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FINALSEAZY HEPATOLOGY Presented by Becky LeveridgeHepatology Paracetamol overdose Cirrhosis Portal Hypertension (Ascites) Hepatic Encephalopathy Spontaneous Bacterial Peritonitis Jaundice Autoimmune Liver Diseases Hepatocellular Carcinoma Hepatitis Post-Lecture notesPARACETAMOL OVERDOSE Question 1 A IgA deficiency A 17-year-old male presents to the emergency department after taking a staggered overdose of paracetamol. She is commenced on N-acetylcysteine but quickly develops B IgE medicated mast cell release shortness of breath. C IgG immune complex formation The following observations are obtained: RR: 33 D Non-IgE mediated mast cell release Sats: 88% BP: 112/72 HR: 104 E IgM immune complex formation Temp: 37.1 What is the most likely underlying cause of her reaction? ≈2% excreted naturally in urine PARACETAMOL OVERDOSE SULFATION & CYP450 GLUCURONIDATION (≈8%) (≈90%) Non-toxic NAPQI metabolites GLUTHATHIONE NO GLUTHATHIONE EXCRETED IN URINE Conjugated NAPQI Unconjugated NAPQI (hepatotoxic) EXCRETED IN URINE N-acetylcysteine Question 2 A Give activated charcoal Measure paracetamol levels in 2 An 18-year-old male presents to the emergency B hours department 2 hours after consuming 40 tablets of paracetamol all at once. C Give Flumazenil He is nauseous and has vomited multiple times. D Give IV bicarbonate What is the most appropriate next step? E Give N-acetylcysteine immediately PARACETAMOL OVERDOSE STAGGERED OVERDOSE/ DOUBT OVER TIME OF INGESTION = ABCDE ASSESSMENT GIVE NAC IMMEDIATELLY PRESENTS < 1 HOUR ACTIVATED CHARCOAL POST INGESTION 8-24 >24 1-4 HOURS 4-8 HOURS HOURS HOURS MEASURE SERUM MEASURE SERUM > 150 mg/Kg MEASURE SERUM PARACETAMOL PARACETAMOL PARACETAMOL 4 HOURS POST INGESTION IMMEDIATELY even if IMMEDIATELY paracetamol concentration not available IS THE PATIENT IS IF ABOVE TREATMENT LINE JAUNDICED / HEPATIC ON NOMOGRAM GIVE IV TENDERNESS / ALT ABOVE N-ACETYLCYSTEINE UPPER LIMIT? (NAC)PARACETAMOL NORMOGRAM 120 110 Treatment line 100 90 80 Plasma- paracetamol 70 If the blood paracetamol concentration falls on or above the line concentration 60 (mg/litre) the patient will need to receive treatment with NAC 50 40 30 20 10 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Time (hours) • Arterial pH < 7.3, 24 hours after ingestion Or all of the following: King’s College • INR > 6.5 Hospital criteria for liver transplantation (Paracetamol Liver Failure) • Creatinine > 300umol/L • Grade III or IV encephalopathyCIRRHOSIS Liver Disease Irreversible ALCOHOL remodelling of the Liver due to Fibrosis METABOLIC HEPATITIS CAUSES INFLAMMATORY CAUSES IRREVERSIBLE STEATOSIS CHRONIC LIVER CIRRHOSIS DISEASE VASCULAR CAUSES MEDICATIONS FIBROSIS HEPATOCELLULAR CARCINOMA CRYPTOGENIC ALCOHOLIC HEP ATIITS PATHOPHYSIOLOGY CLINICAL FEATURES • Jaundice • Alcohol-mediated liver inflammation and • Fever dysfunction • Anorexia • Tender hepatomegaly (RUQ pain) • Severe alcoholic hepatitis (SAH) = high short-term mortality • Features of chronic liver disease • Alcohol withdrawal symptoms e.g. tremors DIAGNOSIS TREATMENT • Exclude other causes of hepatitis (non-invasive liver screen) • Supportive care • AST/ALT ratio > 2:1 • Corticosteroids • ↑GGT • ↑ INRirubin • Early liver transplantation in SAH • Liver biopsy • Minimum abstinence period • Mallory-Denk bodies CHILD-PUGH SCORE FOR CIRRHOSIS 1 point 2 points 3 points Albumin >35 28–35 <28 Bilirubin <34 34–50 >50 Clotting (PT) <4.0 4.0–6.0 >6.0 Distension (ascites) None Mild Moderate – Severe Encephalopathy None Grade I-III Grade III-IV Class A > 5-6, mild disease, one year survival 100% Class B > 7-9, moderate disease, one year survival 81% Class C > 10-15, severe disease, one year survival 45%PORTAL HYPERTENSION (Ascites) Post-Hepatic: H e - Budd-Chiari Syndrome a - Right sided heart failure c - Constrictive pericarditis e n PORTAL SALT & WATER Hepatic: HYPERTENSION RETENTION - Liver Cirrhosis o a v n Prehepatic: ASCITES - Portal vein thrombosis - Splenic vein thrombosis SERUM ASCITES-ALBUMIN GRADIENT (SAAG) = serum albumin (g/dL) - ascitic fluid albumin (g/dL) ↑ ↓ SAAG (<1.1 g/dL) SAAG (>1.1 g/dL) = ↑ Serum albumin - ↓ Ascites Albumin = serum albumin - ascitic fluid albumin ↑ Capillary hydrostatic pressure ↑ Capillary permeability / ↓ Oncotic pressure BLOOD PERITONEAL CAVITY WATER (Transudate) WATER + ALBUMIN (Exudate) NEPHROTIC SYNDROME PANCREATITIS LIVER CIRHOSSIS RIGHT HEART FAILURE HEPATIC MALIGNANCY PERITONEAL CARCINOMATOSIS TUBERCULOSIS ASCITES MANAGEMENT SALT & FLUID PARACENTESIS DIURETICS TIPS RESTRICTION Diagnostic paracentesis is Daily salt intake of no Spironolactone 1 line For refractory ascites recommended in all patients more than 5 – 6.5 g with new-onset ascites Can be combined with furosemide (Long-termmanagement) Serial paracentesis to remove large volume ascites if refractory to medical therapy Question 3 A Subcutaneous unfractioned heparin A 57-year-old man presents to the emergency department with lethargy. He has a past medical history of cirrhosis due to hepatitis C. B Oral ciprofloxacin On examination, he has asterixis, pretibial oedema and C IV 0.9% NaCl shifting dullness. It is estimated that there is 8 litres of ascitic fluid within D IV human albumin solution the patient's abdominal cavity. Therefore, a large volume paracentesis with an ascitic drain is planned. E Subcutaneous LMWH What must be prescribed before performing this procedure to reduce mortality risk? ASCITES MANAGEMENT SALT & FLUID PARACENTESIS DIURETICS TIPS RESTRICTION Diagnostic paracentesis is Daily salt intake of no Spironolactone 1 line For refractory ascites recommended in all patients more than 5 – 6.5 g with new-onset ascites Can be combined with furosemide (Long-termmanagement) Serial paracentesis to remove large volume ascites if refractory to medical therapy Question 4 A Liver transplant A 47 year old male presents to the emergency department with yellowing sclera and malaise. He has a past medical history of liver cirrhosis. B Broad Spectrum IV antibiotics Examination revealed an enlarged mass on the right C Spironolactone upper quadrant and a severely distended abdomen with shifting dullness. D Chest X-ray A diagnostic paracentesis shows a E Therapeutic paracentesis 3 polymorphonuclear count of 88/mm , total protein of 1.4g/dL, and albumin of 0.9 g/dL. What is the most appropriate next step in this patient? ASCITES MANAGEMENT SALT & FLUID PARACENTESIS DIURETICS TIPS RESTRICTION Diagnostic paracentesis is Daily salt intake of no Spironolactone 1 line For refractory ascites recommended in all patients more than 5 – 6.5 g with new-onset ascites Can be combined with furosemide (Long-termmanagement) Serial paracentesis to remove large volume ascites if refractory to medical therapyHEPATIC ENCEPHALOATHY Question 5 A Rifampicin An 42 year old female presents to SDEC with gross severe jaundice and ascites. B Lactulose She was first diagnosed with liver cirrhosis 3 years ago C Rifaximin and has been admitted with confusion and altered consciousness secondary to her cirrhosis 3 times since initial diagnosis. D N-acetylcysteine Given the most probable diagnosis, what medication E Octreotide would be most appropriate to prescribe? HEPATIC ENCEPHALOPATHY PATHOPHYSIOLOGY CLINICAL FEATURES • Cirrhosis → ↓ hepatic metabolism → accumulation of neurotoxic • Diurnal sleeping disturbance metabolites, especially ammonia → cerebral oedema and ↑ intracranial pressure →neurological symptoms • Asterixis >loss of motor control • Precipitated by situations of ↑ ammonia • Infections (e.g. spontaneous bacterial peritonitis) • Neurological disturbances • GI Bleeding • Hypovolemia (dehydration) • Inattention, impaired decision making • Metabolic alkalosis • Hypokalaemia • Disturbances in consciousness GRADING TREATMENT (Clinical diagnosis – Ammonia is not useful) 1. Changes in behaviour with minimal change in level of • Assess precipitating factors consciousness 2. Gross disorientation, drowsiness, asterixis, inappropriate • Clear neurotoxins behaviour 3. Marked confusion, incoherent speech, sleeping most of the time • Regular bowel movements but arousable to vocal stimuli 4. Comatose, unresponsive to pain; decorticate or decerebrate • Lactulose (1st line) posturing • Rifaximin (2 line)SPONTANEOUS BACTERIAL PERITONITIS Question 6 A Doxycycline A 57-year-old female has advanced liver cirrhosis and B Penicillin started to develop ascites. C Rifampicin A ascititc tap is performed and showed a protein concentration of 12 g/l but no evidence of any D Ciprofloxacin organisms. E Azithromycin What is the most appropriate management to reduce the risk of spontaneous bacterial peritonitis? SPONTANEOUS BACTERIAL PERITONTITIS PATHOPHYSIOLOGY CLINICAL FEATURES • Sudden peritonitis • Often no signs of peritonism • Infection of ascites, most commonly by Escherichia coli • Infection without a perforation of the bowel • Fever and chills • ‘Spontaneous’ ➔ source of infection is not known • Worsening ascites • Usually occurs in severe cirrhosis (Child-Pugh C) • New-onset/ worsening encephalopathy • Nausea/ vomiting DIAGNOSIS TREATMENT • Broad-spectrum IV antibiotics (Cefotaxime) until • Ascitic fluid white cell count ≥ 250/mm and predominantly sensitivities guide further treatment neutrophils • Ascites cultures ➔ often negative • Offer prophylactic oral ciprofloxacin or norfloxacin for people with cirrhosis and ascites with an ascitic protein of 15 g/litre or less until the ascites has resolvedJAUNDICE Prehepatic Hepatic Cholestatic • Hepatocellular damage, Bilirubin • Biliary obstruction • Overproduction of bilirubin due to excessive haemolysis • Increased unconjugated bilirubin reuptake disruption, Intra-hepatic • Increased Cholestasis • Increased unconjugated or conjugated bilirubin conjugated bilirubin ▪ Alcohol related liver disease ▪ NAFLD Biliary disease: Gallstones, Pancreatic ▪ Drug-induced liver injury cancer, Cholangiocarcinoma Haemolysis: Haemolytic anaemia, Thalassaemia, Malaria, Drugs – antimalarials ▪ Dubin-Johnson syndrome ▪ Hepatocellular carcinoma (HCC) Autoimmune: PBC,PSC ▪ Wilson’sdiseases ▪ Alpha-1 antitrypsin deficiency Drugs: Co-amoxiclav, flucloxacillin, ▪ Vascularliverdisease COCP Gilberts Syndrome • Most common inherited hyperbilirubinemia • Mild reduction of UDP-GT activity • ↑ Isolated unconjugated bilirubin Inherited Crigler–Najjar Syndrome Type I • Absent UDP-GT enzymes Hyperbilirubinaemia • ↑ unconjugated bilirubin • High risk of kernicterus Syndromes Dublin-Johnson Syndrome • Defective MRP 2→ impaired excretion of conjugated bilirubin from the hepatocytes into the bile ducts • ↑ conjugated bilirubin • Dark, granular pigmentation on liver biopsyAUTOIMMUNE LIVER DISEASES Question 7 A Budd-Chiari Syndrome A 43-year-old female presents to her GP with fever, jaundice and moderate hepatomegaly. B Primary sclerosing cholangitis Investigations confirm the following autoantibodies: C Autoimmune hepatitis type 1 Anti-smooth muscle: Positive Anti-nuclear: Positive D Primary biliary cirrhosis Antimitochondrial: Negative E Autoimmune hepatitis type 2 What is the most likely diagnosis? AUTOIMMUNE LIVER DISEASES AUTOIMMUNE HEPATITIS TYPE 1 PRIMARY BILIARY CHOLANGITIS PRIMARY SCLEROSING CHOLANGITIS EPIDEMIOLOGY FEMALES > MALES FEMALES >> MALES MALES > FEMALES RULE OF Ms: IgM, AMA, Middle aged female DESTRUCTION OF ONLY DESTRUCTION OF BOTH INTRAHEPATIC PATHOPHYSIOLOGY CHRONIC RELAPSING HEPATITIS INTRAHEPATIC BILE DUCTS BILE DUCTS & EXTRAHEPATIC BILE DUCTS INFLAMMATORY BOWEL DISEASE ASSOCIATIONS OTHER AUTOIMMUNE DISEASES OTHER AUTOIMMUNE DISEASES (Ulcerative colitis) CLINICAL FEATURES Often asymptomatic, fatigue, arthralgia, RUQ PRURITUS, fatigue, jaundice, often asymptomaticPruritus, fatigue, Charcot’s triad (cholangitis), pain, weight loss, nausea, amenorrhoea increases the risk of osteoporosis and osteopenia 10% develop Cholangiocarcinoma LIVER FUNCTION TESTS HEPATOCELLULAR PATTERN OF INJURY CHOLESTATIC PATTERN OF INJURY CHOLESTATIC PATTERN OF INJURY IMMUNOGLOBULINS IgG IgM AUTOANTIBODIES ANA,ASMA, ANTI-SLA/LP ANTI-MITOCHONDRIAL ANTIBODIES P-ANCA Hepatocellular LFTS, autoantibodies, Cholestatic LFTS + AMA positive + Abdominal USS DIAGNOSIS Liver biopsy +/- liver biopsy Cholestatic LFTS + MRCP (‘string of beads sign’) Prednisolone & Azathioprine UrsodeoxycholicAcid NOT Ursodeoxycholic acids TREATMENT Hepatitis A & Hepatitis B vaccination Prurit➔s Cholestyramine Pruritu➔ Cholestyramine End stage liver dise➔stransplantation Fat malabsorpti➔n Fat-soluble vitamins Fat malabsorpti➔n Fat-soluble vitamins End stage liver dis➔astransplantation End stage liver dis➔astransplantation Type 2 autoimmune hepatitis is characterized by LKM1 antibodies and affects children only.HEPATOCELLULAR CARCINOMA Question 8 A CEA A 67year-old male presents to the GP with a 7-month history of weight loss and progressive jaundice. B CA 19-9 For the last 12 years he has been drinking 55 units of alcohol a week. C AFP On examination he has a distended abdomen with D PSA shifting dullness. E ALT Which of the following blood tests would be most useful to aid diagnosis? HEPATOCELLULAR CARCINOMA PATHOPHYSIOLOGY CLINICAL FEATURES • Often asymptomatic • Picked up during surveillance • Primary malignancy of the liver, rare • Constitutional symptoms e.g. weight loss • Major complications of cirrhosis • RUQ pain, hepatomegaly, palpable mass • HCC can occur in chronic hepatitis B without cirrhosis • Paraneoplastic syndromes • Very poor prognosis • REMEMBER ➔ the most common malignant lesion of the • Hypoglycaemia liver is liver metastasis (NOT primary HCC) • Erythrocytosis • Hypercalcaemia • Stigmata of chronic liver disease DIAGNOSIS TREATMENT • ↑ serum alpha-fetoprotein (AFP) ▪ CONSERVATIVE: avoid alcohol, improve lifestyle • CT abdomen habits (diet & exercise) • Liver biopsy ▪ MEDICAL: Atezolizumab plus bevacizumab ,or • Often contraindicated due to risk of bleeding sorafenib, or lenvatinib • Patients with cirrhosis are offered HCC surveillance ▪ SURGICAL: resection, transplantation, thermal • Abdominal ultrasound every 6 months ablation, chemoembolisation. Tumour Markers MARKER TUMOUR ASSOCIATIONS HEPATOCELLULAR CARCINOMA YOLK SAC TUMOUR ALPHA-FETOPROTEIN (AFP) CANCER ANTIGEN 19-9 (CA 19-9) PANCREATIC CANCER CANCER ANTIGEN 125 (CA 125) OVARIAN CANCER CARCINOEMBRYONIC ANTIGEN (CEA) COLORECTAL CANCER PANCREATIC CANCER CANCER ANTIGEN 15-3 (CA 15-3) BREAST CANCER PSA (prostate specific antigen) PROSTATE CANCER HUMAN EPIDERMAL GROWTH FACTOR-2 (HER-2) BREAST CANCER OESOPHAGEAL CANCERHEP A TITIS 1) ALCOHOLIC HEPATITIS 2)AUTOIMMUNE HEPATITIS 3) VIRAL HEPATITIS HEP A TITIS HEPATITIS A HEPATITIS B HEPATITIS C HEPATITIS D HEPATITIS E (Linked to Hepatitis A) Non-enveloped RNA Virus Enveloped DNA virus Enveloped RNA virus Enveloped RNA virus Non-enveloped RNA virus VIRUS Bodily fluids Bodily fluids Faeco-oral (e.g. shellfish, ice) Bodily fluids Faeco-oral TRANSMISSION Infected blood Infected blood Infected blood Perinatald (Birthing) Travel Sexual contact IV drug use, tattooing Can ONLY be transmitted to Travel RISK FACTORS Drinking contaminated water Blood transfusions Blood transfusions patients infected with Drinking contaminated water IV drug use, tattooing Sexual contact (uncommon) hepatitis B virus Severe when co-infection Causes severe fulminant SEVERITY Mild (Asymptomatic) Sometimes severe Usually, subclinical with hepatitis B hepatitis in pregnant woman CLINICAL Fever, malaise, loss of appetite, RUQ pain, jaundice FEATURES NO YES YES (HIGH) YES NO CHRONICITY Acute hepatitis Chronic hepatitis Chronic hepatitis Cirrhosis LIVER Acute hepatitis Cirrhosis Hepatocellular carcinoma (Same as Hepatitis B) Acute hepatitis DISEASES Hepatocellular carcinoma Hepatitis B vaccine VACCINATION Vaccine available Vaccine available No vaccine available = Vaccine available in China HBIG -> certain situations Protective against HDV (Not UK) HBsAg INDICATES INFECTION INDICATES IMMUNITY Anti-HBs vaccination)lved infection or HEP A TITIS SEROLOGY HBeAg INDICATES INCREASED REPLICATION / INFECTIVITY INDICATES REDUCED REPLICATION / Anti-HBe INFECTIVITY Anti- INDICATES ACUTE HBc(IgM) INFECTION Anti- INDICATES CHRONIC INFECTION OR HBc(IgG) RESOLVED HEP A TITIS B SEROLOGY HEALTHY CHRONIC CHRONIC CURED DUE TO CURED DUE TO (no exposure or ACUTE INFECTION INFECTION PRIOR PRIOR vaccination) INFECTION (ACTIVE) INFECTION VACCINATION (INACTIVE) HBsAg ACTIVE = INACTIVE = HBeAg Anti-HBc(IgM) Anti-HBc(IgG) Anti-HBe Anti-HBsPLEASE FILL OUT THE FEEDBACK FORM PLEASE TUNE IN TO OUR REMAINING SESSIONS THIS WEEKPOST LECTURE NOTESLIVER DISEASES IN PREGNANCY Pregnancy Liver Diseases Acute Fatty Liver of Pregnancy Intrahepatic Cholestasis HELLP Syndrome • Most common pregnancy- • Life threatening, rare disease that usually • Severe complication of associated liver disease, occurs in the third trimester pregnancy that usually occurs usually occurs in third trimester • Extensive fatty infiltration of the liver > in the third trimester • Pruritus, jaundice acute liver failure • ↑ bile acids, ↑ ALP, ↑ ALT, ↑ • Pre-eclampsia, multiple gestations, • Occurs usually in patients with AST, ↑ conjugated bilirubin pre-eclampsia nulliparity are risk factors • RUQ pain, nausea, vomiting, • Ursodeoxycholic acid to • Jaundice, RUQ pain, coagulopathy, no signs of liver failure manage symptoms & reduce hypoalbuminaemia > ascites • Characterised by haemolysis, bile acids • Risk of disseminated intravascular • Increased risk of stillbirth coagulation, hypoglycaemia, high serum elevated liver enzymes & low • Bile acids ≥ 100 micromol/L ammonia platelets • Risk of rapid deterioration (e.g. consider delivery at 36 weeks • ↑ ALT, ↑ AST, ↑ bilirubin DIC, pulmonary oedema, AKI) gestations • Liver biopsy can confirm diagnosis but multi-organ failure • Bile acids < 100 micromol/L: should not be performed in pregnancy consider delivery at 36-39 • Requires immediate delivery (Only weeks gestation treatment)PANCREA TIC CANCER P ANCREATIC CANCER PATHOPHYSIOLOGY CLINICAL FEATURES • Painless obstructive jaundice • Primary pancreatic ductal adenocarcinoma • The adenocarcinoma most commonly occurs in • Yellow skin and sclera the head of the pancreas • Pale stools • Once a tumour in the head of the pancreas • Dark urine grows large enough it can compress the bile • Generalised itching ducts, resulting in obstructive jaundice. • Non-specific upper abdominal pain • Weight loss and anorexia DIAGNOSIS TREATMENT ▪ BEDSIDE: history & clinical examination ▪ CONSERVATIVE: smoking cessation, limit alcohol consumption ▪ BLOODS: FBC, U&E, LFTs, CA19-9 biomarker ▪ MEDICAL: chemotherapy (FOLFIRINOX: folinic ▪ IMAGING: pancreatic protocol CT, acid, fluorouracil, irinotecan, and oxaliplatin) abdominal ultrasound, MRCP ▪ SURGICAL: total pancreatectomy, distal pancreatectomy, the modified Whipple procedure (pylorus-preserving pancreaticoduodenectomy)HEREDITARY HAEMOCHROMA TOSIS HEREDITARY HAEMOCHROMATOSIS PATHOPHYSIOLOGY CLINICAL FEATURES • Often asymptomatic or non-specific (e.g. lethargy) • Autosomal recessive condition affecting iron metabolism • Symptomsonlypresentat the age of 40–60 • HFE gene defect ➔ ↑ intestinal iron absorption ➔ • Earlydisease –fatigue, abdominal pain, arthralgia and erectile dysfunction iron overload • Endocrine – diabetes mellitus, hypogonadism • Cardiac – arrhythmias, cardiomyopathy, heart failure • Iron commonly accumulates in liver, pancreas &heart, joints • Hepatic – hepatomegaly, cirrhosis, HCC • Symptoms usually start at 40-60 years old • MSK– bronzeskin, pseudogout • Delayed presentation in pre-menopausal woman • Neurological – mood disturbances, memory impairment • Delayed symptoms in pre-menopausal woman DIAGNOSIS TREATMENT • Iron studies • ↑ ferritin (1 step) • Reduce iron & vitamin C consumption • Phlebotomy ➔ 1 line treatment • ↑ transferrin • Desferrioxamine • ↑ serum iron • Used if phlebotomy contraindicated e.g. severe • Liver biopsy • Prussian blue stain shows iron overload anaemia • Genetic testingBUDD CHIARI SYNDROME BUDD-CHIARI SYNDROME PATHOPHYSIOLOGY CLINICAL FEATURES • Obstruction of hepatic venous outflow • Associated with hypercoagulable states • Abdominal pain • Myeloproliferative disorders e.g. PRV • Tender hepatomegaly • Malignancy • Oral contraceptives (COCP) • Ascites • Pregnancy • Risk of acute liver failure • Features of liver failure DIAGNOSIS TREATMENT • Ascitic fluid analysis > SAAG >1.1 • Thrombolysis • Lifelong anticoagulation • Abdominal ultrasound +/- Doppler • CT/MRI >Caudate lobe appears normal • Ascites management • Consider TIPSS & liver transplantWILSON’S DISEASE WILSON’S DISEASE PATHOPHYSIOLOGY CLINICAL FEATURES • Autosomal recessive disorder affecting copper • Features of liver failure metabolism • Kayser-Fleischer rings • ATP7B gene mutation on chromosome 13 • ↓ hepatic copper excretion • Dark-coloured rings around cornea • ↓ serum caeruloplasmin • Neurological disturbances • ↑ copper absorption from the small intestine • e.g. parkinsonism, tremors (no sensory • ↑ free serum copper ➔ accumulates in tissues symptoms) DIAGNOSIS TREATMENT • Copper studies • Avoid food with high copper content • ↓ serum caeruloplasmin • ↑ free serum copper • e.g. shellfish, nuts, organ meat • ↓ total serum copper • ↑ 24 hour urinary copper • Chelating agents • Slit-lamp examination • e.g. penicillamine • Genetic studiesREYES SYNDROME REYE’S SYNDROME PATHOPHYSIOLOGY CLINICAL FEATURES • Aspirin use in individuals < 19 years of age with a • Preceding viral infection febrile illness • Acute encephalopathy • Cerebral oedema >↑ ICP • Mitochondrial injury & inhibition of fatty acid oxidation • ↑ ammonia , metabolic acidosis, liver steatosis • Features of liver failure DIAGNOSIS TREATMENT • Supportive care • Clinical diagnosis • Rule out other causes • Decrease intracranial pressure • Liver biopsy • Correction of hypoglycemiaALPHA-1 ANTITRYPSIN DEFICIENCY ALPHA-1 ANTITYRPSIN DEFICIENCY PATHOPHYSIOLOGY CLINICAL FEATURES • Autosomal co-dominant disorder >defective production of • Respiratory symptoms (dyspnoea, wheeze) alpha 1-antitrypsin (A1AT) • Features of liver failure (not all patients) • Liver: accumulation of AAT in liver → hepatitis and cirrhosis • Should be suspected in children/young • Lungs: deficient AAT → uninhibited neutrophil elastase activity → panacinar emphysema adults with severe COPD DIAGNOSIS TREATMENT • Low serum A1AT (<10 μmol/L) • Supportive care • Spirometry & Chest X-ray • Smoking cessation • Liver biopsy > PAS positive globules • Treat respiratory disease • Genetic testing • Liver transplantationNAFLD NON-ALCOHOLIC FATTY LIVER DISEASE PATHOPHYSIOLOGY CLINICAL FEATURES • Excess of fat accumulating in the liver, in the absence of • Mostly asymptomatic excessive alcohol consumption or any other underlying liver • Hepatomegaly disease. • Obesity • Risk factors = obesity, Insulin resistance • Features of liver failure • Increasing prevalence DIAGNOSIS TREATMENT • Identify risk factors • Weight loss, exercise • Calculate fatty liver index (FLI) • Optimise risk factors (e.g. statins) • Enhanced liver fibrosis (ELF) testing • Pioglitazone, Vitamin E • Liver biopsy • Liver transplantationENTAMOEBA HISTOLYTICA ENTAMOEBA HISTOLYTICA PATHOPHYSIOLOGY CLINICAL FEATURES • Causes amoebiasis (solitary abscess in right lobe) • Africa • Bloody diarrhoea • Southern Asia • Right upper quadrant pain • Central America • Jaundice • Fever DIAGNOSIS TREATMENT • Stool MC&S • Colonoscopy with biopsy • Antibiotics (e.g. metronidazole) • Abdominal ultrasound/ CT/ MRI • Abscess aspiration • Analysis of aspirated contents (anchovy-paste)