Main symptoms and syndromes in diseases of bile ducts: chronic cholecystitis, cholangitis, cholelithiasis.
Main clinical and laboratory signs of hepatitis and liver cirrhosis.
Main clinical symptoms in chronic pancreatitis.
Main symptoms and syndromes in diseases of biliary system: chronic cholecystitis, cholangitis, cholelithiasis
Cholecystitis
Cholecystitis is the inflammation on the gall bladder.
The incidence of the disease is rather high; women are mostly affected. Acute and chronic cholecystites are differentiated.
Chronic cholecystitis may develop after acute cholecystitis but in most cases it develops gradually as an independent disease.
Etiology:
1. Bacterial infection diseases:
– nasopharyngeal infection (chronic tonsillitis, sinusitis);
– diseases of oral cavity (stomatitis, paradontosis);
– urinary tract diseases (prostatitis, uretritis);
– gynecological diseases;
– intestinal infection;
– viral affection of the liver.
The most typical microbiological agents are: E. Coli, Enterococci, Staphylococci, Streptococci.
2. Нelmintic invasion: opistorchosis, asckaridosis, lambliosis.
3. Duodenal-billiary reflux (regurgitation of pancreatic juice or duodenal content to the gall bladder)
4. Cholecistitis of toxic or allergic nature.
5. Chronic inflammatory diseases of alimentary tract
6. Acute cholecystitis.
Predisposing factors:
1. Bile congestion coursed by:
– dyskinesia of bile ducts;
– obesity ;
– pregnancy;
– psycho emotional stresses;
– non-observation of dietary mode, fatty and fried food; rare meals;
– food poor in dietary fibers;
– inactive mode of life;
– congenital defects of bile ducts or gall bladder.
2. Reflectory influences from other internal organs.
3. Dysbacteriosis.
4. Metabolic disorders (obesity, diabetes mellitus, podagra)
5. Hereditary predisposition.
Pathogenesis
Infection may enter to the gall bladder by following ways:
– enterogenic (from the intestine, in the case of reflux);-
– haematogenic;
– lymphogenic.
Inflammation in the gall bladder develops only in the case when infection contamination is combined with bile congestion, changes of bile properties, dystrophy of gall bladder walls or immunodepression.
Classification of chronic cholecystitis
1. By etiological agent, it is caused by: E. Coli, Enterococci, Staphylococci, Streptococci, Pneumococci, Salmonella ets.
2. By degree of severity: mild form, moderate and heavy form
3. By the course of the disease: recurrent, monotonous, and intermittent.
4. Phases of the disease: exacerbation, relapse.
5. Complications: non-complicated; complicated (pericholecystitis, cholangitis, pancreatitis ).
Clinical picture:
Complaints:
– Pain in the right hypochondrium;
– Dyspeptic syndrome (bitter or metallic taste in the mouth; regurgitation (belching), nausea, abdominal flatulence, diarrhea or constipation);
– Psyсhoemotional disorders;
– fever; the temperature is often subfebrile.
– skin itching.
Biliary pain / chronic cholecystitis
The symptoms are of intermittent, dull RUQ pain – constant or colicky. It may occur at any time and is not necessarily related to meals. It resolves spontaneously within a few hours and is not associated with systemic upset. These symptoms are a common indication for cholecystectomy, but it is difficult to determine that patients’ symptoms are caused by their gallstones in this group. Symptoms of non-specific, post-prandial pain, bloating and fatty food intolerance are not good discriminators and 25% of patients who undergo cholecystectomy for these symptoms will experience continued discomfort postoperatively.
Typical pain irradiation in diseases of internal organs
Objective signs: The appearance of the patient and his nutrition are usually normal.
– Moderate obesity is sometimes observed.
– Examination of the abdomen can reveal its flatulence.
– Yellowish tint of the skin;
Data of palpation: sensitivity or mild pain; sometimes pronounced tenderness in the region of gall bladder projection.
Following typical symptoms may be revealed by palpation:
1.Vasilenko`s symptom – sharp pain in the region of the gall bladder when it is tapped over at the height of inspiration.
2. Obraztsov-Murphy symptom – sharp pain in the right hypochondrium when the examiner` hands press the gall bladder at the height of inspiration.
3. Ortner`s symptom – pain during tapping over the right costal arch by the edge of the hand.
4. The de Mussy-Georgievsky symptom – tenderness at the point of the phrenic nerve, between the heads of the sterno-cleidomastoid muscle.
Liver: usually is of normal sizes, but becomes enlarged in complications (hepatitis, cholangitis). The gall bladder is impalpable.
Laboratory and instrumental examination:
1. Blood count: moderate leucocytosis; mildly increased ESR.
2. Biochemical blood analysis: increased content of seromucoid, fibrin, α2-globulines, γ–globulines.
3. Duodenal probing:
Signs of inflammation (mucus, leucocytes, desquamated epithelium) can be found in B bile.
Portion B bile is sometimes impossible to obtain (this indicate disordered contractility of the gall bladder). Bacteriological studies of B bile reveal microbial flora.
Duodenal probing: 1 – tube; 2 – esophagus; 3 – stomach;4 – pancreas; 5 – Oil tube; 6 – large duodenal nipple; 7 – duodenum;
I – common bile duct (incoming portion A);
II – gallbladder (incoming portion B);
III – hepatic duct (incoming portion C).
4. X-Ray study. There are following methods: cholecystography, cholangiography, endoscopic (retrograde) cholangiopancreatography.
5. Cholecystography shows changes in the configuration of the gall bladder and the absence of its distinct contours. This indicates upset concentrating capacity of the gall-bladder mucosa. After taking of stimulators of contraction (like egg yolk or magnesium sulfate) the gall bladder contracts insufficiently.
6. Sonographyc signs of chronic cholecystitis :
– thickening of gall bladder walls more then 2 mm;
– induration of walls;
– uneven and deformed contour of the gall bladder, enlargement or diminishing of its dimensions; adhesions;
– decreased or absent mobility of the organ in respiratory phases;
– non-homogeneous content of the gall bladder; „ bile sediments.”
Ultrasonography. Acute cholecystitis
Ultrasonography. Chronic cholecystitis
6. Computer tomography: gives possibility to estimate location, dimensions, shape of the gall bladder, thickness of its walls, gallstone presence.
7. Thermography: reveals local deviation of temperature up to 0,3 – 2C, the zone of the gall bladder looks more light.
Treatment:
Stage of exacerbation:
1. bed mode during 7 – 10 days
2. diet № 5a, warm drink;
food intake 5 – 6 time a day by small portions
3. elimination of pain:
– M-cholinolitics (atropine sulfate, metacin, plathyphyllin, gastrocepin).
– Spasmolitics ( papaverin, no-spa ).
– Analgetics (analgin, baralgin).
4. Improvement of bile excretion: cholagoges (sunflower oil, allochol, cholenzyme, cholagone, liobile, nicodine, cholagogic species). This group of preparations is contraindicated in gallstones
5. Antibioticotherapy (broad-spectrum antibiotics – erythromicin, ampicillin, oxacyllin, lyncomicin, tetracyclin, oletetrin, ceftriaxon )
6. Detoxication(wild-rose decoction, mineral water, intravenous infusion of Hemodes, 5% Glucose solution, ISS ets.).
7. Physiotherapy.
In the period of relapse:
Anti- exacerbation courses of treatment 1-2 times a year: periodical duodenal probing, cholagogues in 3-4 week courses (e.g. allochol per os, 1-2 tablets 3 times a day after meals, cholagogic species in the form of infusions, 10—20:200 ml, half-glass 3 times a day, 30 minutes before meals). Sanatorium and health-resort therapy is also indicated.
Prophylaxis.
The disease and recurrent exacerbations should be prevented by taking measures to control bile congestion (exercises, walks and trips, regular and frequent meals with certain restriction) and treatment of focal infections.
Choledocholithiasis
Cholelithiasis is characterized by formation of stones in the gall bladder or, less frequently, in the bile ducts. The incidence of the disease is rather high. According to the data of postmortem examination, stones arc found in the gall bladder of every tenth patient who dies from various causes.
Cholesterol does not crystallise out because of a combination of factors including: 1. the detergent activity of bile salts (paradoxically produced from cholesterol) and the polar lipid lecithin 2. gallbladder motility. Gallstones develop when these mechanisms fail and there is an originating nidus for stone formation which is often mucin or bacteria. 80% of gallstones are cholesterol or mixed cholesterol stones where cholesterol is the major constituent. Pigment stones form the bulk of the rest and comprise predominantly bile pigment and are most common in chronic haemolytic states.
Ethiology
Bile is a super-saturated solution of cholesterol
Cholesterol is solubilized in bile by the formation of mixed micelles that consist predominantly of bile salt and phospholipid. Micelles form when the concentration of bile salts in water is between 2 and 4 mM, the so-called critical micellar concentration (CMC). The negatively charged hydrophilic region of the bile salt molecule faces outward into the water phase, whereas the uncharged hydrophobic region is directed inward. These three components—bile salts, phospholipids, and cholesterol—exist in equilibrium between the free state and micelle constituents. At the CMC for bile salts, the equilibrium shifts strongly in the direction of the micelle. If bile salt concentrations are insufficient, the hydrophobic cholesterol molecules will precipitate to form a nidus for a gallstone.
Pigments stones
Like cholesterol unconjugated bilirubin is insoluble and precipitates in gall bladder. Conjugation of bilrubin prevents this precipitation. When unconjugated bilirubin lever is high in conditions such as hemolytic anemia or infection in the biliary tree causing deconjugation of bilirubin via bacterial beta-glucuronidase, bilirubin precipitates forming gallstones.
Types of gallstones
Gall stones vary from pure cholesterol (white), through mixed, to bile salt predominant (black).
(Gall stones)
Epidemiology.
Incidence varies with age: 5% at age 20, rising to 30% over 50
Prevalence of gall stones according to age
There is a 2:1 predominance in females. There are wide ethnic variations with American Pima Indians having an incidence of 70% in females aged 20. Scandinavia also has high incidences excreted in the bile, subsequently being concentrated in the gallbladder. This shows gallstones as filling defects within the gallbladder and demonstrates that the cystic duct is not obstructed. Following a fatty meal, the ability of the gallbladder to contract can also be measured. A functioning gallbladder and a non-obstructed, cystic duct are prerequisites for consideration of bile dissolution therapy.
Stones which have migrated into or formed within the CBD may be asymptomatic and be discovered by an elevation in the alkaline phosphatase level. They are usually associated with biliary type pain and intermittent jaundice and can cause obstruction. Removal of these stones is essential as there is a high complication rate.
Clinical features
1. Asymptomatic: about 80% of cases are asymptomatic
2. Symptomatic gallstones manifest either as biliary colic or cholecystitis. Biliary colic occurs if the stone is acutely impacted in the cystic duct. Pain is felt in the epigastrium (in 70% cases) or right upper quadrant (in 20% cases), radiating to the interscapular region or tip of the right scapula.
Complications
1. Acute and chronic cholecystitis
2. Gallstones may pass into common bile duct, giving rise to biliary obstruction that produces pain in right upper quadrant with or without obstructive jaundice.
3. Rarely gallstone may perforate through the wall of an inflamed gall bladder into the intestine, producing a fistula and if stone is large it impacts in terminal ileum causing intestinal obstruction.
4. Mucocoele or empuema of gallbladder; completely obstruction of cystic duct leads to slow distension of the gallbladder from continuous secretion of mucus, forming mucocoele. If this material becomes infected empyema develops.
Investigations
Appearance of patient with mechanical jaundice
Investigations
For patients with uncomplicated cholelithiasis, blood work results usually are normal. However, utilize the lab to detect complications of gallstone disease; complications might alter the course of treatment.
Obtain a chemistry panel, including electrolytes, liver enzymes, and bilirubin.
Choledocholithiasis can manifest only with elevation of serum alkaline phosphatase or bilirubin.
Nearly 50% of patients with symptomatic gallstone disease will have abnormal transaminases.
A complete blood count is obtained routinely in patients suspected of cholelithiasis.
CBC might serve as a preoperative lab test normally obtained in patients undergoing major surgery, such as laparoscopic cholecystectomy.
An elevated white blood cell count alerts the clinician to the possibility of acute cholecystitis, a condition requiring more urgent treatment.
Serum lipase and amylase levels are helpful in cases of diagnostic uncertainty or suspected concurrent pancreatitis.
Coagulation parameters measured by prothrombin (PT) and partial thromboplastin time (PTT) might be abnormal in the severely jaundiced patient due to dysfunction in vitamin K absorption. These tests are routinely ordered preoperatively, especially in patients who are medically anticoagulated with warfarin.
Imaging Studies:
Upright and supine abdominal radiographs are useful.
Approximately 15% of gallstones are radiopaque and can be seen on plain x-ray.
A porcelain gallbladder (heavily calcified) should be removed surgically because of increased risk of gallbladder cancer.
Other causes of abdominal pain diagnosed with the assistance of x-rays include perforated viscus, bowel obstruction, calcific pancreatitis, and renal stones.
Other Tests:
Ultrasound
Ultrasound (US) is the most sensitive and specific test for the detection of gallstones.
US provides information about the size of the common bile duct and hepatic duct and the status of liver parenchyma and the pancreas.
Thickening of the gallbladder wall and presence of pericholecystic fluid are radiographic signs of acute cholecystitis.
Ultrasonography is the important procedure for the diagnosis of chronic gallbladder disease. In 90% to 95% of cases of cholelithiasis, ultrasonography demonstrates the echo of the calculus and the acoustic shadow behind the calculus.
Gallstone visible due to ultrasound examination
Computerized tomography scanning.
CT scanning often is used in workup of abdominal pain without specific localizing signs or symptoms.
CT scanning is not a first-line study for detection of gallstones because of greater cost and invasive nature of the test.
When present, gallstones usually are seen on CT scan.
99mTc-image display and analysis scintigraphy scan
99mTc-image display and analysis (IDA) scintigraphy (HIDA) scan does not detect gallstones.
HIDA scan identifies an obstructed gallbladder (eg, gallstone impacted in the neck of the gallbladder).
HIDA scan is the most sensitive and specific test for acute cholecystitis.
A poorly contracting gallbladder (biliary dyskinesia) might cause the patient’s symptoms, and HIDA scan makes the diagnosis.
Acute acalculous cholecystitis is diagnosed most accurately with HIDA scan.
CT-scan in cholecystitis
Endoscopic retrograde cholangiopancreatography
(ERCP) is the technique of choice to demonstrate CBD stones as it also allows therapeutic interventions at the same time.
Endoscopic retrograde cholangiopancreatography reveals abnormalities in a patient with gallstones. Multiple radiolucent areas establish the diagnosis of stones in the gallbladder (broken arrow) and common bile duct (solid arrow).
This cholangiogram, obtained during endoscopic retrograde cholangiopancreatography, shows a normal gallbladder (black arrow) and a narrowed biliary tree with many areas of segmental stenosis (white arrows), diagnostic of primary sclerosing cholangitis.
Cholangiograma. Cholecystitis.
Cholangiograma. Gallstones.
CT-scan in cholecystitis
CT- scan. Gallstones
Cholangitis
Cholangitis is the inflammatory process of bile ducts. This occurs when there is infection in the biliary tree, usually as a result of CBD stones. Patients present with biliary pain, jaundice, fever and often rigors. The septicaemia is usually due to Gram-negative organisms, is frequently severe and may be lifethreatening.
Classification: – Acute and chronic cholangitis.
– Catarrhal and purulent.
Acute purulent cholangitis is characterized by “Charcot’s triad” or “intermittent hepatic fever”: high body temperature, chills, sweating, as well as jaundice. Liver is enlarged and painful. Spleen is sometimes enlarged.
Blood analysis: neutrophil leukocytosis, accelerated ESR, elevation of alkaline phosphatase and aminotransferase levels.
Chronic cholangitis. The course of may be latent, recurrent or prolonged with septic component.
Clinical manifestation: Sensation of heaviness or dull pain in the right hypochondrium which occur if the patient doesn’t observe dietary mode, in jolt riding or in physical loading. The pain irradiates toward the right shoulder blade.
Dyspeptic syndrome (bitter taste in the mouth, disgust to fatty food, nausea) Skin itching.
Asthenodepressive syndrome (weakness, rapid fatigability). Prolonged periods of not-motivated subfebrile fever with periodical chills.Yellowish tint of mucous coats.The liver is enlarged, mild and painful.
Blood analysis: neutrophil leukocytosis, accelerated ESR. Activity of alkaline phosphatase rises. Duodenal probing: inflammatory changes in all portions of bile.
Pathogenesis of cholangitis
Ultrasonography. Cholangitis.
Cholangiograma. Cholangitis.
Treatment
Cholecystitis.
Acute cholecystitis requires analgesia, intravenous support and antibiotics, and usually settles with these measures. Subsequent cholecystectomy may then be performed when the acute episode has resolved. Careful selection of patients with chronic cholecystitis is important as not all patients are pain-free when the gallbladder is removed; symptoms may abate spontaneously and not recur; and there is an increasing, associated, operative mortality with advancing age. Laparoscopic cholecystectomy has increased the acceptability of the procedure for patients and has consequently become widely available. There appears to be an increased risk of bile duct injury at the time of the procedure, particularly when carried out by inexperienced surgeons. However, the replacement of a large subcostal scar with three porthole incisions reduces postoperative pain and hospital stay from 10 to less than 3 days.
Postcholecystectomy pain.
Following cholecystectomy, some patients continue to experience symptoms such as bloating, fatty food intolerance and dyspepsia. These symptoms usually predated the surgery and are often due to the irritable bowel syndrome. There is also a group of patients who have convincing biliary pain after stones have been removed. Liver function tests may be abnormal and some patients may be jaundiced. ERCP shows a dilated CBD without stones and there may be delayed excretion of contrast medium. This points towards sphincter of Oddi dysfunction which in more severe cases may benefit from endoscopic sphincterotomy.
Medical management of gallbladder stones
Dissolution therapy can be considered in patients with uncomplicated gallstone disease who are unwilling or unfit for surgery. The prerequisites for treatment are that the stones should be non-calcified, the gallbladder should be functioning and the cystic duct not obstructed. The bile acids, chenodeoxycholic acid and ursodeoxycholic acid are available and need to be given for long periods to be successful. They have no effect on pigment stones.
Half of patients with gallstones experience no problems but 35% of patients with gallstones discovered by chance will require treatment over the next 10 years as a result of either pain or complications. A number of clinical conditions may develop as a result of gallstones depending upon their location.
Chronic Pancreatitis
Clinical features
The three important features of chronic pancreatitis are pain, steatorrhoea resulting from exocrine dysfunction and diabetes mellitus resulting from endocrine dysfunction.
Pain. The pain is usually located in the upper abdomen but is poorly localised. It is described as a boring, deep pain which may radiate to the back and is worsened after meals. It may be nocturnal. Its severity is not proportional to steatorrhoea and correlates poorly with loss of exocrine function or structural abnormality. The pain is the most difficult problem to treat and can be frustrating for both the patient and the physician.
Steatorrhoea. Lipase secretion has to be reduced to less than 10% of normal for steatorrhoea to develop and consequently this is a symptom which develops when the disease is advanced. Fat-soluble vitamins (A, D, E and K) are rarely sufficiently malabsorbed to cause symptoms. Stools are passed 2-3 times per day, are pale and may contain droplets of oil.
Diabetes. For overt diabetes to develop, more than 80% of the gland needs to be affected, which means that diabetes is also usually a late complication. However, abnormalities in the glucose tolerance test are detectable much earlier. The vast majority of patients will describe a heavy, sustained alcohol drinking habit and only rarely will there be a significant family history or associated medical history. Examination is usually normal although a mass may be palpable when a pseudocyst or cancer has developed. The spleen may be enlarged when the splenic vein has thrombosed.
Aetiology
Alcohol is the major cause and the history is usually of > 150 g/day for more than 5 years. Less than 20% of heavy drinkers develop chronic pancreatitis and it is unclear why this is so, but there may be a diet rich in fat in those that do develop chronic pancreatitis. A preceding history of recurrent episodes of acute pancreatitis is not usually present. A tropical form of the disease is described which may be associated with protein malnutrition and intraductal stones. Familial and other inherited causes also occur although in up to 30%, the cause is obscure. It is unclear what initiates and perpetuates the chronic inflammation and fibrosis that develop within the pancreas. One theory is that a diet rich in lipid increases protein secretion by the pancreas. This may cause precipitation of these proteins in pancreatic ducts resulting in partial obstruction, which, when associated with toxic metabolites from alcohol, initiates the process. Another proposal is that chronic pancreatitis is a result of recurrent episodes of acute pancreatitis.
Risk factors for chronic pancreatitis include:
– Prolonged alcohol use
– Certain hereditary conditions, such as cystic fibrosis
– Gallstones
– Conditions such as high triglycerides and lupus
Three groups have been described:
1. chronic calcified pancreatitis – fibrosis, intraductal protein plugs and stones result in ductal injury; alcohol is the major cause.
2. chronic obstructive pancreatitis – obstruction of the main duct with proximal, uniform, ductal dilatation and subsequent atrophy and fibrosis; this is much less common and is due to either an intraductal tumour or a stricture.
3. chronic inflammatory pancreatitis – fibrosis and a mononuclear infiltrate associated with conditions such as Sjogren’s syndrome and primary sclerosing cholangitis.
Symptoms of chronic pancreatitis
The symptoms of chronic pancreatitis are similar to those of acute pancreatitis. Patients frequently experience constant pain in the upper abdomen that radiates to the back. In some patients, the pain may be disabling. Other symptoms may include weight loss caused by poor absorption (malabsorption) of food. This malabsorption occurs because the gland is not secreting enough enzymes to break down the food normally. Also, diabetes may develop if the insulin-producing cells of the pancreas become damaged.
Diagnosis
The triad of pain, steatorrhoea and diabetes is unlikely to occur until late in the disease and patients more usually present with pain. There may be no signs of chronic liver disease as this too only develops in one-fifth of heavy drinkers. Simple blood tests are not usually helpful although there may be diabetes or at least an impaired glucose tolerance test. Serum lipase and amylase elevation is unusual and only tends to occur if the pancreatic duct is blocked or there is a pseudocyst. An obstructive pattern in the liver profile may occur if stricturing of the CBD has developed. The important differential diagnoses include peptic ulcer, biliary tract disease, mesenteric ischaemia and gastric or pancreatic malignancy, and appropriate investigation is necessary to exclude these.
Pancreatitis is primarily suspected when a person reports symptoms of pancreatitis and also has risk factors such as heavy alcohol use or gallstone disease. To confirm acute pancreatitis, the doctor measures levels in the blood of the two digestive enzymes, amylase and lipase. High levels of these two enzymes strongly suggest acute pancreatitis.
Diagnosis can be difficult but is aided by a number of techniques such as pancreatic function tests and radiographic imaging of the pancreas. In more advanced stages of the disease, when malabsorption or diabetes is present, blood, urine, and stool tests will confirm the progression.
Diagnostic tests for pancreatitis include:
Pancreatic function test, to determine if the pancreas is producing the appropriate levels of digestive enzymes
Glucose tolerance test to measure damage to the cells in the pancreas that make insulin
Ultrasound, which can produce images of the pancreas so that abnormalities may be detected
CT scan (computed tomography scan), which can produce images of the pancreas so that abnormalities may be detected
ERCP (endoscopic retrograde cholangiopancreatography) to look at the pancreatic and bile ducts using contrast and X-rays
Endoscopic ultrasound (EUS) and biopsy, an exam in which a fine needle is inserted into a localized abnormality of the pancreas.
Pancreatic function tests
A number of tests are available to assess endocrine pancreatic function. Some tests quantify enzyme production, measured following intubation of the duodenum and stimulation of the pancreas either by hormones or a test meal, while other tests quantify production of metabolites of reactions catalysed by pancreatic enzymes.
It is important to try to minimise disease progression and this is best done by total alcohol avoidance particularly in those in whom alcohol is the cause.
ST scan
ERCP
Ultrasound examination
Analgesia requirement should be titrated against need but often spirals upwards to considerable opiate requirement and subsequent addiction. Care should be taken in controlling associated side-effects such as constipation which can lead to abdominal pain inappropriately attributed to the pancreas. Pancreatic enzyme supplementation is usually used and may be helpful as may an anti-oxidant cocktail given daily. Coeliac axis nerve block may lead to temporary improvement in pain but frequently symptoms recur. Surgery including partial resections and drainage procedures may be helpful in the most severe cases but it is difficult to obtain controlled data for these procedures. Resection of tissue including endocrine cells results in brittle diabetes which is difficult to manage.
Steatorrhoea
Dietary enzyme supplementation usually controls this. Lipase inactivation by gastric acid may result in more than the expected 30 000 units of lipase per meal estimated to be required to prevent steatorrhoea. Gelatin capsules and acid suppression therapy may help.
Diabetes
This is often brittle and wide fluctuations in blood glucose are seen with exogenous insulin.
Complications
Pseudocysts may occur in up to 25% of patients with chronic pancreatitis and if they are of significant size require drainage either surgically or endoscopically. Bleeding may occur into a pseudocyst or there may be erosion into surrounding vessels. Splenic vein thrombosis may occur resulting in gastric and oesophageal varices. Pancreatic cancer is more common in patients with chronic pancreatitis and represents the major differential diagnosis when obstructive jaundice occurs with a stricture of the CBD. Differentiation between the two conditions is difficult and serum markers (CA 19-9), CT and biopsy may all be necessary to confirm the diagnosis.
Treatment for chronic pancreatitis
Chronic pancreatitis can be somewhat difficult to treat. Doctors will try to relieve the patient’s pain and improve the nutritional and metabolic problems that result from loss of pancreatic function. Patients are generally given pancreatic enzymes or insulin, if these substances are not being secreted or released by the pancreas. Pancreatic enzyme pills are usually prescribed to be taken with meals to aid iutrient absorption. A low-fat diet may also be helpful.
Surgery may help relieve abdominal pain, restore drainage of pancreatic secretions, treat chronic pancreatitis caused by blockage of the pancreatic duct, or reduce the frequency of attacks.
Patients must stop drinking alcoholic beverages, follow their doctor and dietitian’s dietary recommendations, and take the proper medications in order to have fewer and milder attacks of pancreatitis.
Can Pancreatitis Be Prevented?
Since most cases of pancreatitis are caused by alcohol abuse, prevention is directed at responsible drinking, or no drinking at all. If heavy drinking is a concern, talk to your doctor or health care provider about a referral to an alcohol treatment center. In addition, you may benefit from a support group such as Alcoholics Anonymous.
Chronic Hepatitis
Chronic hepatitis is a chronic diffuse or focal inflammatory affection of the liver.
Aetiology. The following groups of chronic hepatitis are distinguished:
(1) infectious and parasitogenic; infectious hepatitis develops secondary to virus hepatitis, brucellosis, tuberculosis, syphilis, and some other diseases;
(2) toxic hepatitis caused by industrial, medicamentous, domestic and food chronic poisoning by hepatotropic toxic substances (chloroform, trinitrotoluene, aminazine, lead compounds, etc);
(3) toxico-allergic hepatitis, which develops not only in response to direct toxic effect of some medicines or hepatotropic chemicals, but also due to hypersensitivity of the liver cells of the entire body to these substances (medicamentous hepatitis, hepatitis associated with collagenosis);
(4) metabolic hepatitis, which arises due to metabolic disorders in the liver, associated with protein-vitamin deficiency, and also in fat dystrophy and amyloidosis.
In 40—70 per cent of cases chronic hepatitis develops as an outcome of an acute epidemic or serum hepatitis. Hepatitis is mostly diffuse affection of the liver. Liver affections are focal in tuberculosis (tuberculous granulomas, caseous abscesses or tuberculoma), syphilis (gumma), some protozoal disease (amoebic abscesses), fungal and bacterial affections (usually abscesses), and in some other cases.
Pathogenesis. This is mostly determined by the aetiology of the disease. When exposed chronically to hepatotropic toxic substances, the hepatocytes become progressively affected (to necrobiosis); the secondary inflammatory reaction of the liver mesenchyma is equally imponant in the pathogenesis of chronic hepatitis. Hepatitis of virus nature is probably associated with persistence of the virus in the liver cells and with the progressive cytopathic effect of this virus, which kills the hepatocytes to cause inflammatory reaction of the connective tissue. In many cases autoimmune processes are of primary importance. They arise in response to the primary affection of the liver tissue by any aetiological factor. Obstructed bile excretion and bile congestion, cholangitis and cholangiolitis (with subsequent extension of inflammation onto the liver tissue), and also some medicamentous poisonings (phenothiazine derivatives) are decisive in the pathogenesis of the so-called cholestatic hepatitis.
Clinical picture. Chronic hepatitides are characterized by
(1) dyspeptic symptoms;
(2) jaundice (it may be absent in some cases);
(3) moderate enlargement and induration of the liver and the spleen;
(4) dysfunction of the liver as determined by laboratory tests and radiohepatography. But the clinical picture and also the course of each clinico-morphological form of hepatitis have their special features.
Chronic benign hepatitis is characterized by obliterated clinical picture. The patients complain of heaviness or dull pain in the right hypochondrium, decreased appetite, bitter taste in the mouth, nausea and eructation.
Coated tongue is ibserved during inspection
Lips are usualy bright-red in hepatitis (fig.2.1.) and spider angiomata develop (fig.2.2.)
Jaundice is usually absent or it is moderate. Objective studies reveal a mildly enlarged liver with a smooth surface and a moderately firm edge, which is slightly tender to palpation. Enlargement of the spleen is not marked.
Spider angiomata
Hepatomegalia is an important sign of hepatitis
Hepatomegalia is often followed by splenomegalia
Laboratory studies. The blood bilirubin content is usually normal; in the presence of jaundice it increases to about 17-50 μmol/l; the blood globulin content is mildly increased, activity of the erzymes is either normal or only slightly changed; the prothrombin content is normal or slightly decreased; the bromsulphthalein test is slightly positive.
Chronic active hepatitis is characterized by complaints and objective symptoms: weakness, loss of weight, fever, pain in the right hypochondrium, loss of appetite, nausea, regurgitation, meteorism, skin itching, jaundice, and frequent nasal bleeding. The liver is enlarged, firm, with a sharp edge. The spleen is enlarged.
Jaundice and xanthelasma in patient with hepatitis
Laboratory tests often reveal anaemia, leucopenia, thrombocytopenia (a sign of hypersplenism), and increased ESR. Functional tests are changed considerably: they show hyperbilirubinaemia, hyperproteinaemia, hypergammaglobulinaemia, positive protein-sedimentation tests, increased activity of transaminase, aldolase, and alkaline phosphotase; decreased activity of cholinesterase. The serum iron content is significantly increased while the prothrombin index is sharply decreased; excretion of brom-sulphthajein is delayed.
Contractura of falangies flexors is observed in active hepatitis
Puncture biopsy of the liver and (for special indications) laparoscopy establish the special histological and macroscopic changes in the liver characteristic of these forms. These techniques are also used for differentiation of chronic hepatitis from other diseases of the liver (cirrhosis, amyloidosis, etc). It should be noted that histological and histochemical studies of liver bioptates often reveal early morphological changes in the liver which precede the clinical and laboratory signs of chronic hepatitis.
Chronic cholestatic hepatitis is mainly characterized by the cholestatic syndrome: jaundice (subhepatic), severe skin itching, hyperbilirubinaemia, increased activity of alkaline phosphatase in the blood, and high cholesterol of blood. Persistent subfebrile temperature and regular increased ESR are also not infrequent.
Course. A benign hepatitis can last to 20 years; exacerbations are rare and arise only in the presence of strong provoking factors. Liver cirrhosis develops in rare cases. Complete clinical recovery i« sometimes possible, especially so if the patient is specifically treated. The morphological structure of the liver is restored in such cases.
Aggressive hepatitis is characterized by relapses, whose frequency depends on various factors. Frequent relapses accelerate progressive dystrophic, inflammatory and cicatricial changes in the liver and stimulate development of cirrhosis. Prognosis in this form of hepatitis is bad.
The course and prognosis in cholestatic hepatitis depend on it’s aetiology and the possibility of removing the obstacle to bile outflow (in compression of the common bile duct by a tumour, cicatricial or inflammatory stenosis, etc.).
Treatment. The cause of chronic hepatitis should be removed in the first instance: complete discontinuation of taking alcohol or exposure to harmful substances, etc.
During exacerbations, the liver should be spared as much as possible, and regeneration of liver cells stimulated (bed rest, diet, parenteral use of vitamins, glucose, etc).
Cirrhosis of the Liver
Cirrhosis of the liver is a chronic progressive disease characterized by increasing hepatic insufficiency in connection with dystrophy of the liver cells, cicatricial cirrhosis, and structural reconstruction of the liver.
Aetiology. Cirrhosis of the liver is a polyaetiological disease. It may develop due to:
(1) infection (virus of epidemic hepatitis);
(2) alcoholism,
(3) protein- and vitamin-deficient diet;
(4) toxico-allergic factor;
(5) cholestasis.
Of the mentioned aetiological factors, the leading role in this country belongs to the virus of epidemic hepatitis. Cirrhosis caused by the virus is probably explained by its long persistence in the liver cells.
Chronic alcoholic poisoning is also a very important aetiological factor If affects absorption of vitamins and proteins in the intestine to provoke cirrhosis of the liver. It also acts directly and specifically on metabolism of the liver cells. The alimentary factor (malnutrition, mainly protein- and vitamin deficit) is a frequent cause of liver cirrhosis in some developing countries. In this country the alimentary factor (malnutrition) is only of endogenous origin: deranged absorption of proteins and vitamins (in grave chronic diseases of the gastro-intestinal tract, in patients with total resection of the stomach, resection of the intestine, chronic pancreatitis, and in another cases). Toxic cirrhosis of the liver arises in repeated and chronic exposure to carbon tetrachloride, compounds of phosphorus or arsenic, in poisoning (inedible mushrooms, seeds of heliotrope). Toxico-allergic cirrhosis of the liver includes also affections connected with hypersensitivity (autoallergy) to various drugs (aminazine, chloroform, some antibiotics, sulpha preparations, etc); hypersensitivity can cause dystrophy and necrosis of the liver parenchyma.
Obturation of intra- and extrahepatic bile ducts and their inflammation use congestion of bile and cholestasis, and are important factors in the delopment of biliary cirrhosis.
The aetiological factor does not always determine the way of development of liver cirrhosis. One and the same factor can cause various morphological variants of cirrhosis (portal, postnecrotic, and biliary); at the same time various aetiological factors can cause similar morphological changes.
Pathogenesis. The pathogenesis of liver cirrhosis is closely connected with morphogenesis. The greatest importance in the developmental mechanism of liver cirrhosis belongs to recurrent necrosis of the liver cells which is provoked by aetiological factors and cause collapse of the reticular framework of the liver, formation of cicatrices, and derangement of circulation in the adjacent portions of the preserved liver parenchyma. Intact hepatocytes or lobe fragments begin their intense regeneration under the effect of growth stimulants supplied from the necrotic focus. The formed large nodes of regenerated tissue compress the surrounding tissue with the invested vessels; the hepatic veins are compressed especially strongly. The blood outflow becomes upset to provoke portal hypertension and formation of anastomoses between the branches of the portal and hepatic veins that facilitate intrahepatic circulation. Blood now bypasses the liver parenchyma to impair drastically its blood supply, to cause new ischaemic necroses, and to stimulate the progress of cirrhosis even in the absence of the primary aetiological factor. Collagenous connective tissue grows intensively, connective tissue partitions (septa) grow into the parenchyma from the periportal fields to cause fragmentation of the liver lobules. These false lobules can later become the source of nodular regeneration. Chronic direct exposure to certain toxic hepatotropic substances, and also autoimmune and some other mechanisms are important in the pathogenesis of certain forms of cirrhosis.
Pathological anatomy. Three main morphological variants of liver cirrhosis are distinguished: portal (septal), postnecrotic, and biliary.
Portal (septal) cirrhosis of the liver is usually the result of alimentary insufficiency and alcoholism; less frequently it is secondary to Botkin’s disease (virus hepatitis). Its development is underlain by formation of connective-tissue septa interconnecting periportal fields with the central zone of the lobule and causing its fragmentation. Macroscopically the liver may be enlarged or diminished. Small nodes of regenerated tissue, circumscribed by narrow septa of connective tissue, are distributed uniformly over the entire surface of the liver. The nodes are almost equal in size. The microscopic picture: marked fatty infiltration of the liber cells is observed in alimentary or alcoholic cirrhosis; these changes may be absent if cirrhosis that develops after virus hepatitis. “False bile ductules”, leucocyte infiltration, and compressed small veins are found in the stroma between the nodes of regenerated tissue.
Micronodular cirrhosis
Postnecrotic cirrhosis of the liver develops as a result of submassive and massive necrosis of the liver cells due to virus and (less frequently) toxic hepatitis. Macroscopic picture is characterized by irregular changes in the liver, which is usually diminished in size. Nodes of various form and size can be seen on the liver surface. Microscopy shows irregular nodes of regenerated tissue and intact portions of the parenchyma. Broad fields of collapsed collagenized stroma with closely running portal tracts, venules, and cell infiltrates can be found between the nodes of the regenerated tissue. Inflammatory infiltration is marked.
Micronodular cirrhosis
Biliary cirrhosis of the liver has two variants. Primary biliary cirrhosis (pericholangiolitic) arises after epidemic hepatitis or toxico-allergic action of some medicinal preparations. Its development is underlain by obstruction of fine intrahepatic bile ductules which accounts for bile congestion. Macroscopy: the liver is enlarged and consolidated and is dark-green or olive in colour; it is microgranular. Extrahepatic bile ducts are patent. Microscopy is characterized by the presence of intralobular and periportal cholestases. The periportal fields are broad, with fibrosis around proliferating cholangioles; intralobular fibrosis develops around intralobular cholangioles with dissociation of the liver cells and their groups. Secondary biliary cirrhosis arises as a result of prolonged obstruction of extrahepatic bile ducts by stones, tumour, etc. It provokes dilation of the bile ducts, development of cholangitis, and pericholangitis; cirrhosis of the liver develops if these changes progress.
In addition to the described variants of cirrhosis, they may also be mixed: morphological signs of other variants may join the main variant. Activity of cirrhosis is charactered by the presence of new dystrophic and regenerative processes in the parenchyma, intense inflammatory infiltrations in the stroma, proliferation of cholangioles, indistinct borders betweeodular parenchyma and internodular stroma. A neglected cirrhotic process is characterized by replacement of liver tissue by nodes of regenerated tissue, markedly pronounced portal hypertension, large quantity of vascular connective-tissue septa growing into the parenchyma (portohepatic anastomoses). According to the morphological picture, fine- and largenodular cirrhosis is distinguished. Mixed variants also occur.
Clinical picture. Portal cirrhosis of the liver occurs mostly between the ages of 40 and 60. The incidence in men is twice higher than in women. Postnecrotic and biliary cirrhosis of the liver develop in younger patients, mostly in women.
Clinical manifestations of liver cirrhosis depend on the degre of affection of the liver cells and the associated hepatic dysfunction and portal hypertension, on the stage of the disease (compensated or decompensated), and also on the activity of the process. The following symptoms of the disease are most characteristic of majority of patients with various forms of liver cirrhosis.
Pain in the region of the liver, in the epigastrium, or diffuse pain in the whole abdomen is usually dull and boring, intensifying after meals, especially after fatty food, ample drinking and physical exercise. Pain is usually associated with enlargement of the liver and distension of the capsule, or with necrotic foci located near the capsule, with perihepatic symptoms, and also concurrent inflammatory affections of the bile ducts.
Dyspepsia in the form of decreased appetite to complete anorexia, the feeling of heaviness in the epigastrium after meals, nausea, vomiting, meteorism and dyspeptic stools (especially after fatty meals) depend mainly on deranged secretion of bile and hence defective digestion. But they can also be associated with the attending dyskinesia of the bile ducts or alcoholic gastroenteritis.
Decreased work capacity, general weakness, fatigue and insomnia are often observed in cirrhosis of the liver. Fever is usually irregular and sometimes of the undulant type. It often attends postnecrotic cirrhosis of the liver and is explained by necrotic destruction of the liver cells. Marked fever is characteristic of the active period and infectious cirrhosis.
A haemorrhagic syndrome is observed in 50 per cent of patients with cirrhosis of the liver. Profuse bleeding from varicose veins of the oesophagus and the stomach can often be early signs of portal cirrhosis; they are caused by increased pressure in the veins of the oesophagus and the stomach. In other variants of cirrhosis nasal, gum, uterine and skin haemorrhages develop in marked decompensation. They depend on the decreased coagulability of blood due to liver dysfunction.
Signs of cirrhosis are as follows. Cachexia is especially characteristic of patients with portal cirrhosis of the liver. In long-standing disease the subcutaneous fat disappears along with atrophy of muscles, especially of the upper shoulder girdle. The appearance of such patients is quite specific: the face is very thin with grey or subicteric skin; the lips and the tongue are bright-red; the cheek bone region is affected by erythema; the extremities are thin and the abdomen is large (due to ascites, enlarged liver and spleen); the subcutaneous veins of the abdominal wall are dilated, the legs are oedematous. Malnutrition is usually associated with disordered digestion and assimilation of food, and impaired synthesis of proteins in the affected liver.
Jaundice (except the cases with biliary cirrhosis) is a sign of hepatocellular insufficiency associated with necrosis of the liver cells. The affected hepatocytes partly lose their capacity to capture bilirubin from blood and to bind it with glucuronic acid. Bilirubin excretion into bile is disordered as well. Free (indirect) and bound (direct) bilirubin of blood serum therefore also increases. Jaundice is usually characterized by partial decolouration of faeces and by the presence of bile in the duodenal contents. Jaundice is often attended by skin itching. Jaundice associated with biliary cirrhosis resembles obstructive jaundice; severe skin itching is observed. The intensity of jaundice varies from light subicteric to marked jaundice (depending on the degree of obstruction of the bile ducts). In prolonged obstruction of the extrahepatic duct the skin acquires a grecnish tint which depends on oxidation of bilirubin to biliverdin. Moreover, brown pigmentation of the skin may also be observed. It depends on accumulation of melanin.
“Minor” signs of cirrhosis can also be revealed during examination the patient. These signs are as follows:
– spider angiomata (they develop years before marked symptoms of the disease develop), their number increases and the colour intensifies during exacerbation of disease;
– erythema of the palms;
– Erythema of the palmsred lustrous lips, scarlet mucosa of the mouth, scarlet (lacquered) tongue;
– gynaecomastia (increased mammary glands) and other female sex characters developing in men (decreasing growth of hair on the face, chest, abdomen, and the head);
Gynaecomastia
Gynaecomastia in patient with liver cyrrhosis
– xanthomatous plaques on the skin (observed in patients with biliary cirrhosis of the liver);
– Hippocrates fingers with hyperaemic skin at the nail beds.
Inspection of the abdominal skin can reveal dilation of the veins that can be seen through the thinned skin of the abdominal wall (caput medusae). Collateral venous system can be seen on the chest as well. Haemorrhoidal veins are often dilated.
Ascites is the most characteristic sign of portal cirrhosis. Ascites may develop slowly and the abdomen grow to huge size; the patient develops dyspnoea. Oedema may develop; hydrothorax may also occur in some cases. In other variants of cirrhosis, ascites develops at later stages of disease.
Appearance of the abdomen in ascites
Ascites
Enlarged liver can be palpated in 50-75 per cent of patients with it cirrhosis. The enlargement can be insignificant, only determinable by pencussion, or considerable when the liver occupies the entire left part of the abdominal cavity. The liver is firm, the surface is sometimes irregular, the lower edge is sharp. Enlargement of the spleen is often attended by increased activity (hypersplenism).
Gynaecomastia
Contractura of falangies flexors
Laboratory findings. An active cirrhotic process is characterized anaemia, leucopenia, thrombocytopenia, and increased ESR. Anaemia can be due to hypersplenism and gastro-intestinal haemorrhage, hepatocellular insufficiency, and often increased haemolysis, which is accompanied by reticulocytosis of the peripheral blood.
The blood serum bilirubin content becomes considerable only in the final stage of the disease. At the same time, the affection of the excretory function of the cirrhotic liver can be assessed by the presence of the conjugated fraction of bilirubin (bound bilirubin). Its content increases iormal and increased total bilirubin. The free bilirubin content increases in the blood serum as a result of upset conjugation of bilirubin in the liver cells and haemolysis. The blood serum bilirubin content varies in biliary cirrhosis of the liver from 26 to 340 mkmol/l, mostly at the expense of bound bilirubin.
The presence of much urobilin in the urine indicates liver insufficiency. The amount of urobilin in the urine and stercobilin in the faeces decreases in the presence of pronounced jaundice when a small amount of bilirubin enters the intestine. Bilirubin is found in the urine of patients with jaundice.
The upset excretory function of the liver is manifested by retention of bromsulphthalein in the blood (during its intravenous administration) and also by radioisotopic hepatography and scanning of the liver.
Affection of liver cells is manifested by characteristic changes in the protein indices: decreased concentration of serum albumins and hypergammaglobulinaemia which in turn decreases the albumin-globulin coefficient. Activation of the inflammatory process in the liver involves an increase in the a2-globulins, while jaundice causes an increase in b-globulins. During remissions, all these changes become less pronounced. The blood level of lipids and cholesterol also increases considerably in the presence of biliary cirrhosis. A sensitive index of liver dysfunction is the decreased activity of cholinesterase. Transaminase activity increases in exacerbation of liver cirrhosis. Activity of alkaline phosphatase also increases in biliary cirrhosis.
The decreased prothrombin content (which is synthesized by the liver cells), increased antithrombin coaguiative activity and decreased total coagulative activity of plasma are important in the aetiology of haemorrhagic diathesis in liver cirrhosis.
Ultrasaund examination
Scanning image
Laparoscopy and especially biopsy of the liver help reveal intravital morphological signs of each variant of liver cirrhosis. Varicose veins of the oesophagus are revealed by X-rays.
It is not always possible to differentiate between all variants of liver cirrhosis from the data of clinical and instrumental methods of examination, nevertheless, by comparing the mentioned signs, one caotice that the symptoms of portal hypertension in portal cirrhosis of the liver are often revealed long before the functional insufficiency develops. Hepatic insufficiency only develops at a later stage of the disease. But in the presence of postnecrotic cirrhosis of the liver, the symptoms of hepatic insufficiency develop early. They largely determine the entire clinical picture of the disease. Chronic jaundice (obstructive type) prevails in the clinical picture of biliary cirrhosis along with satisfactory general condition of the patient, who suffers from skin itching, sometimes fever (associated with chills); the blood alkaline phosphatase and cholesterol content increases. Transcutaneous cholangiography is used to determine the cause of cholestasis. The procedure is done when indicated.
Complaints of patients with compensated liver cirrhosis are not serious. The disease is often revealed accidentally during examination (enlarged liver and spleen). Remissions may be long (measured by years). Decompensated active cirrhosis is characterized by marked symptoms of the disease and rapid progressive course.
Course. The course of the disease is usually progressive. The overall term of the disease is usually 3 to 5 years; in rare cases the disease may last 10 years and even longer (usually in biliary cirrhosis of the liver).
The terminal period of the disease, irrespective of the form of cirrhosis, is characterized by gastro-intestinal haemorrhage and progressive signs of functional insufficiency of the liver, with finally developing coma. These are two most frequent direct causes of death of patients with liver cirrhosis. Gastro-intestinal haemorrhage (blood vomiting and melaena) is caused by the rupture of varicose nodes in the lower third of the oesophagus or, less frequently, in the stomach. A direct cause of varicose haemorrhage is physical strain or local affection of the mucosa (e.g. by coarse food). Profuse haemorrhage (if it does not cause death) can cause anaemia with subsequent impairment of the function of the liver cells and accelerated development of hepatic coma.
Treatment. Cirrhosis of the liver in the compensation stage is treated by preventing its further affection with alcohol, toxic substances, etc., and also by rational organization of work regimen and nutrition (high-calorie diet rich in protein and vitamins). During decompensation stage, hospital treatment is required. Glucocorticosteroid hormones are given in the active process (except cases complicated by dilation of the oesophageal veins); syrepar (hydrolysate of cattle liver), essential (a complex preparation containing essential phospholipids), and vitamins are also prescribed. Patients with ascites are prescribed a diet restricted in salt and diuretics (periodically). If ascites cannot be cured by diuretics, the fluid is released by paracentesis.
In order to decrease the lipid content of the serum in primary biliary cirrhosis, lipoic acid preparations are prescribed. Skin itching is removed by cholestyramine(preparation binding fatty acids). Surgical treatment is indicated in cases with secondary biliary cirrhosis of the liver, e.g. in obstruction of the bile duct by a stone.
