the most common cause of nephrotic syndrome in children, focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN) like membranous glomerulonephritis which is the main cause of nephrotic syndrome in adult. They are considered to be "diagnoses of exclusion", i.e. they are diagnosed only after secondary causes have been excluded. Secondary Secondary causes of nephrotic syndrome have the same histologic patterns as the primary causes, though may exhibit some differences suggesting a secondary cause, such as inclusion bodies. They are usually described by the underlying cause. Secondary causes by histologic pattern: Hepatitis B & Hepatitis C Sjögren's syndrome Systemic lupus erythematosus(SLE) Diabetes mellitus Sarcoidosis Amyloidosis Drugs (such as corticosteroids, gold, intravenous heroin) Malignancy (cancer) Bacterial infections, e.g. leprosy & syphilis Protozoal infections, e.g. malaria Focal segmental glomerulosclerosis (FSGS) Hypertensive nephrosclerosis Human immunodeficiency virus (HIV) Obesity Kidney loss Minimal change disease (MCD) Drugs, especially NSAIDs in the elderly Malignancy, especially Hodgkin's lymphoma Leukemia Allergy Bee sting Diagnosis The gold standard in diagnosis of nephrotic syndrome is 24 hour urine protein measurement. Aiding in diagnosis are blood tests and sometimes imaging of the kidneys (for structure and presence of two kidneys), and/or a biopsy of the kidneys. The following are baseline, essential investigations: 24 hour bedside urinary total protein estimation. Urine sample shows proteinuria (>3.5 g per 1.73 m2 per 24 hours). It is also examined for urinary casts, which are more a feature of active nephritis. Comprehensive metabolic panel (CMP) shows hypoalbuminemia: albumin level ≤2.5 g/dL (normal=3.5-5 g/dL). Lipid profile. High levels of cholesterol (hypercholesterolemia), specifically elevated LDL, usually with concomitantly elevated VLDL is typical. Electrolytes, urea and creatinine (EUCs): to evaluate renal function. Further investigations are indicated if the cause is not clear: Biopsy of kidney (in case of adult patients only). Auto-immune markers (ANA, ASOT, C3, cryoglobulins, serum electrophoresis). Ultrasound of the whole abdomen. Treatment Treatment includes: Supportive Monitoring and maintaining euvolemia (the correct amount of fluid in the body): Monitoring urine output, BP regularly. Fluid restrict to 1 L. Diuretics (IV furosemide). Monitoring kidney function: do EUCs daily and calculating GFR. Treat hyperlipidemia to prevent further atherosclerosis. Prevent and treat any complications [see below] Albumin infusions are generally not used because their effect lasts only transiently. Prophylactic anticoagulation may be appropriate in some circumstances.[5] Specific Immunosuppression for the glomerulonephritides (corticosteroids[6], ciclosporin). Standard ISKDC regime for first episode: prednisolone -60 mg/m2/day in 3 divided doses for 4 weeks followed by 40 mg/m2/day in a single dose on every alternate day for 4 weeks. Relapses by prednisolone 2 mg/kg/day till urine becomes negative for protein. Then, 1.5 mg/kg/day for 4 weeks. Frequent relapses treated by: cyclophosphamide or nitrogen mustard or ciclosporin or levamisole. Achieving better blood glucose level control if the patient is diabetic. Blood pressure control. ACE inhibitors are the drug of choice. Independent of their blood pressure lowering effect, they have been shown to decrease protein loss. Diet Reduce sodium intake to 1000–2000 mg daily. Foods high in sodium include salt used in cooking and at the table, seasoning blends (garlic salt, Adobo, season salt, etc.) canned soups, canned vegetables containing salt, luncheon meats including turkey, ham, bologna, and salami, prepared foods, fast foods, soy sauce, ketchup, and salad dressings. On food labels, compare milligrams of sodium to calories per serving. Sodium should be less than or equal to calories per serving. Eat a moderate amount of high protein animal food: 3-5 oz per meal (preferably lean cuts of meat, fish, and poultry) Avoid saturated fats such as butter, cheese, fried foods, fatty cuts of red meat, egg yolks, and poultry skin. Increase unsaturated fat intake, including olive oil, canola oil, peanut butter, avocadoes, fish and nuts. Eat low-fat desserts. Increase intake of fruits and vegetables. No potassium or phosphorus restriction necessary. Monitor fluid intake, which includes all fluids and foods that are liquid at room temperature. Fluid management in nephrotic syndrome is tenuous, especially during an acute flare. Dubin–Johnson syndrome Dubin–Johnson syndrome is an autosomal recessive disorder that causes an increase of conjugated bilirubin in the serum without elevation of liver enzymes (ALT, AST). This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile. It is usually asymptomatic but may be diagnosed in early infancy based on laboratory tests. Symptoms of Dubin-Johnson Syndrome: The list of signs and symptoms mentioned in various sources for Dubin-Johnson Syndrome includes the 8 symptoms listed below: Intermittent jaundice Pain in right hypochondrium Liver enlargement This beneficial effect is supposedly due to bilirubin IXα's being recognised as a potent antioxidant. A study by Lin et al. associated moderately elevated levels of bilirubin in people with GS and the (TA)7/(TA)7 genotype with 1/3 the risk for both coronary heart disease and cardiovascular disease as compared to those with the (TA)6/(TA)6 genotype (i.e. a normal, non-mutated gene locus). A paper by Schwertner and Vitek summarizes many of the pre-2008 findings between cardiovascular disease and elevated serum bilirubin concentrations. The authors go on to discuss intentional, artificial rising of bilirubin levels as a means of prevention of cardiovascular disease and other oxidative and inflammatory diseases. Pathophysiology: The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile.[1] Pigment deposition in lysosomes causes the liver to turn black. Differential diagnosis: While this syndrome is considered harmless, it is clinically important because it may be confused with much more dang Liver tenderness Black liver Dark pigment deposits in parenchymal cells Presence of bilirubin in urine Increased blood levels of conjugated bilirubin Dubin-Johnson syndrome has an autosomal recessive pattern of inheritance. DJS is due to a defect in the multispecific anion transporter (cMOAT) gene (ABC transporter superfamily). It is an autosomal recessive disease and is likely due to a loss of function mutation, since the mutation affects the cytoplasmic / binding domain. Prognosis: Prognosis is good, and treatment of this syndrome is usually unnecessary. Most patients are asymptomatic and have normal life spans. Some neonates will present with cholestasis. Hormonal contraceptives and pregnancy may lead to overt jaundice and icterus (yellowing of the eyes and skin). Zollinger–Ellison syndrome Zollinger–Ellison syndrome is a triad of gastric acid hypersecretion, severe peptic ulceration, and non-beta cell islet tumor of pancreas (gastrinoma). In this syndrome increased levels of the hormone gastrin are produced, causing the stomach to produce excess hydrochloric acid. Often the cause is a tumor (gastrinoma) of the duodenum or pancreas producing the hormone gastrin. Gastrin then causes an excessive production of acid which can lead to peptic ulcers in almost 95% of patients. Pathophysiology: Gastrin works on stomach parietal cells causing them to secrete more hydrogen ions into the stomach lumen. In addition, gastrin acts as a trophic factor for parietal cells, causing parietal cell hyperplasia. Thus there is an increase in the number of acid-secreting cells, and each of these cells produces acid at a higher rate. The increase in acidity contributes to the development of multiple peptic ulcers in the stomach and duodenum (small bowel). Patients with Zollinger–Ellison syndrome may experience abdominal pain and diarrhea. The diagnosis is also suspected in patients without symptoms who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment. Gastrinomas may occur as single tumors or as multiple, small tumors. About onehalf to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and lymph nodes near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type I (MEN I). MEN I patients have tumors in their pituitary gland and parathyroid glands in addition to tumors of the pancreas. Symptoms: Epigastric pain (stomach ache) Diarrhoea Melena Vomiting Weight loss Diagnosis Clinical suspicion of Zollinger–Ellison syndrome may be aroused when the above symptoms prove resistant to treatment, when the symptoms are especially suggestive of the syndrome, or endoscopy is suggestive. The diagnosis of Zollinger–Ellison syndrome is made by several laboratory tests and imaging studies. Secretin stimulation test, which measures evoked gastrin levels Blind loop syndrome Physiology: The obstruction of a section of intestine causes ineffective bile salt mediated digestion of fats, causing fatty stools and poor absorption of fat and fat-soluble vitamins. Vitamin B12 deficiency may occur because the increased bacterial population can consume the vitamin. Causes: Blind loop syndrome is a complication of surgical operations of the abdomen, as well as inflammatory bowel disease or scrleroderma. Another cause is jejunoileal diverticula. Symptoms: Loss of appetite Nausea Diarrhea Fullness after a meal Fatty stools Unintentional weight loss Signs and tests: A physical examination may reveal a mass or distention of the abdomen. Tests which may be useful for diagnosis include: Abdominal x-ray Abdominal CT scan Short bowel syndrome Signs and symptoms: The symptoms of short bowel syndrome can include: Abdominal pain Diarrhea and steatorrhea (oily or sticky stool, which can be malodorous) Fluid retention Weight loss and malnutrition Fatigue Patients with short bowel syndrome may have complications caused by malabsorption of vitamins and minerals, such as deficiencies in vitamins A, D, E, K, and B12, calcium, magnesium, iron, folic acid, and zinc. These may appear as anermia, hyperkeratosis (scaling of the skin), easy bruising, muscle spasms, poor blood clotting, and bone pain. Causes: Short bowel syndrome in adults is usually caused by surgery for: Crohn's disease, an inflammatory disorder of the digestive tract Volvulus, a spontaneous twisting of the small intestine that cuts off the blood supply and leads to tissue death Tumrors of the small intestine Injury or trauma to the small intestine Necrotizing enterocolitis (premature newborn) Bypass surgery to treat obesity, a now commonly performed surgical procedure intestine Surgery to remove diseases or damaged portion of the small Pathophysiology: In healthy adults, the small intestine has an average length of approximately 6 meters (19.7 feet). Short bowel syndrome usually develops when there is less than 2 meters (6.6 feet) of the small intestine left to absorb sufficient nutrients. Short bowel syndrome caused by the surgical removal of a portion of the bowel may be a temporary condition, due to the adaptive property of the small intestine. In a process called intestinal adaptation, physiological changes to the remaining portion of the small intestine occur to increase its absorptive capacity. These changes include: Enlargement and lengthening of the villi found in the lining Increase in the diameter of the small intestine Slow down in peristalsis or movement of food through the small intestine Management: Symptoms of short bowel syndrome are usually addressed by prescription medicine. These include: Anti-diarrheal medicine (e.g. loperamide, codeine) Vitamin, mineral supplements and L-Glutamine powder mixed with water H2 blocker and proton purmp inhibitors to reduce stomach acid Lactase supplement (to improve the bloating and diarrhoea associated with lactose intolerance) Surgery, including intestinal lengthening, tapering, and small bowel transplant. Parenteral nutrition (PN or TPN for total parenteral nutrition - nutrition administered via intravenous line). Nutrition administered via gastrostomy tube Juvenile polyposis syndrome Solitary juvenile polyps most commonly occur in the rectum and present with rectal bleeding. The World Health Organization criteria for diagnosis of juvenile polyposis syndrome are one of either: 1. More than five juvenile polyps in the colon or rectum; or 2. Juvenile polyps throughout the gastrointestinal tract; or 3. Any number of juvenile polyps in a person with a family history of juvenile polyposis. Clinical Presentation: Age of onset is variable. The term 'Juvenile' in the title of Juvenile Polyposis Syndrome refers to the histological type of the polyps rather than age of onset. Affected individuals may present with rectal bleeding, abdominal pain, diarrhea or anemia. On colonoscopy or sigmoidoscopy polyps that vary in shape or size are present. The polyps can be sessile or pedunculated hamartomatous polyps[3]. Most juvenile polyps are benign, however, malignancy can occur. Lifetime risk of developing cancers of the gastro-intestinal tract range from 9% to 50%.[4] Genetics: Juvenile Polyposis Syndrome can occur sporadically in families or be inherited in an autosomal dominant manner. Two genes associated with Juvenile Polyposis Syndrome are BMPR1A and SMAD4 [5] Gene testing may be useful when trying to ascertain which non-symptomatic family members may be at risk of developing polyps, however having a known familial mutation would be unlikely to change the course of treatment. A known mutation may also be of use for affected individuals when they decide to start a family as it allows them reproductive choices. While mutations in the gene PTEN were also thought to have caused Juvenile Polyposis Syndrome, it is now thought that mutations in this gene cause a similar clinical picture to Juvenile Polyposis Syndrome but are actually affected with Cowden syndrome or other phenotypes of the PTEN harmatoma tumour syndrome. Prognosis: Solitary polyps have no significant risk of cancer. But multiple polyps (>5), polyposis syndrome, of the colon carries a 10% risk of developing into cancer. This is mainly because of juvenile polyps developing adenomatous tissue. Screening and treatment: People with juvenile polyps they require yearly upper and lower endoscopies with polyp excision and cytology. Their siblings may also need to be screened regularly.[citation needed] Malignant transformation of polyps requires surgical colectomy. Gardner's syndrome Gardner syndrome, also known as familial colorectal polyposis,[1] is an autosomal dominant form of polyposis characterized by the presence of multiple polyps in the colon together with tumors outside the colon.[2] The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts,[3] as well as the occurrence of desmoid tumors in approximately 15% of affected individuals. The countless polyps in the colon predispose to the development of colon cancer; if the colon is not removed, the chance of colon cancer is considered to be very significant. Polyps may also grow in the stomach, duodenum, spleen, kidneys, liver, mesentery and small bowel. In a small number of cases, polyps have also appeared in the cerebellum. Cancers related to GS commonly appear in the thyroid, liver and kidneys. At this time, there is no cure, and in its more advanced forms, it is considered a terminal diagnosis with a life expectancy of 35–45 years; treatments are surgery and palliative care, although some chemotherapy has been tried with limited success.[citation needed] Genetics: Gardner syndrome has an autosomal dominant pattern of inheritance. Gardner syndrome is inherited in an autosomal dominant manner. Typically, one parent has Gardner syndrome. Each of their children, male and female alike, are at 50% risk of inheriting the gene for Gardner syndrome. The risk increases in each succeeding generation, as affected occurs (cluster studies appear by registry). Cause: Gardner syndrome is now known to be caused by mutation in the APC gene located in chromosome 5q21 (band q21 on chromosome 5). This is the same gene as is mutant in familial adenomatous polyposis (FAP), a more common disease that also predisposes to colon cancer. New genetic and molecular information has caused some genetic disorders to be split into multiple entities while other genetic disorders merge into one condition. After existing for most of the second half of the 20th century, Gardner syndrome has vanished as a separate entity. It has been merged into familial adenomatous polyposis (FAP) and is now considered simply a phenotypic variant of FAP. Diagnosis: Gardner syndrome can be identified based on oral findings, including multiple impacted and supernumerary teeth, multiple jaw osteomas which give a "cotton-wool" appearance to the jaws, as well as multiple odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE), in addition to multiple adenomatous polyps of the colon. Gardner syndrome is also associated with FAP (Familial Adenomatous Polyposis) and may manifest as aggressive fibromatosis (desmoid tumors) of the retroperitoneum. Management: The initial treatment generally involves antibiotics for the bacterial overgrowth, along with vitamin B12 supplementation. If antibiotics are not successful, surgical correction of the obstruction to allow better flow of food through the intestine may be considered Solitary rectal ulcer syndrome Solitary rectal ulcer syndrome is an uncommon rectal disorder that can present with bleeding, passage of mucus, straining during defecation, and a sense of incomplete evacuation. The lesion was first reported in 1829, but its clinical manifestations and histopathology were not described until 1969. Because it is rare, its incidence is uncertain, but has been estimated in one study to be 1 in 100,000. In one retrospective study of 80 patients, the median age was 48 years with a range of 14 to 76 years. Men and women appear to be affected equally although gender differences have been suggested in various reports. Clinical Features: The name of the syndrome is misleading, since patients can often present with lesions that are neither solitary nor ulcerated. The lesions are located in the anterior rectal wall within 10 cm of the anal verge in the majority of patients. Endoscopic findings vary and can include mucosal ulcerations, polypoid and mass lesions, or simply erythema. As a result, misdiagnosis is common. In one study, as many as 26 percent of patients had been initially diagnosed incorrectly, most commonly as having a nonspecific ulcer, inflammatory bowel disease, or adenomatous change. Symptoms are variable or may be absent. In one series the most common symptoms were rectal bleeding (56 percent), straining (28 percent), and pelvic fullness (23 percent) [6]. Mucous discharge, incontinence, tenesmus, and pain were less frequently described. Pathogenesis: The pathogenesis of the solitary rectal ulcer is incompletely understood. However, a number of factors appeared to have a causative role in individual reports. It is possible that different etiologies may contribute to the development of the final lesion. A common observation in a number of reports is rectal prolapse and paradoxical contraction of the puborectalis muscle, which can result in rectal trauma by two different mechanisms. Hepatorenal syndrome Hepatorenal syndrome (often abbreviated HRS) is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. HRS is usually fatal unless a liver transplant is performed, although various treatments, such as dialysis, can prevent advancement of the condition. HRS can affect individuals with cirrhosis (regardless of cause), severe alcoholic hepatitis, or fulminant hepatic failure, and usually occurs when liver function deteriorates rapidly because of an acute injury such as an infection, bleeding in the gastrointestinal tract, or overuse of diuretic medications. HRS is a relatively common complication of cirrhosis, occurring in 18% of cirrhotics within one year of their diagnosis, and in 39% of cirrhotics within five years of their diagnosis. Deteriorating liver function is believed to cause changes in the circulation that supplies the intestines, altering blood flow and blood vessel tone in the kidneys. The renal failure of HRS is a consequence of these changes in blood flow, rather than direct damage to the kidney; the kidneys themselves appear normal to the naked eye and tissue is normal when viewed under the microscope, and the kidneys even function normally when placed in an otherwise healthy environment (such as if transplanted into a person with a healthy liver). The diagnosis of hepatorenal syndrome is based on laboratory tests of individuals susceptible to the condition. Two forms of hepatorenal syndrome have been defined: Type 1 HRS entails a rapidly progressive decline in kidney function, while type 2 HRS is associated with ascites (fluid accumulation in the abdomen) that does not improve with standard diuretic medications. The risk of death in hepatorenal syndrome is very high; the mortality of individuals with type 1 HRS is over 50% over the short term, as determined by historical case series. The only long-term treatment option for the condition is liver transplantation. While awaiting transplantation, people with HRS often receive other treatments that improve the abnormalities in blood vessel tone, including supportive care with medications, or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS), which is a small shunt placed to reduce blood pressure in the portal vein. Some patients may require hemodialysis to support kidney function, or a newer technique called liver dialysis which uses a dialysis circuit with albumin-bound membranes to bind and remove toxins normally cleared by the liver, providing a means of extracorporeal liver support until transplantation can be performed. Hepatorenal syndrome is a particular and common type of kidney failure that affects individuals with liver cirrhosis or, less commonly, with fulminant liver failure.[1] The syndrome involves constriction of the blood vessels of the kidneys and dilation of blood vessels in the splanchnic circulation, which supplies the intestines.[2] The classification of hepatorenal syndrome identifies two categories of renal failure, termed type 1 and type 2 HRS, which both occur in individuals with either cirrhosis or fulminant liver failure. In both categories, the deterioration in kidney function is quantified either by an elevation in creatinine level in the blood, or by decreased clearance of creatinine in the urine.[3] Type 1 hepatorenal syndrome Type 1 HRS is characterized by rapidly progressive renal failure, with a doubling of serum creatinine to a level greater than 221 μmol/L (2.5 mg/dL) or a halving of the creatinine clearance to less than 20 mL/min over a period of less than two weeks. The prognosis of individuals with type 1 HRS is particularly grim, with a mortality rate exceeding 50% after one month.[4] Patients with type 1 HRS are usually ill, may have low blood pressure, and may require therapy with drugs to improve the strength of heart muscle contraction (inotropes) or other drugs to maintain blood pressure (vasopressors). Type 2 hepatorenal syndrome In contrast, type 2 HRS is slower in onset and progression. It is defined by an increase in serum creatinine level to >133 μmol/L (1.5 mg/dL) or a creatinine clearance of less than 40 mL/min, and a urine sodium < 10 μmol/L. It also carries a poor outlook, with a median survival of approximately six months unless the affected individual undergoes liver transplantation. Type 2 HRS is thought to be part of a spectrum of illness associated with increased pressures in the portal vein circulation, which begins with the development of fluid in the abdomen (ascites). The spectrum continues with diureticresistant ascites, where the kidneys are unable to excrete sufficient sodium to clear the fluid even with the use of diuretic medications. Most individuals with type 2 HRS have diuretic-resistant ascites before they develop deterioration in kidney function. Signs and symptoms: Both types of hepatorenal syndrome share three major components: altered liver function, abnormalities in circulation, and renal failure. As these phenomena may not necessarily produce symptoms until late in their course, individuals with hepatorenal syndrome are typically diagnosed with the condition on the basis of altered laboratory tests. Most people who develop HRS have cirrhosis, and may have signs and symptoms of the same, which can include jaundice, altered mental status, evidence of decreased nutrition, and the presence of ascites. Specifically, the production of ascites that is resistant to the use of diuretic medications is characteristic of type 2 HRS. Oliguria, which is a decrease in urine volume, may occur as a consequence of renal failure; however, some individuals with HRS continue to produce a normal amount of urine. As these signs and symptoms may not necessarily occur in HRS, they are not included in the major and minor criteria for making a diagnosis of this condition; instead HRS is diagnosed in an individual at risk for the condition on the basis of the results of laboratory tests, in the exclusion of other causes. Causes: Hepatorenal syndrome usually affects individuals with cirrhosis and elevated pressures in the portal vein system (termed portal hypertension). While HRS may develop in any type of cirrhosis, it is most common in individuals with alcoholic cirrhosis, particularly if there is concomitant alcoholic hepatitis identifiable on liver biopsies.[8] HRS can also occur in individuals without cirrhosis, but with acute onset of liver failure, termed fulminant hepatic failure. Certain precipitants of HRS have been identified in vulnerable individuals with cirrhosis or fulminant hepatic failure. These include bacterial infection, acute alcoholic hepatitis, or bleeding in the upper gastrointestinal tract. Spontaneous bacterial peritonitis, which is the infection of ascites fluid, is the most common precipitant of HRS in cirrhotic individuals. HRS can sometimes be triggered by treatments for complications of liver disease: iatrogenic precipitants of HRS include the aggressive use of diuretic medications or the removal of large volumes of ascitic fluid by paracentesis from the abdominal cavity without compensating for fluid losses by intravenous replacement. Diagnosis: There can be many causes of kidney failure in individuals with cirrhosis or fulminant liver failure. Consequently, it is a challenge to distinguish hepatorenal syndrome from other entities that cause renal failure in the setting of advanced liver disease. As a result, additional major and minor criteria have been developed to assist in the diagnosis of hepatorenal syndrome. The major criteria include liver disease in the setting of portal hypertension; renal failure; the absence of shock, infection, recent treatment with medications that affect the function of the kidney (nephrotoxins), and fluid losses; the absence of sustained improvement in renal function despite treatment with 1.5 litres of intravenous normal saline; the absence of proteinuria, or protein in the urine; and, the absence of renal disease or obstruction of renal outflow as seen on ultrasound. The minor criteria are the following: a low urine volume (less than 500 mL (18 imp fl oz; 17 US fl oz) per day), low sodium concentration in the urine, a urine osmolality that is greater than that in the blood, the absence of red blood cells in the urine, and a serum sodium concentration of less than 130 mmol/L. Many other diseases of the kidney are associated with liver disease and must be excluded before making a diagnosis of hepatorenal syndrome. Individuals with pre-renal failure do not have damage to the kidneys, but as in individuals with HRS, have renal dysfunction due to decreased blood flow to the kidneys. Also, similarly to HRS, pre-renal failure causes the formation of urine that has a very low sodium concentration. In contrast to HRS, however, pre-renal failure usually responds to treatment with intravenous fluids, resulting in reduction in serum creatinine and increased excretion of sodium.[3] Acute tubular necrosis (ATN) involves damage to the tubules of the kidney, and can be a complication in individuals with cirrhosis, because of exposure to toxic medications or the development of decreased blood pressure. Because of the damage to the tubules, ATN affected kidneys usually are unable to maximally resorb sodium from the urine. As a result, ATN can be distinguished from HRS on the basis of laboratory testing, as individuals with ATN will have urine sodium measurements that are much higher than in HRS; however, this may not always be the case in cirrhotics.[5] Individuals with ATN also may have evidence of hyaline casts or muddy-brown casts in the urine on microscopy, whereas the urine of individuals with HRS is typically devoid of cellular material, as the kidneys have not been directly injured.[3] Some viral infections of the liver, including hepatitis B and hepatitis C can also lead to inflammation of the glomerulus of the kidney.[9][10] Other causes of renal failure in individuals with liver disease include drug toxicity (notably the antibiotic gentamicin) or contrast nephropathy, caused by intravenous administration of contrast agents used for medical imaging Pathophysiology: The renal failure in hepatorenal syndrome is believed to arise from abnormalities in blood vessel tone in the kidneys. The predominant theory (termed the underfill theory) is that blood vessels in the renal circulation are constricted because of the dilation of blood vessels in the splanchnic circulation (which supplies the intestines), which is mediated by factors released by liver disease. Nitric oxide, prostaglandins, and other vasoactive substances, have been hypothesized as powerful mediators of splanchnic vasodilation in cirrhosis. The consequence of this phenomenon is a decrease in the "effective" volume of blood sensed by the juxtaglomerular apparatus, leading to the secretion of renin and the activation of the renin-angiotensin system, which results in the vasoconstriction of vessels systemically and in the kidney specifically. However, the effect of this is insufficient to counteract the mediators of vasodilation in the splanchnic circulation, leading to persistent "underfilling" of the renal circulation and worsening renal vasoconstriction, leading to renal failure. Studies to quantify this theory have shown that there is an overall decreased systemic vascular resistance in hepatorenal syndrome, but that the measured femoral and renal fractions of cardiac output are respectively increased and reduced, suggesting that splanchnic vasodilation is implicated in the renal failure. Many vasoactive chemicals have been hypothesized as being involved in mediating the systemic hemodynamic changes, including atrial natriuretic factor, prostacyclin, thromboxane A2, and endotoxin. In addition to this, it has been observed that the administration of medications to counteract splanchnic vasodilation (such as ornipressin, terlipressin, and octreotide) leads to improvement in glomerular filtration rate (which is a quantitative measure of renal function), in patients with hepatorenal syndrome, providing further evidence that splanchnic vasodilation is a key feature of its pathogenesis. The underfill theory involves activation of the renin-angiotensin-aldosterone system, which leads to an increase in absorption of sodium from the renal tubule (termed renal sodium avidity) mediated by aldosterone, which acts on mineralocorticoid receptors in the distal convoluted tubule. This is believed to be a key step in the pathogenesis of ascites in cirrhotics as well. It has been hypothesized that the progression from ascites to hepatorenal syndrome is a spectrum where splanchnic vasodilation defines both resistance to diuretic medications in ascites (which is commonly seen in type 2 HRS) and the onset of renal vasoconstriction (as described above) leading to hepatorenal syndrome. Budd–Chiari syndrome In medicine (gastroenterology and hepatology), Budd–Chiari syndrome is the clinical picture caused by occlusion of the hepatic veins. It presents with the classical triad of abdominal pain, ascites and hepatomegaly. Examples of occlusion include thrombosis of hepatic veins. The syndrome can be fulminant, acute, chronic, or asymptomatic. It occurs in 1 out of a million individuals [1] and is more common in females. Some 10-20% also have obstruction of the portal vein. Signs and symptoms: The acute syndrome presents with rapidly progressive: severe upper abdominal pain, jaundice, hepatomegaly (enlarged liver), ascites, elevated liver enzymes, and eventual encephalopathy. The fulminant syndrome presents early with encephalopathy and ascites. Severe hepatic necrosis and lactic acidosis may be present as well. Caudate lobe hypertrophy is often present. The majority of patients have a slower-onset form of Budd–Chiari syndrome. This can be painless. A system of venous collaterals may form around the occlusion which may be seen on imaging as a "spider's web." Patients may progress to cirrhosis and show the signs of liver failure. An asymptomatic form may be totally silent and discovered only incidentally. It is generally not concerning. Causes: The cause cannot be found in about half of the patients Primary (75%): thrombosis of the hepatic vein Secondary (25%): compression of the hepatic vein by an outside structure (e.g. a tumor) Hepatic vein thrombosis is associated with the following in decreasing order of frequency. (A)Polycythemia vera (B)pregnancy (C)post partum state (D)use of oral contraceptive (E)paroxysmal nocturnal hemoglobinuria (F)Hepatocellular carcinoma. Infection such as TB Congenital venous webs Occasionally inferior vena caval stenosis Often, the patient is known to have a tendency towards thrombosis, although Budd–Chiari syndrome can also be the first symptom of such a tendency. Examples of genetic tendencies include Protein C deficiency, Protein S deficiency, the Factor V Leiden mutation, and Prothrombin Mutation G20210A.[2] An important non-genetic risk factor is the use of estrogen-containing (combined) forms of hormonal contraception. Other risk factors include the antiphospholipid syndrome, aspergillosis, Behçet's disease, dacarbazine, pregnancy, and trauma. Many patients have Budd–Chiari syndrome as a complication of polycythemia vera (myeloproliferative disease of red blood cells). Patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) appear to be especially at risk for Budd–Chiari syndrome, more than other forms of thrombophilia: up to 39% develop venous thromboses and 12% may acquire Budd-Chiari. A related condition is veno-occlusive disease, which occurs in recipients of bone marrow transplants as a complication of their medication. Although its mechanism is similar, it is not considered a form of Budd–Chiari syndrome. Other toxicologic causes of veno-occlusive disease include plant & herbal sources of pyrrolizidine alkaloids: Borage, Boneset, Coltsfoot, T'u-san-chi, Comfrey, Heliotrope (sunflower seeds), Gordolobo, Germander, and Chaparral. Pathophysiology: Any obstruction of the venous vasculature of the liver is referred to as Budd– Chiari syndrome, from the venules to the right atrium. This leads to increased portal vein and hepatic sinusoid pressures as the blood flow stagnates. The increased portal pressure causes: 1) increased filtration of vascular fluid with the formation of protein-rich ascites in the abdomen; and 2) collateral venous flow through alternative veins leading to gastric varices and hemorrhoids. Obstruction also causes centrilobular necrosis and peripheral lobule fatty change due to ischemia. If this condition persists chronically what is known as Nutmeg liver will develop. Renal failure may occur, perhaps due to the body sensing an "underfill" state and subsequent activation of the renin-angiotensin pathways and excess sodium retention. Diagnosis: When Budd–Chiari syndrome is suspected, measurements are made of liver enzyme levels and other organ markers (creatinine, urea, electrolytes, LDH). Budd–Chiari syndrome is most commonly diagnosed using ultrasound studies of the abdomen and retrograde angiography. Ultrasound may show obliteration of hepatic veins, thrombosis or stenosis, spiderweb vessels, large collateral vessels, or a hyperechoic cord replacing a normal vein. Computed tomography (CT) or magnetic resonance imaging (MRI) is sometimes employed although these methods are generally not as sensitive. Liver biopsy is nonspecific but sometimes necessary to differentiate between Budd–Chiari syndrome and other causes of hepatomegaly and ascites, such as galactosemia or Reye's syndrome. Treatment: A minority of patients can be treated medically with sodium restriction, diuretics to control ascites, anticoagulants such as heparin and warfarin, and general symptomatic management. The majority of patients require further intervention. Milder forms of Budd-Chiari may be treated with surgical shunts to divert blood flow around the obstruction or the liver itself. Shunts must be placed early after diagnosis for best results. The transjugular intrahepatic portosystemic shunt (TIPS) is similar to a surgical shunt. It accomplishes the same goal but has a lower procedure-related mortality, which has led to a growth in its popularity. Patients with stenosis or vena caval obstruction may benefit from angioplasty. Limited studies on thrombolysis with direct infusion of urokinase and tissue plasminogen activator (tPA) into the obstructed vein have shown moderate success in treating Budd–Chiari syndrome; however, it is not routinely attempted. Liver transplantation is an effective treatment for Budd-Chiari. It is generally reserved for patients with fulminant hepatic failure, failure of shunts, or progression of cirrhosis that reduces the life expectancy to 1 year. Long-term survival after transplantation ranges from 69-87%. The most common complications of transplant include rejection, arterial or venous thromboses, and bleeding due to anticoagulation. Up to 10% of patients may have a recurrence of Budd–Chiari syndrome after the transplant. Prognosis: Several studies have attempted to predict the survival of patients with Budd– Chiari syndrome. In general, nearly 2/3 of patients with Budd-Chiari are alive at 10 years. [6] Important negative prognostic indicators include ascites, encephalopathy, elevated Child-Pugh scores, elevated prothrombin time, and altered serum levels of various substances (sodium, creatinine, albumin, and bilirubin). Survival is also highly dependent on the underlying cause of the Budd–Chiari syndrome. For example, patients with myeloproliferative disorders may progress to acute leukemia independent of Budd–Chiari syndrome. Caroli disease Caroli disease is a rare inherited disorder characterized by dilatation of the intrahepatic bile ducts. There are two types of Caroli disease, the most common being the simple, or isolated case where the bile ducts are widened by ectasia. The second, more complex, cause is commonly known as Caroli Syndrome. This complex form is also linked with portal hypertension and congenital hepatic fibrosis. The differences between the causes of the two cases have not yet been discovered. Caroli disease is also associated with liver failure and polycystic kidney disease. The disease affects about 1 in 1,000,000 people, with more reported cases of Caroli syndrome than of Caroli disease. [2] Caroli disease also is known as communicating cavernous ectasia, or congenital cystic dilatation of the intrahepatic biliary tree. Caroli disease is distinct from other diseases that cause ducal dilatation caused by obstruction, in that it is not one of the many choledochal cyst derivatives. Symptoms: The first symptoms typically include fever, intermittent abdominal pain, and hepatomegaly. Occasionally jaundice occurs. Caroli disease usually occurs in the presence of other diseases, such as autosomal recessive polycystic kidney disease, cholangitis, gallstones, bilary abscess, septicemia, liver cirrhosis, renal failure, and cholangiocarcinoma (7% affected).[1] People with Caroli disease are 100 times more at risk for cholangiocarcinoma than the general population After recognizing symptoms of related diseases, Caroli disease can be diagnosed. Detection images: Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. Commonly the disease is limited to the left lobe of the liver. Images taken by CT-scan, X-ray, or MRI will show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT-Scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver.[6] A high contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, therefore, a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease. Morbidity: Caroli disease is typically found in Asia and diagnosed in children under the age of 22. Cases have also been found in both infants and adults. As medical imaging technology improves, diagnostic age decreases. Morbidity is common and is caused by complications of cholangitis, sepsis, choledocholithiasis, and cholangiocarcinoma. These morbid conditions often prompt the diagnosis. Portal hypertension may be present, resulting in other conditions including splenomegaly, hematemesis and melena. These problems can severely affect the patient's quality of life. In a ten year period between 1995 and 2005, only ten patients were surgically treated for Caroli disease, with an average patient age of 45.8 years. After reviewing 46 cases of Caroli disease before 1990, it was found that 21.7% of the cases were the result of an intraheptic cyst or non-obstructive biliary tree dilation, 34.7% were linked with congenital hepatic fibrosis, 13% were isolated choledochal cystic dilation, and the remaining 24.6% had a combination of all three. Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within approximately 5–10 years. Causes: The cause appears to be genetic; the simple form is an autosomal dominant trait while the complex form is an autosomal recessive trait.[1] Females are more prone to Caroli disease than males.[3] Family history may include kidney and liver disease due to the link between Caroli Disease and ARPKD.[10] PKHD1, the gene linked to ARPKD, has been found mutated in patients with Caroli syndrome. PKHD1 is expressed primarily in the kidneys with lower levels in the liver, pancreas, and lungs, a pattern consistent with phenotype of the disease, which primarily affects the liver and kidneys.[1][10] The genetic basis for the difference between Caroli disease and Caroli syndrome has not been defined. Treatment: The treatment depends on clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. Sometimes, if the disease is isolated in one specific area, a lobectomy may be performed to remove the affected lobe, relieving symptoms and removing the risk of malignancy. There is good evidence that malignancy complicates Caroli disease in approximately 7% of cases. Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid for hepatolithiasis. Ursodiol is given to treat cholelithiasis. In diffuse cases of Caroli disease, treatment options include conservative or endoscopic therapy, internal biliary bypass procedures and liver transplantation in carefully selected cases. Surgical resection has been used successfully in patients with monolobar disease.n orthotopic liver transplant is another option, used only when antibiotics have no effect, in combination with recurring cholangitis. With a liver transplant, cholangiocarcinoma is usually avoided in the long run. Family studies are necessary to determine if Caroli disease is due to inheritable causes. Regular follow-ups, including ultrasounds and liver biopsies, are performed Postcholecystectomy syndrome Postcholecystectomy syndrome (PCS) describes the presence of abdominal symptoms after surgical removal of the gallbladder (Cholecystectomy). Symptoms of postcholecystectomy syndrome may include: Upset stomach, nausea, and vomiting. Gas, bloating, and diarrhea. Persistent pain in the upper right abdomen[1] Symptoms occur in about 5 to 40 percent of patients who undergo cholycystectomy. [2] The pain associated with post-cholecystectomy syndrome is usually ascribed to either sphincter of Oddi dysfunction or to post-surgical adhesions [3] . Approximately 50% of cases are due to biliary causes such as remaining stone, biliary injury, dysmotility and choledococyst. The remaining 50% are due to non-biliary causes. This is because upper abdominal pain and gallstones are both common but are not always related. Crigler–Najjar syndrome Crigler-Najjar Syndrome or CNS is a rare disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of blood. The disorder results in an inherited form of non-hemolytic jaundice, often leading to brain damage in infants. This syndrome is divided into two types: type I and type II, with the latter sometimes called Arias syndrome. These two types, along with Gilbert's syndrome, Dubin-Johnson syndrome, and Rotor syndrome, make up the five known hereditary defects in bilirubin metabolism. Unlike Gilbert's syndrome, only a few hundred cases of CNS are known to exist. Crigler-Najjar syndrome, type I This is a very rare disease (estimated at 0.6 - 1.0 per million live births), and consanguinity increases the risk of this condition (other rare diseases may also be present). Inheritance is autosomal recessive. Intense jaundice appears in the first days of life and persists thereafter. Type 1 is characterised by a serum bilirubin usually above 345 µmol/L (310 - 755) (whereas the reference range for total bilirubin is 2 - 14 μmol/L). No UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide A1) expression can be detected in the hepatic tissue. Hence, there is no response to treatment with phenobarbital[1] (which causes enzyme induction). Most patients (type IA) have a mutation in one of the common exons (2 to 5), and have difficulties conjugating several additional substrates (several drugs and xenobiotics). A smaller percentage of patients (type IB) have mutations limited to the bilirubin-specific A1 exon; their conjugation defect is mostly restricted to bilirubin itself. Prior to the availability of phototherapy, these children died of kernicterus (=bilirubin encephalopathy), or survived until early adulthood with clear neurological impairment. Today, therapy includes exchange transfusions in the immediate neonatal period, 12h/d phototherapy heme oxygenase inhibitors to reduce transient worsening of hyperbilirubinemia (although the effect decreases over time) oral calcium phosphate and -carbonate to form complexes with bilirubin in the gut, liver transplantation prior to the onset of brain damage, and before phototherapy becomes ineffective at later age Crigler-Najjar syndrome, type II Differs from type I in several aspects: bilirubin levels are generally below 345 µmol/L (100 - 430; thus, there is overlap), and some cases are only detected later in life because of lower serum bilirubin, kernicterus is rare in type II bile is pigmented, instead of pale in type I or dark as normal, and monoconjugates constitute the largest fraction of bile conjugates UGT1A1 is present at reduced but detectable levels (typically <10% of normal), because of single base pair mutations therefore, treatment with phenobarbital is effective, generally with a decrease of at least 25% in serum bilirubin. In fact, this can be used, along with these other factors, to differentiate type I and II. The inheritance pattern of Crigler–Najjar syndrome type II has been difficult to determine, but is generally considered to be autosomal recessive. Differential diagnosis: Neonatal jaundice may develop in the presence of sepsis, hypoxia, hypoglycemia, hypothyroidism, hypertrophic pyloric stenosis, galactosemia, fructosemia, and so on. Hyperbilirubinemia of the unconjugated type may be caused by increased production hemolysis (e.g. hemolytic disease of the newborn, hereditary spherocytosis, sickle cell disease) ineffective erythropoiesis massive tissue necrosis or large hematomas) decreased clearance drug-induced physiological neonatal jaundice and prematurity liver diseases such as advanced hepatitis or cirrhosis breast milk jaundice and Lucey-Driscoll syndrome Crigler–Najjar syndrome and Gilbert syndrome. In Crigler–Najjar syndrome and Gilbert syndrome, routine liver function tests are normal, and hepatic histology usually is too. There is no evidence for hemolysis. Druginduced case typically regress after discontinuation of the substance. Physiological neonatal jaundice may peak at 85 - 170 µmol/L, and decline to normal adult concentrations within 2 weeks. Prematurity results in higher levels. Hepatopulmonary syndrome In medicine, hepatopulmonary syndrome is a syndrome of shortness of breath and hypoxemia (low oxygen levels in the blood of the arteries) caused by vasodilation (broadening of the blood vessels) in the lungs of patients with liver disease. Dyspnea and hypoxemia are worse in the upright position (which is called platypnea and orthodeoxia, respectively). Diagnosis: The hepatopulmonary syndrome is suspected in any patient with known liver disease who reports dyspnea (particularly platypnea). Patients with clinically significant symptoms should undergo pulse oximetry. If the syndrome is advanced, arterial blood gasses should be measured on air. A useful diagnostic test is contrast echocardiography. Intravenous microbubbles (> 10 micrometers in diameter) from agitated normal saline that are normally obstructed by pulmonary capillaries (normally <8 to 15 micrometers) rapidly transit the lung and appear in the left atrium of the heart within 7 heart beats. Similarly, intravenous technetium-99m–labeled albumin may transit the lungs and appear in the kidney and brain. Pulmonary angiography may reveal diffusely fine or blotchy vascular configuration. The distinction has to be made with an intracardiac right-to-left shunt. Disease mechanism The hepatopulmonary syndrome results from the formation of microscopic intrapulmonary arteriovenous dilatations in patients with both chronic and acute liver failure. The mechanism is unknown but is thought to be due to increased hepatic production or decreased hepatic clearance of vasodilators, possibly involving nitric oxide. The vascular dilatations cause overperfusion relative to ventilation, leading to ventilation-perfusion mismatch and hypoxemia. There is an increased alveolar-arterial partial pressure of oxygen gradient while breathing room air. Additionally, late in cirrhosis, it is common to develop high output failure, which would lead to less time in capillaries per red blood cell, exacerbating the hypoxemia. Treatment Currently the only definitive treatment in liver transplant. Alternative treatments such as supplemental oxygen or somatostatin to inhibit vasodilation remain anecdotal.