Seminar 9 - Hepatobiliary Disease Flashcards

Question

What causes hyperoestrogenemia in liver failure

Answer 1

They will have impaired oestrogen metabolism leading to rising levels

Answer 2

Most sadly succumb to disease

Answer 3

It stores about 50 ml of bile which produced by the liver until the body needs it for digestion, at which point it release it

Answer 4

Cholelithiasis - gallstones Acute and chronic cholecystitis Gallbladder cancer - cholangiocarcinoma

Answer 5

Causes within the liver Includes: hepatitis, alcohol related liver disease, PBC, certain drugs, cholestasis of pregnancy and cancer that has spread to the liver

Answer 6

Urobilinogen

Answer 7

uptake and conjugation problems

Answer 8

Liver function and blood coagulation

Answer 9

IV antibiotics and IV fluids Nil by mouth US to confirm diagnosis May require an urgent cholecystectomy if a gallstone ileus

Answer 10

Inflammatory bowel disease - typically UC Around 2/3 of PSC patients will have it Only 8% of UC patients have PSC though

Answer 11

Chronic hep b infection that’s either medically suppressed but there are now viral mutants not controlled by meds or a superimposed hep D infection on top of chronic hep B Patients with chronic PSC or fibropolycystic disease with superimposed ascending cholangitis

Answer 12

Piperacillin and tazobactam empirically then specific management. If high risk given ciprofloxacin prophylactically

Answer 13

Leukemia/lymphoma - 33% Breast - 30% Colon - 7%

Answer 14

Symptoms must occur within 26 weeks of the liver injury Typically occur within 8 weeks

Answer 15

A type of cholecystitis where the exudate is virtually pure pus

Answer 16

Excretory issues

Answer 17

Iron becomes evident first as golden-yellow hemosiderin granules in cytoplasm of periportal hepatocytes that stain with Prussian blue You then get progressive deposition in the rest of lobule, bile duct epithelium, Kupffer cells

Answer 18

True If the liver is transplanted the lungs will return to normal within the following year

Answer 19

True | This occurs in around 40% of patients

Answer 20

Features are variable and sometimes minimal Serosa is usually smooth and glistening but maybe doubled by fibrosis Fibrous adhesions represents prior acute inflammation The wall is variably thickened and has an opaque grey white appearance The mucosa itself is generally well preserved

Answer 21

The amount taken The persons GSH reserves Other medications - long term treatment with cytochrome P450 inducers

Answer 22

Prominent neutrophils (can satellite around ballooned hepatocytes) Common lymphocytic infiltrates Spotty necrosis/apoptosis

Answer 23

Clinical symptoms cholecystitis tend to be more insidious since they are obscured by the underlying conditions precipitating the attack It is harder to diagnose and therefore has a higher mortality

Answer 24

Excessive amounts of copper accumulate in liver This leads to fibrous/granular hardening in soft tissue of liver Eventually results in cirrhosis

Answer 25

Caused by excessive iron absorption, most of which is deposited in the liver & pancreas Can be hereditary or secondary

Answer 26

Fatty acids can undergo B-oxidation in the liver They are used in TCA cycle or to make ketone bodies - energy Occurs during stress and fasting

Answer 27

hormonal effects on bile flow during pregnancy

Answer 28

A drug/ toxin ( i.e. paracetamol overdose)

Answer 29

NO | It is water soluble

Answer 30

``` Amiodarone Methotrexate Isoniazid Phenytoin Nitrofurantoin Methyldopa ```

Answer 31

The reported incidence has increased in recent years | However, the increase is probably due to improvement in data collection and analysis.

Answer 32

A pear-shaped organ which is is about 7–10cm long and dark green in colour Connects to the hepatobiliary system via the cystic duct Has a muscular wall which contracts to release bile

Answer 33

Does not have the striking manifestations of the acute form | It is usually characterized by recurrent attacks of steady epigastric or right upper quadrant pain

Answer 34

Drug induced liver injury

Answer 35

It is deconjugated in the lumen of the colon by bacterial B-glucuronidases This produces urobilinogen

Answer 36

The appearance of bile within the elements of the liver, usually associated with secondary cell injury

Answer 37

Caused by dilatation of intrapulmonary capillaries and pre-capillary vessels up to 500um in size This is potentially caused by the diseased liver not clearing factors such as endothelin 1 that will stimulate endothelial cell production of vasodilators such as NO

Answer 38

Multi-drug resistance 3

Answer 39

Managed by renal team and may require haemodialysis/haemofiltration

Answer 40

Slight male predominance

Answer 41

These drugs cause mitochondrial dysfunction which leads to microvesicular steatosis

Answer 42

Majority is produced through the breakdown of RBC by reticuloendothelial macrophages in the spleen, liver and bone marrow. The rest comes from turnover of proteins containing haem in the liver - P450 cytochromes

Answer 43

False - ish It typically affects the large and medium ducts Smaller intra-hepatic ducts are not directly involved in inflammation but may have mild injury + prominent ductular reaction due to cholestasis. You do get atypical cases of small-duct PSC!

Answer 44

Drug interference | Seen in some Gilberts patients

Answer 45

Occurs as a co-infection Causes acute hepatitis which is self-limiting Superinfection: 80% chronic HDV (minority: clearance

Answer 46

Liver disease such as: Cirrhosis - decreased production Inflammation - acute phase response temporarily decreases production Protein-losing enteropathies or nephrotic syndrome - excessive loss of albumin

Answer 47

False Not all substances are retained to the same extent in various cholestatic disorders In some conditions, serum bile salts may be markedly elevated while bilirubin is only modestly elevated and vice versa. However, demonstrable retention of several substances is needed to establish a diagnosis of cholestasis

Answer 48

Usually manifests within 8 weeks of liver injury with many patients progressing to coma within a week

Answer 49

Usually characterized by the presence of glands embedded in desmoplastic stroma In some cases cytologic atypia and stromal response are minimal -> in these instances identification of perineural and vascular invasion help establish the diagnosis

Answer 50

Gallbladder large and distended - tense Bright red blotchy violaceous to green-black discolouration imparted by subserosal haemorrhages The serosa is frequently covered by a fibrous exudate that may be fibrinopurulent in severe cases

Answer 51

Women - 90% of patients are female

Answer 52

The liver breakdown excess amino acids from the diet and metabolises them to a form that can be used or excreted

Answer 53

will cause intracranial bleeds and DIC

Answer 54

``` Specific demographic populations (Native Americans) Age ++ Female (oc pill, pregnancy, hormones) Obesity/metabolic syn. Rapid weight loss ```

Answer 55

Penacillamine

Answer 56

Through fluid overload, secondary infection, organ damage and coma If left untreated many patients will die in first weeks of the syndrome with 50% dying in 2 weeks and 80 % in 3 months

Answer 57

Slightly enlarged, dense & chocolate brown colour (dark brown to nearly black liver parenchyma) Colour is due to extensive iron deposition Also get fibrous septa development This creates a small, shrunken liver w/ micronodular pattern of cirrhosis

Answer 58

neuroendocrine tumours, squamous cell carcinoma and sarcomas

Answer 59

Cirrhosis Diabetes Heart failure Can lead to organ failure

Answer 60

Pigment gallstones are complex mixtures of calcium salts (insoluble ones from unconjugated bilirubin and inorganic ones) Disorders that are associated with elevated levels of unconjugated bilirubin in bile increase the risk of developing pigment stones e.g. haemolytic anaemia, severe ileal dysfunction or bypass, bacterial contamination of biliary tree

Answer 61

Presents as dyspnoea and cyanosis | The dyspnoea is worse in the upright position due to gravity exacerbating the ventilation perfusion mismatch

Answer 62

True | Because they are so unwell in the first place

Answer 63

Infection HE Multi-organ failure in that order

Answer 64

There will be established cirrhosis and extensive vascular shunting due to existing chronic liver disease This means there is a large amount of liver parenchyma with a borderline vascular supply making it vulnerable If there is a superimposed insult the liver is more likely to decompensate severely causing the acute on chronic liver failure

Answer 65

The aetiology is not well understood The frequent presence of circulating serum auto-antibodies, association with autoimmune diseases (UC) and the association with certain HLA haplotypes suggests that PSC is an immune-mediated disorder - though not a classic autoimmune Likely has a trigger (unknown - environmental or immunological) in a genetically susceptible individual Theory that effector T-cells which were activated e.g., during colitis, migrate to liver where they recognise a cross-reacting bile duct antigen Infections or changes to intestinal microbiome recruit mucosal T cells to the liver and incite changes in cholangiocytes causing inflammatory injury

Answer 66

Fatty acids can be synthesised within the hepatocytes

Answer 67

carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, rifabutin, efavirenz, nevirapine, and St John’s wort

Answer 68

Scattered lymphocytes, plasma cells and macrophages in mucosa and in subserosa

Answer 69

False They do not Also don't predict response to therapy

Answer 70

Occurs in first 24hrs | Can be symptomatic or present with N+V and abdominal pain

Answer 71

``` Alanine transaminase (ALT) Aspartate aminotransferase (AST) Alkaline phosphatase (ALP) Gamma-glutamyltransferase (GGT) Bilirubin Albumin Prothrombin time (PT) ```

Answer 72

Bile is the digestive fluid produced by hepatocytes | It plays a critical role in the elimination of bilirubin, excess cholesterol and aids in fat absorption

Answer 73

AKI that often accompanies paracetamol toxicity | May see renal tubular necrosis as a result

Answer 74

Main causes; chronic hep b and c infection, NAFLD/NASH, alcoholic liver disease Additional causes ; PBC, PSC, nodular regenerative hyperplasia, chronic schistosomiasis, fibropolycyctic liver disease, hemochromatosis, a 1 antitrypsin deficiency, Wilsons disease, Budd-Chiari syndrome, autoimmune hepatitis and drugs Can also be idiopathic

Answer 75

More common in children than adults Seen in 35% of childhood cases of PSC So they also present younger

Answer 76

False | Can be caused by unconjugated or conjugated bilirubin.

Answer 77

subepithelial and subserosal fibrosis accompanied by mononuclear cell infiltration

Answer 78

This is when there's a buildup of cholesteryl esters and they stick to the wall of the gallbladder forming polyps It is associated with cholesterol gallstones

Answer 79

Only given blood products if bleeding is an issue ( FFP and platelets would be given) May be given phytomenadione 10mgIV

Answer 80

Prominent lymphoid aggregates/ fully formed lymphoid follicles in portal tracts - portal tracts expand Steatosis (common) Bile duct injury

Answer 81

Cholecystitis is inflammation of the gallbladder that develops over hours Usually because a gallstone obstructs the cystic duct

Answer 82

liver transplant

Answer 83

Conjugated

Answer 84

500-1,000mg QDS to a maximum of 4,000mg/day

Answer 85

No | Can be abnormal in around 17% of the population and normal LFTs doesnt always exclude liver disease.

Answer 86

1st line: Antihistamines (mild-mod itch) 2nd line: Cholestyramine and colestipol (bile binding resins) 3rd line: rifampicin

Answer 87

Bacterial B-glucuronidases

Answer 88

Inflammation of the gallbladder May be acute, chronic or acute superimposed on chronic It’s almost always occurs in association with gallstones

Answer 89

Patients may be asymptomatic at diagnosis - around 50% Some will present with or develop symptoms of pruritus and jaundice. Ascending cholangitis, chronic pancreatitis and chronic cholecystitis can also be the PC

Answer 90

No effective medical therapy is available. Cholestyramine (bile acid-binding resin) used to alleviate pruritus. Endoscopic dilatation or stenting can relieve biliary obstruction Liver transplantation is the only treatment option for patients with advanced liver disease

Answer 91

Causes a hepatocellular pattern of injury This can lead to acute hepatitis dominated by inflammation & necrosis Similar to viral & autoimmune hepatitis Centrizonal necrosis

Answer 92

Tend to not show scar formation or regeneration because they take place over hours to days - not enough time for formation May see confluent necrosis in the perivenular region and preserved areas of normal liver

Answer 93

Progressive destruction of the liver parenchyma that occur over a period greater than 6 months Results in fibrosis and cirrhosis

Answer 94

Fatigue Pruritus Symptoms slowly increase over time ``` Also get hypercholesterolaemia (xanthelasmas), steatorrhea and vitamin D malabsorption related osteomalacia May see hyper-bilirubinaemia – jaundice RUQ pain Other autoimmune diseases Splenomegaly ± portal HTN (Adv. Disease) ``` OR could be asymptomatic

Answer 95

Raised ALT and AST - released from the injured hepatocytes Acute: raised ALT and AST, normal/raised ALP and GGT, bilirubin is usually also raised. Chronic: ALT/AST and ALP/GGT and bilirubin are all normal or raised.

Answer 96

obstructive causes and hepatocellular causes

Answer 97

HE Oesophageal variceal bleed Bacterial infections Hepatocellular carcinoma

Answer 98

In the liver

Answer 99

Most common - Graft infection or Sepsis Bleeding, clotting, failure or rejection of the liver, bile duct leakage and shrinkage, infection, mental confusion and seizures The immunosuppression used in the transplantation process can cause osteoporosis, diabetes, high cholesterol and HTN

Answer 100

Usual outcome: Persistent infection and chronic hepatitis | Chronic disease in 80-90% HCV-infected individuals; 20% progress to cirrhosis

Answer 101

They can be reabsorbed from the intestines and brought back to the liver (enterohepatic circulation) to be taken up by the hepatocytes This restores the pool of acids

Answer 102

increasing age will increase rate of progression

Answer 103

Obstruction - gallstone, tumour | Cholangiopathies - PBC, PSC

Answer 104

Conjugated

Answer 105

Intensely pigmented - brown

Answer 106

Cholestasis | Obliterated central veins

Answer 107

It is an autoimmune disease so likely a mixture of genetics and environment

Answer 108

Ongoing injury and continued destruction of the bile ducts results in secondary parenchymal damage, fibrosis, cirrhosis, and end-stage liver disease

Answer 109

True | A raised ALP is often how the disease is detected in them.

Answer 110

Areas of necrosis Collapse of liver lobules Seen as ill-defined areas that are pale yellow

Answer 111

Increase activity levels (esp. post-menopausal women). | Bisphosphonates, esp. alendronate.

Answer 112

The bilirubin enters the bloodstream bound to serum albumin and is transported to the liver. It is taken up by the hepatocytes at their sinusoidal membranes. Sinusoids are where blood passes through the hepatocytes

Answer 113

``` Tablets/ capsules Soluble Liquid Suppositories IV ``` It and is widely available OTC, either alone or in combination with other analgesics

Answer 114

May have mixed picture - both conjugated and unconjugated in blood

Answer 115

Yes - it develops over days to weeks | Although it is much more common in chronic failure

Answer 116

1) supersaturation of bile with cholesterol 2) hypomotility of the gallbladder 3) accelerated cholesterol crystal nucleation 4) hypersecretion of mucus in the gallbladder, which traps the nucleated crystals leading to accretion of more cholesterol and the appearance of macroscopic stones

Answer 117

A toxic dose taken over more than 1 hour | >150mg/kg within 24hrs may produce serious toxicity

Answer 118

Cholesterol stones - composed mainly of crystalline cholesterol monohydrate Pigment stones - composed mainly of bilirubin calcium salts Most cases are a mix of both.

Answer 119

False | It is a disease of non-smokers

Answer 120

Can develop spontaneous bacterial peritonitis Bacteria, usually E. coli, strep pneumonia or klebsiella, seep through the peritoneal membrane from the GI tract to cause inflammation and infection

Answer 121

The incidence is higher in the intensive-care population, particularly in patients in burn and trauma units.

Answer 122

False | It's a misnomer - the pain is usually constant

Answer 123

More than 10-fold increase in ALT and a less than 3-fold increase in ALP

Answer 124

Papilla is regulated by the sphincter of odi

Answer 125

Liver inflammation (alcoholic hepatitis) & Fibrosis: Prominent Ballooned hepatocytes Inflammation & necrosis Perivenular/Pericellular fibrosis

Answer 126

True | 98% specificity

Answer 127

Steatosis, Lobular inflammation, Ballooned hepatocytes Steatosis appears as mixed small and large fat droplets When established: steatosis/ballooned hepatocytes may be reduced or absent Mallory hyaline, Neutrophilic infiltrates Fibrosis develops around central vein as a fine “chicken wire pattern” of pericellular collagen deposition - individual and clustered hepatocytes are surrounded by thin scars This can progress to periportal and bridging fibrosis and eventually cirrhosis

Answer 128

All of the bile constituents are moved across the canicular membrane of the hepatocytes by a variety of transporter proteins.

Answer 129

Characterised by inflammatory destruction of small- and medium-sized intrahepatic bile ducts Eventually the ducts will be lost and fibrosis develops as a consequence

Answer 130

Starts with an unknown trigger - genetic or environmental Could be something like infection or chemicals in genetically susceptible individuals The trigger leads to the formation of auto-antigens against bile duct epithelial cells T-lymphocytes will then start to attack auto-antigens” expressed on bile duct cells This leads to injury which causes retention of bile salts (toxic substances build up) and secondary hepatocellular injury occurs Anti-microbial antibodies (AMAs) also play a role

Answer 131

Phagocytic enzymes

Answer 132

Palmar erythema - due to local vasodilatation) Spider angioma - central arteriole that is dilated and pulsating with small vessels radiating from it Hypogonadism - causing testicular atrophy, hair loss and gynaecomastia in men

Answer 133

Excess glucose is stored as glycogen in the liver and can be converted back to glucose when required (e.g. exercise) The liver can also generate glucose (gluconeogenesis) through the conversion of amino acids, lactate, pyruvate and glycerol

Answer 134

Due to alterations of bile formation and flow causing retention of bilirubin and other solutes that are normally eliminated in bile

Answer 135

Flat in-situ lesions with varying degrees of dysplasia Mass forming adenoma-like lesions termed intracystic papillary tubular neoplasm Intestinal metaplasia.

Answer 136

True | May require administration of fat-soluble vitamins and monitoring

Answer 137

Cholelithiasis (gallstones) | because of the close relationship between the two.

Answer 138

Inflammation and injury of the medium- and large-sized bile ducts, leading to fibrosis and multi-focal stricturing of the ducts

Answer 139

Characterised by varying combinations of cholestasis & ductular reactions This can lead to chronic cholestasis

Answer 140

Most commonly has massive hepatic necrosis and broad areas of parenchymal loss which will be surrounded by islands of either preserved or regenerating hepatocytes Affected livers are usually small and shrunken and may be soft and congested Rarely ALF may have widespread liver cell dysfunction without obvious cell death

Answer 141

Liver disease/dysfunction.

Answer 142

False | the risk diminishes with time

Answer 143

Enlarged heart with hemosiderosis (striking brown coloration)

Answer 144

Enlarged, soft, yellow, greasy - fatty liver Fatty change: completely reversible if abstention from further intake of alcohol Macrovesicular steatosis - predominant; (Unusual) Microvesicular steatosis: alcoholic foamy degeneration Seen in chronic heavy alcohol use This is also associated with ER & mitochondrial damage

Answer 145

Causes swelling of periportal hepatocytes (clear cytoplasm’s w/ granular strands, aka. feathery degeneration) May develop Mallory hyaline.

Answer 146

Cirrhosis Fibrosis - pattern will vary with cause Parenchymal nodules - variable size Vascular thrombosis - extent varies

Answer 147

Will present with rigidity, hyperreflexia and asterixis | It has the potential to cause seizures and cerebral oedema (and the associated symptoms)

Answer 148

Can indicate the cause ALT > AST suggests chronic liver disease AST > ALT suggests cirrhosis and acute alcoholic hepatitis

Answer 149

Lipid peroxidation via iron-catalyzed free radical reactions Stimulation of collagen formation by activation of hepatic stellate cells Interaction of ROS and iron with DNA - leads to lethal cell injury (predisposes the person to HCC)

Answer 150

Bilirubin, bile salts, cholesterol and phospholipids.

Answer 151

Inflammation variable Rokitansky-Aschoff sinuses - forms a pocket? Other findings – porcelain gallbladder (very rare), hyalinizing cholecystitis, xanthogranulomatous cholecysitis and hydrops of the gallbladder

Answer 152

Involves the basal ganglia

Answer 153

Cholestasis is observed in people of every age group However, newborns and infants are more susceptible due to immature livers

Answer 154

A toxic dose taken within 1 hour | >75mg/kg is generally considered the threshold for serious toxicity

Answer 155

GI bleeds, high alcohol intake, alcoholic hepatitis or drug induced liver injury BUT no cause is found in 50% of decompensations

Answer 156

Viral infection Will also see regeneration This is because the insult occurs over weeks to months so has time to occur

Answer 157

Conjugated This is because it is water soluble Therefore can be picked up on urine tests

Answer 158

Often antimicrobial drugs | Occur after 1-3 months of exposure

Answer 159

Acetaldehyde (product of alcohol dehydrogenase) CYP2E1 induction Impaired methionine metabolism Damage caused by these causes inflammation With chronicity you get liver fibrosis & deranged vascular perfusion

Answer 160

``` Cholestasis Hepatic encephalopathy Coagulopathy Ascites Portal HTN Hepatorenal syndrome Hepatopulmonary syndrome Multiorgan failure ``` Also infections, circulatory collapse and metabolic acidosis and renal failure

Answer 161

Maintenance of blood glucose (carbohydrate metabolism) Lipid metabolism – both lipogenesis and lipolysis Protein synthesis Protein catabolism Ammonium metabolism Vitamin D activation

Answer 162

Middle-aged to old people

Answer 163

They initially will have an enlarged liver due to hepatocyte swelling, inflammatory infiltrate and oedema but it will shrink dramatically as the parenchyma is destroyed

Answer 164

Women - 3 times more common | Up to the age of 50 years, and is about 1.5 times more common in women than in men thereafter

Answer 165

Cytolysis with centrilobular necrosis

Answer 166

False | Most patients are free of jaundice

Answer 167

Strawberry gallbladder - looks like one | Foamy lipid laden macrophages in the lamina propria

Answer 168

No treatment but supportive care of chronic liver disease complications May become chronic

Answer 169

90% of cases caused by gallstone | The other 10% are acalculus

Answer 170

Portal hypertension is the triggering event Confounded by increased production of vasodilators by endothelial cells in the splanchnic vasculature This causes systemic vasodilatation and renal hypoperfusion leading to RAAS activation In the setting of Portal Hx and persistent vasodilator release the main effect of RAAS is to further reduce GFR and renal perfusion = renal failure

Answer 171

Above 2-2.5mg/dL (normal level is between 0.3 and 1.2 mg/dL)

Answer 172

Jaundice Cholangitis Acute Pancreatitis

Answer 173

Early changes of acute cholecystitis include oedema congestion and mucosal erosion. neutrophils are sparse unless there is superimposed infection

Answer 174

It is a chronic autoimmune disease in which the intrahepatic bile ducts i are slowly destroyed. Previously called primary biliary cirrhosis

Answer 175

The amount that is unbound (instead of bound to albumin) also rises and can exert its toxic effect on the tissues In brain it causes neuro issues such as kernicterus

Answer 176

Occurs after 96 hours or more The resolution phase Clinical recovery and normalisation of LFTs in 3-4 weeks Complete histological recovery will take several months

Answer 177

It is a chronic progressive cholestatic liver disease, characterised by inflammation and fibrosis of the intrahepatic and/or extrahepatic bile ducts, resulting in diffuse, multi-focal stricture formation. Preserved segments become dilated

Answer 178

Start with painkillers, low fat diet and weight loss and observe for 3-6 months If Recurrent episodes of pain / colic then consider / refer for surgery Cholecystectomy is the surgery of choice (usually laparoscopic) If unfit for surgery – Ursodeoxycholic acid 10mg/kg/day

Answer 179

It is released from hepatocytes in the liver and travels via canaliculi to intralobular ducts then the collecting ducts before entering the left and right hepatic ducts. These converge to form the common hepatic duct. This duct is joined by the cystic duct which connects to the gall bladder. This meeting point is the beginning of the common bile duct. The CBD passes posteriorly to the first part of the duodenum and head of the pancreas before joining the main pancreatic duct. This forms the hepatopancreatic ampulla (commonly known as the ampulla of Vater). Both ducts can empty into the second part of the duodenum via the major duodenal papilla.

Answer 180

Affects 10-20% of adults in high income countries, uncommon in low-income countries

Answer 181

Alcoholic liver disease Chronic hep B and C infections NAFLD/NASH Haemochromatosis

Answer 182

Men | male-to-female ratio of 2:1

Answer 183

Phase I metabolism consists of reduction, oxidation, or hydrolysis reactions. These reactions serve to convert lipophilic drugs into more polar molecules by adding or exposing a polar functional group

Answer 184

``` PT >20 seconds or INR >2.0 pH < 7.3 or [ H+] > 50 Hypoglycemia Conscious level impaired Creatinine > 200 mmol/l Any patient with encephalopathy, coagulopathy or renal impairment ```

Answer 185

Diarrhoea or pale stools

Answer 186

Not specifically The only real difference is the presence or absence of the calculus

Answer 187

Via phase II enzymes | It undergoes hepatic sulfation and glucuronidation before being excreted in the urine (the products are urine soluble)

Answer 188

Cryptogenic liver failure

Answer 189

``` Sepsis Immune suppression Major trauma Diabetes Infection ```

Answer 190

Characteristic slate-gray skin pigmentation

Answer 191

Child Pugh, MELD-Na and UKELD scores | CP > 12 has a mean survival of 6 months

Answer 192

direct acting antivirals, interferon- alpha

Answer 193

When it is not required in the GI tract - between meals

Answer 194

Using the Kings College score

Answer 195

Requires several months

Answer 196

Involved in the metabolic activation of vitamin D | Converts it to calcifediol before being transported to kidneys for final steps of activation

Answer 197

Through severe hypoxemia and respiratory failure

Answer 198

Poisoning - e.g. paracetamol overdose Infection - Hep A or B Ischaemia of liver.

Answer 199

obstructive bile duct lesion, small-duct PSC, drug-induced cholestasis.

Answer 200

Rarely greater than 1.5 centimeters in diameter They are almost invariably present in great number with an inverse relationship between size and number (greater the number the smaller the size)

Answer 201

Caused by the hypothalamic pituitary axis dysfunctioning either because of nutritional deficiency or primary hormonal changes They will have altered menstruation and fertility

Answer 202

Ursodeoxycholic acid - acts to increase bile formation Phenobarbital - in chronic cases

Answer 203

Jaundice - may be minimal at early stages N and V Then progresses to hepatic encephalopathy and coagulopathy May see hypoglycaemia and hepatic foetor (musty smelling breath)

Answer 204

phlebotomy, iron chelators

Answer 205

Liver Brain Cornea Kidneys

Answer 206

Jaundice is a yellow discoloration of the skin, mucosa and or/sclera

Answer 207

heart, lungs and kidneys

Answer 208

Defined by the presence of jaundice, coagulopathy and encephalopathy in pts with no prior liver disease

Answer 209

Presents as jaundice and icterus | Causes an increased risk of bacterial infection that can be life threatening

Answer 210

Promoting formation of free radicals by Fenton reaction - reactive oxygen species cause liver damage and cirrhosis Binding to sulfhydryl groups of cellular proteins Displacing other metals from hepatic metalloenzymes

Answer 211

Haem oxygenase

Answer 212

True | Biliary intraepithelial neoplasia can develop and eventually lead to cholangiocarcinoma

Answer 213

``` HLA class II on hepatocyte surface allows exposure of liver cell membrane constituents to APCs They present antigens to TH0 ``` ``` TH1: IL-2 & IF-γ -> enhance expression of HLA class I & II TH2: Interleukins 4, 5 and 10 -> stimulate autoantibody production by B lymphocyte ```

Answer 214

Due to persistent cholestasis It can result in the patients scratching their skin raw – seen clinically It can also lead to life threatening bacterial infections

Answer 215

Rarely greater than 1.5 centimetres in diameter They are almost invariably present in great number with an inverse relationship between size and number (greater the number the smaller the size)

Answer 216

The exact mechanism of acalculous cholecystitis is unclear It may be due to ischaemia - inflammation and oedema of the wall can compromise blood flow Injury may be the result of retained concentrated bile (extremely noxious substance) Can be caused by accumulation of microcrystals of cholesterol a.k.a. biliary sludge - viscous bile and mucus causing cystic duct obstruction in the absence of stones In the presence of prolonged fasting, the gallbladder does not receive a cholecystokinin (CCK) stimulus to empty SO the concentrated bile remains stagnant in the lumen

Answer 217

Usually markedly elevated but may fall due to hepatocyte death ( not a sign of improvement)

Answer 218

False | Ducts are too small to be detected using radiology such as MRCP so must rely on lab results

Answer 219

Primary bile duct stones | They develop in the dilated, backed up ducts

Answer 220

It is increasing

Answer 221

Nonalcohol fatty liver disease Presence of hepatic steatosis in individuals who do not or seldom consume alcohol Cause lipid to accumulate in hepatocytes

Answer 222

Starts in acinar zone 3 as pericellular or perisinusoidal, fibrosis with a “chicken wire” appearance Continued damage leads to portal/periportal fibrosis then bridging fibrosis & cirrhosis (”Laennec cirrhosis”) Chances of full restoration of normal function diminish

Answer 223

True | Malnourished patients should be given thiamine and folate supplements

Answer 224

Chronic liver disease

Answer 225

diabetic patients who have symptomatic gallstones

Answer 226

Can cause cerebral oedema which is potentially fatal through raising ICP

Answer 227

YES | Recurs in 15-20%

Answer 228

75% of Native Americans have cholesterol stones. Non-Western groups normally pigment stones arising due to bacterial infection.

Answer 229

They range up to several centimeters in diameter rarely a very large stone may virtually fill the fundus.

Answer 230

Most asymptomatic – may be decades before symptoms develop ``` Biliary colic is the main symptom: Stone impacts in cystic duct causing a gradual build-up pain in RUQ Radiates to back / shoulder May last 2-6 hours Associated with indigestion / nausea ```

Answer 231

Endothelial injury to sinusoids and central veins | This causes sinusoidal obstruction syndrome

Answer 232

It can occur at any age (including childhood) Typically presents during the third - fifth decade of life, with a mean age of 40 years at the time of diagnosis

Answer 233

Chronic inflammation causes injury that is centered on the bile ducts Develop vanishing bile duct syndrome Loss of bile ducts and overt ductopenia This can progress to cirrhosis and liver failure

Answer 234

Disease is reversible and can affect the overall function of your liver Failure is irreversible and considered the final stage of many liver diseases Includes any condition that causes the loss of some/all functionality of your liver

Answer 235

Obstruction of hepatic bile ducts leads to proximal duct dilation The hallmark on liver biopsies is portal expansion due to oedema, prominent ductular reaction at the portal-parenchymal interface, and infiltrating neutrophils associated with ductules (PERICHOLANGITIS) In ascending cholangitis, the neutrophils also involve the bile duct epithelium and lumens Persistent obstruction leads to fibrosis, which can eventually proceed to biliary cirrhosis Swelling of periportal hepatocytes (feathery degen.), bile pigment and Mallory hyaline is seen in periportal hepatocytes in advanced disease Superimposed ascending cholangitis in advanced disease+ liver failure

Answer 236

Diagnosis involves laboratory tests and cholangiography | Gold standard is ERCP or MRCP

Answer 237

No clear difference but several conditions have a female dominance e.g. cholestasis of pregnancy and biliary atresia

Answer 238

Paracetamol

Answer 239

Acetaminophen

Answer 240

The liver is also responsible for removing coagulation factors form the circulation The loss of this function can result in DIC (excess coagulation) This can also be fatal

Answer 241

Causes mild, reversible, hepatic steatosis

Answer 242

bilirubin glucuronides | I.e. bilirubin with the glucuronic acid molecules

Answer 243

alcohol abstinence

Answer 244

The common bile duct and the main pancreatic duct joining together

Answer 245

``` FBC, coagulation screen, blood glucose, U and Es, LFTs Paracetamol levels Blood and urine cultures Hepatic serology for hepatitis CXR USS of liver and pancreas ```

Answer 246

Prevents paracetamol being fully absorbed in stomach | Only used if it's been less than 4 hours from ingestion

Answer 247

Bile ducts have a diffusely thickened, fibrotic duct wall They show epithelial injury and neutrophilic infiltrates superimposed on chronic inflammation. Obstruction of the medium- and large-sized bile ducts - oedema and inflammation lead to narrowing of the lumen This leads to progressive circumferential fibrosis and strictures The fibrosis has an onion skin appearance Ultimately results obliteration of the smaller ducts (ductopenia) and bile stasis (cholestasis). Retained bile salts may further contribute to bile duct damage.

Answer 248

acetaminophen | Also sold generically and under brand names

Answer 249

Severe pruritus Hyperoestrogenaemia Hypogonadism in females Leuconychia – white nails that have lunula undermarcated from low albumin Terry's nails – the distal 3rd is reddened by telangiectasia but they are white proximally Clubbing Dupuytren's contractures Xanthelasma Hepatomegaly – may have a small liver in chronic disease

Answer 250

lifestyle alteration and management of factors of metabolic syndrome

Answer 251

They contain similar substances to black stones with some added cholesterol and calcium salts of palmitate and stearate They have a laminated, soft, greasy consistency and radiolucent

Answer 252

Generalised features - anorexia, weight loss and weakness Advanced disease may present with HE, jaundice and easy bruising from coagulopathy They may have portal HTN = ascites, splenomegaly AND portohepatic shunting = causing varices, haemorrhoids and caput medusae

Answer 253

True estimated prevalence of 5.58 per 100,000 in the UK. Though thought to be underestimated

Answer 254

Reactive metabolites generated in the liver by cytochrome P-450 This is active in central zone of lobule Leads to necrosis of perivenular hepatocytes

Answer 255

The timing of onset of symptoms and disease will vary depending on the underlying cause but in general it has a much longer onset than ALF ( months/ years vs. days/weeks/months)

Answer 256

It enters the duodenum via the bilirubin

Answer 257

Patients may present with metabolic acidosis, elevated lactate and possibly coma

Answer 258

QoL significantly impaired from itch albumin < 28 g/l or prothrombin time > 6 seconds prolonged (INR > 1.5) or bilirubin > 50 mmol/l (>100 mmol/l if biliary cirrhosis) Child Pugh > 7. MELD also considered Ascites esp if doesn’t respond well to diuretic SBP Renal failure Spontaneous hepatic encephalopathy GI bleeds from portal Hx esp if assoc. with HE HE

Answer 259

False | 5% of otherwise typical PBC patients don’t have AMAs.

Answer 260

Physiologic jaundice of newborn - low enzyme levels, Breastmilk jaundice - deconjugating enzymes in milk Genetic deficiency in UGT1A1 (enzyme responsible for glucuronidation) e.g. Gilberts syndrome

Answer 261

Phase II pathways become saturated, and hepatic GSH stores are depleted More paracetamol goes through the phase I pathway and so the toxic metabolite NAPQI builds up, particularly in centrilobular hepatocytes in zone 3 NAQPI binds to hepatic proteins which leads to cell membrane damage and mitochondrial dysfunction This results in hepatocellular injury and death Depletion of GSH means cells are also more susceptible to oxidative damage

Answer 262

Its caused by a continuous process that involves fibrosis, distortion of the livers architecture and regeneration nodule formation Initially the fibrosis will be reversible but will then transition to an irreversible form with regeneration nodule formation and the development of cirrhosis The rate of progression depends on cause, environmental and host factors There ay also be a role of genetic polymorphisms in the rate of progression of reversible to irreversible fibrosis

Answer 263

Usually have previous episodes of pain related to gallbladder Attacks begin with progressive RUQ or epigastric pain lasting > 6 hours Associated with fever, anorexia, tachycardia, sweating, nausea, etc. Often appears suddenly and may require surgery (emergency) Alternatively symptoms can be mild and resolve without intervention

Answer 264

Over the past 50 years ALF secondary to Hepatitis A and B have declined whereas ALF caused by acetaminophen has increased

Answer 265

They are at risk then of oesophageal varices which may be fatal Spontaneous bacterial peritonitis which can also be fatal

Answer 266

A less than 10-fold increase in ALT and a more than 3-fold increase in ALP suggests cholestasis.

Answer 267

True - 4x increased risk | Colonoscopy and screening biopsies – annually

Answer 268

May produce a firm poorly circumscribed mass or may diffusely infiltrated the wall of gallbladder simulating the gross appearance of chronic cholecystitis

Answer 269

Due to blockage of the bile ducts - gallstones, tumours etc | Get backflow of conjugated bilirubin into the blood

Answer 270

Alcoholic liver disease

Answer 271

A severe case of cholecystitis where the gallbladder becomes green black and necrotic Mat have small to large perforations Caused by the invasion of gas forming organisms like clostridia or coliforms

Answer 272

LTFs are a type of blood test that assess the levels of a variety of markers. They can indicate liver function (obviously!) and injury.

Answer 273

Coagulopathy, HE, hypoalbuminemia = oedema, sepsis, SBP, hypoglycaemia, portal hx and its complications ( spenomeagaly, ascites, HE), portopulmonary Hx, life threatening infections fro scratching

Answer 274

Elevated urea and creatinine and reduced urination

Answer 275

This is where there is an already cirrhotic liver that then has an acute decompensation which results in one or more organs failing and reduces the patients mortality Can either be due to unrelated injury on top of already cirrhotic liver or can be caused by a flare in the cause of the original cirrhosis

Answer 276

Conjugation occurs in the endoplasmic reticulum of the hepatocytes

Answer 277

fever, generalised abdominal pain, tenderness and absent bowel sounds May occur on a background of ascites

Answer 278

Occurs as the hepatocytes are responsible for synthesising clotting factors 2, 5, 7, 9, 10, 11, 12 and fibrinogen so as the liver fails they are no longer produced causing coagulopathy

Answer 279

A form of renal failure in individuals with no functional or morphological issues of the kidney but that have hepatic failure

Answer 280

Patients with non alcoholic steatohepatitis develop severe hepatic dysfunction and decomposition due to rapid weight loss or malnutrition Sepsis causing hypotension or acute cardiac failure causing hypoperfusion Malignancy from a primary tumours (hepatocellular carcinoma or cholangiocarcinoma in particular) or liver mets from another site Superimposed drug or toxic injury

Answer 281

ursodeoxycholic acid

Answer 282

Gall bladder perforation or fistula

Answer 283

They secrete pro-inflammatory cytokines and produce reactive oxygen species

Answer 284

Treating the underlying cause Much of the medical treatment for cholestasis is disease specific Most require a referral to GI or hepatology (particularly if severe or prolonged)

Answer 285

Often in those with IBD, ERCP/MRCP looks normal – liver biopsy required

Answer 286

Bilirubin Albumin Prothrombin time

Answer 287

Cirrhosis This is marked by dense bands of fibrosis surrounding parenchymal nodules throughout the liver The surface of the liver capsule becomes lumpy with bulging regenerative nodules and depressed areas of scarring

Answer 288

Seen as the immediate breakdown product but also in the gut as enzymes here de-conjugate them

Answer 289

anticoagulation, thrombolysis or angioplasty with or without stenting, TIPS, or liver transplant

Answer 290

Appear injured and swollen with cleared-out cytoplasm & cytoskeletal damage - extensive Can lead to formation of Mallory hyaline - tangled skeins of intermediate filaments

Answer 291

haemolytic anaemia, internal haemorrhage reabsorption or ineffective erythropoiesis like pernicious anaemia or thalassaemia More blood getting broken down = more bilirubin

Answer 292

``` Occurs from 48-96hrs Presents with: Worsening symptoms of hepatic failure Jaundice Encephalopathy Coagulopathy AKI Multi organ failure ```

Answer 293

bile salt export pump - BSEP

Answer 294

It is water soluble and non-toxic

Answer 295

head kept at 20 degrees and given mannitol, lactulose and rifaximin

Answer 296

Risk of all the manifestations of ALF - discussed on other cards Also get hypoglycaemia which if severe and untreated can be fatal

Answer 297

``` Alcoholic FLD NAFLD Chronic infection - hep B or C PBC Rarer causes include: Wilson’s disease, hemochromatosis and alpha-a1 antitrypsin deficiency. ```

Answer 298

Swollen ER of hepatocytes | Filled with HBsAg - gives a ‘ground-glass’ appearance as you get accumulation of hep B surface antigen in ER

Answer 299

It is found mainly in hepatocytes (also kidney and muscle), | It enters blood following hepatic injury

Answer 300

Common in USA and Northern Europe. Smaller incidence in Africa and Indian subcontinent

Answer 301

Portal lymphocytic or lymphoplasmacytic, inflammation w/ fibrosis

Answer 302

Protein catabolism can produce ammonium ions which are toxic They can be used to make urea in the liver (or excreted in kidneys)

Answer 303

It induces liver microsomes that contain CYP2E1 CYP2E1 metabolism of alcohol produces ROS This leads to damage of cellular protein, membranes, mitochondria which promotes apoptosis

Answer 304

Based on their location in the biliary tree Can be intrahepatic or extrahepatic And perihilar and distal

Answer 305

Likely develops from a precursor lesions | A lengthy stepwise process occurs, eventually leading to the full blown cancer

Answer 306

True | Thought to be because NAPQI inhibits aerobic respiration through blocking e- transfer in oxidative phosphorylation

Answer 307

Chronic, progressive hepatitis associated with: Genetic predisposition Autoantibodies Therapeutic response to immunosuppression

Answer 308

Yes | If found incidentally while operating for separate cause

Answer 309

(markedly) raised ALP and raised GGT. AST and ALT may be mildly raised as well. GGT can be used to confirm the raised ALP is a liver issue and not bone as it is not found there.

Answer 310

Lipids accumulate in the hepatocytes Fat-laden cells are highly sensitive to lipid peroxidation products generated by oxidative stress This causes damage to mitochondrial & plasma membranes which leads to apoptosis/necrosis Exacerbated by pro-inflammatory state that accompanies insulin resistance Once cell injury becomes established you get release of cytokines locally from Kupffer cells This leads to activation of stellate cells, collagen deposition, cirrhosis and chronicity

Answer 311

Malnutrition - fasting or ED Cachexia Chronic alcohol overuse Some chronic illnesses - HIV, CF This will increase risk/severity of paracetamol overdose

Answer 312

Self-limiting infection | Becomes chronic in immunocompromised hosts only

Answer 313

Lacks the glucuronic acid molecules | Is insoluble and toxic

Answer 314

Portal expansion due to oedema Prominent ductular reaction at the portal-parenchymal interface Infiltrating neutrophils associated with ductules - pericholangitis

Answer 315

Jaundice - caused by unconjugated bilirubin entering blood Pain - RUQ pain, radiating to right shoulder, minutes to hours in duration, normally after a fatty meal Pruritus Skin xanthomas - focal accumulations of cholesterol Pale stools and dark urine - caused by absence of bile in gut

Answer 316

You get impairment of bile formation and release Substances like bilirubin accumulate in cells which backs up/ is exocytosed into the extracellular space and then the bloodstream Hyperbilirubinaemia and cholestasis normally go hand in hand

Answer 317

In the absence of medical attention attack usually subsides in around a week and frequently within a day However as many as 25% of patients develop progressively more severe symptoms and require immediate surgery

Answer 318

Annual ultrasonography of GB | Have a lifetime risk of 20%

Answer 319

Normally, bilirubin joins with bile in the liver, moves through the bile ducts into the digestive tract, and is eliminated from the body. Most bilirubin is eliminated in stool, but a small amount is eliminated in urine.

Answer 320

The: pattern of liver injury (inflammation) may progress to chronic hepatitis, cirrhosis and even liver failure even upon discontinuation of the offending drug Can be seen w/o any manifestation of clinical illness Injury centered on bile ducts

Answer 321

The common hepatic duct and the cystic duct

Answer 322

It is a slowly progressive disease and progression to end-stage liver disease occurs in 20% to 25% of patients over 15 to 20 years Also associated with hepatocellular carcinoma - overall incidence 6% More common in men with advanced disease

Answer 323

A continuous, progressive deterioration of liver functions for more than 6 months Functions affected includes synthesis of clotting factors, other proteins, detoxification of harmful products of metabolism and excretion of bile

Answer 324

Large-duct is more common - the classic type Small duct accounts for only 3-16% of cases

Answer 325

Those in Africa and Asia

Answer 326

Hepatotoxin: acetaminophen | Toxic agent: NAPQI produced by cytochrome P-450 system

Answer 327

Allows bile to be delivered to the GI tract Transports bile to the gallbladder for storage It has a key role in the elimination of bilirubin, excess cholesterol, xenobiotics and trace metals - via excretion of bile.

Answer 328

Causes repeated inflammation This leads to progressive destruction & regeneration of liver parenchyma Results in fibrosis & cirrhosis

Answer 329

An isolated rise in bilirubin. | Seen in Gilbert's and haemolysis

Answer 330

Presence of round-to-oval cytoplasmic globular inclusions in hepatocytes Strongly PAS-positive and diastase-resistant Appear first in periportal hepatocytes then progresses to appear in central hepatocytes

Answer 331

True It accounts for roughly half the cases of acute liver failure with around 30% mortality in the US In the US, accidental OD is the most common cause, but intentional OD is most frequent in the UK

Answer 332

Children - 50% pf paediatric cases are idiopathic | Only 15% of adult cases

Answer 333

Staining for collagen

Answer 334

Loss-of-function mutations in the genes HAMP, HJV, TFR2 and HFE These cause a chronic elevation of erythroferrone level which leads to an abnormal deficiency of hepcidin This causes iron overload

Answer 335

True | >70% survival at 7 years.

Answer 336

It is caused by high levels of bilirubin in the plasma, also called hyperbilirubinemia Means that there is an imbalance between rate of hepatic uptake, conjugation and excretion of bilirubin.

Answer 337

Caused by an impairment of bile flow | e.g. biliary atresia

Answer 338

Self-limiting - usually recover within 3 months and get better within 6 months No lasting damage Does not become chronic

Answer 339

Steatosis/fatty change Alcoholic steato-hepatitis Fibrosis leading to cirrhosis

Answer 340

It occurs predominantly in males and does not respond to immunosuppressive treatment.

Answer 341

graft infection and sepsis

Answer 342

17% | 10% will result in death or liver transplantation

Answer 343

Pathologic polymerization of the variant AAT causes intrahepatocyte accumulation of AAT molecules This causes chronic hepatitis which can progress to cirrhosis

Answer 344

Pre-hepatic Hepatic Post-hepatic Divided based on

Answer 345

Facilitated by the enzyme glucuronyl transferase, it becomes conjugated with one or 2 molecules of glucuronic acid

Answer 346

Found in liver, heart, muscle and RBCs | It enters blood following injury

Answer 347

Around 50 | Most are diagnosed in the early stages

Answer 348

An autosomal recessive disorder caused by mutation of ATP7B gene The implicated ATPase is required for copper transport Leads to excess copper in the body - impaired hepatic transport

Answer 349

Unconjugated

Answer 350

Yellow, round, finely granular hard external On transection reveals crystalline palisade Usually radiolucent if pure cholesterol – difficult to find!

Answer 351

Acute liver failure

Answer 352

Given for aspiration risk | Although risk of pneumonia if incorrectly placed

Answer 353

Extensive inflammation and hepatocellular injury at interface

Answer 354

Decision to treat based on nomogram for plasma paracetamol concentration >4 hrs post-ingestion Treat empirically in the case of staggered OD and if it is >8 hrs post-ingestion

Answer 355

Up to 40% do not respond to medical treatment but have a good outcome with liver transplantation so this is the option for them

Answer 356

Circulating auto-antibodies + T-lymphocytes in peripheral stroma. Association with HLA-B8 + other MHC antigens Association with ulcerative colitis

Answer 357

True | However, risk is greatest at lower plasma paracetamol concentrations – NAPQI may be protective?

Answer 358

``` Biliary obstruction Cholangitis Drug induced liver injury Sepsis TPN-associated cholestasis Cholestasis of pregnancy Alcoholic hepatitis ```

Answer 359

They are found in the sterile gallbladder bile Contain a mixture of calcium compounds - oxidized polymers of calcium salts from unconjugated bilirubin, small amounts of calcium carbonate, calcium phosphate etc. 75% are radiopaque They are spiculated (spiky), molded and quite friable

Answer 360

Excess production of bilirubin Reduced hepatic uptake Impaired conjugation Poor excretion due to transporter deficiencies, hepatic disease or impaired bile flow.

Answer 361

patchy bile duct involvement, few portal tracts involved

Answer 362

Easy bruising Can progress to life threatening intracranial bleeds As the liver is also responsible for removing coagulation factors form the circulation loss of this function can result in DIC which can also be fatal

Answer 363

Stercobilin

Answer 364

Urinary and central line catheters inserted to assess fluid status Also increase risk of infection

Answer 365

corticosteroids and other immunosuppressants

Answer 366

Rarer causes include ; Budd Chiari or ischemia, metabolic disorders, malignancies ( Leukemia/lymphoma (33%), breast (30%) and colon (7%)

Answer 367

Fluid and salt restriction, diuretic, spironolactone and potentially paracenteses

Answer 368

It appears more black and lamellated (many layer like onion) compared to a pure stone Around 10-20% will contain enough calcium to make them radioopaqie

Answer 369

It results from repeated bouts of acute cholecystitis Associated with cholelithiasis in more than 90% of cases

Answer 370

Hallmark - lymphocytic infiltration and epithelial injury of small interlobular ducts Another key finding is florid duct lesion (portal lymphocytic +/- granulomatous bile duct damage) Poorly formed epithelial granulomas commonly seen in the portal tracts and can be centered on bile ducts With disease progression you will see ductopenia and loss of bile ducts entirely Periportal changes/accumulation of bile in periportal regions aka “cholate stasis” is common

Answer 371

Hepatitis A, B, C, D, E Also non-hepatotropic viruses e.g. EBV, cytomegalovirus, HSV, adenovirus, yellow fever virus

Answer 372

age >50 years Cholangitis Choledocholithiasis - gallstone in the common bile duct Cholecystolithiasis - gallstone in gallbladder In Asia, chronic bacterial and parasitic infections have been implicated Various driver mutations involved

Answer 373

Irregular biliary strictures and dilatations | “beading” in large intra-hepatic and extra-hepatic biliary tree

Answer 374

MRP2 - multi-drug resistant protein 2

Answer 375

Due to some form of liver impairment (drug toxicity or hepatitis) Leads to a decreased ability to conjugate May have mixed picture - both conjugated and unconjugated in blood

Answer 376

All patients should be managed in intensive care as ALF often characterised by rapidly deteriorating neurological status, haemodynamic instability and renal failure, and are at high risk of complications (eg sepsis) All patients should be assessed for suitability for a liver transplant

Answer 377

No Unconjugated bilirubin is not water soluble so cannot be excreted in the urine SO wouldn't show up in sample

Answer 378

The conjugation of bile acids and either taurine or glycine

Answer 379

You get dilation of the pulmonary vessels which cause right to left shunting causing a ventilation perfusion mismatch and impairing oxygenation of blood causing hypoxemia

Answer 380

Amino acids are used to synthesise protein in the liver such as albumin, CRP, clotting factors, thrombopoietin and angiotensin

Answer 381

Thin incomplete scars associated with variable ductular reaction and architectural changes

Answer 382

It is a product of alcohol dehydrogenase Induces lipid peroxidation & acetaldehyde-protein adduct formation This disrupts cytoskeleton & membrane function

Answer 383

liver transplant

Answer 384

Hepatocellular accumulation of the misfolded protein causes liver disease You get hepatocyte death, chronic hepatitis and cirrhosis Increased risk of HCC

Answer 385

HHC results from a mutation involving the hemochromatosis gene (HFE) that leads to increased iron absorption from the gut

Answer 386

cholesterol gallstones | obesity

Answer 387

Easy bruising

Answer 388

The haem is first broken down to biliverdin by haem oxygenase before biliverdin reductase converts it to bilirubin.

Answer 389

It is produced by the deconjugation of bilirubin in the colon It colourless Later oxidised to stercobilin or urobilin

Answer 390

Paracetamol overdose | Other drug toxicity

Answer 391

Yes | This can point towards the underlying pathophysiology

Answer 392

Gallstones - seen in 95% of cases However, only 1-2% of patients with gallstones will develop cancer

Answer 393

Pericentral zone 3 hepatocytes | Seen in drug induced liver disease

Answer 394

False | The morphology will vary depending on the exact cause

Answer 395

sterolines 1 and 2

Answer 396

oestrogen impairs bile acid secretion so it accumulates in cell along with bilirubin which backs up/ is exocytosed into the extracellular space and then the bloodstream

Answer 397

A toxic by-product of haem breakdown | Yellow bile pigment

Answer 398

In progresses over days, weeks or months in ALF

Answer 399

They are effective detergents so combine with cholesterol and phospholipids to form micelles This makes the cholesterol and phospholipids soluble but also protects the biliary epithelium from the toxic effect of the bile acids

Answer 400

Antimitochondrial antibodies (AMAs) – 95% positive Antinuclear antibodies (ANAs) – 20-50% +ve Many patients have raised IgM (unknown reasons)

Answer 401

Green-brown plugs of bile pigment in hepatocytes and dilated canaliculi Rupture of canaliculi can lead to extravasation of bile, which is phagocytosed by Kupffer cells (found lining the sinusoids) Accumulation of bile salts in hepatocytes results in a swollen, foamy appearance of cytoplasm “feathery degeneration” - sign of advanced disease

Answer 402

Cholesterol is soluble in bile because it forms micelles with bile salts (acts as detergent) When cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and nucleates into solid cholesterol monohydrate crystals.

Answer 403

Autoimmune hepatitis

Answer 404

The majority are then oxidised to stercobilin which is then excreted in faeces. Some is reabsorbed by the lumen and returned to the liver where they are recycled back into the bile. Small amount reaches the kidneys and is oxidised into urobilin which can then be excreted in the urine.

Answer 405

Mechanisms isn't fully understood but thought to be due to concomitant portal Hx, excessive pulmonary vasoconstriction and vascular remodelling

Answer 406

Cholethiasis

Answer 407

Females generally have a lower rate of progression

Answer 408

True | ~20% of cases will transform

Answer 409

Liver failure and cholangiocarcinoma

Answer 410

Cholecystokinin | This is a peptide hormone that is synthesized by the small intestine

Answer 411

Found in high concentrations in the liver, bile duct and bone tissues and placenta Naturally raised in growing children - from bone

Answer 412

PSC follows a protracted course | Will develop cirrhosis in 10-15years

Answer 413

This is rising pulmonary pressure due to liver disease

Answer 414

Loss of small intrahepatic bile ducts (“ductopenia”); bile accumulates in periportal or peri-septal regions

Answer 415

It is resolved by restoration of liver function, such as liver transplantation

Answer 416

Colon cancer - but only in those with IBD as well

Answer 417

dyspnea on exertion and finger clubbing

Answer 418

Only 5% is metabolised this way The active through cytochrome P450 enzymes (CYP2E) to form NAPQI which is toxic This combines with glutathione (GSH) in hepatocytes to form a non-toxic product which can be excreted through urine

Answer 419

Causes acute synovitis due to hemosiderin deposition in joint linings

Answer 420

Jaundice, ascites, HE, coagulopathy, hepatorenal syndrome or variceal haemorrhage

Answer 421

Fibrosis develops as a consequence of the original insult and the secondary effects of toxic bile acids retained in the liver Ultimately results in cirrhosis.

Answer 422

It depends on the underlying cause In most cases the ALF is due to massive hepatocyte necrosis +/- apoptosis causing liver failure Hepatonecrosis occurs because they have cellular swelling and cell membrane disruption due to depletion of ATP The necrosis can be due to direct toxic injury but is more likely to be caused by a mix of toxicity and immune mediated hepatocyte destruction

Answer 423

Anti-HBs antibody begins to rise following resolution of acute disease, generally after disappearance of HBsAg If not, progression to chronic liver disease & HCC (Persistence of HBeAg)

Answer 424

Asians Chronic haemolytic anaemias Biliary infection GI disease (Crohn’s, ileal surgery)

Answer 425

Yes | It is insoluble without it

Answer 426

False | not a primary cause of death but serious morbidity

Answer 427

False | Once destroyed, regeneration of bile ducts is either not possible or inefficient

Answer 428

Hep C with an HIV co-infection

Answer 429

Phase II reactions consist of adding hydrophilic groups to the original molecule, a toxic intermediate or a nontoxic metabolite formed in phase I, that requires further transformation to increase its polarity

Answer 430

Raised ICP causing brainstem herniation due to the cerebral oedema in HE Coagulopathy causing intracranial bleeds and DIC Portal Hx causing varices which can bleed fatally or ascites which lead to SBP which can be fatal Hepatorenal syndrome causing fluid overload, secondary infection, coma and organ failure Hepatopulmonary Syndrome causing severe hypoxemia and respiratory failure Multi-organ failure due to hypoperfusion from the hyperdynamic circulatory state Cholestasis potentially leading to life threatening infection Hypoglycaemia causing severe neurological damage and death Metabolic acidosis in paracetamol overdose causing cardiac arrhythmia

Answer 431

Characterized by continuing hepatocellular inflammation This leads to fibrosis and necrosis Causes cirrhosis + increasing risk for HCC development End up with liver failure

Answer 432

Monitor liver function every 4 weeks for 3 months then every 3 months.

Answer 433

Viral hepatitis | Presentation over several weeks

Answer 434

Causes out-with the liver | Includes: gallstones, bile duct stricture, cancer of a bile duct, cancer of the pancreas, pancreatitis

Answer 435

Treatment with oral ursodeoxycholic acid slows disease progression Obeticholic acid is recommended in patients with an inadequate response to ursodeoxycholic or those who cannot tolerate it Liver transplant is necessary in those whom medical treatment fails Used for those who develop end-stage liver disease

Answer 436

Normal urine + normal stools = pre-hepatic cause Dark urine + normal stools = hepatic cause Dark urine + pale stools = post-hepatic cause (obstructive)

Answer 437

Hepatocytes

Answer 438

It decreases glutathione which sensitizes liver to oxidative injury

Answer 439

Results from chemical irritation/inflammation of gallbladder by stones This leads to distention of the gallbladder As the gallbladder becomes distended, blood flow and lymphatic drainage are compromised, leading to mucosal ischemia and necrosis. Prostaglandins released from the wall of the distended gallbladder contribute to mucosal and mural inflammation, distension and increased intraluminal pressure which compromises blood flow to the mucosa Bacterial infection can be superimposed

Answer 440

Copper is deposited in the cornea | Causes Kayser-Fleischer rings - green to brown deposits of copper in Descemet membrane in limbus of cornea

Answer 441

Typical cholestatic picture: normal/raised ALT, high ALP, GGT + bilirubin Raised ALP is a diagnostic feature

Answer 442

The nature and duration of the causative insult

Answer 443

``` Into 4 stages Stage 1 - 0-24hrs Stage 2 - 24-48 hrs Stage 3 - 48-96 hrs Stage 4 - >96 hours ```

Answer 444

Drugs metabolised in the liver

Answer 445

Dietary substitutions In older patients, a diet that is rich in carbs and proteins can be substituted for a diet containing long-chain triglycerides. In infants, that may not be possible, and substitution of a formula containing medium-chain triglycerides may improve fat absorption and nutrition.

Answer 446

Extensive inflammation and hepatocellular injury at interface Numerous plasma cells in clusters and lymphocytes in cytoplasm of hepatocytes at interface –> Emperipolesis Confluent necrosis, Panacinar necrosis, Bridging necrosis Rosettes: a circular arrangement of hepatocytes around a dilated canaliculus

Answer 447

``` PSC Secondary sclerosing cholangitis PBC Drug induced liver injury TPN-associated cholestasis Congestive hepatopathy Biliary atresia Infiltrative disorders - sarcoid ```

Answer 448

Any condition that causes inflammation or damage to the liver in an acute course (<6 months)

Answer 449

It facilitates the emulsification of fat in intestinal lumen which is necessary for it to be absorbed.

Answer 450

It is bound to serum albumin | This is required as bilirubin is insoluble at physiological pH

Answer 451

They contribute to jaundice, pruritus, episodes of bacterial cholangitis, and progression to biliary cirrhosis

Answer 452

the hepatopancreatic ampulla

Answer 453

The majority is stored in hepatocytes but all cells can store Also most iron is stored in ferritin which is also produced by the liver

Answer 454

bile salts, copper | Usually excreted

Answer 455

Usually present in the neck of the gallbladder or the cystic duct

Answer 456

Inflammatory cells often cross limiting plate - leads to injury of periportal hepatocytes Fibrosis develops w/ increasing liver damage Fibrous septa develop -> portoportal bridging

Answer 457

NAC is a precursor to GSH, so increases the amount of GSH available to metabolise NAPQI Reduces the production of the toxic metabolite NAC also enhances sulfate conjugation of unmetabolized paracetamol, functions as an anti-inflammatory and antioxidant, and has positive inotropic effects. It also increases local nitric oxide concentrations and promotes microcirculatory blood flow, enhancing local oxygen delivery to peripheral tissues - reduces mortality?

Answer 458

Used to treat mild-moderate acute/ chronic pain as well as an anti-pyrexial agent

Answer 459

An autosomal recessive disorder of protein folding marked by very low levels of circulating α1- antitrypsin This causes inhibition of proteases which are normally released from neutrophils at sites of inflammation

Answer 460

Chronic hepatitis - moderate to severe portal inflammation & hepatocyte necrosis, admixed with fatty change & features of steatohepatitis Ballooned hepatocytes Prominent Mallory hyaline Perisinusoidal fibrosis - leads to cirrhosis

Answer 461

Free copper taken up by hepatocytes There is a failure to incorporate in ceruloplasmin and impaired copper excretion into bile This causes toxic injury to the liver

Answer 462

Idiosyncratic (most common) | Dose-dependent

Answer 463

Increased haemolysis | Issue occurs before the bilirubin reaches the liver so will be unconjugated - live cannot keep up with demand

Answer 464

It is an acute liver illness that occurs within 26 weeks of the initial liver insult in the absence of any pre-existing liver disease It results in encephalopathy and coagulopathy

Answer 465

Causes steatosis, dysfunction of mitochondria, microtubules and cellular membranes & oxidative stress This can lead to inflammation and hepatocyte death

Answer 466

Occurs from 24-48hrs You get resolution of nausea and vomiting RUQ pain and tenderness Deranged LFTs and PT

Answer 467

The left and right hepatic ducts

Answer 468

Gallstones | More than 90% of biliary tract disease is attributable to them

Answer 469

They are used to distinguish between hepatocellular damage and cholestasis.

Answer 470

Dubin-Johnson and Rotor syndromes - autosomal recessive conditions

Answer 471

Doses consistently <75mg/kg in 24hrs are unlikely to be toxic, but this risk increases if taken consistently and repeatedly over >2 days

Answer 472

biliverdin reductase

Answer 473

It will either remain compensated with adequate liver function which may or may not have symptoms OR they can decompensate

Answer 474

Chronic inflammation

Answer 475

Deposition of hemosiderin in liver, pancreas, myocardium, pituitary gland, adrenal gland etc. Cirrhosis Pancreatic fibrosis

Answer 476

Mutant polypeptide misfolds and aggregates This causes ER stress and triggers the unfolded protein response, a signaling cascade that may lead to apoptosis This can result in hepatocyte death

Answer 477

Acute hepatic failure In severe overdoses the injury affects all parts of the lobules, resulting in acute hepatic failure. ALF causes severe injury and massive necrosis of hepatocytes resulting in severe liver dysfunction that can lead to multi-organ failure and death

Answer 478

Hepatitis A, B and E are the leading causes worldwide and are also more common in the developing countries

Answer 479

True The initial events can occur in the absence of bacterial infection but later in the course bacterial infection may be superimposed and exacerbate the inflammatory process

Answer 480

Atypical pANCA (MPO-ANCA) targeting a nuclear envelope protein is seen in 65%

Answer 481

In the US 4.5 million adults ( 1.8% of the adult population) have CLF with 41,473 deaths annually on average from the disease

Answer 482

direct extension into other organs Fistula formation, Peritoneal and biliary spread Metastasis to the liver and portahepatic lymph nodes occur

Answer 483

Raised immunoglobulins, esp. IgM Abundant autoantibodies – antimicrobial antibody (AMA) against E2 component of pyruvate dehydrogenase complex (PDC-E2). Granulomas in the liver and regional lymph nodes. Association with other autoimmune diseases e.g., Sjogren syndrome, Hashimoto’s thyroiditis, scleroderma.

Answer 484

A group of changes to consciousness ranging from subtle changes in behaviour to severe confusion and stupor to coma and death

Answer 485

When 80-90% of the patients liver function is lost and it is no longer able to perform the tasks required of it It usually results in encephalopathy and coagulopathy

Answer 486

Liver transplant Once the liver can no longer carry out its normal function and maintain homeostasis this is the best chance of survival Without mortality is 80% Should also try to treat the underlying cause

Answer 487

Given as IV infusion as a standard regime based on patient weight Originally 3-bag but now moving towards 2 bags over shorter period

Answer 488

Chronic obstructive pulmonary disease - most common manifestation in adults Chronic hepatitis and cirrhosis - more likely to occur in children

Answer 489

More than 95% are adenocarcinomas Most are of the infiltrating nodular or diffusely infiltrating type Purely nodular or papillary are less frequent subtypes.

Seminar 9 - Hepatobiliary Disease Flashcards

(540 cards)