liver failure

Question 1

ACUTE LIVER FAILURE
* Acute liver failure is defined as acute liver injury with —- and deranged —- (INR
> — ) in a patient with a previously normal liver
* Acute liver failure is a rare but often life threatening syndrome that is due to — from many causes
* The causes vary throughout the world. Most involve
viral hepatitis but — overdose is common
in UK
* Histologically there is — of acini involving a substantial part of the liver
* Severe 000 may be seen in pregnancy, — syndrome or intravenous —

Answer 1

encephalopathy
coagulation
>1.5
hepatitis
paractemol
necrosis
fatty change
reye syndrom
iv tetracyclin

Question 2

SOME CAUSES OF ACUTE HEPATIC
FAILURE
* Virus - hepatitis A, hepatitis B, cytomegalovirus,
haemorrhage fever virus
* Drug - there are many, paracetamol, antibiotics,
antidepressants, salicylate (Reye syndrome),
NASID’s, herbal medicines
* Toxins, organic solvents, mushroom toxin
* Hepatic failure in pregnancy - acute fatty liver of
pregnancy, HELLP syndrome

Answer 2

• Vascular causes – Budd-Chiari syndrome, portal
  vein thrombosis
• Alpha-1 antitrypsin deficiency, Reye syndrome,
  Wilson’s disease
• Malignancies – secondary extensive metastases
  and infiltration
• Heatstroke

Question 3

CLINICAL FEATURES OF ACUTE LIVER
FAILURE
* Jaundice
* Hepatic encephalopathy
* Fever, vomiting, low blood pressure, low blood glucose
*= 000 in 80% of patients
* Impaired 000
* Kidney injury – hepatorenal syndrome
* Acute tubular necrosis

Answer 3

cerebral oedema
gluconegnesis

Question 4

PORTAL HYPERTENSION
* Classified by level/site of origin of portal hypertension
* Commonest cause is —
* Pathogenesis in cirrhosis:
 Initiated: increased — to portal blood flow
 Augmented: – portal blood flow
Classification of causes of portal hypertension:
* Pre-hepatic: portal vein —-
* Hepatic:
 —
 Non-cirrhotic e.g. portal tract — due to schistosomiasis
* Post-hepatic: obstruction venous outflow from liver = — (rare)

Answer 4

cirrhosis
resistance
increased
thrombosis
cirrhosis
fibrosis
Budd
Chiari syndrome

Question 5

CONSEQUENCES OF PORTAL
HYPERTENSION
* Porto-systemic collaterals develop:
 Extrahepatic - where portal venous and systemic
venous circulations anastomose:
- — (oesophageal and gastric, risk of bleed)
- Rectal, periumbilical (‘caput medusae’)
* — of portal venous blood (reduced liver function)
* Haemodynamic alterations:
 — and — syndrome
* — (congestive)
 2 degree — (low blood counts e.g. Plts)

Answer 5

Marcie
shunting
asicte and hepatorenal
splenomegaly
hypersplesim

Question 6

Dilated abdominal wall veins due to collateral drainage through
portosystemic anastomoses in periumbilical area is known as

Answer 6

capcut medusa

Question 7

OESOPHAGEAL AND GASTRIC VARICES
* 30% bleed
 30% die, high rate of recurrence
* Heavy alcohol users:
 Remember: not all upper GI bleeds are varices
* Variceal bleed:
 Resuscitate, drugs to reduce portal blood flow
 Prevent/treat complications (aspiration, infection,
HE)
 Endoscopic treatment of varices by band ligation
 Endoscopic sclerotherapy not favoured
(complications)
 If above fail: placement of— or —

Answer 7

TIPS , surgery

Question 8

OESOPHAGEAL AND GASTRIC VARICES
Primary prevention
* Screen to identify and treat moderate to severe before
first bleed
* Endoscopic band ligation and/or non-selective beta
blockers
Secondary prevention
* Treat to prevent recurrent bleeding
* Endoscopic band ligation and/or non-selective —

Answer 8

beta blockers

Question 9

ASCITES
* Fluid in —-
* — commonest cause (>80%)
 Haemodynamic changes a/w portal hypertension
 Water and salt retention, preferentially
accumulates as ascites in cirrhosis associated with
portal hypertension
* Other causes of ascites
 Malignancy (ovarian cancer classic, but also GI
cancers)
 Rare: non-cirrhotic portal hypertension
 Rare: heart failure, pancreatitis, TB
* Abdominal distension, shifting/flank —

Answer 9

peritoneal cavity
cirrhosis
dullness

Question 10

ASCITES (CONTINUED)
* Paracentesis = — of ascites fluid
 Diagnostic tap – do cell count, microbiology (blood
culture bottles), albumin, cytology
 Therapeutic tap - diuretic-resistant ascites in
cirrhosis
* Transudate: ( — hydrostatic pressure, — oncotic pressure) liver cirrhosis, heart failure,
nephrotic syndrome.
* Exudate: (—- , —- ) malignancies,
infection

Answer 10

tap
increase
low
inflammation and cancer

Question 11

SPONTANEOUS BACTERIAL PERITONITIS
(SBP)
* Infection of — fluid without evidence of — treatable intra-abdominal cause
* Infection associated with cirrhosis ( — , — )
* Early diagnosis, prompt treatment, better outcome
* Subtle/silent presentation
* Low threshold for paracentesis of ascites fluid
* Suspect:
 Fever, abdominal pain/tenderness, altered mental
state
 — if ascites fluid cell count >250 polys/mm3
 Antibiotic prophylaxis if high risk (e.g. previous SBP or
bleed)

Answer 11

ascites
surgically
e coli and klbesille
treat

Question 12

HEPATORENAL SYNDROME
* Renal impairment secondary to — disease
* Haemodynamic effects of portal hypertension reduce
renal — , typically a/w —
* Diagnosis of exclusion – no other kidney pathology:
 Hypovolaemia/shock (e.g. infection, bleeding)
 Acute tubular necrosis (shock or nephrotoxic
drugs)
* Poor prognosis

Answer 12

liver
perfusion
ascite

Question 13

HEPATIC ENCEPHALOPATHY
Spectrum of neuro-psychiatric abnormalities seen in a/w
liver dysfunction and/or porto-systemic shunting
* Functional disturbance of brain, potentially —
* If severe a/w cerebral — and cerebral —
Classification:
* Type A: — liver failure
* Type B: porto-systemic — with — liver
* Type C: cirrhosis (= — )
* Episodic (may be recurrent) HE +/- persistent HE
* Episodic HE may be precipitated or not
* Spectrum of effects: on consciousness, behaviour,
intellectual function, neuromuscular function
stages ;
1- —-
2- —-
3- —
4—

Answer 13

reversible
oedema and hypoperfusin
acute
shunting w normal liver
decompensation
confusion , drowsiness , somnolence , coma ( minimal HE can be revealed by psychometric testing )

Question 14

HEPATIC ENCEPHALOPATHY 2
* Why does it happen?
 Reduced —– (endogenous and exogenous,
including from gut) due to reduced liver function
 Unprocessed portal blood shunted through/past liver
* Pathogenesis - no definite single cause
 — accumulation (nitrogenous compounds)
 Altered —– (GABA, glutamate), glial
fxn
* Precipitants in known cirrhosis:
 Infection
 Bleeding, other causes of hypoperfusion
 Dehydration (diuretics, paracentesis, V & D)
 Drugs (sedatives – opiates, benzos) or alcohol
 Constipation
 Need for —- or surgical —-

Answer 14

detoxification
ammonia
neurotransmission
TIPS , shunts

Question 15

HEPATIC ENCEPHALOPATHY 3
Treatment:
* Identify and correct precipitating factors
* Reduce ammonia production in enema, empty bowel of
nitrogenous substances
 —-
 Non-absorbable antibiotic (—-)
 Fluids
 Stop —- therapy

Answer 15

lactulose
rifamixin
diertics

Question 16

HOW CIRRHOSIS PRESENTS
* May be asymptomatic
* Skin itch
* Jaundice
* easy bruising
* Swelling of legs and abdomen
* Complications of cirrhosis

Question 17

COMPENSATED VERSUS
DECOMPENSATED CIRRHOSIS
Compensated (“—-”)
* May or may not have biochemical/radiological
abnormality
* May or may not have signs of chronic liver
disease/portal hypertension
* May or may not have varices on OGD (gastroscopy)
Potentially unstable state
* Further injury may trigger decompensation:
* Infection, bleeding, hypotension, alcohol,
medications, dehydration, trauma, surger

Answer 17

silent

Question 18

Decompensated (i.e. key complications)
* Ascites (may become refractory to treatment)
* Hepatic encephalopathy
* Variceal haemorrhage
* Hepatorenal syndrome (HRS)
* Jaundice
* Infection (esp. spontaneous bacterial peritonitis)
* Hepatocellular carcinoma

Question 19

INVESTIGATION OF LIVER & BILIARY
TRACT DISEASE
* Presentation:
 Screen or vague/non-specific symptoms (“fishing”
with tests)
 Known possible risk factors
 Clinically obvious presentation
* History (risk factors) & examination
* Liver blood tests (as screen or to establish cause)
* Liver imaging (radiology and gastroenterology)
* Liver biopsy
* Non-invasive assessment of hepatic fibrosis

Question 20

LIVER BLOOD TESTS
* “Liver profile” =
ALT, AST, Alk Phos, GGT, bilirubin, albumin
* Related to liver cell (hepatocellular) damage:
—- ( — , — )
* Related to obstruction to bile flow (cholestasis):
 — , —-
 —
* Related to liver function
 — – abnormality not liver or biliary tract specific
 — – may reflect chronic damage
 Coagulation function (PT/INR) – acute damage

Answer 20

transaminase ALT AST
alkaline phospahte , ggt
bilirubin
bilirubin
albumin

Question 21

HEPATOCELLULAR DAMAGE LIVER
ENZYMES
* Alanine transaminase (obsolete ‘SGPT’)
* Aspartate transaminase (obsolete ‘SGOT’)
 Both leak from —- hepatocytes
 ALT sensitive/specific marker for —-
damage
 AST less specific, also in muscle, myocardium, kidney
 Level of rise poor correlation with severity/prognosis
 Very high in acute hepatocellular damage
 May be only mildly elevated or normal despite chronic
liver disease
 AST/ALT ratio can be informative
- Usually <1, if >2 suggests —–related damage

Answer 21

damaged
hepatocellular
alcohol

Question 22

OBSTRUCTIVE (CHOLESTATIC) LIVER
ENZYMES
Alkaline phosphatase
* Situated on hepatocyte border of bile canaliculi
* Hepatocytes react to obstruction to bile flow with Alk
Phos leak
* Other sources: bone, placenta
Gamma-glutamyl transferase (GGT)
* Obstruction to bile flow, therefore:
* Good for correlating with elevated alkaline
phosphatase to demonstrate that Alk Phos is of liver
origin
* Also induced by alcohol, drugs
* Very sensitive but not specific at all
* Isolated rise not usually investigated

Question 23

LIVER FUNCTION TESTS
Albumin
* Long half life
* Low albumin therefore reflects — injury to liver
* Very non-specific but useful in context
Clotting time (prothrombin time/INR)
* Clotting factors short half life
* Rise correlates with degree of acute damage to liver
* PT sent in coagulation tube to haematology lab
Bilirubin

Answer 23

chronic

Question 24

• Bilirubin normal < — umol/l
• Jaundice = icterus, yellow discolouration of tissues
  (skin and sclera)
• Clinical jaundice = bilirubin > — umol/l
• “Biochemical jaundice” >— <— umol/l = —- without —
• Cholestasis = failure of normal bile flow, stasis of bile
   Jaundice variety of causes, not just cholestasis
   Cholestasis has other features apart from jaundice

Answer 24

<18
> 50
>18 <50
hyperbiliruibnaemia wihtout jaundic

Question 25

BILIRUBIN METABOLISM * Haem breakdown produces --- * --- bilirubin initially  Highly water- --- , circulates bound to albumin  Unconjugated bilirubin actively taken up by hepatocyte * Liver cell conjugates bilirubin with ----  Conjugated bilirubin water soluble, can be excreted in bile  Conjugation usually efficient (UDPGT-1 enzyme)  Conjugated hyperbilirubinaemia causes ---

Answer 25

birliuibn unconjucated water insoluble glucuronate bilirbinura

Question 26

BILIRUBIN METABOLISM (CONTINUED) * Bilirubin oxidised in bowel to ---- (= --- colour) * Only paediatric labs measure unconjugated (direct) bilirubin and conjugated (indirect) bilirubin separately

Answer 26

urobilingoen

Question 27

CLASSIFICATION OF JAUNDICE Mechanism/clinical context * Excess production of bilirubin * Abnormalities in uptake/conjugation/excretion enzymes * Hepatocellular disease * Cholestasis/obstruction  Infiltrative diseases in liver  Intrahepatic biliary tract disease  Extrahepatic biliary tract obstruction/disease Site * Pre-hepatic – Hepatic - Post-hepatic Biochemical * Unconjugated (indirect) versus conjugated (direct)

Question 28

CAUSES OF JAUNDICE Isolated hyperbilirubinaemia – consider separately * Unconjugated almost always +/- sometimes jaundice * Haemolysis - Always consider haemolysis if isolated high bilirubin - Do: FBC + film, reticulocyte count, haptoglobin, LDH * Gilbert’s syndrome (typically mild elevation) Jaundice a/w liver and biliary tract disease * Predominantly conjugated, a/w other abnormal liver blood tests * Not useful in distinguishing hepatocellular damage and obstruction/cholestasis or acute from chronic * What is the context? Pattern of other liver blood tests?

Answer 28

CAUSES OF JAUNDICE (CONTINUED) * Jaundice a/w liver and biliary tract disease: * Acute damage * Acute obstruction/cholestasis * Acute liver failure (+ HE) * Acute flares of chronic disease  e.g. alcoholic hepatitis, reactivation of chronic HBV, autoimmune hepatitis * End stage of chronic liver disease * Ultrasound easy to perform to exclude extrahepatic duct obstruction

Question 29

GILBERT’S SYNDROME * Genetic defect in bilirubin --- enzyme * 3% of population * Isolated, mild --- * Bilirubin levels typically rise in a/w with --- , --- (= identified on fasting bloods or in hospital) * Important: don’t label as --- liver disease * Isolated mildly raised bilirubin (almost always unconjugated), other liver function tests normal:  Consider Gilbert’s, but exclude haemolysis and drugs

Answer 29

conjugation unconjucated hyperbiliruibaena fasting and illness

Question 30

CHOLESTASIS – DEFINITION & INTRAHEPATIC * Cholestasis is a condition where bile flow is reduced or blocked, can have various causes, categorized as intrahepatic (within the liver) or extrahepatic (outside the liver): Intrahepatic Causes * Liver Diseases: Acute hepatitis, cirrhosis, and primary biliary cholangitis. * Drugs: Certain medications like amoxicillin/clavulanate, chlorpromazine, and oral contraceptives. * Pregnancy: Hormonal effects in the third trimester (cholestasis of pregnancy). * Infections: Sepsis or secondary syphilis. * Other Conditions: Alcohol-related liver disease and autoimmune disorders like primary sclerosing cholangitis.

Answer 30

Extrahepatic Causes: * Obstructions: Gallstones, bile duct strictures, or tumours (e.g. pancreatic or bile duct cancer). * Inflammation: Pancreatitis or cholangitis. * Congenital Issues: Biliary atresia and choledochal cysts. * Trauma: Biliary tract injuries

Question 31

EFFECTS OF CHOLESTASIS * ---- hyperbilirubinaemia  Jaundice, dark urine (bilirubinuria, often appears first) * Obstruction to bile flow into gut  May get pale stools * If chronic obstruction to bile salt excretion into gut  --- : retained bile salts, esp. in PBC  Fat malabsorption (steatorrhoea)  Fat-soluble vitamin (ADEK) malabsorption  Hypercholesterolaemia * Elevated alkaline phosphatase/GGT * Imaging critical – dilated ducts? If yes, cause?

Answer 31

conjugated pruritus

Question 32

extra hepatic duct obstruction is ---

Answer 32

surgical jaundice

Question 33

LIVER BIOPSY * Indications: * Diffuse liver disease  Diagnosis of cause  Grade necroinflammatory activity and stage (fibrosis)  Sampling variability is an issue for diffuse disease * Focal liver lesion  Cyst vs haemangioma vs tumour-like lesion vs tumour (benign, malignant, primary or secondary)  US, CT, MR + context usually diagnostic of most lesions

Question 34

LIVER BIOPSY (CONTINUED) * Approaches:  Percutaneous - radiological guidance, needle core of tissue  Transjugular – if ---  Laparoscopic – --- * Risks: pain, bleed, bile leak, trauma  2-3% hospitalised, 1/10000 mortality  C/I: clotting problems, anti-clotting drugs, biliary obstruction  Do: platelet count/coag screen, group and screen blood * Balance risks of biopsy versus benefit  Will it affect management (prognosis, therapy)?  Biopsy performed with diminishing frequency * Standard handling in laboratory:  H&E plus routine “special” stains for fibrosis and iron  Immunohistochemistry for tumours

Answer 34

coagulatopathy focal lesions