Question 1

Describe creatines life cycle?

Accepted Answer

made in liver - transported to brain, muscle and other organs - phosphorylated - phosphocreatine. during reaction creatine and phosphocreatine are catalyzed by creatine kinase - spotaneous conversion to creatinine may occur which is excreted in kidneys.

Question 2

Why Beta 2 agonist e.g salbutamol potentially dangerous?

Accepted Answer

stimulate glycogenolysis - increase glucose - insulin - K channels inserted into adipose and skeletal tissues - K levels decrease - dangerous

Question 3

What % of total blood volume does liver hold?

Accepted Answer

10% - it can expand to accommodate high fluids volumes - occurs in CCF

Question 4

what % of bacteria entering the portal vein make it pass the liver?

Accepted Answer

Less than 1%. Kuppfer cells rapidly ingest bacteria.

Question 5

How long would u live without liver?

Accepted Answer

few days most - major metabolising powerhouse - essential for body

Question 6

How long will your vitB12 storage in the liver last?

Accepted Answer

A year

Question 7

where is the 2 largest iron store apart from RBC?

Accepted Answer

Liver

Question 8

describe the pathway rbc take when they are broken?

Accepted Answer

RBC -- haemoglobin -- globin + heme-- free iron and porphyrin free iron --transferrin transports in blood porphyrin -- biliverdin (gives bruising green colour) -- reduced to unconjugated bilirubin --gradually released from macrophage into plasma --combines strongly with serum plasma -- liver --glucuronic 80% sulfate 10% other10% conjugation -- conjugated bilirubin --intestine -- 1/2 converted to urobilinogen -- highly soluble reabsorbed some then resecreted back into gut some excreted in kidney and oxidizes forming urobilin. In gut oxidizes to form stercobilin.

Question 9

whats albumin t1/2?

Accepted Answer

2 weeks so may be normal even with liver disease

Question 10

If you have a normal LFT does it always mean the liver is fine? What do ALT/AST, GGT and ALP tell You? And name some tests for liver function? What's more specific for hepatocellular injury? AST or ALT? Where is AST also found? where is ALP situated in the liver? and where else is it in the body? what causes it to rise?

Accepted Answer

A normal liver function test does not necessarily exclude liver disease. Blood levels of the following enzymes usually reflect the integrity of hepatocytes or cholestasis (not “liver function” in isolation): Alanine and aspartate aminotransferases (ALT/AST), γ-glutamyltransferase (GGT), Alkaline phosphatase (ALP). The following tests may provide useful information on how well the liver is functioning: Serum albumin, Bilirubin, Prothrombin time. Alanine aminotransferase (ALT) is considered more specific than aspartate aminotransferase (AST) for hepatocellular injury because it is predominantly represented in the liver, with low concentrations in other tissues. AST is also expressed in the heart, skeletal muscle, and red blood cells. AST and ALT are both intracellular enzymes, so their presence in the bloodstream can be an indicator of hepatocellular injury (not necessarily hepatocellular death). Both liver and bone diseases can cause a pathological elevation of serum alkaline phosphatase (ALP), although increased ALP may originate from the placenta, kidney, intestine, and leukocytes. You can find increased serum ALP in some physiological conditions, such as adolescence (bone origin) and pregnancy (placenta origin). Cell membranes of hepatic sinusoids and bile canaliculi. Liver, GI tract, Bone, placenta, kidney. Levels rise with intra and extrahepatic obstruction, and with sinusoidal obstruction

Question 11

Wheres is GGT located? what produce it in the liver? what can isolated GGT rise indicate? What are ALP and GGT markers of?

Accepted Answer

many cells and tissues - highest conc in liver - produced by hepatocytes and small bile duct epithelium. Isolated rise could be due to drugs e.g alcohol, phenytoin. The enzyme γ-glutamyltransferase (GGT) is present in renal tubules, the liver, pancreas, and intestine. Although intracellular GGT levels are higher in organs other than the liver, GGT activity in the serum comes mainly from the liver. GGT is contained in the microsomes, and drugs such as anticonvulsants and oral contraceptives can induce its activity. Both ALP and GGT are synthesized and released by cells lining the bile ducts, and they can be released into the bloodstream by cholestasis and the accumulation of bile salts. For this reason, ALP and GGT can act as markers of cholestasis.

Question 12

What does Leucopenia indicate in terms of the liver? Leucocytosis? What causes normochromic normocytic anaemia? thrombocytopenia?

Accepted Answer

portal HTN and hypersplenism. hepatitis, cholangitis. Acute GI haemorrhage.cirrhosis - due to decreased thrombopoietin production in the liver.

Question 13

Describe how you would evaluate someone with abnormal LFTs?

Accepted Answer

Evaluate the clinical context: history suggestive of liver disease and/or symptoms and signs of liver disease, or with the presence of extrahepatic conditions that may involve the liver? The second step is to identify whether the injury is predominantly hepatocellular or cholestatic. Also degree of elevation of LFTs and the rate and characteristics of the increase or decrease over time. The third step is to identify the disease responsible for the biochemical abnormality. The fourth step is to determine the severity of liver injury and how useful the final diagnosis is in terms of treatment and prognosis. You can do this invasively via a liver biopsy or by non-invasive biochemical tests, clinical scores, or using transient elastography. The following factors in the patient’s history can help you to make a diagnosis: AGE; Younger patients are more likely to have diseases that usually manifest early in life (such as Wilson’s disease). Gender: The female to male ratio of autoimmune liver diseases is 4:1. Ethnicity: Hereditary haemochromatosis is more common in people of northern European descent, while it is rare in Africans. History of travel: In patients who have travelled to developing countries, you should think of viral hepatitis or other tropical diseases. Use of alcohol, drugs, and herbal remedies. Herbal remedies are often overlooked because they are considered harmless. However, they may frequently be associated with hepatotoxicity. MAJOR SURGERY? A history of blood transfusions should trigger you to check serology for hepatitis B and C virus infections.

Question 14

Describe what jaundice is? What is pseudojaundice and how can you differentiate it from true jaundice? AETIOLOGY of prehepatic jaundice?

Accepted Answer

Jaundice, or icterus, is the result of accumulation of bilirubin in the bloodstream and subsequent deposition in the skin, sclera, and mucous membranes. The normal range for total bilirubin is 3.4 to 20 micromol/L (0.2-1.2 mg/dL). Jaundice may not be clinically evident until serum levels exceed 51 micromol/L (3 mg/dL). Pseudo-jaundice is usually caused by carotenaemia, a clinical condition characterised by yellow pigmentation of the skin and increased beta-carotene levels in the blood. In most cases, the condition follows prolonged and excessive consumption of carotene-rich foods, such as carrots, pumpkin, and sweet potatoes. The sclerae are always spared, which readily distinguishes carotenaemia from jaundice. AETIOLOGY: Either Pre Hepatic (non conjugated). Intrahepatic (conjugated) or post hepatic (conjugated)

Question 15

AETIOLOGY of hepatocellular jaundice?

Accepted Answer

Infectious cause (hep a,b). Other possible infective causes include leptospirosis, brucellosis, Coxiella burnetii and glandular fever. Drugs or hepatic ischaemia. when it exceeds 50 umol/L. Alcoholic hepatitis. Autoimmune hepatitis (10-20% of chronic hepatitis). Can be associated with other autoimmune diseases. Drug-induced hepatitis: paracetamol is by far the most common cause of drug-induced liver disease. Hepatotoxic chemicals - eg, phosphorous, carbon tetrachloride and phenol. Decompensated cirrhosis.

Question 16

AETIOLOGY OF PRE HEPATIC JAUNDICE, AETIOLOGY of intrahepatic obstructive jaundice and AETIOLOGY of extrahepatic obstructive jaundice?

Accepted Answer

PRE HEPATIC: Excess RBC breakdown: Inherited red cell disorders (sickle cell, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency) Acquired haemolysis (autoantibody mediated, lead toxicity, ABO incompatibility). Failure of bilirubin conjugation: Gilbert’s syndrome, Crigler-Najjar syndrome. AETIOLOGY OF INTRAHEPATIC INCLUDES: Cirrhosis. Viral hepaittis. Autoimmune hepatitis. NASH. WIlson. HH. PBC. CF. Drugs (for example, phenothiazines). Dubin-Johnson syndrome and Rotor's syndrome. AETIOLOGY OF EXTRAHEPATIC INCLUDES: Common duct stone. Cancer of the head of the pancreas. Tumour of the ampulla of Vater. Pancreatitis. Cancer of the gallbladder. chronic pancreatitis. PSC.

Question 17

give 3 early features and 3 late features of cholestatic jaundice?

Accepted Answer

Early - dark urine, pruritus, pale stools. Late - ADEK malabsorption, weight loss, steatorrhoea, xanthelasma.

Question 18

How do you investigate jaundice?

Accepted Answer

urine for bilirubin and LFTs: -- urobilogen present, LFT normal and isolated bilirubin rise = prehepatic/hepatic jaundice - conjugated rise (Dubin johnson or Rotor syndrome) unconjugated - blood film - + = coombs test and haemolyis. If -ve and subnormal amounts of urobilogen present then gilberts. -- conjugated bilirubin and abnormal LFTs - US - biliary obstruction - obstructive jaundice - MRCP or ERCP. No evidence of biliary disease - hepatocellular jaundice - copper iron and clotting studies and hepatitis antibodies. Raised urinary bilirubin with absent or reduced urobilinogen is suggestive of obstructive jaundice. Urinary bilirubin is normally absent but is conjugated when present (dark urine). Normal or raised urinary bilirubin with elevated urobilinogen suggests hepatocellular failure or increased red cell breakdown.

Question 19

Why is there almost no atherosclerosis in alcoholics?

Accepted Answer

Liver damage - decrease gluconeogensis - low glucose - FFA and ketones used instead

Question 20

what is hepatic encephalopathy? AETIOLOGY? CLASSIFICATION?

Accepted Answer

Syndrome of mostly reversible impairment of brain function occurring in patients with acute/chronic liver failure. A neuropsychiatric syndrome caused by acute or chronic hepatic insufficiency. This condition is a common manifestation in patients with end-stage liver disease but may also be seen in patients with acute liver failure and in non-cirrhotic patients requiring portacaval shunting. AETIOLOGY: HE likely reflects a combination of metabolic encephalopathy, brain atrophy, and/or brain oedema rather than a single clinical entity. The exact mechanisms causing brain dysfunction in patients with liver failure are not well understood. Ammonia has been implicated as a neurotoxin in the pathogenesis of the disease, as ammonia levels are significantly increased in patients with acute and chronic liver failure. However, a lack of strong correlation between serum ammonia levels and the degree of encephalopathy suggests that other factors are also likely to play a part in its development. For patients with chronic liver disease, precipitating factors may include gastrointestinal bleeding, infection, use of sedatives/tranquilisers, hypokalaemia, alkalosis, increased protein intake, and constipation. Gastrointestinal bleeding and increased protein intake lead to increased ammonia production. Hypokalaemia is often accompanied by the movement of extracellular hydrogen ions into cells to maintain electrical neutrality. The subsequent metabolic alkalosis is thought to promote the conversion of ammonium ions (NH4+), charged particles that do not cross the blood-brain barrier, into un-ionised ammonia (NH3), which can cross the blood-brain barrier, thus promoting the disease. In these patients, precipitating causes should be quickly identified and treated. CLASSIFICATION: Type A. Encephalopathy associated with acute liver failure. Type B. Encephalopathy associated with portosystemic bypass and no intrinsic hepatocellular disease. Type C. Encephalopathy associated with cirrhosis and portal hypertension or systemic shunt: Episodic HE (precipitated, spontaneous, or recurrent). Persistent HE (mild, severe, or treatment dependent). Minimal HE. WESTHAVEN CLASSIFICATION ACCORDING TO SEVERITY.

Question 21

pathogenesis of hepatic encephalopathy?

Accepted Answer

cirrhosis results in blood bypassing liver due to high resistance - this stops toxic substances being detoxified and allows them to enter systemic circulation. The gut is the primary source of ammonia that is absorbed into the circulation through the portal venous system. PATHOPHYSIOLOGY: Ammonia is a by-product of colonic bacterial catabolism of nitrogenous sources such as ingested protein and secreted urea nitrogen. It is also produced from glutamine by enterocytes. Impaired liver function leads to impaired ammonia clearance. In addition, cirrhosis leads to portosystemic shunting, which reduces ammonia clearance further. Hyperammonaemia may alter cerebral concentration of amino acids and thus affect neurotransmitter synthesis. Hyperammonaemia may also lead to increased intracellular astrocyte osmolarity, inducing astrocyte swelling, and rarely leads to increased intracranial pressure. Elevated serum ammonia levels can also alter neuronal electric activity. Increased activation of the inhibitory GABA-benzodiazepine neurotransmitter system and alterations of glutamatergic function have also been implicated in the pathogenesis.

Question 22

what is the main neurotoxin in hepatic encephalopathy? why does it rise? what does it do?

Accepted Answer

NH4 - colonic bacteria digest urea, muscle wasting in cirrhosis - muscle is important site for extrahepatic NH4 removal. It is used to synthesise GABA and glutamate in astrocytes - causing these cells to swell and resultant brain oedema.

Question 23

name 2 other toxic chemicals from enteric flora in hepatic encephalopathy?

Accepted Answer

phenols and mercaptans

Question 24

why high infection rates in cirrhotic patients?

Accepted Answer

high NH4 - causes neutrophil swelling and dysfunction

Question 25

name 5 early features of HE? STEP by STEP approach to HE?

Accepted Answer

bradykinesia, asterixis, hyperreflexia, transient decerebrate posture (arms and legs straight toes pointed down) fetor hepaticus. This condition is a diagnosis of exclusion and the manifestations may be subtle. In patients with chronic liver disease, a precipitating factor may be causing the development of HE, such as hypovolaemia, gastrointestinal bleeding, hypokalaemia, metabolic alkalosis, hypoxia, sedative use, hypoglycaemia, infection, or hepatic or portal vein thrombosis. Patients with acute hepatic failure will have had a rapid deterioration in liver function and may display coagulopathy. HISTORY: A careful history needs to be taken regarding possible exposures to viral infection, drugs (paracetamol overdose is most common cause), and toxins. It is also necessary to exclude other causes of mental status alteration. These include infection, electrolyte abnormalities (sodium, calcium, and potassium), glucose abnormalities, hypoxaemia, uraemia, toxin exposures (alcohol or sedative medications), and primary CNS abnormalities, such as bleeding or infection. Patients may describe symptoms relating to mild neurological deficit such as sleep disturbances (insomnia or hypersomnia), euphoria, or depression, and motor disturbances such as asterixis and ataxia. More advanced neurological deficits manifest themselves as somnolence, which may be followed by unconsciousness or coma. EXAMINATION: ABDO EXAM, Altered reflexes and nystagmus also may be present. In one case series, 17% of patients had focal deficits, with the most common being hemiplegia. INVESTIGATIONS: 1st: Electrolytes, LFTs, a renal profile, FBC, microbial cultures, coagulation profile, urinalysis, and toxin screen should be ordered. A chest x-ray and head CT will help to narrow the differential diagnosis in that the presence of other abnormalities may help to rule out other diagnoses. While head CT or MRI may detect brain oedema, these changes are neither sensitive nor specific for HE. An upper-quadrant ultrasound should be considered in all patients with unexplained acute decompensation, as acute portal or hepatic vein thrombosis can be the cause. OTHER INVESTIGATIONS: Utility of ammonia levels is controversial - very low levels or very high levels may be helpful in the appropriate clinical context. Monitoring ammonia trends may be helpful in monitoring therapy, but it is not required to make a diagnosis. An EEG may help in diagnosing mild HE and in excluding occult seizure activity in comatose patients. HE may be associated with a decrease in brain wave frequency and amplitude. In patients with ascites, a diagnostic paracentesis should also be performed to rule out spontaneous bacterial peritonitis, which may precipitate HE. DD: BRAIN TUMOURS, SUBDURAL HAEMATOMA, ACUTE STROKE, MENINGITIS, Encephalitis, Uraemia, Hyper- or hypoglycaemia, Hypercarbia, Benzodiazepine overdose, Wernickes, Spontaneous bacterial peritonitis.

Question 26

how is HE classified according to severity?

Accepted Answer

These criteria are based on severity. WESTHAVEN CLASSIFICATION: Grade 0: Normal. Grade I. Mild impairment: CHANGE IN BEHAVIOUR WITH MINIMAL CHANGE IN LEVEL OF CONSCIOUSNESS. Grade II. Moderate impairment: lethargy, grossly impaired intellectual function, disorientation to time, inappropriate or bizarre behaviour, slurred speech, hypoactive reflexes, ataxia. Grade III. Severe impairment: somnolence, confusion, disorientation, paranoia or anger, hyperactive reflexes, nystagmus, Incoherent speech. Babinski's reflex, clonus. Grade IV. Coma: unconsciousness, dilated pupils.

Question 27

TX options for HE? Complications?

Accepted Answer

ACUTE: ALL PATIENTS: 1st SUPPORTIVE AND REVERSE CAUSE: supportive care involves frequently monitoring the patient's neurological and mental status. Comatose patients should be admitted to intensive care and endotracheal intubation considered if their airway is compromised. Intracranial pressure monitoring may be needed for patients with significant intracerebral oedema. Close monitoring of serum glucose and the prothrombin time are necessary if HE is accompanied by acute liver failure. If precipitating factors have been identified through the history and physical examination, these need to be corrected. These include gastrointestinal bleeding, infections, electrolyte disturbances and renal failure, sedative or narcotic ingestion, excessive dietary protein intake, acute hepatic or portal vein thrombosis, and recent placement of a transjugular intra-hepatic portosystemic shunt (TIPS). Abdominal ultrasonography may help to identify portal or hepatic vein thrombosis, or hepatocellular carcinoma. Occasionally TIPS must be occluded if the condition cannot otherwise be managed. PLUS LACTULOSE: Rectal enema may be used if patient is in coma or impending coma. The patient should be switched to oral therapy as soon as possible. 2nd LINE: antibiotics and supportive care: Use of antibiotics is not clear-cut. Antibiotics should be limited to patients who are intolerant of, or resistant to, lactulose. IF ONGOING: Lactulose and referral to Liver transplant. Patients should be instructed to avoid narcotics, alcohol, and benzodiazepines. Neomycin may also be used to lower amino acid production by decreasing the concentration of ammonia-forming colonic bacteria. Other antibiotics have also been used - eg, metronidazole, vancomycin, rifaximin. In treating hepatic encephalopathy lactulose also works by reducing the absorption of ammonia from the gut. lactulose and lacitol - increase NH4 removal by being broken down into short chain FA by intestinal bacteria which lowers colonic pH converts NH3-NH4 which is non absorbable. Antibiotics - alter flora Benzodiazepine receptor antagonists - flumazenil - blocks action of GABA. COMPLICATIONS: aspiration pneumonia, CEREBRAL OEDEMA:Unlike in acute liver failure, where cerebral oedema is common, in HE without acute liver failure this is an extremely rare complication.

Question 28

What is budd chari syndrome?

Accepted Answer

Includes hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava and the right atrium, regardless of the cause of the obstruction. Classic triad of symptoms is abdominal pain, ascites, and hepatomegaly. BCS is a rare but potentially life-threatening condition affecting 1/100,000 of the general population worldwide. AETIOLOGY: A myeloproliferative disorder (MPD) is the main procoagulant disorder in 50% of patients. Thrombophilic disorders are the next most frequent causes of BCS. Factor V Leiden mutation is present in around 30% of patients. OTHER CAUSES: antiphospholipid syndrome, hyperhomocysteinaemia, Behcet's syndrome and ulcerative colitis. Pregnancy and immediate post-partum period are associated with hormonal changes, inferior vena cava (IVC) compression, and physiological hyperfibrinogenaemia, which predispose to BCS. Often idiopathic. Secondary BCS may result from external compression or invasion of the venous lumen by abscess, tumours, trauma, or cysts. Compression or kinking of the hepatic veins can occur following hepatic resection or transplantation. BCS may occur following blunt abdominal trauma, either from compression by intrahepatic haematoma, inferior vena cava thrombosis related to trauma, or herniation of the liver through a ruptured diaphragm.The diagnosis of BCS is suggested by clinical suspicion and further confirmed by imaging techniques. BCS should be suspected in patients with a personal or family history of thrombophilia who present with the classic triad of abdominal pain (specifically RUQ abdominal pain), ascites, and hepatomegaly. Patients may also have or develop splenomegaly and GI bleeding as a consequence of the underlying myeloproliferative disease, portal vein thrombosis, or as sequelae of cirrhosis (with portal hypertension) that develops in the chronic form of BCS. Careful cardiovascular exam and the absence of the hepatojugular reflux are required to rule out cardiac conditions with similar presentation, such as tricuspid regurgitation, constrictive pericarditis, and right atrial myxoma. Leg oedema and dilated venous collaterals on the trunk indicate inferior vena cava (IVC) compression or thrombosis. The fulminant form of BCS is uncommon. Patients rapidly develop jaundice, hepatic encephalopathy, renal failure, and coagulopathy. The liver is enlarged and tender. The symptoms of the fulminant form of BCS are similar to those in acute hepatitis. Colour and pulsed Doppler ultrasonography is considered the first-line investigation of choice for patients with suspected BCS. The combination of specific findings (thrombosis, stenosis, fibrotic cord, or insufficient re-canalisation of hepatic and/or caval veins) and caudate lobe hypertrophy has the highest predictive value to identify patients with BCS. Abdominal CT and/or MRI are then used to visualise the hepatic veins and the whole length of the IVC and demonstrate occlusion of hepatic veins, IVC, or both. MRI is more accurate than CT and allows optimal delineation of venous obstruction for therapeutic decisions. However, it is more expensive. Hepatic venography (invasive) is considered the definitive diagnostic tool. The presence of a spider web pattern on hepatic venography confirms the diagnosis of BCS. It is needed to determine the extent of thrombosis and a measure of the portacaval venous pressure gradient, which is often useful before portacaval shunting procedures. It also facilitates transjugular liver biopsy, which can be helpful to assess presence of cirrhosis and exclude alternative or concomitant liver diagnoses. Hepatic venography is carried out when the suspicion of BCS is high, even in the absence of typical findings on other radiological imaging. It should also be performed when percutaneous or surgical shunting is considered. Contrast-enhanced 3-dimensional magnetic resonance angiography is done when it is impossible to cannulate the hepatic veins during hepatic venography. TESTS: FBC. LFT. Renal function and coagulation studies should be performed as baseline, and may be abnormal in fulminant BCS. Search for hypercoagulation condition. TREATMENT: 1st LINE: Asymptomatic patients require anticoagulation as underlying prothrombotic states are often present, unless there are contra-indications. Use low molecular weight heparin or heparin (in the absence of known allergy). Treatment of the underlying predisposing thrombophilic condition should be as per standard care: for example, hydroxyurea and aspirin in myeloproliferative disease. IF symptomatic: less than 72 hours from symptom onset or fresh clot seen on venography: 1st LINE: thrombolysis. Adjunct: anticoagulation, symptom control: Ascites is treated with diuretics (e.g., furosemide, spironolactone). History of bleeding due to portal hypertension is managed with pharmacological or endoscopic therapy. 2nd LINE: Hepatic angioplasty (balloon dilation with or without stent insertion) of localised narrowed hepatic vein is reported to relieve symptoms in 70% of patients. IVC balloon dilation is usually sufficient to open up the obstruction (web or stenosis). IVC stent insertion is usually needed when balloon dilation is insufficient alone, or when there is recoil, or recurrent stenosis. Transjugular intrahepatic portosystemic shunt (TIPS) is considered the most common interventional procedure for BCS. For the shunt to function, the portacaval pressure gradient should be less than 10 mmHg.

Question 29

where does cantlies lie pass through?

Accepted Answer

tip of GB fossa and IVC

Question 30

Name a congenital abnormality of the GB?

Accepted Answer

phrygian cap

Question 31

whats normal upper limit of bilirubin? whens jaundice detected in the sclera?

Accepted Answer

17umol/L and over 35umol/L

Question 32

what are hepatic stellate cells also called? what are pit cells?

Accepted Answer

Itos cells highly mobile liver specific NK cells

Question 33

whats acholuric jaundice?

Accepted Answer

excess unconjugated bilirubin and no bile pigments in urine. - hepatocellular jaundice. Unconjugated bilirubin is water insoluble it does not enter urine resulting in unconjugated hyperbilirubinaemia. Results from overproduction of bilirubin, impaired hepatic uptake (RHF, drugs such as contrast agents and rifampicin) OR Impaired conjugation.

Question 34

What is dubin-Johnson? and Rotor syndrome?

Accepted Answer

DUBIN JOHNSON: is an autosomal recessive condition manifested by chronic conjugated hyperbilirubinaemia and accumulation of a dark pigment in the liver parenchymal cells. It is a benign condition with normal life expectancy. It is generally diagnosed between the ages of 10 and 30 years. The primary defect in the DJS is impaired transport of glucuronides and other anionic conjugates from the hepatocytes into bile due to mutation of MRP2. This protein is an integral membrane glycoprotein expressed mainly in the canalicular (apical) membrane of hepatocytes where it functions as an ATP-dependent export pump for endogenous and exogenous anionic conjugates. The conjugated hyperbilirubinaemia seen in DJS results from defective transport of bilirubin glucuronide across the membrane that separates the hepatocyte from the bile canaliculi. Deficient excretion of bilirubin glucuronides at the canalicular membrane in the presence of otherwise normal intrahepatic metabolism results in reflux of conjugated bilirubin back into the circulation. A striking characteristic of DJS is the brown to black discoloration of the liver. It is hypothesised that these pigments accumulate in the liver because of impaired secretion of various metabolites from the hepatocyte into the bile. There is usually elevation of conjugated bilirubin in serum, but other LFTs such as aminotransferases, alkaline phosphatase, and gamma-glutamyl transferase are usually normal. This helps to differentiate between DJS and extrahepatic biliary obstruction. The diagnosis is suggested by demonstrating an increase in the ratio of urinary coproporphyrin I to coproporphyrin III. In DJS, over 80% of the coproporphyrin excreted is type I. liver biopsy can be used for definite diagnosis and rule out other conditions. treatment is just reassurance. Primary defect is a mutation in an apical canalicular membrane protein responsible for excretion of bilirubin. Jaundice is worsened by an intercurrent illness, pregnancy, and oral contraceptives. Total bilirubin levels usually range between 25.7 and 102.6 micromol/L (1.5 and 6 mg/dL), and more than one half of the total bilirubin is conjugated. Normal life expectnancy. ROTOR SYNDROME: A familial disorder of bilirubin metabolism characterised by a benign, non-haemolytic jaundice, due to chronic elevation of predominantly serum conjugated bilirubin. The unconjugated bilirubin fraction is also elevated. The impairment in storage and excretion of bilirubin and other organic anions leads to defective secretion of conjugated bilirubin into the bile, which results in its reabsorption into the blood and excretion in the urine. The excess circulation and accumulation of bilirubin (hyperbilirubinaemia) results in jaundice. Unlike Dubin-Johnson syndrome, there is no hepatic pigmentation. Total urinary coproporphyrin excretion can be used to differentiate from Dubin Johnson syndrome. It is a diagnosis of exclusion. Again normal life expectnancy so just reassurance. SO both are congenital impairment of excretion of conjugated bilirubin into bile

Question 35

what makes up calots triangle? whats in the middle of it? when is it enlarged?

Accepted Answer

common hepatic duct, cystic duct and liver border. Lunds node - cholecystitis or cholangitis.

Question 36

what is hepatorenal syndrome? AETIOLOGY? PATHOPHYSIOLOGY? HISTORY? INVESTIGATIONS? DIAGNOSIS? TREATMENT? COMPLICATIONS?

Accepted Answer

Hepatorenal syndrome (HRS) is the development of renal failure in patients with severe liver disease (acute or chronic) in the absence of any other identifiable cause of renal pathology. The probability of developing HRS in patients with cirrhosis is approximately 40% in 5 years. HISTORY: Other causes of renal failure need to be excluded. Nephrotoxic drugs, hypovolaemia/shock, renal parenchyma disease. The patient should be asked about their current medicine use and whether there has been any recent change, such as an increase in diuretic dosage or use of NSAIDs. A history of repeated vomiting or diarrhoea, or GI bleeding (such as haematemesis or melaena stools) suggests volume depletion. Fever, a productive cough, dysuria, and abdominal pain may indicate the presence of infection. PATHOPHYSIOLOGY: Portal HTN. THen splanchnic vasodilation. Decreased effective circulating volume. Activation of the RAAS. Renal vasoconstriction and hepatorenal syndrome. TESTS: FBC, U and Es, LFTs, and coagulation profile. Alternative causes, such as on-going bacterial infection, need to be excluded. A septic work-up consisting of blood, urine, and ascitic fluid culture, urinalysis, and CXR is performed to exclude sepsis. Renal ultrasound is also performed to exclude an obstructive cause of renal failure. RISK FACTORS: SBP, pneumonia, GI bleed. CLASSIFICATION: TYPE 1: Acute kidney injury that is rapidly progressive, poor prognosis, develops after precipitated event usually, e.g SBP. TYPE 2: Moderate renal failure, fluctating course. Steady and slowly progressive. DIAGNOSIS: Cirrhosis with ascites, Serum creatinine over 133 micromol/L (over 1.5 mg/dL), Absence of shock, Absence of hypovolaemia. Absence of renal parenchymal disease (suggested by proteinuria or haematuria). TREATMENT: Type 1: ADMIT. Monitor fluid status. Treat infections AGGRESSIVELY. AVOID nephrotoxic drugs! SPLANCHNIC VASOCONSTRICTORS: terlipressin leads to an increased blood pressure and GFR, through constriction of splanchnic blood vessels. Also give albumin. alternative: Noradrenaline. TIPS for ascites if do not respond to medication. Renal replacement therapy may be necessary. TYPE 2: may be admitted but do not have to. LIVER TRANSPLANTATION IS best option for both. PROGNOSIS: Prognosis for patients with HRS is poor. Type 1 HRS has a hospital survival of less than 10%, and median survival time is 2 weeks. Type 2 HRS has a median survival time of around 6 months.

Question 37

why is albumin an unreliable marker for malnutrition?

Accepted Answer

Its production is at expense of other protein and has long t1/2.

Question 38

What is biliary atresia? AETIOLOGY? PATHOPHYSIOLOGY? INVESTIGATIONS? TREATMENT? COMPLICATIONS? PROGNOSIS?

Accepted Answer

Biliary atresia is a progressive idiopathic, necroinflammatory process that may involve a segment or the entire extrahepatic biliary tree. Even with appropriate, timely surgical intervention, it is often an unrelenting inflammatory process. A devastating disease requiring prompt early diagnosis preferably before 6 to 8 weeks of age. All or part of extrahepatic bile ducts are obliterated by inflammation and subsequent fibrosis leading to biliary obstruction and jaundice - fatal if untreated - commonest cause of prolonged neonatal jaundice. Biliary atresia occurs in approximately 1 in 18,000 live births in Western Europe. Very common in taiwan. AETIOLOGY: unknown. Theories include: Viral infection/toxin exposure, Defects in morphogenesis: potentially caused by a toxin at a critical time in embryological development, Genetic predisposition, Immune or autoimmune dysregulation. PATHOPHYSIOLOGY: The hepatic or common bile duct is obliterated or discontinuous for a portion between the porta hepatis and the duodenum. This inflammation is the hallmark of the disease, and even after hepatoportoenterostomy the inflammatory process can continue to ascend through the intrahepatic biliary tree, leading to fibrosis, cirrhosis, portal hypertension, and subsequent nutritional deficits. CLASSIFCATION: Type I: common bile duct atresia with patent proximal ducts. Type II: common hepatic duct atresia with cystic structures in the porta hepatis. Type III: right and left hepatic duct atresia to the level of the porta hepatis (most common). In the neonatal period, the condition should be excluded if conjugated bilirubin is greater than 20% of the total or greater than 34.2 micromol/L (2 mg/dL). History and examination findings alone are not sufficient to make the diagnosis, but a child typically presents with onset of obstructive jaundice between birth and 6 to 8 weeks of age. Biliary atresia is very unlikely if a child is older than 8 weeks old at the onset of jaundice. INVESTIGATIONS: 1st: Total bilirubin with direct or conjugated fraction; a level of greater than 34.2 micromol/L (2 mg/dL) or 20% of the total is consistent with but not specific to the diagnosis. Review of the newborn screen to exclude thyroid dysfunction, galactosaemia, cystic fibrosis, and rare metabolic disorders. It may be necessary to repeat one or more of these tests if the diagnosis is still suspected (e.g., urinary succinyl acetone for tyrosinaemia). LFTs and a clotting screen. A high level of gamma-GT supports biliary disease, and clotting disorders are a serious complication, more common if presenting late. FBC will help ascertain the overall health of the child. Low WBC count and platelets may be seen with advanced liver disease, or a raised WBC count may support an alternative infectious cause. Abdominal ultrasound is indicated if biliary atresia remains a possible diagnosis. A choledochal cyst can be visualised, and the triangular cord sign is highly suggestive of the condition but rarely seen. If no abnormality is detected, the next step is hepatobiliary scintigraphy. If the radioactive tracer is excreted into the bowel within 24 hours, this excludes the condition but, as the test lacks specificity, failure of excretion does not confirm it. If no tracer is excreted, a needle biopsy of the liver is recommended. A cholangiogram demonstrating a lack of patency is the diagnostic standard, and in combination with a characteristic liver biopsy the diagnosis is confirmed. ERCP can be used to diagnose it too. FURTHER TESTS TO exclude differentials: CXR. Alagille's syndrome has characteristic features (e.g., butterfly or haemivertebrae) that may be seen on CXR, and dextrocardia may be identified in biliary atresia splenic malformation syndrome. Infection screen. The most common infections causing jaundice are toxoplasmosis, herpes, rubella, syphilis, adenovirus, enterovirus, and CMV. Bacterial sepsis or a urinary tract infection may also be responsible. Serum amino acids to exclude type 1 tyrosinaemia. Alpha-1 antitrypsin levels and protease inhibitor typing to exclude alpha-1 antitrypsin deficiency, which can present in a similar fashion to biliary atresia. Random cortisol level to exclude adrenal insufficiency. TREATMENT: ACUTE: 1st LINE: hepatoportoenterostomy also called Kasai portoenterostomy - expose porta hepatis and attach small intestine to exposed liver surface. It should ideally be performed before 45 to 60 days of life, to prevent liver damage. ADJUNCT: ursodeoxycholic acid Thought to be hepatoprotective and facilitates bile flow. If hepatoportoenterostomy is unsuccessful, liver transplantation would be the only treatment. COMPLICATIONS: growth failure, rickets, portal hypertension, SBP, osteopenia, GI bleed, ascites. PROGNOSIS: Overall, it is thought that 70% or more of affected children will ultimately require liver transplantation.

Question 39

What are the 2 types of liver abscesses? what are common causes of each?

Accepted Answer

A localised infection in the liver parenchyma that may be bacterial, fungal, or parasitic in origin. Patients typically present with non-specific constitutional symptoms, RUQ abdominal pain, and tenderness. Therefore important to have a low threshold for consideration of this. Liver abscess is an uncommon disease. AETIOLOGY: Pyogenic liver abscess is often a polymicrobial infection. The most commonly isolated organisms are Escherichia coli, Klebsiella species, Streptococcus constellatus, S anginosus, S intermedius (prior 3 organisms were previously classified as S milleri group), other streptococcal species, Enterococcus, and anaerobes, including Bacteroides fragilis and Fusobacterium necrophorum. Staphylococcus aureus and Pseudomonas species are less common causes of liver abscess. Recurrent pyogenic cholangitis (associated with hepatolithiasis) due to Salmonella typhi may cause pyogenic liver abscess. Abscesses caused by Klebsiella species have been associated with extra-hepatic complications, including endophthalmitis and CNS infections. The incidence of Klebsiella liver abscess is increasing. In immunocompromised hosts, fungal abscess of the liver may occur. Amoebic abscess may occur following infection with the parasite Entamoeba histolytica. E histolytica infection (with possible amoebic abscess development) is endemic in Central and South America, Africa, and Asia. PATHOPHYSIOLOGY: Liver abscesses form by spread of infection from 1 of the following sources: Biliary tree, Portal vein, Hepatic vein, Extension of contiguous infection, Penetrating trauma. The biliary tract is the most common identifiable source of pyogenic liver abscess. Historically, pyogenic liver abscess was most commonly a complication of untreated or inadequately treated appendicitis. The portal vein drains the GI tract, gall bladder, and pancreas. Pylephlebitis (portal vein inflammation) from inflammatory bowel disease, pancreatitis, appendicitis, or diverticulitis can result in liver abscess. Liver cirrhosis is a strong risk factor. Pyogenic Liver abscesses tend to be polymicrobial. Cancer (either primary hepatocellular cancer or extra-hepatic primary cancer) and diabetes are other risk factors. As well as immuocompromised. Liver abscess may occur following chemoembolisation or percutaneous ablation of hepatic neoplasms, endoscopic biliary sphincterotomy, and hepatic cryotherapy. In approximately 40% of cases, no specific cause of liver abscess is identified. Such cases may result from bacteraemia in patients with poor dentition. Bacteraemia, endocarditis, or other intravascular infections are infrequently complicated by liver abscess. CLASSIFICATION: Pyogenic: Typically referring to bacterial causes. Complicating fungal infection may occur in people with immunosuppression. Amoebic: Caused by infection with the parasite Entamoeba histolytica. Patients originate from or have visited endemic areas. INVESTIGATION/PRESENTATION: Imaging of the liver and cultures of the abscess fluid are key to making the diagnosis and identifying the causative organism(s). Underlying biliary tract abnormalities, age over 50 years, malignancy, diabetes mellitus, and interventional biliary or hepatic procedures are strongly associated risk factors for the development of pyogenic liver abscess. Patients who are from or have visited areas endemic for amoebiasis are at increased risk of amoebic liver abscess. Generally, symptoms occur in an insidious manner, can be non-specific, and are of variable duration. Fever, RUQ tenderness, and hepatomegaly are usually found on physical examination. However, the absence of these findings does not exclude the diagnosis of liver abscess. The most common symptoms at presentation of pyogenic abscess are fever, chills, fatigue, nausea, vomiting, and abdominal pain. If the diaphragm is inflamed because of adjacent infection, then cough, shortness of breath, and pleuritic pain may also be present. Pain may be referred to the right shoulder tip in these cases. Patients with fungal liver abscess present with similar symptoms. 1st TESTS: FBC. Serum albumin, aminotransferase, bilirubin, and alkaline phosphatase levels, PT and activated partial thromboplastin time (aPTT), Blood cultures. If amoebic abscess is suspected, serology may be diagnostic. Where there is co-existent diarrhoea, the Entamoeba histolytica enzyme immunoassay (EIA) can detect the antigen of Entamoeba histolytica in a stool specimen. C-reactive protein is a non-specific test that can be used to monitor the inflammatory response and therefore response to treatment. The preferred initial imaging tests are contrast-enhanced abdominal CT scan and abdominal ultrasound. MRI is more sensitive than ultrasonography and CT for small abscesses but is expensive and more limited in availability. The sensitivity of CT for liver abscess is higher than that for ultrasound (over 95% vs 86%-90%). Usually, a CT scan is performed. Aspiration of the abscess fluid confirms the diagnosis of abscess and directs antibiotic therapy. Aspiration/sampling should be avoided if there is evidence of abnormal coagulation. It is also CI if a hydatid cyst is suspected, because of the low, but real, risk of anaphylaxis. However, aspiration may occasionally be performed in patients with possible hydatid disease (parasitic disease with tapeworms) when the diagnosis of amoebic liver abscess remains a possibility, or when the aspiration is performed as part of the therapy. TREATMENT: antibiotic, supportive treatment (IV fluids), drainage, Patients with amoebic liver abscess (either confirmed or presumed highly likely as the cause of the abscess) are treated with a nitroimidazole. For most abscesses, drainage is an important step in treatment, along with antibiotic therapy.

Question 40

name the commonest benign liver tumour? and name 2 maligant ones? how common are fungal, viral or parasite liver abscesses?

Accepted Answer

haemangioma. HcC and intrahepatic cholangiocarcinoma. RARE.

Question 41

TREATMENT OF ACUTE LIVER FAILURE?

Accepted Answer

1st: Intensive care monitoring (HDU OR IDU) is mandatory once hepatic encephalopathy is present, as these patients can rapidly develop into Multiple organ failure. The natural history of ALF may be characterised by a rapid deterioration in neurological status, high risk of complications including sepsis and cerebral oedema, haemodynamic instability, and renal failure. BEWARE SEPSIS, HYPOGLYCAEMIA, GI BLEEDS AND HE. Need ABG (helps transplant centres with regards to discussion around prognosis, high lactate in paracetamol OD indicates a poor prognosis). Fluid Resus: avoid Hartmans because of the lactate. Coagulopathy is used as a marker for prognosis, so tend not to correct it unless patient is bleeding. ENCEPHALOPATHY: Efforts should be made to minimise elevations of intracranial pressure. The head of the patient's bed should be raised to approximately 30 degrees. Monitor vital signs and urine output and pupils and daily weights. Check fbc, ue, LFTs and INR daily. Enteral nutritional support with calorie-dense feeds should also be initiated early during the hospital course. Should also have a liver transplant assessment, and should check for HE regularly. In patients with advanced encephalopathy (grade 3 or 4), surveillance cultures from blood, urine, and sputum should be obtained periodically given the high risk of bacterial and fungal infection. Blood glucose levels should be monitored every 1 to 2 hours by finger stick to assess for hypoglycaemia. Serum electrolytes, including phosphate, potassium, and magnesium, should be monitored at least twice daily and corrected aggressively. Then treat cause: IF ADAD OD: NAC. If HSV hepatitis: aciclovir. Autoimmune hepaitits: Methylpredisnolone. Acute Hep B: Entecavir or tenofovir are the preferred agents. Budd Chiari syndrome: anticoagulation and TIPS. Wilsons disease: plasmapheresis, continuous veno-venous haemofiltration (CVVH), albumin dialysis, or plasma exchange. Lactulose, often with neomycin, is given to reduce ammonia production. Protein restriction may not be as important as is traditionally taught. 20 % Mannitol IV may reduce raised intracranial pressure. Try to avoid sedatives, as they make assessment difficult. Fresh-frozen plasma, platelet concentrates, antifibrinolytic drugs, vit K, prothrombin complex concentrates and recombinant activated factor VII are often used to treat or prevent abnormal bleeding. Treat seizures with lorazepam.

Question 42

DESCRIBE ACUTE LIVER FAILURE? DD? AETIOLOGY? PATHOPHYSIOLOGY? TESTS? HISTORY? IMAGING?

Accepted Answer

Acute liver failure (ALF) is a rare syndrome defined by a rapid decline in hepatic function characterised by jaundice, coagulopathy (INR over 1.5), and hepatic encephalopathy in patients with no evidence of prior liver disease. The interval from the onset of jaundice to the development of encephalopathy occurs within 26 weeks. After 26 weeks it is chronic liver failure. HYPERACUTE: within 7 days (paracetamo). ACUTE: 8 to 28 days (usually viral) SUBACUTE: 5 to 12 weeks (Drug related, autoimmune, metabolic causes). The term acute liver failure is preferred over fulminant hepatic failure or acute hepatic necrosis, although these terms have been used historically to classify hepatic failure. ALF is a rare event. Fulminant Hepatic failure is a clinical syndrome resulting from massive necrosis of liver cells leading to severe impairment of liver function. Fulminant is also described as onset of HE occurring within 2 weeks of jaundice onset. AETIOLOGY: THE MOST common aetiology of ALF is paracetamol hepatotoxicity, accounting for approximately 46% of all cases. Other causes of ALF include idiosyncratic drug-induced liver injury (11%), acute hepatitis B (8%), autoimmune hepatitis (6%), shock liver (4%), and acute hepatitis A (3%). Up to 14% of cases remain indeterminate. Altogether, over half of all ALF cases are associated with a drug-induced reaction. Other Causes: Leptospirosis, Viral hepatitis (CMV). Drugs: Halothane, isoniazid. Toxins: Amanita phalloides mushroom. Vascular: budd chiari syndrome. Others: alcohol, PBC, HH, alpha 1 anti trypsin deficiency. Wilsons. Fatty liver of pregnancy. Malignancy. HELLP. PATHOPHYSIOLOGY: Most cases are characterised by massive hepatocyte necrosis, which may ultimately result in organ failure. However, ALF without histological evidence of hepatocellular necrosis can also be seen; examples of this include acute fatty liver of pregnancy and Reye's syndrome. HISTORY: Ask about: Date of onset of jaundice and encephalopathy. Alcohol use. Medication, including prescription medicines, illicit drugs and alternative medicines. Family history of liver disease (Wilson's disease or haemochromatosis). Exposure risk factors for viral hepatitis (travel, transfusions, sexual contacts, occupation, body piercing). Toxin ingestion (mushrooms, organic solvents, phosphorus contained in fireworks). Past medical history. Assess risk factors such as malnutrition, chronic Hep B, pregnancy, old age (over 40). Chronic liver diseases such as autoimmune hepatitis and chronic hepatitis B may present as an acute exacerbation with the clinical features of ALF. Abdominal pain, nausea, vomiting, and malaise are common symptoms to consider, while abdominal or right upper quadrant tenderness may present less frequently. West Haven Criteria should be used to describe the severity of hepatic encephalopathy. DEFINITION: ALF is defined by the onset of jaundice, coagulopathy (INR over 1.5), and hepatic encephalopathy in patients with no prior history of liver disease. TESTS: FBC(infection, GI bleed), U&;E, LFTs, Clotting, glucose, Paracetamol level (if low does not exclude OD), CMV and EBV serology, alpha 1, caeruloplasmin, blood and uring culture, ascitic tap. IMAGING: Initial imaging should include CXR, to confirm possible aspiration pneumonia or to rule out other pulmonary abnormalities, and abdominal Doppler imaging to assess hepatic vein thrombosis associated with Budd-Chiari syndrome. Head CT is useful for further evaluation of cerebral oedema or other underlying pathology in advanced encephalopathy. Blood, urine, and sputum cultures should be obtained at regular intervals once advanced grade of encephalopathy develops. Although a liver biopsy may provide additional information to suggest potential aetiologies of ALF in indeterminate cases, it is not a required test to confirm a diagnosis. A liver biopsy may also be helpful in the diagnosis of conditions such as suspected autoimmune hepatitis or acute HSV hepatitis. If a liver biopsy is considered, a transjugular approach is preferable given the increased risk of bleeding associated with coagulopathy during ALF. DD: Severe acute hepatitis (may be jaundice, and bleeding problems but not HE). Cholestasis. Haemolysis.

Question 43

Name 8 causes of Liver failure?

Accepted Answer

paracetamol = most common Infection = viral hepatitis (B,C, CMV, EBV) Leptospirosis(transmited from urine of infected animals. Drugs = isoniazid, halothane Toxins = cocaine, ecstasy vascular = Budd Chiari syndrome, ischaemia Neoplastic = HCC Metabolic = Wilsons disease, galactosemia (most common carb metabolism disorder - galactose builds up) alpha 1 antitrypsin deficiency Other - HELLp syndrome(haemolysis, elevated liver enzymes, low platelets, pre eclampsia) autoimmune hepatitis, primary biliary cirrhosis

Question 44

What are CYP enzymes? Whats more common acute liver failure or acute on chronic liver failure?

Accepted Answer

host of enzymes that use iron to oxidize things. called p450 due to wavelength they absorb. they make toxic substances more soluble and so easily secreted. found in microsomal part of cytoplasm (ER). ACUTE ON CHRONIC LIVER FAILURE.

Question 45

describe the process of paracetamol poisoning?

Accepted Answer

oral APAP -- absorbed stomach and SI -- peak serum at 2 hours -- metabolised firstly by conjugation (mainly glucuronidation or sulfation) to non toxic water soluble compounds -- excreted in kidneys. In OD conjugation is saturated -- so CYP enzymes (mainly CYP2E1) oxidizes APAP producing NAPQI - hepatotoxic metabolite -- which is quickly conjugated with glutathione. This however gets overrun NAPQI binds to hepatocellular proteins and causes mitochondrial damage and oxidative stress -- hepatocellular injury and death. The presence of CYP2E1 in the kidney may be a factor in variable degrees of renal injury occasionally seen following paracetamol overdose

Question 46

What is Tx for APAP OD? Adverse effects of NAC?

Accepted Answer

N-acetylcysteine Tx (NAC) - precursor to glutathione and increases blood flow by increasing NO production. must be given within 8 hours . Adverse effects of acetylcysteine are common, including rash, urticaria, bronchospasm, and anaphylactoid reactions. Anaphylactoid reactions are immediate, systemic reactions that mimic anaphylaxis, but are not mediated by immunoglobulin E. If an anaphylactoid reaction occurs, the infusion should be discontinued temporarily and, rarely, treatment with antihistamines and/or salbutamol may be given. In most cases, the acetylcysteine infusion can be restarted at a reduced rate. Acetylcysteine protects the liver if infused up to, and possibly beyond, 24 hours of ingesting paracetamol. It is most effective if given within eight hours of ingestion, after which effectiveness declines. No proven benefit if given before 4 hours after ingestion.

Question 47

describe the clinical features in APAP OD?

Accepted Answer

assymptomatic 1st 24 hours. then necrosis - RUQ pain and jaundice. Then Acute Liver failure. Then encephalopathy, oliguria and hypoglycaemia and lactic acidosis. Liver damage is maximal three to four days after paracetamol overdose and may lead to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Therefore, despite a lack of significant early symptoms, patients who have taken an overdose of paracetamol should be transferred to hospital urgently. A number of transient metabolic abnormalities can occur, due to altered metabolism of renal prostaglandins. This may include hypokalaemia, hypophosphataemia, and metabolic acidosis with raised lactate concentrations. Paracetamol overdose is a recognised precipitant of acute haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

Question 48

What herbal therapy is important in APAP Od?

Accepted Answer

st johns wort - is a CYP450 inhibitor - used to tx depression

Question 49

In APAP OD, when is the graph applicable? what is the standard NAC regime?

Accepted Answer

The graph is applicable for samples from four hours to 15 hours after ingestion of paracetamol. Before four hours, samples may be misleading. Although the graph is often extrapolated to 24 hours, there is limited evidence to support this. Between 15 and 24 hours, the graph is close to the limit for paracetamol detection in many hospital laboratories, and so the prognostic accuracy is uncertain. If more than 15 hours have elapsed since ingestion, treatment should be considered irrespective of the paracetamol concentration. Acetylcysteine treatment should start immediately in patients who present eight to 24 hours after taking an acute overdose of more than 150 mg/kg of paracetamol, even if the plasma paracetamol concentration is not yet available. Acetylcysteine can be discontinued if the plasma paracetamol concentration is later found to be below the treatment line on the paracetamol treatment graph, provided that the patient is asymptomatic and liver function tests, serum creatinine, and INR are normal. The standard regimen of 300 mg/kg. For paracetamol overdose, the BNF recommends that acetylcysteine should be given in a total dose that is divided into three consecutive intravenous infusions over a total of 21 hours. The first infusion is about 150 mg/kg, the second is about 50 mg/kg, and the third is about 100 mg/kg. So the standard regimen totals 300 mg/kg over 21 hours. The dose of acetylcysteine is based on weight (in kg) up to a maximum of 110 kg.

Question 50

What is NAC commercial name? how does it work?

Accepted Answer

parvolex. Acetylcysteine readily crosses hepatocyte cell membranes and is deacetylated to cysteine, which can be incorporated into glutathione, therefore helping to clear NAPQI.

Question 51

management in APAP OD? Who should be referred to hospital?

Accepted Answer

Oral activated charcoal within 1 hour of ingestion measure APAP levels within 4 hr after and 15 hour after ingestion - if above line on graph give NAC. If any doubt NAC should be given without delay. Rarely, hepatotoxicity may develop with single ingestions as low as 75 mg/kg of paracetamol taken in less than one hour. Patients who have ingested 75 mg/kg or more of paracetamol in less than one hour should be referred to hospital. Administration of activated charcoal should be considered if paracetamol in excess of 150 mg/kg is thought to have been ingested within the previous hour.

Question 52

name 3 groups who perform worse in APAP OD?

Accepted Answer

underlying hepatic impairment. microsomal enzyme indution(CYP450) - alcohol, phenytoin. Acute glutathione depletion states. NAPQI concentrations are higher, particularly in people with induced activity of the P450 system (for example, people who chronically drink excessive amounts of alcohol, or people who take carbamazepine, rifampicin, or phenytoin) and in people who have insufficient glutathione in their liver (for example, malnourished people, elderly people, people with HIV infection, or people who take recurrent paracetamol overdoses).

Question 53

NAme 5 signs of liver failure?

Accepted Answer

jaundice, HE, fetor hepaticus(smell like pear drops) signs of cirrhosis and constructional aprexia (cannot copy a 5 pointed star)

Question 54

12 tests in liver failure

Accepted Answer

FbC - infection, GI bleed U+E LFT Clotting (PT/INR) glucose CMV/EBV serology ferritin alpha 1 antitrypsin deficiency caeruloplasmin ascitic tap CXR, Abdo US

Question 55

Use of ascitic drainage? CI for both ascitic drainage and tap?

Accepted Answer

Ascitic drainge: This is used to relieve abdominal pain or secondary respiratory distress in refractory ascites. However, first line therapy for reducing ascites is a combination of dietary sodium restriction and diuretics, typically using spironolactone in conjunction with furosemide. In the vast majority of cases these regimens are sufficient to reduce the ascites, but where they are ineffective or intolerable (eg due to side effects), then the ascites is classified as refractory, and ascitic drainage becomes the best option for therapeutic relief. CI to ascitic tap or drainage: Patient refusal or distress, Pregnancy, Abdominal obstruction or distended bowel loops, Cellulitis overlying the puncture site, Severe coagulopathy (most patients with chronic liver disease have mild coagulopathy, but this is generally not considered a contraindication. PROCEDURE: The needle should not puncture the rectus abdominus. Puncturing the rectus abdominus carries the risk of rupture of the inferior epigastric blood vessels as they pass through the rectus sheath. These vessels are large, and damage to them can result in considerable haemorrhage. The most common complication is the formation of an abdominal haematoma, occurs in 1%. THINGS TO DO BEFORE THE PROCEDURE: Ensure the patient has voided urine, or insert a urinary catheter prior to the procedure, in order to avoid puncturing a distended bladder. Check they have IV access. Check results of FBC, U+Es, and coagulation screen. Inform about risks: bowel perforation, infection, bleeding, hypotension, recurrence. Identify and mark the site for needle or drain insertion in the left (or if unsuitable then right) lower quadrant 15 cm lateral to the umbilicus at the edges of the rectus sheath, avoiding any distended veins or scars visible on the abdominal wall. For ascitic tap use 21G needle and Aspirate 10-20 ml of fluid and then withdraw the needle, and decant into the various bottles. When ascitic fluid samples have been bottled and labelled in sterile universal containers, they should be sent for albumin content (to be compared with serum albumin - see below), cytology, amylase (if pancreatitis suspected), microscopy and Gram stain, culture, and sensitivity. Where more than 5 litres of ascitic fluid has been drained, plasma expansion has been shown to improve clinical outcome.Withdrawal of 5 L or more of ascites can precipitate post-paracentesis circulatory dysfunction (PPCD): Hyponatraemia, Acute kidney injury and Increased plasma renin activity. Therefore albumin should be infused. Rather than other measures of protein content, the ascitic albumin level should be deducted from the serum albumin level. This gives the serum ascites-albumin gradient (SA-AG). High ascitic albumin levels indicate exudative ascites, and low ascitic albumin levels indicate transudative ascites. The SA-AG gradient correlates with the portal pressure, and is a way of correcting the ascitic albumin level against the portal pressure and serum albumin concentration. Therefore, a low SA-AG gradient is exudative, whilst a high SA-AG gradient is transudative. Causes of transudative (SAAG 11 or more g per L) include: Cirrhosis, Budd-Chiari syndrome, Veno-occlusive disease, Alcoholic hepatitis and Congestive heart failure. Causes of exudative (SAAG less than 11 g per L): Infection, Nephrotic syndrome, Malignancy, Pancreatitis. Bowel Obstruction. Ascites is always pathological. Ascites is associated with intra-abdominal malignancies, including ovarian cancer, hepatocellular carcinoma (HCC), and lymphoma. Ascites commonly recurs following drainage. Patients can be mobilised immediately after an ascitic tap. Even after ascitic drainage, provided there is no significant hypotension, there is no reason not to mobilise these patients either.

Question 56

management of liver failure? 6 things?

Accepted Answer

antidote if needed Lactulose and antiB mannitol - Decrease ICP FFP monitor glucose Liver transplant

Question 57

3 things to consider when prescribing in hepatic failure?

Accepted Answer

avoid drugs that constipate - opoids- build up of toxins warfarin effects are enhanced hepatotoxic drugs- APAP, azathioprine, isoniazid,

Question 58

Describe Paracetamol OD? HISTORY? DEFINITIONS? TESTS? TREATMENT? PROGNOSIS?

Accepted Answer

The recommended dose of paracetamol is 4 g (or 75 mg/kg) in 24 hours for an adult patient. Any ingestion exceeding this is regarded as an overdose. However, toxicity is extremely unlikely if 4 g (or over 75 mg/kg) in a period of 1 hour. The definition of hepatotoxicity after paracetamol overdose is a serum AST concentration at least 1000 IU/L. In the UK it is the most common agent of intentional self harm. 1 tablet equals 500mg. If you ingest less than 150mg/kg. so 10.5g if 70kg adult. Then risk of severe liver damage is unlikely. Current limit set so you can only buy 8g at one time (16 tablets). If you consume more than 250mg/kg or 17.5g if 70kg adult then risk of severe liver damage is likely. If you consume more than 12g in total it is potentially fatal. HISTORY: It is essential to attempt to establish the timing of the overdose as this will affect subsequent patient management. Many patients who present within the first 24 hours after ingestion of a potentially toxic dose of paracetamol will be asymptomatic. Early non-specific signs that may be present in the first 24 hours include anorexia, nausea, vomiting, or vague abdominal pain. Patients may present with reduced consciousness level or coma if they have ingested a combined preparation of paracetamol and an opioid, or have co-ingested alcohol or other drugs that may reduce the consciousness level. Clinical signs of hepatotoxicity will usually develop about 2 to 3 days after ingestion, with RUQ pain and tenderness, nausea, and vomiting; patients may become clinically jaundiced. Liver injury usually becomes maximal at 48 to 96 hours and is characterised by massive elevation of serum AST and ALT activity, mild hyperbilirubinaemia, and prolongation of the prothrombin time. Although most patients will recover, some may progress to have fulminant hepatic failure with encephalopathy, coma, and renal failure (hepatorenal syndrome). In survivors, hepatic regeneration is normally rapid and complete, with normalisation of liver function tests within 1 to 3 weeks. Renal injury is rare, and when it occurs, serum creatinine typically begins to rise soon after serum aminotransferase activity has peaked. Occasionally, renal injury occurs without liver injury. Early presentation with coma and severe metabolic acidosis without hepatotoxicity is also rare and usually associated with massive overdose (serum paracetamol level over 5290 micromol/L [800 micrograms/mL]). SPECIAL CONSIDERATIONS: For pregnant patients, the toxic dose should be calculated using the patient's pre-pregnancy weight. For patients weighing over 110 kg, the toxic dose should be calculated using a maximum of 110 kg instead of the patient's actual weight. TESTS: Serum paracetamol levels: A timed plasma paracetamol level is drawn at least 4 hours after ingestion to risk-stratify likelihood of liver injury and the need for acetylcysteine treatment. Patients who present within 4 hours following ingestion should have a paracetamol level checked at 4 hours. The serum level is plotted on a nomogram to determine whether treatment with antidote (acetylcysteine) is required. In the UK, levels are plotted on a graph showing plasma paracetamol concentration versus time from ingestion that has a single line joining 100 mg/L at 4 hours with 15 mg/L at 15 hours. In repeated supratherapeutic overdose, the level of paracetamol may be low or undetectable, and is not used to determine treatment. However, levels are used to monitor therapy. It is important to note that serum paracetamol levels cannot be used for the management of intravenous overdose of paracetamol. It is recommended that the advice of a medical toxicologist is sought regarding the management of intravenous overdose of paracetamol. AST and ALT levels: Levels are done initially and repeated in the course of patient management. Prothrombin time/INR, arterial pH, arterial lactate level, and metabolic panel with serum creatinine: These are used to monitor severity of hepatic failure and assist in patient stratification for optimal benefit in liver transplantation. OTHER TESTS: Serum salicylate level: should be checked in unconscious patients or those in whom there is a suspicion of co-ingestion of salicylates. Urine drug screen: may be used in patients who are unconscious to determine if other substances have been taken. DD: SHOCK LIVER (OCCURS IN PERIODS OF SUSTAINED HYPOTENSION). ACUTE HEP A, ACUTE HEP B. OTHER HEPATOTOXINS ( exposure to mushrooms (e.g., Amanita phalloides) or herbal preparations (e.g., cascara, chaparral, comfrey, kava, ma-huang) or HEPATOTOXIC DRUGS). TREATMENT: IN ACUTE SINGLE INGESTION: Serum paracetamol level should be checked 4 hours after ingestion or at presentation. The level should be plotted on the paracetamol treatment graph. If the plot falls on or above the appropriate treatment line, or a level will not be obtained prior to 8 hours after ingestion, the patient should be treated with acetylcysteine. If the plotted level falls below the treatment line, there is no risk of liver damage and acetylcysteine is not required. Those patients require only supportive treatment. Blood tests are done at 4 hours after ingestion and again after completion of intravenous therapy (21 hours). Blood tests should be checked 12 hours after commencing the oral regime. If the paracetamol level is undetectable and the serum AST/ALT is falling, acetylcysteine treatment can be stopped. Otherwise, paracetamol levels and serum AST or ALT should then be checked every 24 hours subsequently until the criteria are met to stop acetylcysteine (undetectable paracetamol level and falling ALT/AST). If vomiting occurs within 1 hour of oral acetylcysteine, an anti-emetic (e.g., ondansetron) is administered and oral acetylcysteine dose is re-administered. REFER FOR LIVER TRANSPLANT IF MET CRITERIA. STAGGERED PARACETAMOL INGESTION: Acetylcysteine is the treatment of choice for staggered overdose. It is given intravenously.

Question 59

DESCRIBE cirrhosis? AETIOLOGY? PATHOPHYSIOLOGY? CLASSIFICATION?

Accepted Answer

Cirrhosis is a diffuse pathological process, characterised by fibrosis and conversion of normal liver architecture to structurally abnormal nodules known as regenerative nodules. Histologically there is bridging fibrosis too. It can arise from a variety of causes and is the final stage of any chronic liver disease. It leads to portal hypertension, liver insufficiency, and hepatic failure.It is irreversible. AETIOLOGY: Cirrhosis can derive from any chronic liver disease. The most common causes are chronic hepatitis C and alcoholic liver disease, followed by non-alcoholic fatty liver disease (steatohepatitis) and chronic hepatitis B. Other less common but important causes of cirrhosis include cholestatic, autoimmune, and metabolic liver diseases. When the aetiology of cirrhosis cannot be determined, it is considered 'cryptogenic'. Metabolic disorders: non-alcoholic fatty liver disease, obesity, haemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, abetalipoproteinaemia. Cholestatic and autoimmune liver diseases: primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis. Biliary obstruction: mechanical obstruction, biliary atresia, cystic fibrosis. Hepatic venous outflow obstruction: Budd-Chiari syndrome, veno-occlusive disease, right-sided heart failure. Drugs and toxins: amiodarone, methotrexate. PATHOPHYSIOLOGY: Alcohol - both enzymes that break it down produce NADH. Excess NADH - inhibits gluconeogenesis and stimulates fatty acid oxidation and fatty deposits in liver which activate kuppfer cells - produce cytokines inflammation. chronic alcohol also upregulates P450E1 more free radicals produced which leads to inflammation. It also depletes antioxidants which again leads to inflammation. Inflammation causes stellate cells to form hyperactive fibroblastic cells and deposit collagen and proteoglycans. Increased collagen deposition causes fenestrae to decrease and capillarisation of sinusoids also the space of disse becomes thicker and stellate have contractile properties which leads to portal HTN and hepatocytes die of due to decreased perfusion of nutrients as space of disse thicker. BMJ VERSION: This leads to an accumulation of collagen types I and III in the hepatic parenchyma and space of Disse. The result of collagen deposition in the space of Disse is termed 'capillarisation' of the sinusoids, a process in which the hepatic sinusoids lose their characteristic fenestration, thereby altering the exchange between hepatocytes and plasma. With activation, hepatic stellate cells also become contractile, which may be a major determinant of increased portal resistance during liver fibrosis and cirrhosis. This process is usually progressive and perturbs blood flow through the liver, thereby leading to increased pressure within the portal venous system, as well as shunting blood away from the liver. These changes lead to portal hypertension, which underlies ascites and the development of gastro-oesophageal varices, as well as the diversion of nutrient-carrying blood from passing through the liver. This, along with the loss of functional hepatocytes from progressive liver injury, contributes to the loss of normal protein production from the liver, leading to malnutrition which contributes to ascites formation, and reduction in clotting factors. Furthermore, the normal liver helps to detoxify portal blood and, when the blood flow is disturbed, these products from the intestine bypass the liver and reach the brain, contributing to hepatic encephalopathy. CLASSIFICATION: COMPENSATED: In compensated cirrhosis, biochemical, radiological, or histological findings consistent with the pathological process of cirrhosis are present with preservation of hepatic synthetic function and no evidence of complications related to portal HTN, such as ascites, gastro-oesophageal varices and variceal bleeding, hepatic encephalopathy, and/or jaundice. DECOMPENSATED: occurs when there is evidence of the development of complications of liver dysfunction with reduced hepatic synthetic function and portal HTN including ascites, gastro-oesophageal varices and variceal bleeding, hepatic encephalopathy, and/or jaundice.

Question 60

How much liver parenchyma needs to be destroyed before signs of liver failure? What are some causes of hepatic decompensation? What has acute on chronic liver failure been described as?

Accepted Answer

80-90%. Infection/sepsis (urinary, chest, cholangitis), Alcohol related hepatitis or alcohol consumption. Drugs (NSAIDs, others), GI Bleeding (variceal and non variceal). Ischaemic Liver injury (sepsis or hypotension). Acute portal vein thrombosis. Development of HCC. Been described as a distinct type of hepatic decompensation accompanied by extrahepatic organ failure, systemic inflammation, and susceptibility to infection.

Question 61

APPROACH TO CIRRHOSIS? SIGNS/SYMPTOMS of cirrhosis?

Accepted Answer

Look for risk factors, Full exam. A full panel of blood tests and an upper GI endoscopy should also be undertaken in all patients. Cirrhosis should be differentiated from non-cirrhotic conditions that can also lead to portal HTN. These include disorders such as constrictive pericarditis; vascular disorders such as Budd-Chiari syndrome, portal vein and splenic vein thrombosis, and inferior vena cava obstruction; infectious agents such as schistosomiasis; sarcoidosis, nodular regenerative hyperplasia, and idiopathic portal hypertension, also known as hepatoportal sclerosis. It is also important to exclude exposure to substances that may cause portal hypertension such as vitamin A intoxication and arsenic. As well, certain non-hepatic conditions may lead to the development of cirrhosis, as is the case with congestive hepatopathy where congestive heart failure or cardiopulmonary disease lead to passive hepatic congestion, which may lead to cirrhosis with time. Patients with cirrhosis may be asymptomatic or have non-specific constitutional symptoms, such as fatigue, weakness, and weight loss, as well as recurrent infections and decreased libido. Symptoms of decompensation include abdominal distension due to ascites and hepatomegaly, coffee-ground vomitus and black stool (melaena) secondary to GI haemorrhage, altered mental status in hepatic encephalopathy, lower extremity swelling, jaundice, and pruritus. Other less common symptoms associated with pulmonary complications of portal hypertension include dyspnoea on exertion. In patients with hepatopulmonary syndrome, platypnoea (shortness of breath with sitting up) and orthodeoxia (deoxygenation with sitting up) are classically described; patients may also develop clubbing and cyanosis. In portopulmonary hypertension patients may develop syncope and chest pain/pressure. As all forms of chronic liver disease have the potential to cause cirrhosis, their presence should be elicited. Any history of metabolic syndromes (diabetes, dyslipidaemia, obesity, HTN) or autoimmune disorders should be sought. Any history of past blood transfusions should be elicited. SIGNS/SYMPTOMS: jaundice, scratch marks, splenomegaly, palmar erythema, bruising, leuconychia (hypoalbuminae) Terrys nails (white prox reddended distally) clubbing, dupuytrens contracture, spider naevi, gynaecomastia, xanthelasma (primary biliary cirrhosis), parotid enlargement, asterixis. Cyanosis and finger clubbing in patients with hepatopulmonary syndrome. Other physical findings include hepatic fetor, muscle wasting, and peripheral oedema, and findings of elevated right heart pressure such as elevated jugular venous pulse, increased split of the second heart sound, and pulsatile liver in patients with portopulmonary hypertension.

Question 62

symptoms of cirrhosis? 9 things?

Accepted Answer

fatigue malaise anorexia nausea weight loss easy bruising poor conc bleeding oesophageal varices, ascites.

Question 63

5 complications of liver failure? 3 signs of portal HTN?

Accepted Answer

coagulopathy, hypoglycaemia, encephalopathy, hypoalbuminae, sepsis ascites = caput medusae, ascites, splenomegaly

Question 64

Tests in cirrhosis?

Accepted Answer

LFTs (Normal AST and ALT levels do not preclude the diagnosis of cirrhosis.), albumin, PT/INR, U+E (Hyponatraemia is a common finding in cirrhotic patients with associated ascites and worsens as the liver disease progresses). IRON studies for HH. Viral serology, autoantibodies (antinuclear (ANA) and antismooth muscle (SMA) for autoimmune hepatitis and antimitochondrial (AMA) for primary biliary cirrhosis). alpha fetoprotein (The finding of an elevated alpha-fetoprotein in a patient with cirrhosis should raise the concern for the development of hepatocellular carcinoma. However, this tumour marker may also be elevated on the basis of chronic liver disease and inflammation in the absence of hepatocellular carcinoma), caeruloplasmin (wilsons), alpha 1 antitrypsin. US, CT or MRI. USS is done first. It can also be used to screen for HCC. Ascitic tap. It is recommended that all patients with cirrhosis undergo upper GI endoscopy for screening of gastro-oesophageal varices at the time of diagnosis and at 1- to 3-year intervals thereafter. Liver biopsy remains the most specific and sensitive test for the diagnosis of cirrhosis. However, it is not necessary in patients with advanced liver disease and typical clinical, laboratory, and/or radiological findings of cirrhosis unless there is a need to determine the degree of inflammation, or aetiology. Ultrasound-based elastography is a promising tool for detecting hepatic fibrosis and cirrhosis without the need for liver biopsy.

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