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Although there can be various causes of dog pancreatitis, such as drugs, fatty diet, trauma, etc., the pathophysiology is very complex. Pancreatitis can be idiopathic; no real causation factor can be found. Obese animals as well as animals fed a diet high in fat may be more prone to developing acute and chronic pancreatitis. Certain breeds of dogs are considered predisposed to developing pancreatitis including miniature schnauzers, Cocker Spaniels, and some terrier breeds. Miniature Schnauzers as a breed tend toward developing hyperlipidemia, an excess of circulating fats in the blood. The breed which appears to be at risk for the acute form of pancreatitis is the Yorkshire Terrier, while Labrador Retrievers and miniature Poodles seem to have a decreased risk for the acute form of the disease. It is suggested that genetics may play a part in the risk factor. Dogs suffering from diabetes mellitus, Cushing's disease (hyperadrenocorticism), hypothyroidism and epilepsy are at increased risk for pancreatitis. Diabetes and hypothyroidism are also associated with hyperlipidemia. Those with other types of gastrointestinal conditions and dogs who have had previous pancreatitis attacks are also at increased risk for the disorder.
Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within 5–10 years.
There are seven classes of medications associated with acute pancreatitis: statins, ACE inhibitors, oral contraceptives/hormone replacement therapy (HRT), diuretics, antiretroviral therapy, valproic acid, and oral hypoglycemic agents. Mechanisms of these drugs causing panreatitis are not known exactly; but it is possible that statins has direct toxic effect on the pancreas or through the long term accumulation of toxic metabolites. Meanwhile, ACE inhibitors causes angioedema of the pancreas through the accumulation of bradykinin. Oral contraceptives/HRT causes arterial thrombosis of the pancreas through the accumulation of fat (hypertriglyceridemia). Diuretics such as furosemide has direct toxic effect on the pancreas. Meanwhile, thiazide diuretics causes hypertriglyceridemia and hypercalcemia, where the latter is the risk factor for pancreatic stones. HIV infection itself can cause a person to more likely to get pancreatitis. Meanwhile, antiretroviral drugs may cause metabolic disturbances such as hyperglycemia and hypercholesterolemia, which predisposes to pancreatitis. Valproic acid may have direct toxic effect on the pancreas. There are various oral hypoglycemic agents that contributes to pancreatitis including metformin. But, glucagon-like peptide-1 (GLP-1) is more strongly associated with pancreatits by promoting inflammation.
Atypical antipsychotics such as clozapine, risperidone, and olanzapine can also cause pancreatitis.
Hemosuccus pancreaticus, also known as pseudohematobilia or Wirsungorrhage, is a rare cause of hemorrhage in the gastrointestinal tract. It is caused by a bleeding source in the pancreas, pancreatic duct, or structures adjacent to the pancreas, such as the splenic artery, that bleed into the pancreatic duct. Patients with hemosuccus may develop symptoms of gastrointestinal hemorrhage, such as blood in the stools, maroon stools, or melena. They may also develop abdominal pain. Hemosuccus pancreaticus is associated with pancreatitis, pancreatic cancer and aneurysms of the splenic artery. Angiography may be used to diagnose hemosuccus pancreaticus, where the celiac axis is injected to determine the blood vessel that is bleeding. Concomitant embolization of the end vessel may terminate the hemorrhage. Alternatively, a distal pancreatectomy may be required to stop the hemorrhage.
A number of infectious agents have been recognized as causes of pancreatitis including:
- Viruses
- Coxsackie virus
- Cytomegalovirus
- Hepatitis B
- Herpes simplex virus
- Mumps
- Varicella-zoster virus
- Bacteria
- Legionella
- Leptospira
- Mycoplasma
- Salmonella
- Fungi
- Aspergillus
- Parasites
- Ascaris
- Cryptosporidium
- Toxoplasma
The annual incidence of chronic pancreatitis is 5 to 12 per 100,000 persons, the prevalence is 50 per 100,000 persons.
Cystic fibrosis, is a hereditary disease that affects the entire body, causing progressive disability and early death. It is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The product of this gene helps create sweat, digestive juices, and mucus. The name "cystic fibrosis" refers to the characteristic 'fibrosis' (tissue scarring) and cyst formation within the pancreas, causing irreversible damage, and often resulting in painful inflammation (pancreatitis).
Caroli disease is typically found in Asia, and diagnosed in persons under the age of 22. Cases have also been found in infants and adults. As medical imaging technology improves, diagnostic age decreases.
Risk factors for pancreatic adenocarcinoma include:
- Age, gender, and ethnicity; the risk of developing pancreatic cancer increases with age. Most cases occur after age 65, while cases before age 40 are uncommon. The disease is slightly more common in men than women, and in the United States is over 1.5 times more common in African Americans, though incidence in Africa is low.
- Cigarette smoking is the best-established avoidable risk factor for pancreatic cancer, approximately doubling risk among long-term smokers, the risk increasing with the number of cigarettes smoked and the years of smoking. The risk declines slowly after smoking cessation, taking some 20 years to return to almost that of non-smokers.
- Obesity; a BMI greater than 35 increases relative risk by about half.
- Family history; 5–10% of pancreatic cancer cases have an inherited component, where people have a family history of pancreatic cancer. The risk escalates greatly if more than one first-degree relative had the disease, and more modestly if they developed it before the age of 50. Most of the genes involved have not been identified. Hereditary pancreatitis gives a greatly increased lifetime risk of pancreatic cancer of 30–40% to the age of 70. Screening for early pancreatic cancer may be offered to individuals with hereditary pancreatitis on a research basis. Some people may choose to have their pancreas surgically removed to prevent cancer developing in the future.
- Chronic pancreatitis appears to almost triple risk, and as with diabetes, new-onset pancreatitis may be a symptom of a tumor. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.
- Diabetes mellitus is a risk factor for pancreatic cancer and (as noted in the Signs and symptoms section) new-onset diabetes may also be an early sign of the disease. People who have been diagnosed with Type 2 diabetes for longer than ten years may have a 50% increased risk, as compared with non-diabetics.
- Specific types of food (as distinct from obesity) have not been clearly shown to increase the risk of pancreatic cancer. Dietary factors for which there is some evidence of slightly increased risk include processed meat, red meat, and meat cooked at very high temperatures (e.g. by frying, broiling or barbecuing).
There are no approved treatments for canine pancreatitis. Treatment for this disease is supportive, and may require hospitialization to attend to the dog's nutritional and fluid needs, pain management, and addressing any other disease processes (infection, diabetes, etc.) while letting the pancreas heal on its own. Treatment often involves "resting" the pancreas for a short period of time by nil per os/nothing per os (NPO)/nil by mouth (NBM), in which the patient receives no food or fluids by mouth, but is fed and hydrated by intravenous fluids and a feeding tube. Dehydration is also managed by the use of fluid therapy. However, a specialist from Texas A&M University has stated "There is no evidence whatsoever that withholding food has any beneficial effect." Other specialists have agreed with his opinion.
Canine pancreatitis is complex, often limiting the ability to approach the disease.
In the United States, the annual incidence is 18 cases of acute pancreatitis per 100,000 population, and it accounts for 220,000 hospitalizations in the US. In a European cross-sectional study, incidence of acute pancreatitis increased from 12.4 to 15.9 per 100,000 annually from 1985 to 1995; however, mortality remained stable as a result of better outcomes. Another study showed a lower incidence of 9.8 per 100,000 but a similar worsening trend (increasing from 4.9 in 1963-74) over time.
In Western countries, the most common cause is alcohol, accounting for 65 percent of acute pancreatitis cases in the US, 20 percent of cases in Sweden, and 5 percent of those in the United Kingdom. In Eastern countries, gallstones are the most common cause of acute pancreatitis. The causes of acute pancreatitis also varies across age groups, with trauma and systemic disease (such as infection) being more common in children. Mumps is a more common cause in adolescents and young adults than in other age groups.
Drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer. However, considerable research has failed to firmly establish alcohol consumption as a direct risk factor for pancreatic cancer. Overall, the association is consistently weak and the majority of studies have found no association, with smoking a strong confounding factor. The evidence is stronger for a link with heavy drinking, of at least six drinks per day.
Among the causes of chronic pancreatitis are the following:
The relationship between etiologic factors, genetic predisposition, and the pace of disease progression requires further clarification, though recent research indicates smoking may be a high-risk factor to develop chronic pancreatitis. In a small group of patients chronic pancreatitis has been shown to be hereditary. Almost all patients with cystic fibrosis have established chronic pancreatitis, usually from birth. Cystic fibrosis gene mutations have also been identified in patients with chronic pancreatitis but in whom there were no other manifestations of cystic fibrosis. Obstruction of the pancreatic duct because of either a benign or malignant process may result in chronic pancreatitis.
A 2009 study which followed 189 patients found no excess mortality despite the increased risk of pancreatic cancer.
Locoregional complications include pancreatic pseudocyst (Most common, occurring in up to 25% of all cases) and phlegmon / abscess formation, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, thrombosis of the splenic vein, superior mesenteric vein and portal veins (in descending order of frequency), duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis, pancreatic ascites, pleural effusion, sterile/infected pancreatic necrosis.
treatment of HP resemble that of chronic pancreatitis of other causes. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction.(PMC1774562)
Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage. In the United States, about 30,000 individuals have CF; most are diagnosed by six months of age. In Canada, about 4,000 people have CF. Around 1 in 25 people of European descent, and one in 30 of Caucasian Americans, is a carrier of a CF mutation. Although CF is less common in these groups, roughly one in 46 Hispanics, one in 65 Africans, and one in 90 Asians carry at least one abnormal "CFTR" gene. Ireland has the world's highest prevalence of CF, at one in 1353.
Although technically a rare disease, CF is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world. An exception is Finland, where only one in 80 people carries a CF mutation. The World Health Organization states, "In the European Union, one in 2000–3000 newborns is found to be affected by CF". In the United States, one in 3,500 children is born with CF. In 1997, about one in 3,300 Caucasian children in the United States was born with CF. In contrast, only one in 15,000 African American children suffered from it, and in Asian Americans, the rate was even lower at one in 32,000.
Cystic fibrosis is diagnosed in males and females equally. For reasons that remain unclear, data have shown that males tend to have a longer life expectancy than females, but recent studies suggest this gender gap may no longer exist perhaps due to improvements in health care facilities, while a recent study from Ireland identified a link between the female hormone estrogen and worse outcomes in CF.
The distribution of CF alleles varies among populations. The frequency of ΔF508 carriers has been estimated at one in 200 in northern Sweden, one in 143 in Lithuanians, and one in 38 in Denmark. No ΔF508 carriers were found among 171 Finns and 151 Saami people. ΔF508 does occur in Finland, but it is a minority allele there. CF is known to occur in only 20 families (pedigrees) in Finland.
As the number of published cases of AIP has increased, efforts have been focused on defining AIP as a distinct clinical and pathologic entity and toward developing some generally agreed upon diagnostic criteria and nomenclature. Terms frequently encountered are autoimmune or autoimmune-related pancreatitis, lymphoplasmacytic sclerosing pancreatitis, idiopathic tumefactive chronic pancreatitis, idiopathic pancreatitis with focal irregular narrowing of the main pancreatic duct, and non-alcoholic duct destructive chronic pancreatitis. There are also a large number of case reports employing descriptive terminology such as pancreatitis associated with Sjögren’s syndrome, primary sclerosing cholangitis, or inflammatory bowel disease. Some of the earliest cases were reported as pancreatic pseudotumor or pseudolymphoma.
The ΔF508 mutation is estimated to be up to 52,000 years old. Numerous hypotheses have been advanced as to why such a lethal mutation has persisted and spread in the human population. Other common autosomal recessive diseases such as sickle-cell anemia have been found to protect carriers from other diseases, an evolutionary trade-off known as heterozygote advantage. Resistance to the following have all been proposed as possible sources of heterozygote advantage:
- Cholera: With the discovery that cholera toxin requires normal host CFTR proteins to function properly, it was hypothesized that carriers of mutant "CFTR" genes benefited from resistance to cholera and other causes of diarrhea. Further studies have not confirmed this hypothesis.
- Typhoid: Normal CFTR proteins are also essential for the entry of "Salmonella" Typhi into cells, suggesting that carriers of mutant "CFTR" genes might be resistant to typhoid fever. No "in vivo" study has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever are endemic, is not immediately explicable.
- Diarrhea: The prevalence of CF in Europe might be connected with the development of cattle domestication. In this hypothesis, carriers of a single mutant "CFTR" had some protection from diarrhea caused by lactose intolerance, prior to the appearance of the mutations that created lactose tolerance.
- Tuberculosis: Another possible explanation is that carriers of the gene could have some resistance to TB. This hypothesis is based on the thesis that "CFTR" gene mutation carriers have insufficient action in one of their enzymes – arylsulphatase - which is necessary for "Mycobacterium tuberculosis" virulence. As "M. tuberculosis" would use its host’s sources to affect the individual, and due to the lack of enzyme it could not presents its virulence, being a carrier of "CFTR "mutation could provide resistance against tuberculosis.
The condition is usually congenital, but sporadic cases have also been reported. It may be associated with other congenital defects, commonly with autosomal recessive polycystic kidney disease, the most severe form of PKD. Some suggest that these two conditions are one disorder with different presentation.
Autoimmune pancreatitis (AIP) is an increasingly recognized type of chronic pancreatitis that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone. There are two categories of AIP: Type 1 and Type 2, each with distinct clinical profiles.
Type 1 AIP is now regarded as a manifestation of IgG4-related disease, and those affected have tended to be older and to have a high relapse rate. Type 1 is associated with pancreatitis, Sjogren syndrome, Primary sclerosing cholangitis and Inflammatory bowel disease. Patients with Type 2 AIP do not experience relapse, tend to be younger and not associated with systemic disease. AIP occurring in association with an autoimmune disorder has been referred to as "secondary" or "syndromic" AIP. AIP does not affect long-term survival.
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.
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.
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 feminsation. 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.
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.
Congenital hepatic fibrosis is an inherited fibrocystic liver disease associated with proliferation of interlobular bile ducts within the portal areas and fibrosis that do not alter hepatic lobular architecture. The fibrosis would affect resistance in portal veins leading to portal hypertension.
Pancreatic diseases that affect digestion refers to disorders affecting the exocrine pancreas, which is a part of the pancreas involved in digestion.
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 alcohol abuse 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.
Pancreatic disease may present with or without symptoms. When symptoms occur, such as in acute pancreatitis, a person may suffer from 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.
Periampullary cancer is a cancer that forms near the ampulla of Vater, an enlargement of the ducts from the liver and pancreas where they join and enter the small intestine.It consists of:
1. ampullary tumour from ampulla of Vater,
2. cancer of lower common bile duct, and
3. duodenal cancer adjacent to ampulla.
4. carcinoma head of pancreas
It presents with painless jaundice which may have waxing and waning nature because at times the sloughing of the tumor tissue relieves the obstruction partially.