As well as peptic ulcers,  vomiting blood  may result from abnormal arteries or veins that have ruptured, including  Dieulafoy's lesion  and  Gastric antral vascular ectasia . Congenital disorders of the stomach include  pernicious anaemia , in which a targeted  immune  response against  parietal cells  results in an inability to absorb  vitamin B12 . Other common symptoms that stomach disease might cause include  indigestion  or  dyspepsia ,  vomiting , and in chronic disease, digestive problems leading to forms of  malnutrition . [ 5 ]   : 850–853   In addition to routine tests, an  endoscopy  might be used to examine or take a  biopsy  from the stomach. [ 5 ]   : 848


The  small  and  large intestines  may be affected by  infectious , autoimmune, and physiological states. Inflammation of the intestines is called  enterocolitis , which may lead to  diarrhea .


Acute conditions affecting the bowels include  infectious diarrhea  and  mesenteric ischaemia . Causes of  constipation  may include  faecal impaction  and  bowel obstruction , which may in turn be caused by  ileus ,  intussusception ,  volvulus .  Inflammatory bowel disease  is a condition of unknown aetiology, classified as either  Crohn's disease  or  ulcerative colitis , that can affect the intestines and other parts of the gastrointestinal tract. Other causes of illness include  intestinal pseudoobstruction , and  necrotizing enterocolitis . [ 5 ] : 850–862, 895–903


Diseases of the intestine may cause  vomiting ,  diarrhoea  or  constipation , and altered  stool , such as with  blood in stool .  Colonoscopy  may be used to examine the large intestine, and a person's stool may be sent for  culture  and  microscopy . Infectious disease may be treated with targeted  antibiotics , and inflammatory bowel disease with  immunosuppression . Surgery may also be used to treat some causes of bowel obstruction. [ 5 ] : 850–862


The normal thickness of the small  intestinal wall  is 3–5 mm, [ 8 ]  and 1–5 mm in the large intestine. [ 9 ]  Focal, irregular and asymmetrical gastrointestinal wall thickening on  CT scan  suggests a malignancy. [ 9 ]  Segmental or diffuse gastrointestinal wall thickening is most often due to ischemic, inflammatory or infectious disease. [ 9 ]  Though less common, medications such as  ACE inhibitors  can cause  angioedema  and small bowel thickening. [ 10 ]


The small intestine consists of the  duodenum ,  jejunum  and  ileum . Inflammation of the small intestine is called  enteritis , which if localised to just part is called  duodenitis ,  jejunitis  and  ileitis , respectively.  Peptic ulcers  are also common in the duodenum. [ 5 ] : 879–884


Chronic diseases of  malabsorption  may affect the small intestine, including the autoimmune  coeliac disease , infective  tropical sprue , and congenital or surgical  short bowel syndrome . Other rarer diseases affecting the small intestine include  Curling's ulcer ,  blind loop syndrome ,  Milroy disease  and  Whipple's disease . Tumours of the small intestine include  gastrointestinal stromal tumours ,  lipomas ,  hamartomas  and  carcinoid syndromes . [ 5 ] : 879–887


Diseases of the small intestine may present with symptoms such as  diarrhoea ,  malnutrition ,  fatigue  and  weight loss . Investigations pursued may include  blood tests  to monitor nutrition, such as  iron levels ,  folate  and  calcium ,  endoscopy  and  biopsy  of the duodenum, and  barium swallow . Treatments may include renutrition and  antibiotics  for infections. [ 5 ] : 879–887


Diseases that affect the  large intestine  may affect it in whole or in part.  Appendicitis  is one such disease, caused by inflammation of the  appendix . Generalised inflammation of the large intestine is referred to as  colitis , which when caused by the bacteria  Clostridioides difficile  is referred to as  pseudomembranous colitis .  Diverticulitis  is a common cause of abdominal pain resulting from outpouchings that particularly affect the colon.  Functional colonic diseases  refer to disorders without a known cause, including  irritable bowel syndrome  and  intestinal pseudoobstruction .  Constipation  may result from lifestyle factors,  impaction of a rigid stool  in the rectum, or in  neonates ,  Hirschprung's disease . [ 5 ] : 913–915


Diseases affecting the large intestine may cause blood to be passed with stool, may cause  constipation , or may result in  abdominal pain  or a fever. Tests that specifically examine the function of the large intestine include barium swallows,  abdominal x-rays , and  colonoscopy . [ 5 ] : 913–915


Diseases affecting the  rectum  and  anus  are extremely common, especially in older adults.  Hemorrhoids , vascular outpouchings of skin, are very common, as is  pruritus ani , referring to anal itchiness. Other conditions, such as  anal cancer  may be associated with  ulcerative colitis  or with  sexually transmitted infections  such as  HIV .  Inflammation of the rectum is known as  proctitis , one cause of which is radiation damage associated with  radiotherapy  to other sites such as the  prostate .  Faecal incontinence  can result from mechanical and neurological problems, and when associated with a lack of voluntary voiding ability is described as  encopresis . Pain on passing stool may result from  anal abscesses , small inflamed nodules,  anal fissures , and  anal fistulas . [ 5 ] : 915–916


Rectal and anal disease may be asymptomatic, or may present with pain when passing stools,  fresh blood in stool ,  a feeling of incomplete emptying , or pencil-thin stools. In addition to regular tests, medical tests used to investigate the anus and rectum include the  digital rectal exam  and  proctoscopy . [ citation needed ]


Hepatic diseases refers to those affecting the  liver .   Hepatitis  refers to inflammation of liver tissue, and may be  acute  or  chronic . Infectious  viral hepatitis , such as  hepatitis A ,  B  and  C , affect in excess of (X) million people worldwide. Liver disease may also be a result of lifestyle factors, such as  fatty liver  and  NASH .  Alcoholic liver disease  may also develop as a result of chronic alcohol use, which may also cause  alcoholic hepatitis .  Cirrhosis  may develop as a result of chronic  hepatic fibrosis  in a chronically inflamed liver, such as one affected by  alcohol  or viral hepatitis. [ 5 ] : 947–958


Liver abscesses  are often acute conditions, with common causes being  pyogenic  and  amoebic . Chronic liver disease, such as cirrhosis, may be a cause of  liver failure , a state where the liver is unable to compensate for chronic damage, and unable to meet the metabolic demands of the body.  In the acute setting , this may be a cause of  hepatic encephalopathy  and  hepatorenal syndrome . Other causes of chronic liver disease are genetic or autoimmune disease, such as  hemochromatosis ,  Wilson's disease ,  autoimmune hepatitis , and  primary biliary cirrhosis . [ 5 ] : 959–963, 971


Acute liver disease rarely results in pain, but may result in  jaundice . Infectious liver disease may cause a fever. Chronic liver disease may result in  a buildup of fluid in the abdomen ,  yellowing of the skin  or  eyes , easy bruising,  immunosuppression , and feminization. [ 11 ]   Portal hypertension  is often present, and this may lead to the development of prominent veins in many parts of the body, such as  oesophageal varices , and  haemorrhoids . [ 5 ] : 959–963, 971–973


In order to investigate liver disease, a medical history, including regarding a person's  family history , travel to risk-prone areas, alcohol use and food consumption, may be taken. A  medical examination  may be conducted to investigate for symptoms of liver disease. Blood tests may be used, particularly  liver function tests , and other blood tests may be used to investigate the presence of the Hepatitis viruses in the blood, and ultrasound used. If ascites is present, abdominal fluid may be tested for protein levels. [ 5 ] : 921, 926–927


Pancreatic diseases that affect digestion refers to disorders affecting the  exocrine pancreas , which is a part of the pancreas involved in digestion. [ citation needed ]


One of the most common conditions of the exocrine pancreas is  acute pancreatitis , which in the majority of cases relates to  gallstones  that have impacted in the pancreatic part of the  biliary tree , or due to acute or chronic  hazardous alcohol use  or as a side-effect of  ERCP . Other forms of pancreatitis include  chronic  and  hereditary  forms. Chronic pancreatitis may predispose to  pancreatic cancer  and is strongly linked to alcohol use. Other rarer diseases affecting the pancreas may include  pancreatic pseudocysts ,  exocrine pancreatic insufficiency , and  pancreatic fistulas . [ 5 ] : 888–891


Pancreatic disease may present with or without symptoms. When symptoms occur, such as in  acute pancreatitis , a person may experience acute-onset, severe mid-abdominal pain, nausea and vomiting. In severe cases, pancreatitis may lead to rapid blood loss and  systemic inflammatory response syndrome . When the pancreas is unable to secrete digestive  enzymes , such as with a pancreatic cancer occluding the  pancreatic duct , result in jaundice. Pancreatic disease might be investigated using  abdominal x-rays ,  MRCP  or  ERCP ,  CT scans , and through blood tests such as measurement of the  amylase  and  lipase  enzymes. [ 5 ] : 888–894


Diseases of the  hepatobiliary system  affect the  biliary tract  (also known as the  biliary tree ), which secretes  bile  in order to aid digestion of fats. Diseases of the  gallbladder  and bile ducts are commonly diet-related, and may include the  formation of   gallstones  that impact in the gallbladder ( cholecystolithiasis ) or in the  common bile duct  ( choledocholithiasis ). [ 5 ] : 977–978


Gallstones are a common cause of inflammation of the gallbladder, called  cholecystitis . Inflammation of the  biliary duct  is called  cholangitis , which may be associated with  autoimmune  disease, such as  primary sclerosing cholangitis , or a result of bacterial infection, such as  ascending cholangitis . [ 5 ] : 977–978, 963–968


Disease of the biliary tree may cause pain in the upper right abdomen,  particularly when pressed . Disease might be investigated using  ultrasound  or  ERCP , and might be treated with drugs such as  antibiotics  or  UDCA , or by the surgical  removal of the gallbladder . [ 5 ] : 977–979


The Wikipedia article " Gastrointestinal cancer " describes the specific malignant conditions of the gastrointestinal tract. In general, a significant factor in the etiology of gastrointestinal cancers appears to be excessive exposure of the digestive organs to  bile acids . [ 12 ] [ 13 ]


Hemorrhoids  (or  haemorrhoids ), also known as  piles , are  vascular  structures in the  anal canal . [ 7 ] [ 8 ]  In their normal state, they are cushions that help with  stool  control. [ 2 ]  They become a disease when  swollen  or  inflamed ; the unqualified term  hemorrhoid  is often used to refer to the disease. [ 8 ]  The signs and symptoms of hemorrhoids depend on the type present. [ 4 ]  Internal hemorrhoids often result in painless, bright red  rectal bleeding  when  defecating . [ 3 ] [ 4 ]  External hemorrhoids often result in pain and swelling in the area of the  anus . [ 4 ]  If bleeding occurs, it is usually darker. [ 4 ]  Symptoms frequently get better after a few days. [ 3 ]  A  skin tag  may remain after the healing of an external hemorrhoid. [ 4 ]


While the exact cause of hemorrhoids remains unknown, a number of factors that increase pressure in the abdomen are believed to be involved. [ 4 ]  This may include  constipation ,  diarrhea , and sitting on the  toilet  for long periods. [ 3 ]  Hemorrhoids are also more common during  pregnancy . [ 3 ]  Diagnosis is made by looking at the area. [ 3 ]  Many people incorrectly refer to any symptom occurring around the anal area as hemorrhoids, and serious causes of the symptoms should not be ruled out. [ 2 ]   Colonoscopy  or  sigmoidoscopy  is reasonable to confirm the diagnosis and rule out more serious causes. [ 9 ]


Often, no specific treatment is needed. [ 9 ]  Initial measures consist of increasing  fiber  intake, drinking fluids to maintain hydration,  NSAIDs  to help with pain, and rest. [ 1 ]  Medicated creams may be applied to the area, but their effectiveness is poorly supported by evidence. [ 9 ]  A number of minor procedures may be performed if symptoms are severe or do not improve with conservative management. [ 6 ]   Hemorrhoidal artery embolization (HAE)  is a safe and effective  minimally invasive procedure  that can be performed and is typically better tolerated than traditional therapies. [ 10 ] [ 11 ] [ 12 ]  Surgery is reserved for those who fail to improve following these measures. [ 6 ]


Approximately 50% to 66% of people have problems with hemorrhoids at some point in their lives. [ 1 ] [ 3 ]  Males and females are both affected with about equal frequency. [ 1 ]  Hemorrhoids affect people most often between 45 and 65 years of age, [ 5 ]  and they are more common among the wealthy, [ 4 ]  although this may reflect differences in healthcare access rather than true prevalence. [ 13 ]  Outcomes are usually good. [ 3 ] [ 9 ]


The first known mention of the disease is from a 1700 BC Egyptian  papyrus . [ 14 ]


In about 40% of people with pathological hemorrhoids, there are no significant symptoms. [ 4 ]  Internal and external hemorrhoids may present differently; however, many people may have a combination of the two. [ 8 ]  Bleeding enough to cause  anemia  is rare, [ 5 ]  and life-threatening bleeding is even more uncommon. [ 15 ]  Many people feel embarrassed when facing the problem [ 5 ]  and often seek medical care only when the case is advanced. [ 8 ]


If not  thrombosed ,  external hemorrhoids  may cause few problems. [ 16 ]  However, when thrombosed, hemorrhoids may be very painful. [ 1 ] [ 8 ]  Nevertheless, this pain typically resolves in two to three days. [ 5 ]  The swelling may, however, take a few weeks to disappear. [ 5 ]  A  skin tag  may remain after healing. [ 8 ]  If hemorrhoids are large and cause issues with hygiene, they may produce irritation of the surrounding skin, and thus itchiness around the anus. [ 16 ]


Internal hemorrhoids usually present with painless, bright red  rectal bleeding  during or following a bowel movement. [ 8 ]  The blood typically covers the stool (a condition known as  hematochezia ), is on the toilet paper, or drips into the toilet bowl. [ 8 ]  The stool itself is usually normally coloured. [ 8 ]  Other symptoms may include mucous discharge, a perianal mass if they  prolapse  through the anus,  itchiness , and  fecal incontinence . [ 15 ] [ 17 ]  Internal hemorrhoids are usually painful only if they become thrombosed or  necrotic . [ 8 ]


The exact cause of symptomatic hemorrhoids is unknown. [ 18 ]  A number of factors are believed to play a role, including irregular bowel habits ( constipation  or  diarrhea ), lack of exercise, nutritional factors (low-fiber diets), increased intra-abdominal pressure (prolonged straining,  ascites , an intra-abdominal mass, or  pregnancy ), genetics, an absence of valves within the hemorrhoidal veins, and aging. [ 1 ] [ 5 ]  Other factors believed to increase risk include  obesity , prolonged sitting, [ 8 ] [ dubious  –  discuss ]  a  chronic   cough , and  pelvic floor dysfunction . [ 2 ]  Squatting while defecating may also increase the risk of severe hemorrhoids. [ 19 ]  Evidence for these associations, however, is poor. [ 2 ]  Being a receptive partner in  anal intercourse  has been listed as a cause. [ 20 ] [ 21 ] [ 22 ]


During pregnancy, pressure from the  fetus  on the abdomen and hormonal changes cause the hemorrhoidal vessels to enlarge. The birth of the baby also leads to increased intra-abdominal pressures. [ 23 ]  Pregnant women rarely need surgical treatment, as symptoms usually resolve after delivery. [ 1 ]


Hemorrhoid cushions are a part of normal human anatomy and become a pathological disease only when they experience abnormal changes. [ 8 ]  There are three main cushions present in the normal  anal canal . [ 1 ]  These are located classically at left lateral, right anterior, and right posterior positions. [ 5 ]  They are composed of neither  arteries  nor  veins , but blood vessels called  sinusoids ,  connective tissue , and  smooth muscle . [ 2 ] : 175   Sinusoids do not have  muscle tissue  in their walls, as veins do. [ 8 ]  This set of blood vessels is known as the  hemorrhoidal plexus . [ 2 ]


Hemorrhoid cushions are important for  continence . They contribute to 15–20% of anal closure pressure at rest and protect the  internal  and  external anal sphincter  muscles during the passage of stool. [ 8 ]  When a person bears down, the intra-abdominal pressure grows, and hemorrhoid cushions increase in size, helping maintain anal closure. [ 5 ]  Hemorrhoid symptoms are believed to result when these vascular structures slide downwards or when venous pressure is excessively increased. [ 15 ]  Increased  internal  and  external anal sphincter  pressure may also be involved in hemorrhoid symptoms. [ 5 ]  Two types of hemorrhoids occur: internals from the  superior hemorrhoidal plexus  and externals from the inferior hemorrhoidal plexus. [ 5 ]  The  pectinate line  divides the two regions. [ 5 ]


Hemorrhoids are typically diagnosed by physical examination. [ 6 ]  A visual examination of the anus and surrounding area may diagnose external or prolapsed hemorrhoids. [ 8 ]  Visual confirmation of internal hemorrhoids, on the other hand, may require  anoscopy , insertion of a hollow tube device with a light attached at one end. [ 5 ]  A  digital rectal exam  (DRE) can also be performed to detect possible rectal  tumors ,  polyps , an enlarged  prostate , or  abscesses . [ 8 ]  This examination may not be possible without appropriate  sedation  because of pain, although most internal hemorrhoids are not associated with pain. [ 1 ]  If pain is present, the condition is more likely to be an  anal fissure  or external hemorrhoid rather than internal hemorrhoid. [ 5 ]


Internal hemorrhoids originate above the pectinate line. [ 16 ]  They are covered by  columnar epithelium , which lacks pain  receptors . [ 2 ]  They were classified in 1985 into four grades based on the degree of  prolapse : [ 1 ] [ 2 ]


External hemorrhoids  occur below the dentate (or pectinate) line. [ 16 ]  They are covered proximally by  anoderm  and distally by skin, both of which are sensitive to pain and temperature. [ 2 ]


Many anorectal problems, including  fissures ,  fistulae , abscesses,  colorectal cancer ,  rectal varices , and  itching  have similar symptoms and may be incorrectly referred to as hemorrhoids. [ 1 ]   Rectal bleeding  may also occur owing to colorectal cancer,  colitis  including  inflammatory bowel disease ,  diverticular disease , and  angiodysplasia . [ 6 ]  If  anemia  is present, other potential causes should be considered. [ 5 ]


Other conditions that produce an anal mass include  skin tags ,  anal warts ,  rectal prolapse ,  polyps , and enlarged anal papillae. [ 5 ]   Anorectal varices  due to  portal hypertension  (blood pressure in the  portal venous system ) may present similar to hemorrhoids but are a different condition. [ 5 ]  Portal hypertension does not increase the risk of hemorrhoids. [ 4 ]


A number of preventative measures are recommended, including avoiding straining while attempting to defecate, avoiding constipation and diarrhea either by eating a high-fiber diet and drinking plenty of fluid or by taking fiber supplements and getting sufficient exercise. [ 5 ] [ 24 ]  Spending less time attempting to  defecate , avoiding reading while on the toilet, [ 1 ]  and losing weight for overweight persons and avoiding heavy lifting are also recommended. [ 25 ]


Conservative treatment typically consists of foods rich in  dietary fiber , intake of oral fluids to maintain hydration,  nonsteroidal anti-inflammatory drugs ,  sitz baths , and rest. [ 1 ]  Increased fiber intake has been shown to improve outcomes [ 26 ]  and may be achieved by dietary alterations or the consumption of  fiber supplements . [ 1 ] [ 26 ]  Evidence for benefits from sitz baths during any point in treatment, however, is lacking. [ 27 ]  If they are used, they should be limited to 15 minutes at a time. [ 2 ] : 182   Decreasing time spent on the toilet and not straining is also recommended. [ 28 ]


While many  topical agents  and  suppositories  are available for the treatment of hemorrhoids, little evidence supports their use. [ 1 ]  As such, they are not recommended by the  American Society of Colon and Rectal Surgeons . [ 29 ]   Steroid -containing agents should not be used for more than 14 days, as they may cause thinning of the skin. [ 1 ]  Most agents include a combination of active ingredients. [ 2 ]  These may include a barrier cream such as  petroleum jelly  or  zinc oxide , an analgesic agent such as  lidocaine , and a  vasoconstrictor  such as  epinephrine . [ 2 ]  Some contain  Balsam of Peru  to which certain people may be allergic. [ 30 ] [ 31 ]


Flavonoids  are of questionable benefit, with potential side effects. [ 2 ] [ 32 ]  Symptoms usually resolve following pregnancy; thus active treatment is often delayed until after delivery. [ 33 ]  Evidence does not support the use of  traditional Chinese herbal treatment . [ 34 ]


The use of  phlebotonics  has been investigated in the treatment of low-grade hemorrhoids, [ 29 ] [ 35 ] [ 36 ] [ 37 ]  although these drugs are not approved for such use in the United States or Germany. [ 38 ] [ 39 ]  The use of phlebotonics for the treatment of chronic venous diseases is restricted in Spain. [ 40 ]


A number of office-based procedures may be performed. While generally safe, rare serious side effects such as  perianal sepsis  may occur. [ 6 ]


Hemorrhoidal artery embolization (HAE)  is an additional minimally invasive procedure performed by an  interventional radiologist . [ 10 ]  HAE involves the blockage of abnormal blood flow to the rectal (hemorrhoidal) arteries using microcoils and/or  microparticles  to decrease the size of the hemorrhoids and improve hemorrhoid related symptoms, especially bleeding. [ 11 ]  HAE is very effective at stopping bleeding related symptom with success rate of approximately 90%. [ 12 ]


A number of surgical techniques may be used if conservative management and simple procedures fail. [ 6 ]  All surgical treatments are associated with some degree of complications, including bleeding, infection,  anal strictures , and  urinary retention , due to the close proximity of the rectum to the nerves that supply the bladder. [ 1 ]  Also, a small risk of  fecal incontinence  occurs, particularly of liquid, [ 2 ] [ 42 ]  with rates reported between 0% and 28%. [ 43 ]  Mucosal  ectropion  is another condition which may occur after hemorrhoidectomy (often together with anal stenosis). [ 44 ]  This is where the anal mucosa becomes everted from the anus, similar to a very mild form of  rectal prolapse . [ 44 ]


It is difficult to determine how common hemorrhoids are as many people with the condition do not see a healthcare provider. [ 15 ] [ 18 ]  However, symptomatic hemorrhoids are thought to affect at least 50% of the US population at some time during their lives, and around 5% of the population is affected at any given time. [ 1 ]  Both sexes experience about the same incidence of the condition, [ 1 ]  with rates peaking between 45 and 65 years. [ 5 ]  Some studies have found that they are common in people of higher  socioeconomic status , [ 2 ]  however this may reflect differences in healthcare access rather than true prevalence. [ 13 ]


Long-term outcomes are generally good, though some people may have recurrent symptomatic episodes. [ 15 ]  Only a small proportion of persons end up needing surgery. [ 2 ]


The first known mention of this disease is from a 1700 BC Egyptian  papyrus , which advises: "Thou shouldest give a recipe, an ointment of great protection;  acacia  leaves, ground, titurated and cooked together. Smear a strip of fine linen there-with and place in the anus, that he recovers immediately." [ 14 ]  In 460 BC, the  Hippocratic corpus  discusses a treatment similar to modern rubber band ligation: "And hemorrhoids in like manner you may treat by transfixing them with a needle and tying them with very thick and woolen thread, for application, and do not foment until they drop off, and always leave one behind; and when the patient recovers, let him be put on a course of  Hellebore ." [ 14 ]  Hemorrhoids may have been described in the  Bible , with earlier English translations using the now-obsolete spelling " emerods ". [ 5 ]


Celsus  (25 BC – 14 AD) described ligation and excision procedures and discussed the possible complications. [ 48 ]   Galen  advocated severing the connection of the arteries to veins, claiming it reduced both pain and the spread of gangrene. [ 48 ]  The  Susruta Samhita  (4th–5th century BC) is similar to the words of Hippocrates, but emphasizes wound cleanliness. [ 14 ]  In the 13th century, European surgeons such as  Lanfranc of Milan ,  Guy de Chauliac ,  Henri de Mondeville , and John of Ardene made great progress and development of the surgical techniques. [ 48 ]


In medieval times, hemorrhoids were also known as  Saint Fiacre 's curse after a sixth-century saint who developed them following tilling the soil. [ 49 ]  The first use of the word "hemorrhoid" in English occurs in 1398, derived from the  Old French  "emorroides", from  Latin   hæmorrhoida , [ 50 ]  in turn from the Greek αἱμορροΐς ( haimorrhois ), "liable to discharge blood", from αἷμα ( haima ), "blood" [ 51 ]  and ῥόος ( rhoos ), "stream, flow, current", [ 52 ]  itself from ῥέω ( rheo ), "to flow, to stream". [ 53 ]


Chest pain (angina) or tightness
Shortness of breath, especially during exertion or when lying down
Fatigue or weakness
Irregular heartbeat or heart palpitations
Dizziness or fainting episodes
Gastrointestinal bleeding symptoms:
Occult (hidden) or overt (visible) blood in the stool
Black, tarry stools (melena)
Blood in vomit (hematemesis)
Fatigue or weakness due to chronic blood loss


Heyde's syndrome  is a syndrome of  gastrointestinal bleeding  from  angiodysplasia  in the presence of  aortic stenosis . [ 1 ] [ 2 ]


It is named after Edward C. Heyde, MD, who first noted the association in 1958. [ 3 ]  It is caused by cleavage of  Von Willebrand factor  (vWF) due to high shear stress forces from aortic valvular  stenosis . This results in  Von Willebrand disease type IIA  (acquired). [ 4 ] [ 5 ]


Von Willebrand factor is synthesized in the  walls  of the  blood vessels  and circulates freely in the blood in a folded form. When it encounters damage to the wall of a blood vessel, particularly in situations of high velocity blood flow, it binds to the collagen beneath the damaged endothelium and uncoils into its active form.  Platelets  are attracted to this activated form of von Willebrand factor and they accumulate and block the damaged area, preventing bleeding  [ citation needed ] .


In people with aortic valve stenosis, the stenotic aortic valve becomes increasingly narrowed resulting in an increase in speed of the blood through the valve in order to maintain  cardiac output . This combination of a narrow opening and a higher flow rate results in an increased  shear stress  on the blood.  This higher stress causes von Willebrand factor to unravel in the same way it would on encountering an injury site. [ 6 ] [ 7 ] [ 8 ]  As part of the normal  hemostasis  of the blood, when von Willebrand factor changes conformation into its active state, it is degraded by its natural  catabolic  enzyme  ADAMTS13 , rendering it incapable of binding the collagen at an injury site. [ 4 ] [ 6 ]   As the quantity of von Willebrand factor in the blood decreases, the rate of bleeding dramatically increases. [ 9 ]


The unraveling of high molecular weight von Willebrand factor in conditions of high shear stress is essential in the prevention of bleeding in the vasculature of the  gastrointestinal system  where small arterioles are common, as platelets cannot bind to damaged blood vessel walls well in such conditions. [ 7 ]  This is particularly true in the presence of  intestinal angiodysplasia , where  arteriovenous malformations  lead to very high blood flow, and so the loss of von Willebrand factor can lead to much more extensive bleeding from these lesions. [ 9 ] [ 10 ]   When people with aortic stenosis also have gastrointestinal bleeding, it is invariably from angiodysplasia. [ 4 ] [ 7 ]


It has been hypothesized that defects in high molecular weight von Willebrand factor could actually be the cause of the arteriovenus malformations in intestinal angiodysplasia, rather than just making existing angiodysplasic lesions bleed. This hypothesis is complicated by the extremely high rates of intestinal angiodysplasia in older people (who also have the highest rate of aortic stenosis), and thus requires further research for confirmation. [ 4 ] [ 11 ]


Heyde's syndrome is now known to be gastrointestinal bleeding from angiodysplasic lesions due to acquired vWD-2A deficiency secondary to aortic stenosis, and the diagnosis is made by confirming the presence of those three things. Gastrointestinal bleeding may present as  bloody vomit ,  dark, tarry stool from metabolized blood , or  fresh blood in the stool . In a person presenting with these symptoms,  endoscopy ,  gastroscopy , and/or  colonoscopy  should be performed to confirm the presence of  angiodysplasia . [ 12 ] [ 13 ]  Aortic stenosis can be diagnosed by  auscultation  for characteristic  heart sounds , particularly a  crescendo-decrescendo (i.e., 'ejection')  murmur , followed by  echocardiography  to measure aortic valve area (see  diagnosis of aortic stenosis ). While Heyde's syndrome may exist alone with no other symptoms of aortic stenosis, [ 2 ]  the person could also present with  evidence of  heart failure ,  fainting , or  chest pain . Finally, Heyde's syndrome can be confirmed using blood tests for vWD-2A, although traditional blood tests for von Willebrand factor may result in false negatives due to the subtlety of the abnormality. [ 13 ]  The gold standard for diagnosis is gel electrophoresis; in people with vWD-2A, the large molecular weight von Willebrand factors will be absent from the SDS-agarose electrophoresis plate. [ 2 ]


The definitive treatment for Heyde's syndrome is surgical replacement of the aortic valve. [ 10 ] [ 14 ]  Recently, it has been proposed that  transcatheter aortic valve implantation (TAVI)  can also be used for definitive management. [ 15 ]  Direct surgical treatment of the bleeding (e.g. surgical resection of the bleeding portion of the bowel) is only rarely effective. [ 14 ] [ 16 ]


Medical management of symptoms is possible also, although by necessity temporary, as definitive surgical management is required to bring levels of von Willebrand factor back to normal. [ 4 ]  In severe bleeding,  blood transfusions  and  IV fluid infusions  can be used to maintain blood pressure. In addition,  desmopressin  (DDAVP) is known to be effective in people with von Willebrand's disease, [ 17 ] [ 18 ]  including people with valvular heart disease. [ 19 ] [ 20 ]  Desmopressin stimulates release of von Willebrand factor from blood vessel endothelial cells by acting on the V2 receptor, which leads to decreased breakdown of  Factor VIII . Desmopressin is thus sometimes used directly to treat mild to moderate acquired von Willebrand's disease and is an effective  prophylactic  agent for the reduction of bleeding during heart valve replacement surgery. [ 19 ] [ 20 ]


The exact prevalence of the syndrome is unknown, because both aortic stenosis and angiodysplasia are common diseases in the elderly. A retrospective chart review of 3.8 million people in Northern Ireland found that the incidence of gastrointestinal bleeding in people with any diagnosis of aortic stenosis (they did not subgroup people by severity) was just 0.9%. They also found that the reverse correlation—the incidence of aortic stenosis in people with gastrointestinal bleeding—was 1.5%. [ 21 ]   However, in 2003 a study of 50 people with aortic stenosis severe enough to warrant immediate valve replacement found GI bleeding in 21% of people, [ 10 ]  and another study done in the USA looking at angiodysplasia rather than GI bleeding found that the prevalence of aortic stenosis was 31% compared to 14% in the control group. [ 4 ] [ 22 ]
It is a disease mainly found in older adults but a rare case of Heyde's syndrome has been reported in children. [ 23 ]


The American internist Edward C. Heyde originally described the syndrome in a 1958 letter to the  New England Journal of Medicine , reporting on ten patients with the association. [ 3 ]  Heyde graduated from Johns Hopkins School of Medicine in 1938, served three years in the Army Medical Corps in World War II and joined the Vancouver Clinic, Vancouver, Washington in 1948, practicing medicine there for 31 years. He died on October 13, 2004. [ citation needed ]


In the 45 years following its initial description, no plausible explanations could be found for the association between aortic valve stenosis and gastrointestinal bleeding. Indeed, the association itself was questioned by a number of researchers. [ 5 ] [ 24 ]  Several studies demonstrated a statistically significant association between aortic stenosis and gastrointestinal bleeding, [ 25 ] [ 26 ] [ 27 ]  and in 1987 King et al. even noted the successful resolution of bleeding symptoms with aortic valve replacement in 93% of people, compared to just 5% in people where the bleeding was treated surgically. [ 16 ]  However, the potential causal  association  between the two conditions remained elusive and controversial. [ citation needed ]


Several hypotheses for the association were proposed, the most prominent being the idea that there is no causal relationship between aortic stenosis and gastrointestinal bleeding, they are both just common conditions in the elderly, and they sometimes overlap. Other hypotheses included hypoxia of the colonic mucosa and bowel ischemia due to low blood flow, both of which were discounted by later research. [ 4 ] [ 5 ]  Another early hypothesis of note was proposed by Greenstein et al. in 1986. [ 27 ]  They suggested that GI bleeding could be caused by thinning of the wall of the  cecum  due to abnormal pulse waves in the  ileocolic artery  (an  artery  that supplies blood to the cecum) causing dilation of that artery. Specifically, they note that the usual anacrotic and dicrotic notches were absent from the pulse waves of their people with aortic stenosis. There has been no further research investigating this hypothesis, however, as it has been eclipsed by newer research into acquired von Willebrand's disease. [ citation needed ]


The important role of depletion of von Willebrand factor in aortic stenosis was first proposed in 1992 by Warkentin et al. [ 7 ]  They noted a known association between aortic stenosis (in addition to other cardiac diseases) and acquired von Willebrand's disease type IIA, [ 20 ]  which is corrected by surgical replacement of the aortic valve. They also noted that von Willebrand's disease is known to cause bleeding from angiodysplasia. Based on these facts, they hypothesized that acquired von Willebrand's disease is the true culprit behind gastrointestinal bleeding in aortic stenosis. They also proposed a possible mechanism for the acquired von Willebrand's disease, noting that von Willebrand factor is most active in 'high shear' vessels (meaning small vessels in which blood flows rapidly). They used this fact to hypothesize that this may mean that von Willebrand factor is activated in the narrowed stenotic aortic valve and thus cleared from circulation at a much higher rate than in healthy individuals. [ citation needed ]


This hypothesis received strong support in 2003 by the publication of a report by Vincentelli et al. that demonstrated a strong association between von Willebrand factor defects and the severity of aortic valve stenosis. [ 10 ]  They also showed these defects resolved within hours following  aortic valve replacement surgery  and remained resolved in most people, although in some people the von Willebrand factor defects had returned at six months. Following this observation the shear stress dependent depletion of von Willebrand factor was confirmed, and the protease responsible, ADAMTS13, was identified. [ 4 ]


Lymphocytic esophagitis  is a rare and poorly understood medical disorder involving  inflammation  in the  esophagus . The disease is named from the primary inflammatory process, wherein  lymphocytes  are seen within the esophageal mucosa. Symptoms of the condition include  difficulty swallowing ,  heartburn  and  food bolus obstruction . The condition was first described in 2006 by Rubio and colleagues. Initial reports questioned whether this was a true medical disorder, or whether the inflammation was secondary to another condition, such as  gastroesophageal reflux disease .


The cause of lymphocytic esophagitis is unknown. The disease may cause different symptoms and be caused by different processes in childhood as compared to adulthood. Some studies have shown that it is associated with either other medical conditions involving the esophagus, including  gastroesophageal reflux disease  and  achalasia , or other inflammatory conditions such as  Crohn's disease ,  coeliac disease , and  allergic conditions . The diagnosis is based upon a  biopsy  of the  mucosa  of the esophagus, showing a characteristic appearance of inflammation involving  lymphocytes , and the relative absence of another group of inflammatory cells,  granulocytes .


Complications of the disorder include  stricture of the esophagus , which can lead to  food bolus obstruction , and weight loss. Treatment of lymphocytic esophagitis includes medications meant to target the esophagus topically, such as  budesonide , but also procedures to deal with complications, such as  esophageal dilation .


The most common symptom of lymphocytic esophagitis is  dysphagia , or difficulty swallowing, prevalent in 53 to 57% of individuals with the condition [ 1 ] [ 2 ]  due to inflammation, narrowing or altered movement of the esophagus. Other symptoms include  heartburn ,  abdominal pain ,  nausea  and  food bolus obstruction . [ 1 ] [ 2 ]  Some patients may have no symptoms, as was found in a significant percentage of patients in the first description of the condition, [ 3 ]  although more recent reports indicate that the absence of symptoms is uncommon. [ 1 ]


Food bolus impaction  is a common complication of lymphocytic esophagitis. [ 1 ]  This occurs when food is acutely obstructing the esophagus at an area of narrowing and may require an endoscopic procedure in order to remove or dislodge the obstructing food.


The cause of lymphocytic esophagitis is unknown. [ 4 ]  Attempts to better understand the cause of lymphocytic esophagitis include identification of other diseases that associate with the condition. [ 4 ]  These conditions include other esophageal conditions including  gastroesophageal reflux disease [ 1 ] [ 4 ] [ 5 ]  and  achalasia , [ 5 ]  as well as other inflammatory diseases such as  Crohn's disease , [ 4 ] [ 5 ]   coeliac disease , [ 4 ]  and allergic conditions such as  eczema . [ 4 ]  Additionally use of tobacco may associate with lymphocytic esophagitis. [ 1 ] [ 4 ]  Lymphocytic esophagitis does not occur with high frequency in other gastrointestinal conditions where lymphocytosis is found in the  mucosa , including  lymphocytic colitis  and lymphocytic  gastritis ; however, there is a disease association with  coeliac disease  wherein lymphocytic inflammation occurs in the  small bowel  after exposure to  gluten . [ 4 ]


Little is known about the pathophysiology of lymphocytic esophagitis. [ 4 ]  It has been hypothesized that lymphocytic esophagitis may be either a primary inflammatory disorder, or that the inflammation is triggered by an external stimulus leading to injury of the mucosal lining of the esophagus, such as gastric acid in  GERD . [ 4 ] [ 6 ]


The diagnosis of lymphocytic esophagitis is made by  biopsy  of the  mucosal lining  of the  esophagus . This is typically achieved at the time of  esophagogastroduodenoscopy , a medical procedure wherein an  endoscope  is inserted through the mouth, into the esophagus, in order to visualize and biopsy the mucosa. [ citation needed ]


While the  histologic  changes in the biopsies are characterized by the presence of an inflammatory infiltrate, consisting primarily of  lymphocytes  in the absence of other inflammatory cells such as  granulocytes , the criteria for making the diagnosis are still unclear. [ 1 ] [ 4 ]  The location of the biopsies, cutoff of number of  lymphocytes  found in each high-power field of view of the microscope, the presence of  spongiosis , and the need for  immunohistochemical staining  to define lymphocytes are all unclear still. [ 1 ]


While the diagnosis of lymphocytic esophagitis depends on the biopsy results, certain changes can be visualized directly at the time of  endoscopy . The esophagus may be narrow in calibre, [ 5 ]  may show multiple rings, [ 5 ]  redness, [ 5 ]  linear furrows [ 1 ]  or the mucosal lining may slide demonstrating a "crepe-paper" appearance. [ 1 ]  Complications such as strictures of the esophagus can also be detected with endoscopy. [ 5 ]  These changes are very similar to those found in  eosinophilic esophagitis , a more common and better understood esophageal disorder thought to be of allergic origin. [ 5 ]   Narrow-band imaging  with  magnification endoscopy  is another imaging modality that can show characteristic changes of lymphocytic esophagitis. [ 7 ]


The treatment of lymphocytic esophagitis is still undefined. [ 5 ]  Treatment either targets symptoms, inflammation or complications. For example,  heartburn  is a symptom in lymphocytic esophagitis, and  proton pump inhibitors , which reduce acidity in the stomach, are consequently used for treatment. With respect to treatment of inflammation, steroids that are topical and coat the lining of the esophagus, such as  budesonide  have been used to treat the condition, in one German study. [ 8 ]   Prednisone  has also been used to treat the inflammation of lymphocytic esopahgitis. [ 5 ]  With respect to complications, strictures of the esophagus can be treated with  esophageal dilation . [ 5 ]


There has been little studied about the natural history of lymphocytic esophagitis. [ 4 ]  The longest study of the condition involved a median follow-up of 3.3 years, wherein participants were surveyed, and demonstrated that 87% of patients were alive but that the vast majority (97%) of patients still had symptoms. [ 4 ] [ 9 ]  There have been two reports of  esophageal perforation  associated with the condition, one case occurring during endoscopic treatment of complications. [ 4 ]


The  percentage of individuals  with lymphocytic esophagitis is uncertain. [ 1 ]  Early studies indicated that the prevalence was 0.1% in adults. [ 3 ]  However, reports in children indicate a higher prevalence of 8.5%, [ 10 ]  perhaps suggestive of incidental findings of lymphocytes in endoscopies performed for other reasons. [ 1 ]  The disease may occur more frequently in women over the age of 60. [ 4 ]


There is increasing awareness of lymphocytic esophagitis among physicians, perhaps affecting the prevalence over time. [ 1 ]  The majority of the studies on lymphocytic esophagitis are after 2015. [ 1 ]


The condition was first described in a series of 20 patients at the  Karolinska Institutet  by Carlos Rubio in 2006. [ 3 ]  Much of the reports of the condition over the subsequent several years were focused on ascertaining whether lymphocytic esophagitis was a true condition, and if it was, establishing uniform criteria for its diagnosis. [ 1 ] [ 2 ] [ 4 ]


The majority of the research into lymphocytic esophagitis has been performed after 2015. [ 1 ]  There remain many questions unanswered about the condition, such as establishing its natural history, [ 4 ]  clarifying its diagnostic criteria, [ 1 ]  and ascertaining the best treatment for the condition. [ 4 ]


The  National Digestive Diseases Information Clearinghouse  (NDDIC [ 1 ] ) is an information dissemination service of the  National Institute of Diabetes and Digestive and Kidney Diseases  (NIDDK). The NIDDK is part of the  National Institutes of Health , which is under the  U.S. Department of Health and Human Services .


Established in 1980, the Clearinghouse provides information about digestive diseases to people with digestive disorders and to their families, health care professionals, and the public. The NDDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about digestive diseases.


Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts.


This article about a United States health organization is a  stub . You can help Wikipedia by  expanding it .


A  rectus sheath hematoma  is an accumulation of blood in the sheath of the  rectus abdominis muscle . It causes  abdominal pain  with or without a mass.


The  hematoma  may be caused by either rupture of the  epigastric artery  or by a muscular tear. Several factors have been identified as predisposing risks for rectus sheath hematoma, including coughing, straining, exercise,  hypertension ,  obesity , previous  abdominal surgery ,  subcutaneous injection ,  trauma  and  anticoagulant therapy . With an ageing population and the widespread use of anticoagulant medications, there is evidence that this historically benign condition is becoming more common and more serious. [ 1 ]  Anticoagulant therapy is used to treat many diseases. However, in the COVID-19 pandemic, anticoagulant therapy was frequently used and therefore the incidence of rectus sheath hematoma increased. [ 2 ] [ 3 ]  Given that thrombotic events have been documented in numerous studies, it is advisable to initiate prophylactic and anticoagulant treatment during the early phase of COVID-19 disease.  [ 4 ]


On  abdominal examination , people may have a  positive   Carnett's sign .


Most hematomas resolve without treatment, but they may take several months to resolve.


Reynolds syndrome  is a rare secondary  laminopathy , consisting of the combination of  primary biliary cirrhosis  and  progressive systemic sclerosis .  In some patients this syndrome has also been associated with  Sjögren's syndrome  and  hemolytic anemia .  Typical clinical features include  jaundice , elevated blood levels of  alkaline phosphatase ,  calcinosis cutis ,  telangiectasias , and  pruritus . This disease may cause white or yellow-ish spots on the arms or legs. The syndrome, a special case of scleroderma, is named after the American physician, Telfer B. Reynolds, MD (1921–2004), who first described it.  He is also known for creating one of the world's first  hepatology  programs at the  University of Southern California .


It should not be confused with the more common  Raynaud's phenomenon .


This  genetic disorder  article is a  stub . You can help Wikipedia by  expanding it .


Roemheld syndrome  ( RS ), or  gastrocardiac syndrome , [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  or  gastric cardiac syndrome [ 6 ]  or  Roemheld–Techlenburg–Ceconi syndrome [ 7 ]  or  gastric-cardia , [ 7 ]  was a medical syndrome first coined by  Ludwig von Roemheld  (1871–1938) describing a cluster of cardiovascular symptoms stimulated by gastrointestinal changes. Although it is currently considered an obsolete medical diagnosis, recent studies have described similar clinical presentations and highlighted potential underlying mechanisms. [ 3 ] [ 8 ] [ 9 ] [ 5 ]


Symptoms can be as follows. [ 10 ] [ 11 ]  They are periodic, and occur only during an "episode", usually after eating.


Mechanically induced Roemheld syndrome is characterized by  pressure  in the epigastric and left  hypochondriac  region. Often the pressure is in the  fundus  of the stomach, the  esophagus  or distention of the bowel. It is believed this leads to elevation of the  diaphragm , and secondary displacement of the heart. This reduces the ability of the heart to fill and increases the  contractility of the heart  to maintain homeostasis.


The cranium dysfunction mechanical changes in the gut can compress the  vagus nerve  at any number of locations along the vagus, slowing the heart. As the heart slows, autonomic reflexes are triggered to increase blood pressure and heart rate.


This is complemented by gastro-coronary reflexes [ 12 ]  whereby the coronary arteries constrict with "functional  cardiovascular  symptoms" similar to chest-pain on the left side and radiation to the left shoulder, dyspnea, sweating, up to angina pectoris-like attacks with  extrasystoles , drop of blood pressure, and tachycardia (high heart rate) or sinus bradycardia (heart rate below 60 bpm). Typically, there are no changes/abnormalities related in the  EKG  detected. This can actually trigger a heart attack in people with cardiac structural abnormalities i.e.  coronary bridge , missing coronary, and  atherosclerosis .


If the heart rate drops too low for too long,  catecholamines  are released to counteract any lowering of blood pressure. Catecholamines bind to  alpha receptors  and  beta receptors , decreasing  vasodilation  and increasing  contractility of the heart . Sustaining this state causes  heart fatigue  which can lead to a decline in systolic and  diastolic function , resulting in fatigue and chest pain.


There is significant scope of misdiagnosis of Roemheld syndrome. Diagnosis of Roemheld syndrome usually begins with a cardiac workup, as the gastric symptoms may go unnoticed, and the cardiac symptoms are frightening and can be quite severe. After an  EKG ,  Holter monitor ,  tilt table test ,  cardiac MRI ,  cardiac CT ,  heart catheterization ,  electrophysiology study ,  echocardiogram , and extensive blood work, and possibly a  sleep study , a cardiologist may rule out a heart condition.


Often a  psychiatric evaluation  may follow, as conversion disorder may be suspected in the absence of heart disease or structural heart abnormalities.


In the absence of heart abnormalities, the diagnosis is often made on the basis of symptoms. A  gastroenterologist  will perform a  colonoscopy ,  endoscopy , and  abdominal ultrasound  to locate or rule out problems in the abdomen.


Determining the cause of Roemheld syndrome is still not an exact science. If you have an ultrasound or sleep study, ensure that you know how to reproduce the symptoms, as it is difficult to detect any abnormalities when symptoms have subsided.


Treatment of the primary gastroenterological distress is the first concern, mitigation of gastric symptoms will also alleviate cardiac distress.


Roemheld syndrome is characterized strictly by abdominal maladies triggering reflexes in the heart. There are a number of pathways through which cardiac reflexes can occur: hormones, mechanical, neurological and immunological. [ citation needed ]


Ludwig Roemheld characterized this particular syndrome shortly before his death; one of his research topics around this time was the effects of calorie intake on the heart. In  Elsevier  publications, there is no current research or publishing under the name Roemheld syndrome, and as a result, many cases go undiagnosed. German publishing on the subject remains untranslated as of 2009.


Saint's triad  is a medical condition of concurrence of the following:


Saint's triad is named after the British surgeon Hunterian and Emeritus Professor Charles Frederick Morris Saint CBE (14 August 1886 – 15 February 1973), who established the first school of surgery in South Africa. He emphasised  the importance of considering the possibility of multiple separate diseases in a patient whenever his or her history and the results of the physical examination were atypical of any single condition. [ 2 ]  Traditionally, there is thought to be no pathophysiological basis for the coexistence of these three diseases. Saint emphasized that more than one disease may be responsible for a patient's clinical signs and symptoms, and his  triad  provides a counterexample to the commonly used diagnostic principle that "the explanation of any phenomenon should make as few assumptions as possible," also known as  Occam's Razor . [ 3 ]  The principle underlying Saint's triad is also expressed as  Hickam's dictum .


A twist to this philosophic discussion on the art of diagnosis is that, in recent times, the possibility of an underlying pathophysiology has been considered—obesity is associated with  gallstones ,  hiatal hernia , and  diverticular disease , and there is the suggestion of an underlying  connective tissue  defect such as a "herniosis." [ 4 ]


Gastroenterology  (from the Greek gastḗr- "belly", -énteron "intestine", and -logía "study of") is the branch of  medicine  focused on the  digestive system  and its disorders. [ 1 ]  The digestive system consists of the  gastrointestinal tract , sometimes referred to as the  GI tract,  which includes the  esophagus ,  stomach ,  small intestine  and  large intestine  as well as the accessory organs of digestion which include the  pancreas ,  gallbladder , and  liver . [ 2 ] [ 3 ]


The digestive system functions to move material through the GI tract via  peristalsis , break down that material via  digestion , absorb nutrients for use throughout the body, and remove waste from the body via  defecation . [ 3 ]  Physicians who specialize in the medical specialty of gastroenterology are called gastroenterologists or sometimes  GI doctors .


Some of the most common conditions managed by gastroenterologists include  gastroesophageal reflux disease ,  gastrointestinal bleeding ,  irritable bowel syndrome , inflammatory bowel disease (IBD) which includes  Crohn's disease  and  ulcerative colitis ,  peptic ulcer disease , gallbladder and biliary tract disease,  hepatitis ,  pancreatitis ,  colitis ,  colon polyps and cancer , nutritional problems, and many more. [ 4 ]


Citing from  Egyptian   papyri ,  John F. Nunn  identified significant knowledge of gastrointestinal diseases among practicing physicians during the periods of the  pharaohs .  Irynakhty , of the tenth dynasty,  c.  2125 B.C., was a  court physician  specializing in gastroenterology, sleeping, and  proctology . [ 5 ]


Among  ancient Greeks ,  Hippocrates  attributed  digestion  to  concoction .  Galen 's concept of the  stomach  having four  faculties  was widely accepted up to modernity in the seventeenth century. [ 6 ]


1.  International Classification of Disease ( ICD  2007)/WHO classification :


2.  MeSH  subject Heading :


3.  National Library of Medicine  Catalogue (NLM classification 2006) :


A procedure using a  long thin tube with a camera  that is passed through the  anus  to visualize the  rectum  and the entire length of the colon. The procedure is performed either to look for  colon polyps  and/or  colon cancer  in somebody without symptoms, referred to as  screening , or to further evaluate symptoms including  rectal bleeding ,  dark tarry stools , change in bowel habits or stool consistency (diarrhea, pencil-thin stool), abdominal pain, and unexplained weight loss. Before the procedure, the physician might ask the patient to stop taking certain medications including blood thinners, aspirin, diabetes medications, or  nonsteroidal anti-inflammatory drugs . A  bowel prep  is usually taken the night before and into the morning of the procedure which consists of an  enema  or  laxatives , either pills or powder dissolved in liquid, that will cause diarrhea. The procedure might need to be stopped and rescheduled if there is stool remaining in the colon due to an incomplete bowel prep because the physician can not adequately visualize the colon. During the procedure, the patient is  sedated  and the scope is used to examine the entire length of the colon looking for polyps, bleeding, or abnormal tissue. A  biopsy  or  polyp removal  can then be performed and the tissue sent to the lab for evaluation. The procedure usually takes thirty minutes to an hour followed by a one to two hour observation period. Complications include bloating, cramping, a reaction to anesthesia, bleeding, and a  hole through the wall  of the colon that may require repeat colonoscopy or surgery. Signs of a serious complication requiring urgent or emergent medical attention include severe pain in the abdomen, fever, bleeding that does not improve, dizziness, and weakness. [ 15 ]


A procedure similar to a colonoscopy using a long thin tube with a camera (scope) passed through the  anus  but only intended to visualize the  rectum  and the  last part of the colon  closest to the rectum. All aspects of the procedure are the same as for a colonoscopy with the exception that this procedure only lasts ten to twenty minutes and is done without sedation. This usually allows for the patient to return to normal activities immediately after the procedure is finished. [ 16 ]


A procedure using a  long thin tube with a camera  that is passed through the mouth to view the  esophagus  ("esophago-"),  stomach  ("gastro-"), and the  duodenum  ("duodeno-"). It is also referred to as upper endoscopy or just endoscopy. The procedure is performed for further evaluation of symptoms including persistent  heartburn ,  indigestion ,  vomiting blood ,  dark tarry stools , persistent nausea and vomiting, pain,  difficulty swallowing ,  painful swallowing , and unexplained weight loss. It is also performed for further testing following a lab test that shows  low hemoglobin levels  without a known cause or an abnormal  barium swallow . The procedure can be used to diagnose many disorders through direct visualization or tissue biopsy including  esophageal varices ,  esophageal strictures ,  gastroesophageal reflux disease ,  Barrett's esophagus , cancer,  celiac disease ,  gastritis ,  peptic ulcer disease , and a  H. pylori  infection. Intra-operative techniques can then be used for treatment of certain disorders like  banding  esophageal varices or  dilating  esophageal strictures. The patient will likely be required to not eat or drink anything starting 4 hours prior to the procedure. Sedation is usually required for patient comfort. This procedure usually lasts around thirty minutes followed by a one to two hour observation period. Side effects include  bloating , nausea, and a sore throat for 1 to 2 days. Complications are rare but include reaction to the anesthesia, bleeding, and a  hole through the wall  of the esophagus, stomach, or small intestine which could require surgery. Signs of a serious complication requiring urgent or emergent medical attention include chest pain, problems breathing, problems swallowing, throat pain that gets worse, vomiting with blood or the appearance of " coffee-grounds ", worsening abdominal pain,  bloody  or black tarry stool, and fever. [ 17 ]


A procedure using a  long thin tube with a camera  passed through the mouth into the  first part of the small intestine  to locate, diagnose, and treat disorders related to the  bile  and  pancreatic ducts . These ducts carry fluids that help with digesting food from the liver, gallbladder, and pancreas and can become narrowed or blocked as a result of  gallstones , infection, inflammation,  pancreatic pseudocysts , and tumors of the bile ducts or pancreas. As a result, one may experience back pain,  yellowing of the skin , and an abnormal lab test showing an elevated  bilirubin  level which could necessitate this procedure. However, the procedure is not recommended if the patient has  acute pancreatitis  unless the level of bilirubin remains high or is increasing which could suggest the blockage is still present. The patient will likely be required to not eat or drink anything starting 8 hours prior to the procedure. After the patient is sedated, the physician will pass the scope through the mouth, esophagus, stomach, and into the duodenum to locate the  opening  where the ducts  drain into the small intestine . The physician can then inject dye into these ducts and take X-rays which show a real time view, via  fluoroscopy , allowing the physician to locate and relieve the blockage. This is done through multiple techniques including  cutting the opening  and creating a bigger hole for drainage, removing gallstones and other debris, dilating narrow parts of the ducts, or placing a stent which keeps the ducts open. The physician can also take a  biopsy  of the ducts to evaluate for cancer, infection, or inflammation. Side effects include bloating, nausea, or a sore throat for one to two days. Complications include  pancreatitis , infection of the  bile ducts  or  gallbladder , bleeding, reaction to the anesthesia, and perforation of any structures that the scope or its instruments pass but particularly the duodenum, bile duct, and pancreatic duct. Signs of a serious complication requiring urgent or emergent medical attention include bloody or  black tarry stool , chest pain, fever, worsening abdominal pain, worsening throat pain, problems breathing, problems swallowing, vomit that is bloody or looks like  coffee-grounds . Most of the time complications from this procedure require hospitalization for treatment. [ 18 ]


A condition that is a result of stomach contents consistently coming back up into the esophagus causing troublesome symptoms or complications. [ 19 ]  Symptoms are considered troublesome based on how disruptive they are to a patient's daily life and well-being. This definition was standardized by the Montreal Consensus in 2006. [ 20 ]  Symptoms include a  painful feeling  in the middle of the chest and feeling stomach contents  coming back up  into the mouth. Other symptoms include chest pain, nausea,  difficulty swallowing ,  painful swallowing , coughing, and hoarseness. [ 21 ]  Risk factors include obesity, pregnancy, smoking,  hiatal hernia , certain medications, and certain foods. Diagnosis is usually based on symptoms and medical history, with further testing only after treatment has been ineffective. Further diagnosis can be achieved by  measuring  how much acid enters the esophagus or looking into the esophagus with a  scope . Treatment and management options [ 19 ]  include lifestyle modifications, medications, and surgery if there is no improvement with other interventions. Lifestyle modifications include not lying down for three hours after eating, lying down on the left side, elevating head while laying by elevating head of the bed or using extra pillows, losing weight, stopping smoking, and avoiding coffee, mint, alcohol, chocolate, fatty foods, acidic foods, and spicy foods. Medications include  antacids ,  proton pump inhibitors ,  H2 receptor blockers . Surgery is usually a  Nissen fundoplication  and is performed by a surgeon. Complications of longstanding GERD can include  inflammation of the esophagus  that may cause bleeding or ulcer formation,  narrowing of the esophagus  leading to swallowing issues, a change in the lining of the esophagus that can increase the chances of developing cancer ( Barrett's esophagus ), chronic cough, asthma,  inflammation of the larynx  leading to hoarseness, and  wearing away  of tooth enamel leading to dental issues. [ 19 ] [ 21 ]


A condition in which the lining of the esophagus changes to look more like the lining of the intestine and increases the risk of developing  esophageal cancer . [ 22 ]  There are no specific symptoms although symptoms of GERD may be present for years prior as it is associated with a 10–15% risk of Barrett's esophagus. [ 22 ]  Risk factors include chronic GERD for more than 5 years, being age 50 or older, being non-Hispanic white, being male, having a family history of this disorder,  belly fat , and a history of smoking. [ 23 ]  Protective factors include  H. pylori infection , frequent use of aspirin or other  non-steroidal anti-inflammatory drugs , and diets high in fruits and vegetables. [ 24 ]  Diagnosis can be made by looking into the esophagus with a  scope  and possibly taking a  biopsy  of the lining of the esophagus. Treatment includes managing GERD,  destroying  abnormal parts of the esophagus,  removing abnormal tissue  in the esophagus, and  removing part of the esophagus  as performed by a general surgeon. [ 22 ]  Further management could include periodic surveillance with repeat scopes at certain intervals determined by the physician, likely not more frequently than every three to five years. [ 23 ]  Complications from this disorder can result in a type of cancer called  esophageal adenocarcinoma . [ 24 ]


Gastroenterology is a subspecialty of internal medicine and therefore requires three years of  internal medicine   residency training  followed by three additional years in a dedicated gastroenterology  fellowship . [ 1 ]  This training is certified by the  American Board of Internal Medicine  (ABIM) and the  American Osteopathic Board of Internal Medicine  (AOBIM) and must be completed at a program accredited by the  Accreditation Council for Graduate Medical Education  (ACGME). [ 25 ] [ 26 ] [ 27 ]  Other national societies that oversee training include the  American College of Gastroenterology  (ACG), the  American Gastroenterological Association  (AGA), and the  American Society for Gastrointestinal Endoscopy  (ASGE). [ 28 ] [ 29 ] [ 30 ]


Gastroenterologists see patients both in the clinic and the hospital setting. They can order diagnostic tests, prescribe medications, and perform a number of diagnostic and  therapeutic  procedures including  colonoscopy ,  esophagogastroduodenoscopy  (EGD),  endoscopic retrograde cholangiopancreatography  (ERCP),  endoscopic ultrasound  (EUS), and  liver biopsy . [ 31 ]


Some gastroenterology trainees will complete a "fourth-year" (although this is often their seventh year of graduate medical education) in transplant  hepatology , advanced interventional  endoscopy ,  inflammatory bowel disease ,  motility , or other topics.


Advanced endoscopy, sometimes called interventional or surgical endoscopy, is a sub-specialty of gastroenterology that focuses on advanced endoscopic techniques for the treatment of  pancreatic ,  hepatobiliary , and  gastrointestinal disease . Interventional gastroenterologists typically undergo an additional year of rigorous training in advanced endoscopic techniques including endoscopic retrograde cholangiopancreatography, endoscopic ultrasound-guided diagnostic and interventional procedures, and advanced  resection  techniques including  endoscopic mucosal resection  and  endoscopic submucosal dissection . Additionally, the performance of endoscopic bariatric procedures is also performed by some advanced endoscopists.


Hepatology , or  hepatobiliary medicine , encompasses the study of the  liver ,  pancreas , and  biliary tree , and is traditionally considered a sub-specialty of gastroenterology, while  proctology  encompasses disorders of the  anus ,  rectum , and  colon  and is considered a sub-specialty of  general surgery .


This is a list of  allergies , which includes the  allergen , potential reactions, and a brief description of the cause where applicable.


Many substances can cause an allergic reaction when in contact with the human  integumentary system .


An  anal plug  ( anal tampon  or  anal insert ) is a  medical device  that is often used to treat  fecal incontinence , the accidental passing of bowel moments, by physically blocking involuntary loss of  fecal material . [ 1 ]  Fecal material such as feces are solid remains of food that does not get digested in the small intestines; rather, it is broken down by bacteria in the large intestine. Anal plugs vary in design and composition, but they are typically single-use, intra-anal, disposable devices made out of soft materials to contain fecal material and prevent it from leaking out of the rectum. The idea of an anal insert for fecal incontinence was first evaluated in a study of 10 participants with three different designs of anal inserts. [ 1 ]


Anal plugs may be beneficial to certain risk groups including, but not limited to, frail older people, women following childbirth, people with some neurological or spinal diseases, severe cognitive impairment, urinary incontinence, pelvic organ prolapse, and so on. Typically, anal plugs are used in people whose symptoms do not improve with to typical treatments: this may include changes in diet, physical therapy,  nerve stimulation  targeting the  sacral  and  tibial  nerves, surgical repair of the anus, and utilization of a  colostomy bag . [ 2 ]  Nerve stimulation involves the placement of electrodes near the nerves that travel through a person's hips and down their legs. [ 3 ]  Colostomy bags are bags that collect feces from their intestines through a surgically created hole in a person's belly. [ 4 ]


Children with certain conditions, including  spina bifida  and  anal atresia , may struggle with leaks even after physical therapy and other interventions, so they may benefit from using anal plugs. [ 5 ] [ 6 ]  Spina bifida is a birth defect where a part of the spinal cord is not surrounded by the  vertebrae ; either the spinal cord is still in the back, just not surrounded by the vertebral bones, or it can be bulging out in a sac. [ 7 ]  Anal atresia is another birth defect where the rectum and/or anus is deformed: fecal incontinence is a side effect. [ 8 ]


The one common feature of people who use anal plugs is they all experience fecal incontinence, which is both uncomfortable and embarrassing. Some people may use it temporarily during certain events or while they have certain temporary medical conditions, such as women recovering from childbirth; others may need to use anal plugs for the rest of their lives. Others may opt to also use perineal pads or undergarments such as  diapers  to prevent the soiling of oneself. Management of fecal incontinence is very person-dependent, as anally inserted devices may not be for everyone.


The plug allows individuals control over their bowel movements and may decrease negative side effects due to leakage. People have reported suffering from fewer of anal rashes, decreased soreness, and improved hygiene. [ 2 ]  Anal plugs can also be an affordable option: some countries with universal healthcare, like Germany, buy anal plugs for people who need them. [ 9 ]  During the development and approval of the Renew Insert, which is one of the types of anal plugs that have been developed, researchers found that on average people used 2.6 inserts per day. [ 2 ]  However, this plug is designed to be worn for twelve-hours; the number of inserts needed per day increases when products that have to be changed four times a day are considered. [ 10 ]


Whether anal plugs are a good choice varies based on the person. Trials have shown anywhere from 25 to 80% of people were satisfied enough with plug to continue using it. [ 2 ]


People who have to pay for anal plugs out of pocket may find them to be expensive. Although some countries, such as Germany, may subsidize the cost for people, private insurance may not cover anal plugs. [ 9 ]  Plugs have to be changed a minimum of twice a day, some up to four times per day.


At the same time, discomfort, side effects, and occasional leaks from using anal plugs have been reported. [ 2 ]  A 2015  systematic review  found that anal plugs may be helpful in treating fecal incontinence, provided that they are tolerated and that people actually use them. [ 11 ] [ 12 ]  A 2001 study found that a majority of people could not tolerate an anal plug due to discomfort. Although only 20% decided to continue using the plug on a regular basis, anal plugs were generally successful at controlling fecal incontinence. Since anal plugs are considered an invasive strategy, they can result in pain, soreness, irritation, fecal urgency, and societal embarrassment. [ 2 ]  Bleeding  hemorrhoids  were a rare  adverse event . [ 13 ]  There is not a lot of evidence reported on the efficacy on the different types of anal plugs, so the choice of plug can be up to people and their doctors. [ 2 ]  Some other challenges of the plug include occasional slippage with decreases the efficacy and increases discomfort, but people report more usage for occasions where anal leakage would be publicly troublesome. [ 2 ] [ 13 ]  Anal plugs of smaller volume may resolve some people's discomfort, but still provide coverage for leakage. [ 13 ] [ 14 ]


Due to the complexity of fecal incontinence, the use of anal plugs are not well defined in guidelines and treatment pathways, which decrease the comfortability of medical professional on prescribing and usage of anal plugs. [ 2 ]  Therefore, more studies are needed in order for healthcare providers and regular people to understand when anal plugs are an option worth considering.


Anal plugs may come as tampons or inserts as detailed below. Tampons are similar to  menstruation   tampons , which can expand and absorb substances to prevent leakage. Inserts provide a physical blockage, and are inserted into the rectal cavity to stop feces from escaping. Plugs come in a variety of shapes, sizes, and materials.  Polyurethane  plugs have been found to be preferred over  polyvinyl-alcohol  plugs, and are also associated with less plug loss. [ 11 ]  For all plugs that become stuck in the rectum, it is recommended to see a doctor if it does not come out in the next bowel movement.


The Peristeen (formerly Conveen) Anal Plug produced by  Coloplast  is a disposable polyurethane insert coated in a water-soluble film. [ 15 ]  When exposed to warmth and moisture in the  anal canal , the film dissolves, allowing the plug to expand. It has a conical tip and a cord to tug on for removal. [ 16 ]  It comes in two sizes, and is inserted similarly to a  suppository . This plug may remain inside the rectum for up to 12 hours.


The polyvinyl-alcohol anal tampons A-tam produced by Med SSE-System in Germany come in various sizes and shapes including cone, cylindrical, spiral, concave, convex, and ball-headed. [ 9 ]  The different shapes can address different concerns, based on anal sphincter muscle function, remaining muscle tissue, and gassiness. The plug should be soaked in warm water before inserted, similar to some rectal  suppositories . While the plugs are single-use, the applicator may be used multiple times. Changing out the plug three times a day every 6-8 hours and anal hygiene are also recommended. A prescription is needed for this product.


Renew Inserts are single-use  silicone  plugs that come in two sizes and require a prescription. [ 10 ]  The large size is recommended for adults, while the regular size may be used for children and young adults. Each plug is made of two attached disks and comes connected to a fingertip applicator which is disposed after insertion. The top disk blocks the stool, while the bottom disk secures the insert in place to prevent displacement. It can be removed either by pulling it out or through defecation, removing the concern of losing the plug in the anal canal. [ 13 ]


The ProCon2 device by Incontinent Control Devices, Inc is composed of a blow-up balloon cuff attached to the end of a silicon  catheter  with vent holes at the tip for  flatulence  to escape. [ 17 ]  The catheter is inserted into the anal canal and the balloon cuff is inflated with water or air through a syringe attached to the exposed portion of the catheter. Once inflated, the exposed end of the catheter is pulled until the balloon cuff is met with resistance within the anus. An infrared photo-interruptor sensor in the catheter senses stool in the anal canal, sending a notification to a pager. To remove the device, the catheter is cut to allow the balloon to deflate before pulling it out. Each device is made for single-use only.


The SURGISPON anal tampon is made of a gamma-sterilized gelatin sponge and, unlike the previously mentioned products, is used to stop bleeding in anal and rectal surgeries and post-surgery bleeding and pain. [ 18 ]  The sponge can absorb up to 45 times its weight, liquefying and eventually being excreted in a bowel movement within 1-2 days. It also has an opening in the middle for gas to escape, and may be used as a carrier for delivery of antibiotics,  thrombin , or chemotherapeutics. It is inserted either dry or wet, but for surgeries, it is inserted dry using a  proctoscope .


Anal cleansing is the practice of proper  sanitization  and maintaining healthy hygiene in a person's rectal area. It is usually done post defecation. [ 19 ]  From a science perspective, it helps prevent pathogen exposure, which could lead to infections or diseases. The cleansing process involves rinsing the rectal cavity with water and usually wiping the area with toilet paper or baby wipes. Sometimes, a hand is used for rubbing the area while rinsing it with water. Other times,  bidet system  could be used instead. [ 19 ]  A bidet is a plumbing device that is usually installed as a separate unit beside the bathroom tub to wash one's inner buttocks and anal area.


Reasons to maintain anal hygiene:


Maintaining good anal hygiene contributes to an individual overall health. [ 20 ]  Some of the key benefits include:


Astroviruses  ( Astroviridae ) are a type of  virus  that was first discovered in 1975 using  electron microscopes  following an outbreak of  diarrhea  in humans. [ 1 ]  In addition to humans, astroviruses have now been isolated from numerous mammalian animal species (and are classified as genus  Mamastrovirus ) and from avian species such as ducks, chickens, and turkey poults (classified as genus  Avastrovirus ). Astroviruses are 28–35 nm diameter,  icosahedral  viruses that have a characteristic five- or six-pointed star-like surface structure when viewed by electron microscopy. Along with the  Picornaviridae  and the  Caliciviridae , the Astroviridae comprise a third family of nonenveloped viruses whose  genome  is composed of plus- sense , single-stranded RNA. [ 2 ]  Astrovirus has a non-segmented, single stranded, positive sense  RNA  genome within a  non-enveloped  icosahedral  capsid . [ 3 ]  Human astroviruses have been shown in numerous studies to be an important cause of  gastroenteritis  in young children worldwide. [ 2 ]  In animals, Astroviruses also cause infection of the gastrointestinal tract but may also result in  encephalitis  (humans and cattle), hepatitis (avian) and nephritis (avian). [ 4 ]


This family of viruses consists of two genera,  Avastrovirus  (AAstV) and  Mamastrovirus  (MAstV). [ 5 ]


The  International Committee on Taxonomy of Viruses  (ICTV) established  Astroviridae  as a viral family in 1995. [ 6 ]  There have been over 50 astroviruses reported, although the ICTV officially recognizes 22 species. [ 7 ]  The genus  Avastrovirus  comprises three species; Chicken astrovirus (Avian nephritis virus types 1–3), Duck astrovirus (Duck astrovirus C-NGB), and Turkey astrovirus (Turkey astrovirus 1). The genus  Mamastrovirus  includes Bovine astroviruses 1 and 2, Human astrovirus (types 1–8), Feline astrovirus 1, Porcine astrovirus 1, Mink astrovirus 1 and Ovine astrovirus 1. [ 7 ]


Astroviruses have a star-like appearance with five or six points. Their name is derived from the Greek word "astron" meaning star. They are  non-enveloped   RNA  viruses with cubic  capsids , approximately 28–35 nm in diameter with T=3 symmetry. [ 8 ] [ 9 ]  Human astroviruses are part of the Mammastrovirus genus and contains 8 serotypes. The human astrovirus capsid spikes have a distinct structure. The spike domain in particular has a 3-layered beta-sandwiches fold and a core, 6-stranded beta-barrel structure. The beta-barrel has a hydrophobic core. The triple-layered beta-sandwich is packed outside the beta-barrel. The spike also forms a dimer. This unique structure was found to be similar to the protein projections found on the capsid of the hepatitis E virus. The projection domain of the human astrovirus contains a receptor binding site for polysaccharides. The amino acid sequence of the astrovirus capsid protein does not have similar homology to other known viral proteins, but the closest would be hepatitis E virus. [ 10 ]


Astroviruses infect birds and mammals through the  fecal-oral route . They have a  tissue tropism  for  enterocytes . Entry into the host cell is achieved by attachment to host receptors, which mediates endocytosis. Replication follows the  positive-strand RNA virus  replication model. [ 11 ]  Astrovirus RNA is infectious and functions as a  messenger RNA  for ORF1a and ORF1b. [ 12 ]  A frame-shifting mechanism between these two nonstructural polypeptides translates  RNA-dependent RNA polymerase . [ 13 ]  In replication complexes near intracellular membranes, ORF1a and ORF1b are cleaved to generate individual nonstructural proteins that are involved in replication. The resulting subgenomic RNA contains ORF2 and encodes precursor capsid protein (VP90). VP90 is proteolytically cleaved during packaging and produces immature capsids made of VP70. Following encapsidation, immature capsids are released from the cell without lysis. [ 6 ]  Extracellular virions are cleaved by Trypsin and form mature infectious virions. [ 14 ]


Astroviruses are 28-30 nm non-enveloped viruses with T-3 icosahedral symmetry. They have spherical shapes and consist of a capsid protein shell. Astroviruses have distinctive five or six pointed star-like projections on 10% of the virions (the other virions have smooth surfaces). [ 4 ]  The virion capsid is expressed from a subgenomic mRNA and its precursor undergoes multiple cleavages to make the VP70 protein. Capsids that are made of the VP70 protein are cleaved by trypsin to make particles that are very infectious (VP25/26, VP27/29 and VP34). The spikes that create the star-like appearance on the virion surface are made by two structural proteins (VP25 and VP27) while the capsid shell is made from VP34. [ 15 ]


Astroviruses have a  genome  composed of a single strand of positive sense  RNA . The strand has a  poly A  tail at the  3' end , but no  5' cap  but instead is linked to a  VPg  protein. With the exclusion of polyadenylation at the  3' end , the genome is between 6.8 and 7.9 kb long. The genome is arranged into three  open reading frames  (ORFs), with an overlap of approximately 70 nucleotides between ORF1a and ORF1b. The remaining ORF is known as ORF2. [ 16 ]  ORF2 encode the structural proteins, [ 17 ]  which are -at least- VP26, VP29 and VP32, the most antigenic and immunogenic of these being VP26. This protein is probably involved in the first steps of viral infection, being a key factor in the biological cycle of astroviruses. [ 18 ]  The human astrovirus genome mutation rate has been estimated to be 3.7×10 −3  nucleotide substitutions per site per year with the synonymous changes rate of 2.8×10 −3  nucleotide substitutions per site per year. [ 19 ]  The capability for  genetic recombination  appears to be present in type-3 and type-4 human astroviruses, [ 20 ] [ 21 ]  and in porcine astrovirus strains. [ 22 ]


Replication of astroviruses occur in the cytoplasm. [ 23 ]  Astrovirus RNA is infectious and functions as a  messenger RNA  for ORF1a and ORF1b, with translation initiation thought to be mediated by  VPg  similar to  Caliciviridae . [ 24 ] [ 25 ]  A frame-shifting mechanism between these two nonstructural polypeptides translates  RNA-dependent RNA polymerase  (RdRp). [ 26 ]  In replication complexes near intracellular membranes, ORF1a and ORF1b are cleaved to generate individual nonstructural proteins that are involved in replication. RdRp transcribes subgenomic RNA from the subgenomic promoter, which enables higher production of structural proteins. Subgenomic RNA contains ORF2 which encodes precursor capsid protein (VP90). VP90 is proteolytically cleaved during packaging and produces immature capsids made of VP70. Following encapsidation, immature capsids are released from the cell without lysis. [ 6 ]  Extracellular virions are cleaved by Trypsin and form mature infectious virions. [ 27 ]


The  Astroviridae  capsid is related to those of the  Tymoviridae . The non-structural region is related to the  Potyviridae . It appears that this group of viruses may have arise at some point in the past as a result of recombination event between two distinct viruses and that this even occurred at the junction of the structural and non-structural coding regions. [ 28 ]


Avastrovirus 1–3 are associated with enteric infections in turkeys, ducks, chicken and guinea fowl. In turkey poults 1–3 weeks of age, some symptoms of enteritis include diarrhea, listlessness, liver eating and nervousness. These symptoms are usually mild but in cases of poult enteritis and mortality syndrome (PEMS), which has dehydration, immune dysfunction and anorexia as symptoms, mortality is high. [ 29 ]   Post mortem  examination of the intestines of infected birds show fluid filled intestines. Hyperplasia of enterocytes is also observed in histopathology studies. However, in contrast to other enteric viruses, there isn't villous supply. [ 4 ]


Avastrovirus species often infect extraintestinal sites such as the kidney or liver resulting in hepatitis and nephritis. [ 4 ]  Birds infected by  avian nephritis virus  typically die within 3 weeks of infection. The viral particles can be detected in fecal matter within 2 days and peak virus shedding occurs 4–5 days after infection. [ 30 ]  The virus can be found in the kidney, jejunum, spleen, liver and bursa of infected birds. Symptoms of this disease include diarrhea and weight loss. Necropsies show swollen and discolored kidneys and there is evidence of death of the epithelial cells and lymphocytic interstitial nephritis. [ 4 ]  Another extraintestinal  avastrovirus  is avian hepatitis virus which infects ducks. Hepatitis in ducks caused by this duck astrovirus (DAstV) is often fatal. [ 31 ]


In birds,  Avastroviruses  are detected by antigen-capture ELISA. In the absence of vaccines, sanitation is the prevalent way to prevent  Avastrovirus  infections. [ 4 ]


Mamastroviruses often cause  gastroenteritis  in infected mammals. In animals,  gastroenteritis  is usually undiagnosed because most astrovirus infections are asymptomatic. However, in mink and humans, astroviruses can cause diarrhea and can be fatal. The incubation period for  Mamastrovirus  is 1–4 days. When symptoms occur, the incubation period is followed by diarrhea for several days. In mink, symptoms include increased secretion from  apocrine glands . [ 4 ]  Human astroviruses are associated with gastroenteritis in children and immunocompromised adults. [ 32 ]  2–8% of acute non-bacterial gastroenteritis in children is associated with human astrovirus. These viral particles are usually detected in epithelial cells of the duodenum. [ 4 ]  In sheep, ovine astroviruses were found in the villi of the small intestine. [ 33 ]


Mamastroviruses  also cause diseases of the nervous system. [ 34 ]  These diseases most commonly occur in cattle, mink and humans. In cattle, this occurs sporadically and infects individual animals. Symptoms of this infection include seizure, lateral recumbency and impaired coordination. Histological examinations showed neuronal necrosis and gliosis of the cerebral cortex, cerebellum, spinal cord and brainstem. [ 35 ]


Members of a relatively new virus family, the astroviridae, astroviruses are now recognised as a cause of  gastroenteritis  in children, whose immune systems are underdeveloped, and elderly adults, whose immune systems are generally somewhat compromised. Presence of viral particles in fecal matter and in epithelial intestinal cells indicate that the virus replicates in the gastrointestinal tract of humans. [ 36 ]  The main symptoms are  diarrhoea , followed by nausea,  vomiting ,  fever , malaise and abdominal pain. Some research studies have shown that the incubation period of the disease is approximately three to four days. Astrovirus infection is not usually a severe situation and only in some rare cases leads to  dehydration . The severity and variation in symptoms correlates with the region the case develops in. This could be due to climatic factors influencing the life cycle or transmission method for that particular strain of Astrovirus. Malnutrition and immunodeficiency tend to exacerbate the condition, leading to more severe cases or secondary conditions that could require hospital care. [ 37 ]  Otherwise, infected people do not need hospitalization because symptoms will reduce by themselves, after 2 to 4 days. [ 38 ]


Human infections are usually self-limiting but may also spread systematically and infect immunocompromised individuals. [ 39 ]


Astroviruses most frequently cause infection of the gastrointestinal tract but in some animals they may result in encephalitis (humans and cattle), hepatitis (avian) and nephritis (avian). [ 40 ]


Electron microscopy , enzyme-immunoassay ( ELISA ),  immunofluorescence , and  polymerase chain reaction  have all been used for detecting virus particle, antigens or viral nucleic acid in the stools of infected people. [ 41 ]  A method using real-time RT-PCR, which can detect all human astrovirus genotypes, has been reported. [ 42 ]  Some  RT-qPCR  techniques are able to simultaneously detect human astroviruses and other enteric viruses associated with  gastroenteritis . [ 43 ]  Microarrays are also used to differentiate between the eight different human astrovirus serotypes. [ 2 ]


Astroviruses cause gastroenteritis by causing destruction of the intestinal epithelium, leading to the inhibition of usual absorption mechanism, loss of secretory functions, and decrease in epithelial permeability in the intestines. Inflammatory responses were seen to not affect astrovirus pathogenesis. [ 44 ]


Astroviruses are associated with 5–9% of the cases of gastroenteritis in young children. [ 45 ]  Humans of all ages are susceptible to astrovirus infection, but children, the elderly, and those that are  immunocompromised  are most prone. A study of intestinal disease in the UK, published in 1999, determined incidence as 3.8/1000 patient years in the community (95%  CI , range 2.3–6.4), the fourth most common known cause of viral gastroenteritis. [ 46 ]  Studies in the USA have detected astroviruses in the stools of 2–9% of children presenting symptoms; illness is most frequent in children younger than two years, although outbreaks among adults and the elderly have been reported. Early studies carried out in  Glasgow  demonstrated that a significant proportion of babies excreting virus particles did not exhibit gastrointestinal symptoms. [ 47 ]   Seroprevalence  studies carried out in the  US  have shown that 90% of children have antibody to  HastV-1  by age 9, suggesting that (largely asymptomatic) infection is common. Looking at the pattern of disease, it suggests that antibodies provide protection through adult life until the antibody titre begins to decline later in life. [ 48 ] [ 49 ]


The occurrence of astrovirus infections vary depending on the season. In  temperate  climates, infection is highest during winter months possibly due to lower temperatures which enhance the stability of the virus. [ 50 ]  This is in contrast to  tropical  regions where prevalence is highest during the rainy season. The seasonal distribution in tropical climates can be explained by the effect of rain particularly on the breakdown of  sanitation  in developing countries. [ 47 ]


Human astroviruses are transmitted by the  fecal–oral route . The main mode of astrovirus transmission is by contaminated food and water. Young children in childcare backgrounds or adults in military barracks are most likely to develop the disease. Human astroviruses may be released in large quantities in the stool of infected individuals and contaminate  groundwater ,  fresh water  and  marine water  due to inadequate  wastewater treatment . Fruits and vegetables grown in such contaminated water may also act as sources of viral infection. Poor food handling practices, poor hand hygiene and contamination of inanimate objects are other factors that encourage  enteric  virus transmission. [ 51 ]


Astroviruses can also be transmitted to humans from other animal species. In comparison to individuals who had no contact with turkey, turkey  abattoir  workers were three times more likely to test positive for antibodies against turkey astroviruses. [ 52 ]  Furthermore, some human, duck, chicken and turkey astroviruses are  phylogenetically  related and share genetic features. [ 7 ]


Human astroviruses can be prevented by detection and inactivation in contaminated food and water in addition to disinfection of contaminated fomites. [ 7 ]


In a study by Bjorkholm et al., a 78-year-old patient diagnosed with Waldenstrom's macroglobulinemia was given 0.4 g/kg of astrovirus immunoglobulin for four days, and the symptoms dissolved leading to a full recovery from astrovirus; however, further testing has yet to be completed. [ 53 ]


In a study by Tellez et al., extracts from a plant  Achyrocline bogotensis  was used to develop an antiviral therapy for both rotavirus and astrovirus.  Achyrocline bogotensis  was commonly used for skin and urinary infections. Drug testing methodology involved application of the extract to cell for pre-treatment (blocking), direct viral activity (evidence of killing the virus), and treatment (a decrease in the viral load after an infection is established). The extract demonstrated direct viral activity by killing astroviruses directly and treatment by leading to a decrease in the viral load after an established infection. A pre-treatment effect was not evident during the experiment. [ 54 ]


1975:  Appleton and Higgins first discovered astrovirus in stool samples of children suffering from gastroenteritis by using electron microscopy (EM)


1975:  Madeley and Cosgrove named the 20–30 nm viral particle Astrovirus based on the star-like EM (electron microscopy) appearance


1976-1992:  Lee and Kurtz serotyped 291 astrovirus stool samples in Oxford; discovered serotypes 6 and 7


1981:  Lee and Kurtz were able to grow astrovirus in tripsin-dependent tissue culture by using human embryo kidney cells (HEK)


1985:  Lee and Kurtz discover two serotypes of astrovirus that are used to type 13 strains of community-acquired astrovirus


1987:  Gray et al. discovered that a 22-day long gastroenteritis outbreak in an elderly home was caused by astrovirus type 1 and calicivirus


1988:  Hermann and Hudson use antigen characterization of HEK grown astroviruses to develop monoclonal antibodies


1992:  Cruz et al. analyzed 5,000 stool samples 7.5% of the diarrheal diseases found in Guatemalan ambulatory rural children were caused by astroviruses


1993:  Jiang et al. sequence astrovirus RNA and determine the presence of three ORFs and ribosomal frameshifting


1993:  Monroe et al. classify subgenomic data for astrovirus, providing support for astrovirus to be classified as a viral family


1994:  Oishi et al. determine astrovirus as the main cause of gastroenteritis in schools in Katano City, Osaka, Japan


1995:  Bjorkholm elt al. conducted a clinical study, and 78-year-old male Waldenström's macroglobulinemia patient with astrovirus-associated gastroenteritis was successfully treated with intravenous immunoglobulin


1995:  Jonassen et al. uses PCR to detect all known serotypes (7) of astrovirus


1995:  In their sixth report, ICTV establishes Astroviridae as a viral family


1996:  Glass et al. states an epidemiological shift regarding astrovirus due to improvements in RT-PCT (reverse transcription PCR), monoclonal antibodies, and enzyme immunoassays (EIA); astroviruses are now considered one of the main causes of diarrheal disease worldwide


1996:  Palombo and Bishop the epidemiology of astrovirus infections in children suffering from gastroenteritis in Melbourne, Australia (data collected include total incidence, genetic diversity, serotype characterization)


1998:  Unicomb et al. conduct a clinical study in Bangladesh and conclude astrovirus infections involving nosocomial, acute, and persistent diarrheal diseases


1998:  Gaggero et al. identify human astrovirus type 1 to be the main cause of acute gastroenteritis in Chilean children


1999:  Bon et al. discover astrovirus in a gastroenteritis outbreak in Dijon, France


2001:  Dennehy et al. collected stool samples from hospitalized children suffering from acute gastroenteritis; astrovirus was determined the second leading cause of gastroenteritis after rotavirus


2002:  Guix et al. completes an epidemiological study on the presence of astrovirus in Barcelona, Spain; the total incidence of astrovirus in 2,347 samples was 4.95 with a peak in the number of cases in the winter


2003:  Basu et al. discovered astrovirus in 2.7% of stool samples collected from 346 children suffering from gastroenteritis in Gaborone, Botswana


2009:  Finkbeiner et al. used Sanger sequencing to discover a novel astrovirus in stool samples from children suffering from an acute gastroenteritis outbreak at a childcare center


2009:  Using RT-PCR, Kapoor et al. discover novel astrovirus strains HMOAstV species A, B, C which are very similar to astroviruses found in mink and ovine species; this showed that the virus may have the ability to jump species


Balsalazide  is an anti-inflammatory drug used in the treatment of  inflammatory bowel disease . It is sold under the brand names  Giazo ,  Colazal  in the US and  Colazide  in the UK. It is also sold in generic form in the US by several generic manufacturers.


It is usually administered as the disodium salt. Balsalazide releases  mesalazine , also known as 5-aminosalicylic acid, or 5-ASA, [ 2 ]  in the large intestine. Its advantage over that drug in the treatment of  ulcerative colitis  is believed to be the delivery of the active agent past the small intestine to the large intestine, the active site of ulcerative colitis. It is in the category of  disease-modifying antirheumatic drugs  (DMARDs) family of medications. [ 3 ]  It is unclear exactly how it works. [ 3 ]


Ex 3 is actually for  Ipsalazide . See Ex 4 for Balsalazide proper. Same protocol but uses  β-Alanine .


A  barostat  is a device used to maintain constant pressure in a closed chamber. [ 1 ]  Its main principle is providing constant  pressures  in a  balloon  by means of a  pneumatic   pump . [ 2 ]   Barostats are frequently used in  neurogastroenterology  research, where they are used for measuring  gut wall   tension  or  sensory thresholds  in the gut. [ 3 ]