Block 5: decompensated liver disease Flashcards

1
Q

Decompensated cirrhosis: imaging and special tests

A
  • MRI
  • CT head
  • Abdominal ultrasound
  • Ascitic tap for culture and cell count
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2
Q

SAAG (serum to ascites albumin gradient)

A
  • Identifies portal hypertension and is more accurate then protein based exudate
  • You subtract the ascitic fluid albumin value from the serum albumin value, which should be obtained the same day. Don’t repeat after initial measurement
  • ≥11g/l means there’s portal hypertension
  • This is due to increased hydrostatic pressure within the blood vessels of the hepatic portal system, which in turn forces water into the peritoneal cavity but leaves proteins such as albumin within the vasculature.
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3
Q

Score for GI bleed

A

Glasgow-Blatchford score: assesses likelihood that you need endoscopy or a blood transfusion after an upper GI bleed

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4
Q

cirrhosis: Screening after a decompensation event

A
  • Hepatocellular carcinoma: screening ultrasound and AFP every 6 months
  • Ongoing review with addiction services to help maintain abstinence from alcohol and illicit drugs.
  • Osteoporosis: Screen & treat
  • Ascites & SBP: Monitor regularly for evidence of ascites & treat
  • Variceal Haemorrhage: OGD at diagnosis of cirrhosis and every 2 years
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5
Q

Treatment follow decompensation event (cirrhosis)

A
  • Beta-blocker (non-cardio-selective; carvedilol or propranol) as primary prevention of bleedingrebleed
  • Viral Superinfection: Immunise for HAV and HBV (although this patient has already been exposed to HBV therefore would not require additional vaccination)
  • Vitamin deficiencies: Treat (Vit B Co-strong & Thiamine)
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6
Q

Stages of alcohol related liver disease

A
  • Steatosis: imbalance in triglyceride metabolism causing accumulation within hepatocytes
  • Alcoholic hepatitis: inflammatory response causing neutrophilic infiltration and cytokine release. Jaundice, coagulopathy and encephalopathy
  • Fibrosis and cirrhosis: chronic injury and inflammation activate hepatic stellate cells causing collagen deposition and fibrosis. Cirrhosis is causes by extensive fibrosis and formation of regenerative nodules
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7
Q

Symptoms of alcoholic liver disease

A

fatigue, malaise, abdominal pain, anorexia, weakness, nausea and/or vomiting

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8
Q

Clinical features of alcoholic hepatitis

A
  • Jaundice (common)
  • Right upper quadrant pain (common)
  • Hepatomegaly: Generally an enlarged and smooth edge, but rarely tender to palpation
  • Palmar erythema
  • Peripheral oedema
  • Clubbing
  • Dupuytren’s contracture (present in 30% of patients with alcoholic liver disease)
  • Pruritis: If there is cholestasis leading to bile salt deposition in skin
  • Xanthomas
  • Spider angioma: multiple increase disease severity
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9
Q

Oestrogenic effects of alcoholic hepatitis

A
  • Gynaecomastiaand testicular atrophy (in males)
  • Loss of body hair
  • Amenorrhoea (in females)
  • Loss of libido
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10
Q

Management of acute alcoholic hepatitis

A
  • Glucocorticoids i.e. prednisolone
  • Use Maddrey’s discriminant function (DF) to identify patients with severe acute alcoholic hepatitis: score above >32 indicates liver biopsy and corticosteroids
  • Pentoxifylline can be used as an alternative to glucocorticoids if they are contraindicated (e.g. hepatitis B viral infection, tuberculosis, other serious infection)
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11
Q

Main causes of ALT >1000

A

drugs, ischaemia, viruses

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12
Q

Liver function

A
  • Synthesis: proteins (including albumin), clotting factors, bile, lipids
  • Metabolism: Bilirubin, carbohydrate drugs, waste products and toxin
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13
Q

Bilirubin

A
  • Heme from haemoglobin breaks down into unconjugated bilirubin which is water insoluble, so travels around combines with albumin
  • In the liver its combined glucoronic acid to make conjugated bilirubin which is water soluble
  • Conjugated acid is excreted as bile acid, soted in the gallbladder and released in the small intestine causing lipid breakdown
  • Most bile acid is reabsorbed in the Enterohepatic circulation
  • Total serum bilirubin is usually <21
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14
Q

Unconjugated bilirubin: causes

A
  • Elevated due to increased bilirubin production or decreased hepatic uptake/conjugation
  • Causes of raised unconjugated bilirubin: Gilbert’s syndrome, haemolysis and drug relates (i.e. Rifampicicn)
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15
Q

Gilbert’s syndrome

A
  • A genetic disorder where less of the enzyme that breaks down Bilirubin (UDP-glucuronyltransferase) is produced. It affects 5% of the population. There is an increase in the bilirubin often with fasting or concurrent illness.
  • Confirmation of just a predominant unconjugated hyperbilirubinaemia makes the diagnosis of Gilbert’s syndrome virtually certain. This does not require any treatment and the patient can be completely reassured.
  • Rarely does it cause a bilirubin above 68umol/L
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16
Q

Conjugated bilirubin

A
  • Raised is usually a sign of liver disease which is acute or chronic in nature. Only increase when the liver has lost half of its excretory capacity
  • Causes: obstruction in the common bile duct (gallstones, malignancy i.e. cholangiocarcinoma or Pancreatic cancer), Drugs (i.e. Penicillin), Primary sclerosing cholangitis, Primary biliary cirrhosis, hepatitis, cirrhosis
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17
Q

Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST)

A
  • ALT is more specific to liver. AST is found in cardiac, skeletal and renal tissue and red blood cells
  • Raised with anabolic steroids, EBV, A fib causing low blood pressure, metabolic iron, acute/chronic Hepatitis, Excess iron (Haemochromatosis)
  • Normal is <40. Its mild if the rise is <5, moderate if rise of 5-10, marked if >10
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18
Q

Common causes of acute and chronic hepatitis

A
  • Alcohol – including chronic alcohol abuse and Alcoholic hepatitis
  • Non-alcoholic fatty liver disease (NAFLD)
  • Viral Hepatitis – both acute and chronic
  • Autoimmune Hepatitis
  • Drug toxicity
  • Ischaemia – this can be due to anything which suddenly causes a patient’s blood pressure to drop
  • Metabolic liver disease (Wilson’s / Haemochromatosis)
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19
Q

AST/ALT ratio indicating liver disease

A

An AST/ALT ratio of >2 in alcoholic liver disease; whilst an AST/ALT ratio of <1.0 would be more suggestive of non-alcoholic liver disease.

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20
Q

ALP (alkaline phosphatase)

A
  • Present in biliary tract, bones, placenta
  • Normal ALP <130
  • Physiological causes of raised ALP: 3rd trimester of pregnancy, increased bone turnover (puberty
  • Hepatic causes: bile duct obstruction (stones, malignancy), PSC, PBC, drug induced cholestasis (antibiotics, anabolic steroids)
  • Extra-hepatic causes: bone disease (fractures, Pagets disease, bone metastasis)
21
Q

GGT and isolated ALP rise

A

GGT: when raised with ALP suggests hepatobiliary source. Normal is <70.

Isolated ALP rises can occur in PSC and PBC. However could be other sources, in particular bone metastasis. Isolated GGT is seen in alcohol abuse, as well as COPD and renal failure.

22
Q

Hepatic or biliary cause bloods

A
  • Where Transferases (ALT/AST)&raquo_space; ALP and GGT= Consider a Hepatic cause
  • Where ALP and GGT&raquo_space; Transferases (ALT/AST)= Consider a Biliary/obstructive cause
23
Q

Prothrombin time (PT)

A
  • Measure of extrinsic and common coagulation pathway. Time in seconds for blood to clot
  • INR standardises PT across different labs
  • Measures synthetic function as clotting factors II, V, VII, IX and X are produced in the liver
  • Useful in acute liver injury but only prolonged in chronic liver disease when 80% of liver function is reduced. Useful in advanced liver disease particularly decompensated cirrhosis
  • Causes: liver synthetic dysfunction, deficiency in vitamin K (can be caused by obstructive jaundice)
24
Q

Albumin

A
  • Roles: maintains intravascular colloid osmotic pressure, transporter
  • In chronic liver disease hypoalbuminaemia suggests advanced liver disease
  • Causes of low albumin: Malnutrition, Nephrotic syndrome, Sepsis, Burns, IBD
  • Normal range >30g
25
Q

Consequences of portal hypertension include

A
  • Oesophageal and Gastric Varices
  • Abdominal Ascites
  • Peripheral oedema
  • Hepatic Encephalopathy
  • Low Platelets (due to hypersplenism)
26
Q

Investigations in liver failure: ultrasound and CT

A
  • Ultrasound: good at assessing dilation of biliary tree, stones in gallbladder, size and flow of hepatic and portal veins, space occupying lesions. Hard to tell degree of fibrosis/cirrhosis
  • CT: good at assessing hepatocellular carcinoma (HCC), liver metastases and liver abscesses. It is good at identifying vascular problems, including bleeding, hepatic artery thrombosis or portal vein thrombosis. Sensitive for detecting biliary ductal dilatation, intra-hepatic bile duct tumours, pancreatic tumours and the level of biliary obstruction. Visualise whole abdomen
27
Q

Investigations in liver failure: MRI/MRCP

A
  • MRI: good at visualising blood vessels, ducts and hepatic tissue. It is good at diffuse liver disorders (fatty liver, Haemochromatosis) and assessing focal lesions (haemangiomas, HCC, metastasis). However, more expensive and contraindications. Cant see beyond liver
  • MRCP: detects hepatobiliary and pancreatic systems. Can view biliary dilation, strictures and intra-ductal stones
28
Q

Investigations in liver failure: ERCP, Liver biopsy and fibroscan

A
  • ERCP: endoscopic camera used in tissue sampling and therapy i.e. stone removal from CBD, duct dilation and stent placement. Risk of causing pancreatitis, perforation and bleeding. MRCP tends to be used instead of ERCP for diagnosis
  • Fibroscan: specialist US
  • Liver biopsy: can establish a diagnosis or assess disease severity i.e. staging or grading. Usually done with US guidance, if high risk of bleeding do transjugular
29
Q

Haemochromatosis

A
  • A disorder of iron overload which can affect other organs. Is primary or secondary.
  • Causes iron deposition in the liver, skin, pituitary, heart and pancreas.
  • Progressive iron deposition and organ damage leads to a clinical spectrum beginning with non-specific symptoms of fatigue, arthralgias, hypogonadism and skin bronzing.
  • Development of further organ dysfunction can lead to complications such as cirrhosis andhepatocellular carcinoma,diabetes mellitus,cardiomyopathyand heart failure.
30
Q

Primary Haemochromatosis

A

Inherited disorder, most common is being autosomal recessive due to a defect in the HFE gene, called HFE Haemochromatosis.

31
Q

Causes of secondary haemochromatosis

A
  • Frequent blood transfusions: each new transfusion introduces new iron which is recycled and stored
  • Iron supplementation: over-supplementing, particularly with concurrent vitamin C.
  • Diseases of erythropoiesis: ineffective erythropoiesis leads to iron accumulation
  • Haematological disorders i.e. myelodysplastic syndrome
32
Q

Clinical manifestations of haemochromatosis

A
  • Early: fatigue, arthralgia, impaired sexual function, abdominal pain, mood disturbance
  • Late: skin hyperpigmentation (bronzed, grey), hepatomegaly and cirrhosis, diabetes mellitus, cardiac death, arthroplasty of the 2ndand 3rd metacarpophalangeal joint, Hypogonadism
  • Symptoms appear 40-60 in males and post menopausal in females
33
Q

Mutations in Haemochromatosis

A
  • The two mutations of HFE are C282Y and H63D. Affected by gene expression (penetrance)
  • C282Y/C282Y Homozygous gives a 95% risk of iron overload
  • C282Y/H63D compound heterozygotes gives around 4% risk (increased risk with increased alcohol intake, viral hepatitis)
  • H63D/H63D Homozygous is least likely to cause iron overload
34
Q

Blood results in Haemochromatosis

A
  • Serum ferritin: raised >674 picomols/L in men, >449 picomols/L in women. Often in 1000’s. Can also be raised in chronic alcohol abuse and NAFLD
  • Transferrin saturation: >45%
  • LFT: raised AST and ALT, likely not more than 2x normal
  • FBC: normal
35
Q

Diagnosis of Haemochromatosis

A
  • Patients with elevated SF and T/S should undergo genetic screening; those with a ferritin greater than 1000 µg/l should be referred urgently to secondary care to exclude Cirrhosis.
  • Liver function tests, ultrasound and/or fibroscan should be used to assess degree of liver damage.
  • Diagnosis of HFE Haemochromatosis should not be based on genes it requires increased iron stores.
  • Those with HFE genotype, but not gene expression, e.g. normal SF and TS should have annual iron studies
36
Q

Haemochromatosis: phases of treatment

A
  • Acute iron removal– this is done via venesection (approx. 450ml of blood is removed). This will reduce the SF by approx. 20-25 µg/l. This is continued until SF are 50-100 µg/l.. Treatment may be required for 12 to 18months, weekly to 2 weekly.
  • Maintenance phase– 2-4 venesections a year to keep SF 50-100 µg/l
37
Q

Haemochromatosis: management

A
  • Management involves: venesection (regularly removing blood to remove excess iron- initially weekly). Monitoring serum ferritin, monitoring and treating complications
  • Avoid iron, vitamin C tablets and alcohol
  • Can use iron chelatin therapy if venesection is contraindicated
  • Avoid food with high iron and vitamin C
38
Q

Haemochromatosis: screening

A

Every 6 months with ultrasound and serum AFP for HCC. Anyone with genetic haemochromatosis should be offered genetic counselling and screening for first degree relatives. A C282Y mutation on the HFE gene (chromosome 6) is the most common cause of hereditary haemochromatosis.

39
Q

Complications and investigations of Haemochromatosis

A
  • Secondary diabetes(iron affects the functioning of the pancreas). Fasting blood sugar
  • Liver cirrhosis
  • Endocrine and sexual problems(hypogonadism, erectile dysfunction, amenorrhea and reduced fertility). Testosterone, FSH, LH
  • Cardiomyopathy(iron deposits in the heart). ECG and Echocardiogram
  • Hepatocellular carcinoma
  • Hypothyroidism(iron deposits in the thyroid)
  • Chondrocalcinosis(calcium pyrophosphate deposits in joints) causes arthritis
40
Q

Wilsons disease definition

A

Rare progressive genetic disorder causing accumulation of copper in body tissue. Affects the brain, liver and cornea of the eyes. Untreated can cause liver fibrosis and cirrhosis with central nervous system dysfunction

41
Q

Wilsons disease: pathophysiology

A

Gene mutation results in dysfunction in Wilson’s ATPase, which usually moves copper from along intracellular membranes in the liver. The defective ATPase results in accumulation of copper in the liver, resulting in damage. Over time as the liver becomes damaged the copper is released into the blood and causes other end organ damage. Damage may occur but doesnt become evident till a teenager range 5-35.

42
Q

Wilsons disease: patients may present with

A
  • Liver dysfunction (most common presentation): decompensated liver cirrhosis, acute liver failure (with renal failure and haemolytic anaemia)
  • Central nervous system (usually have establishes liver disease): asymmetrical tremor, poor co-ordination and clumsiness, speech and language problems, Neuropsychiatric illness- commonly severe depression or neurotic behaviour
  • Opththamology: Kayser-Fleischer ring seen on slit lamp, almost always seen in neurological disease and half of other presentation. Sun-flower cataracts – seen on slit lamp. Do not impair vision
43
Q

Wilsons disease: diagnosis

A
  • Presence of Kayser-Felischer ring (dark circles made of copper with circle the cornea) and low serum caeruloplasmin (<0.1g/L) is enough to establish diagnosis. Ceruloplasmin is a protein that stores and carries copper around the blood
  • Other markers of disease: reduced 24 hour urinary copper, serum free copper and hepatic copper (liver biopsy)
44
Q

Wilsons disease: treatment and genetics

A

Treatment: D-penicillamine

Wilson’s disease is caused by a defect in the ATP7B gene located on chromosome 13. Causes increased copper absorption from the small intestine and decreased hepatic copper excretion

45
Q

Wilsons disease: features

A
  • liver: hepatitis, cirrhosis
  • neurological: basal ganglia degeneration, speech, behavioural and psychiatric problems are often the first manifestations. Also: asterixis,chorea,parkinsonism,dementia
  • Kayser-Fleischer rings
  • renal tubular acidosis (esp. Fanconi syndrome)
  • haemolysis
  • blue nails
46
Q

Aortic stenosis findings

A
  • Regular small volume, slow rising pulse
  • Narrow pulse pressure
  • Heaving undisplaced apex beat
  • Harsh ejection systolic (crescendo-descendo) murmur heard at left sternal edge: loudest leaning forward on expiration, may radiate to carotids
  • Thrill or heave in aortic region
47
Q

Aortic regurgitation findings

A
  • Large volume radial pulse which is collapsing
  • Wide pulse pressure: difference between systolic and diastolic
  • Thrusting apex beat
  • Displaced apex beat
  • High pitched early diastolic murmur: loudest leaning forward on expiration
48
Q

Mitral stenosis

A
  • Irregularly irregular pulse
  • Jugular vein distension
  • Tapping apex beat
  • Left parasternal heave
  • Loud first heart sound
  • Mid diastolic rumbling murmur
  • Malar flush
49
Q

Mitral regurgitation findings

A
  • Pulse and BP normal
  • Apex thrusting and displaced
  • Systolic thrill over apex
  • Wide splitting of second heart sound
  • Loud pansytolic murmur at the apex radiating to the axilla