approach to patient with liver disease

APPROACH TO  PATIENT WITH LIVER DISEASE The many causes of liver disease present clinically in a few distinct patterns either a)        Hepatocellular diseases-Features of injury, inflammation and necrosis. b)       Cholestatic (obstructive)-Feature of obstruction of bile flow predominate. -Typical presenting symptoms of liver disease include     -Jaundice     -Generalized Fatigue     -Itching     -Right upper quadrant pain,     -Abdominal distention     -Intestinal bleeding. -However, some patients with liver disease are found to have abnormalities in biochemical liver tests as a part of a routine biochemical tests. Evaluation of patients with liver disease should be directed at (1) Establishing the etiologic diagnosis Hepatocellular versus cholestatic injury, as well as on the specific etiologic diagnosis (2) Estimating the disease severity (grading) Assessing the severity or activity of disease-active or inactive, and mild, moderate, or severe. (3) Establishing the disease stage (staging). Estimating the place in the course of the natural history of the disease, whether acute or chronic; early or late; pre-cirrhotic, cirrhotic, or end-stage. CLINICAL HISTORY -Follow symptoms of liver disease ü  Their nature ü  pattern of onset ü  progression - Liver-specific symptoms of jaundice, dark urine, light stools, itching, abdominal pain, and bloating. -Itching occur early in obstructive jaundice (from biliary obstruction or drug-induced cholestasis) Itching also occurs in chronic liver diseases, typically the cholestatic forms such as primary biliary cirrhosis and sclerosing cholangitis where it is often the presenting symptom, occurring before the onset of jaundice. -RUQ pain or ache ("liver pain") occurs in many liver diseases and is usually marked by tenderness over the liver area. -The pain arises from stretching or irritation of Glisson's capsule, which surrounds the liver. -Severe pain is most typical of gall bladder disease, liver abscess, and severe venoocclusive disease but is an occasional accompaniment of acute hepatitis. -Jaundice is the hallmark symptom of liver disease. Patients usually report darkening of the urine before they notice scleral icterus. Rarely detectable with a bilirubin level less than 51 umol/L. With severe cholestasis there will also be lightening of the color of the stools and steatorrhea. Jaundice without dark urine usually indicates indirect (unconjugated) hyperbilirubinemia and is typical of hemolytic anemia eg malaria and sickle cell and the genetic disorders of bilirubin conjugation eg Gilbert's syndrome, Crigler-Najjar syndrome.. Symptoms suggestive of complications of stage of liver disease: ü  Haematemesis-varices or portal HTN ü  Hemoptysis-chronic heart failure and cardiac cirrhosis. ü  Any other bleeding diasthesis-liver failure. ü  Swelling of legs-low albumin. ü  Abnormal behaviour, confusion or drowsiness PHYSICAL EXAMINATION -In many patients, the physical examination is normal unless the disease is acute or severe and advanced. -The physical examination can reveal signs that point to a specific diagnosis, either in risk factors or in associated diseases. -Typical physical findings in liver disease -General condition -The patient may be wasted because of chronic illness, confused-encephalopathy, dehydrated etc Hands-6 items -Leuconychia-chronic liver disease with hypoalbuminaemia -Finger clubbing -Asterexis -Dupytrens contracture -Palmar erythema -Palmar parlor Others general exam -Spider angiomata -Excoriations -Jaundice -Gynecomastia, scrotal atrophy, parotid enlargement -Edema -Hepatic fetor   Per Abdomen -Prominent veins over the abdomen, and caput medusa -Ascites -Hepatomegaly- Careful assessment of the liver edge may also demonstrate unusual firmness, irregularity of the surface, or frank nodules. -Hepatic tenderness -Splenomegaly -Pulsatile liver-Chronic CCF with Tricuspid regurgitation. -Hepatic bruit-hepatoma, hepatic hemangioma Signs of advanced disease include -Dilated abdominal veins -Asterixis -Mental confusion -Stupor or Coma. A helpful measure of hepatic encephalopathy is a careful mental status examination and use of the trail-making test, which consists of a series of 25 numbered circles that the patient is asked to connect as rapidly as possible using a pencil. The normal range for the connect-the-dot test is 15 to 30 s; it is considerably delayed in patients with early hepatic encephalopathy. INVESTIAGTIONS 1. FHG- Anaemia of chronic illness may be seen. Lymphocytosis-Viral hepatitis. 2. LFT -Liver parenchyma- ALT and AST) -Cholestasis-alkaline phosphatase, γ-glutamyl transpeptidase (GGT) to define whether alkaline phosphatase elevations are due to liver disease -Direct and total serum bilirubin -Synthetic Function of the liver-albumin and prothrombin time. 3.Viral hepatitis serology to define the type of viral hepatitis-Commonly HBV and HBV plus HIV ELISA Hepatitis B Acute- HBsAg and anti-HBc IgM Chronic- HBsAg and HBeAg and/or HBV DNA Hepatitis C Anti-HCV IgG HCV RNA Other hepatitis HAV- Anti HAV IgM HDV- HBsAg and anti-HDV HEV-Anti-HEV IgM 4.RFT’s esp those presenting with ascitis 5.Autoimmune markers –If indicated -Primary biliary cirrhosis (antimitochondrial antibody; AMA, elevated IgM levels, and compatible histology -Sclerosing cholangitis (peripheral antineutrophil cytoplasmic antibody; P-ANCA), cholangiography -Autoimmune hepatitis – ANA-antinuclear antibodies; SMA-smooth-muscle antibody, elevated IgG levels, and compatible histology 6.Familial liver diseases i)α1 Antitrypsin disease- Reduced α1 antitrypsin levels, phenotypes PiZZ or PiSZ ii) Wilsons disease-Decreased serum ceruloplasmin and increased urinary copper; increased hepatic copper level iii) Haemachromatosis-Elevated iron saturation and serum ferritin; genetic testing for HFE gene mutations 7.Tumour markers Elevated α-fetoprotein level >500; ultrasound or CT image of mass  Staging of Liver disease Reliable staging system is the modified Child-Pugh classification with a scoring system of 5 to 15: §  scores of 5 and 6 being Child-Pugh class A (consistent with “compensated cirrhosis”), §  scores of 7 to 9 indicating class B §  10 to 15 class C -This scoring system was initially devised to stratify patients into risk groups prior to undergoing portal decompressive surgery. -The Child-Pugh score is a reasonably reliable predictor of survival in many liver diseases and predicts the likelihood of major complications of cirrhosis such as bleeding from varices and spontaneous bacterial peritonitis. -It was used to assess prognosis in cirrhosis and to provide the standard criteria for listing for liver transplantation (Child-Pugh class B). Child Pugh Classification Factor         1 2 3 Serum bilirubin   µmol/L   <34 34–51 >51 Serum albumin  g/L   >35 30–35 <30 Prothrombin time INR <1.7 1.7–2.3 >2.3 Ascites None Easily controlled Poorly controlled Hepatic encephalopathy None Minimal Advanced Long term follow up for liver disease patients 1.Abstinence from alcohol should be encouraged for all patients with alcohol-related liver disease and in patients with cirrhosis and those receiving interferon-based therapy for hepatitis B or C. 2.Regarding vaccinations, all patients with liver disease should receive hepatitis A vaccine and those with risk factors should receive hepatitis B vaccination as well. Influenza and pneumococcal vaccination should also be encouraged. 3. Patients with liver disease should be careful in use of any medications, other than the most necessary. Drug-induced hepatotoxicity can mimic many forms of liver disease and can cause exacerbations of chronic hepatitis and cirrhosis; drugs should be suspected in any situation where the cause of exacerbation is unknown. 4. Surveillance for complications of chronic liver disease such as variceal hemorrhage and hepatocellular carcinoma. Upper endoscopy to assess the presence of varices and should be given chronic therapy with beta blockers if large varices are found. Patients with cirrhosis also screening and long-term surveillance for development of hepatocellular carcinoma. Eg  US of the liver at 6- to 12-month intervals

Constitutional symptoms such as fatigue, weakness, nausea, poor appetite, and malaise. Nausea - may accompany fatigue or be provoked by odors of food or eating fatty foods. Vomiting -rarely persistent or prominent. Anorexia with weight loss occurs commonly in acute liver diseases but is rare in chronic disease, except when cirrhosis is present and advanced.  Diarrhea -uncommon in liver disease, except with severe jaundice, with malabsorption leading to steatorrhea. -Major risk factors for liver disease ü  Detailed history of alcohol use- more than two drinks (22 to 30 g) per day in women and three drinks (33 to 45 g) in men. Increased risk. Most patients with alcoholic cirrhosis have a much higher daily intake and have drunk excessively for 10 years or more before onset of liver disease. ü  Previous history of yellowness of eyes-viral hepatitis, aflatoxicosis. ü  Medications (including herbal compounds, birth control pills, and over-the-counter medications). ü  History of pulmonary TB treatment or chronic cough-Dessimnated TB .Also adverse effects of anti-TB. ü  Sexual History- For assessing the risk of viral hepatitis should include life-time number of sexual partners. Sexual exposure is a common mode of spread of hepatitis B but is rare for hepatitis C ü  Methods of grain storage and history of other family members having similar symptoms. ü  Exposure to jaundiced or other high-risk persons ü  A history of injection drug use, even in the remote past, is of great importance in assessing the risk for hepatitis B and C. Injection drug use is now the single most common risk factor for hepatitis C. ü  Recent surgery ü  Remote or recent transfusion with blood and blood products .Transfusion with blood or blood products is no longer an important risk factor for acute viral hepatitis. However, blood transfusions received before the introduction of sensitive enzyme immunoassays for antibody to hepatitis C virus (anti-HCV) in 1992 is an important risk factor for chronic hepatitis C. Blood transfusion before 1986, when screening for antibody to hepatitis B core antigen (anti-HBc) was introduced, is also a risk factor for hepatitis B ü  Occupation-schistosomiasis, chemical exposure ü  Accidental exposure to blood or needlestick ü   familial history of liver disease -Wilson's disease; hemochromatosis and a1-antitrypsin (a1AT) deficiency ü  Suggestive of heart failure-orthopnea , paroxysmal nocturnal dysnea-Cardiac cirrhosis -Spider angiomata and palmar erythema occur in both acute and chronic liver disease and may be especially prominent in persons with cirrhosis, during pregnancy. -Spider angiomata are superficial, tortuous arterioles and, unlike simple telangiectases, typically fill from the center outwards. -Occur arms, face, and upper torso; they can be pulsatile and may be difficult to detect in dark-skinned individuals. -Hepatic failure is defined as the occurrence of signs or symptoms of hepatic encephalopathy in a person with severe acute or chronic liver disease. -The first signs of hepatic encephalopathy can be subtle and nonspecific-change in sleep patterns, change in personality, irritability, and mental dullness. Thereafter, confusion, disorientation, stupor, and eventually coma supervene. Physical findings include asterixis and flapping tremors of the body and tongue. -Fetor hepaticus refers to the slightly sweet, ammoniacal odor that is common in patients with liver failure, particularly if there is portal-venous shunting of blood around the liver. -Other causes of coma and confusion should be excluded, mainly electrolyte imbalances, sedative use, and renal or respiratory failure. -Widened pulse pressure and signs of a hyper dynamic circulation can occur in patients with cirrhosis as a result of fluid and sodium retention, increased cardiac output, and reduced peripheral resistance. -Patients with long-standing cirrhosis are prone to develop the hepatopulmonary syndrome with hypoxemia due to pulmonary arteriovenous shunting, characterized by hypoxia that worsens when lying flat. Several skin disorders and changes occur commonly in liver disease. -Hyper pigmentation -chronic cholestatic diseases such as primary biliary cirrhosis and sclerosing cholangitis. -Xanthelasma and tendon xanthomata occur as a result of retention and high serum levels of lipids and cholesterol. A slate-gray pigmentation to the skin also occurs with hemochromatosis if iron levels are high for a prolonged period. -Mucocutaneous vasculitis with palpable purpura, especially on the lower extremities, is typical of cryoglobulinemia of chronic hepatitis C but can also occur in chronic hepatitis B. -Some physical signs point to specific liver diseases. Kayser-Fleischer rings occur in Wilson's disease and consist of a golden-brown copper pigment deposited at the periphery of the cornea; they are best seen by slit-lamp examination.  DIAGNOSTIC IMAGING 1. Ultrasonography-have a high sensitivity for detecting biliary duct dilatation and are the first-line options for investigating the patient with suspected obstructive jaundice. 2. (CT-scan) 3. (MRI) CT and MRI are indicated for the identification and evaluation of hepatic masses, staging of liver tumors, and preoperative assessment. 4.. Magnetic resonance cholangiopancreatography (MRCP 5.ERCP -(MRCP) and (ERCP) are the procedures of choice for visualization of the biliary tree. -MRCP offers several advantages over ERCP; there is no need for contrast media or ionizing radiation, images can be acquired faster, it is less operator dependent, and it carries no risk of pancreatitis. -MRCP is superior to US and CT for detecting choledocholithiasis but less specific. -It is useful in the diagnosis of bile duct obstruction and congenital biliary abnormalities, but ERCP is more valuable in evaluating ampullary lesions and primary sclerosing cholangitis. -ERCP allows for biopsy, direct visualization of the ampulla and common bile duct, and intraductal ultrasonography. -It also provides several therapeutic options in patients with obstructive jaundice, such as sphincterotomy, stone extraction, and placement of nasobiliary catheters and biliary stents. -Doppler US and MRI are used to assess hepatic vasculature and hemodynamics and to monitor surgically or radiologically placed vascular shunts such as transjugular intrahepatic portosystemic shunts (TIPS). - Finally, interventional radiologic techniques allow the biopsy of solitary lesions, insertion of drains into hepatic abscesses, and creation of vascular shunts in patients with portal hypertension.  Liver biopsy Check preparation and the performance of liver biopsy

OSTEOARTHRITIS Definition: Chronic joint disease characterized by progressive deterioration of a joint in which localized loss of cartilage occurs in association with §  Subchondral sclerosis §  cyst formation §  osteophytosis §  capsular and synovial thickening. It is a dynamic condition, characterized by both reparative and degradative processes of the joint cartilage and bone. Classification Primary - No obvious cause found for the changes. Secondary - This is as a result of increased stress, weakened cartilage or abnormal support of cartilage e.g. avascular necrosis 1.Genetic or developmental §  Congenital hip dislocation §  Slipped upper femoral epiphysis §  Chondrodysplasia §  Perthe's disease §  Genu valgum or varum §  Haemophilia 2.Metabolic §  Calcium pyrophosphate dehydrate Arthropathy §  Alkaptonuria §  Hyperuricaemia §  Gaucher's disease 3.Endocrine §  Hypo/Hyperthyroidism §  Acromegaly §  Diabetes mellitus 4. Inflammatory Disorders §  Rheumatoid Arthritis §  Ankylosing spondylitis §  Psoriatic arthritis §  Septic arthritis 5.Trauma §  Fracture (particularly osteochondral fractures) §  Joint instability (e.g. cruciate ligament injury, joint hypermobility syndromes) §  Post meniscectomy §  Osteochondritis dissecans §  Neuropathic joints (Charcot joints) §  Mechanical causes including leg length discrepancy, instability, repetitive (occupational) injuries Age:  Usually old people are affected, but in situations where there are predisposing factors, even younger people are affected. Sex Until middle age, osteoarthritis occurs with the same frequency in men and women, but after the age of  50 symptomatic osteoarthritis is more common in women, and this difference in prevalence widens with increasing age. Most affected joints: Weight bearing joints especially Hips, Knees and Spine.  However any joint can develop OA such as is seen in ankles, elbows, wrists, hallux rigidus, etc. In the hip some changes such as protrucio acetabulare may accompany the osteoarthritic changes necessitating early action. Clinical features: History i) Pain -pain on motion and later also at rest ii) Stiffness morning stiffness that lasts less than 30 minutes stiffness after periods of inactivity during the day, or so-called gelling iii) Swelling + Heberden’s nodes at the distal inetrphalangeal joints and bouchard  nodules in the proximal interphalangeal joints iv) Deformity of the joints. In the hands tends to have a radial deviation deformation ( RA-ulnar deviation.) v) Loss of function. On Examination:  1)  Limited movement with crepitus- -due to incongruity of joint surfaces, muscle or capsular contracture, or mechanical block from osteophytes or loose bodies  2)  Tenderness on active/ passive motion and crepitus, a crackling sound or sensation as the joint is moved, are common findings. 3. Usually absence of signs of acute inflammation, effusion if present is minimal. 4)  Joint enlargement may result from proliferative synovitis, an increase in synovial fluid, or osteophyte formation. 5)   Deformity-genu varus or genu valgus may be observed in the knee involvement. Heberden's nodes are characterized by bony enlargement of the dorsolateral and dorsomedial aspects of the distal interphalangeal joints of the fingers. Flexor and lateral deviation of the distal phalanx are common. Similar nodes at the proximal interphalangeal joints are known as Bouchard's nodes. Investigations: 1.X rays:  Plain xrays are diagnostic in most cases, seen are:- The Kellgren Grading System uses the following 4 radiographic features: a)Joint space narrowing b) Osteophytes c) Subchondral sclerosis d) Subchondral cysts e) subluxation of joint in severe cases 2) Haemogram Usually contributes little to diagnosis.  3)↑ CRP 4)Radionuclide scanning (99mTc) - shows increased activity during the bone phase in the subchondral regions of the affected joints. This is due to increased vascularity & new bone formation.  Differential diagnosis: 1)  Chronic infections. 2)  ANFH 3)  Rheumatoid arthritis 4)  Psoriatic Arthritis. 5)  Gout and pseudogout 6)  Diffuse idiopathic skeletal hyperostosis 7) Patellofemoral Syndrome 8) Prepatellar Bursitis Management of Osteoarthritis:                 1)  History                 2)  Examination                 3) Investigations                 4)  Treatment

NB Anybody living long enough is likely to get OA of one joint or another.  In some situations presence of osteophytes although indicative of OA change is not necessarily a disease requiring treatment e.g. OA in Spine. Predisposing factors 1.        Age 2.        Genetic 3.        Hormonal 4.        Local mechanical stresses 5.        Pre-existing joint disease. 6.        Trauma Cause of Osteoarthritis  Disparity between stresses applied to articular cartilage and the ability of the cartilage to stand the stress. 1)Stress   Load per unit urea.  i.e .Load/Area =   Stress So disparity can occur as a result of increased load or decreased area. Both factors common in Osteoarthritis of the knee, and probably spine. 2. Weak Cartilage: Due to age. Knee joint with Osteoarthritis 3. Abnormal Subchondral Support:  Examples in ANFH. Pathogenesis: -This is thought to be as a result of intrinsic disturbances in the metabolism of cartilage which leads to increase in water content of the cartilage & easier extractability of the matrix proteoglycans which leads to chondrocyte damage & cartilage deformation. -Pathological changes occur in the articular cartilage of synovial joints, synovial fluid, as well as in the underlying (subchondral) bone and overlying joint capsule. -The affected cartilage initially develops small tears known as fibrillations, then larger tears, and eventually it fragments off into joints. -Chondrocytes replicate in an attempt to keep up with the cartilage loss; but are unable to, and the underlying bone is left denuded.  -Bone along the periphery of the joint replicates to form osteophytes, while the subchondral bone along the mid portion of the joint becomes sclerotic, and areas within it eventually may undergo cystic degeneration. -Complex chemical changes leading to: ·         Water content of cartilage increases. ·         Loss of matrix proteoglycans. ·         Cartilage softens. ·         Chondrocytes are damaged. ·         Collagen network damaged. -With loss of cartilage integrity the stress normally borne by cartilage is passed over to bone.  This it cannot stand. Bone crumbles, cysts form in the subchondral bone. -The osteoarthritic joint is characterized by decreased concentration of hyaluronic acid because of reduced production by synoviocytes and increased water content as a result of inflammation Pathology of Osteoarthritis: 1)       Progressive cartilage destruction 2)       Subarticular cysts formation. 3)       Sclerosis of surrounding bone. 4)       Osteophyte formation. 5)        Capsular fibrosis. Treatment: Early: 1)Relief of pain NSAIDS These play major role. Problems: How long should they be given, Dyspepsia Affordability 2)   Increase movement -physiotherapy and several short periods of walking, interspersed with rest periods, are preferable to sustained walking for the patient with osteoarthritis of the hip or the knee. Strenuous exercises and stair climbing should be avoided whenever possible. 3)   Reduce load - Use of walking aids -Wedged insoles that change the angle of the legs - Shock-absorbing footwear that reduces impact - Heel lift if one leg is shorter than the other. -Weight reduction in obese patients 4)   Correction of predisposing factors if possible. Specific exercise programs designed to preserve or to improve the range of motion and to strengthen periarticular muscles frequently result in significant pain relief and improvement in such parameters as strength, endurance, speed, and joint stability. Late  1)  Analgesics and NSAIDs 2)  Physiotherapy Surgical interventions 1.Arthroscopic lavage - Using a saline lavage to wash out the joint 2.Joint realignment (realignment osteotomy) 3.Joint fusion (arthrodesis) - Surgically fusing the joint to eliminate motion 4Joint replacement (arthroplasty NB.Charcot Joints Neuropathic arthropathy 2° to loss of sensation associated with certain chronic disorders. The joint disease is usually progressive, with insidious swelling and instability of a single joint. Although said to be painless, Charcot's joints may be painful, but not in proportion to the joint destruction. Causes (affected joint); ·         Peripheral neuropathy ·         Diabetes (tarsal and metatarsal, ankle) ·         Tertiary syphilis ·         Leprosy ·         Tabes dorsalis (the vertebrae, hips, knees, & ankles) ·         Syringomyelia (Shoulder or elbow) ·         Myelomeningocele ·         Amyloid neropathy ·         Subacute combined degeneration of the spinal cord