Liver Failure & Cirrhosis (ALD, NASH) & Varices Flashcards Preview

Gastroenterology & Hepatology > Liver Failure & Cirrhosis (ALD, NASH) & Varices > Flashcards

Flashcards in Liver Failure & Cirrhosis (ALD, NASH) & Varices Deck (27)
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1

Define;

  • Acute Hepatic Failure
  • Acute-on-Chronic Hepatic Failure (aka decompensation)
  • Fulminant Hepatic Failure
    • Hyperacute Fulminant Hepatic Failure
    • Acute Fulminant Hepatic Failure
    • Subacute Fulminant Hepatic Failure

Acute Hepatic Failure

  • Liver failure occuring suddenly in previously health liver

Acute-on-Chronic Hepatic Failure

  • Decompensation of chronic liver disease

Fulminant Hepatic Failure

  • Clinical syndrome resulting from massive necrosis of liver cells leading to severe impairment of liver function
  • Hyperacute Fulminant Hepatic Failure
    • Encephalopathy within 7d of onset of jaundice
  • Acute Fulminant Hepatic Failure
    • Encephalopathy within 8-28d of onset of jaundice
  • Subacute Fulminant Hepatic Failure
    • Encephalopathy within 5-26wks of onset of jaundice

2

Define Cirrhosis

What is its histological findings?

Irreversible liver damage.

Histologically - loss of normal hepatic architecture + fibrosis and nodular regeneration

3

What risk is increased with the acuteness of onset of encephalopathy in Fulminant Hepatic Failure

The more acutely Encephalopathy develops; the increased risk of cerebral oedema occuring

4

What are the causes of liver failure?

  • Infections
    • Viral Hepatitis (HBV, HCV, CMV)
    • Yellow fever
    • Leptospirosis
  • Drugs
    • Paracetamol overdose
    • Halothane (anaesthetic)
    • Isoniazid (TB)
  • Toxins
    • Amanita phalloides mushroom
    • Carbon tetrachloride
  • Vascular
    • Budd-Chiari syndrome
    • Veno-occlusive disease
  • Others
    • Alcohol
    • 1° Biliary Cirrhosis
    • Haemochromatosis
    • Autoimmune hepatitis
    • a1-antitrypsin deficiency
    • Wilson's disease
    • Fatty liver of pregnancy
    • HELLP syndrome
    • Malignancy

5

What are the causes of cirrhosis?

Most commonly;

  • Chronic alcohol abuse
  • HBV & HCV
  • Non-alcoholic steatohepatitis
  • Genetic disorders;
    • a1-antitrypsin deficiency
    • Haemachromatosis
    • Wilson's disease
  • Anything that causes Hepatic Failure potentially can cause Cirrhosis

6

Outline the pathophysiology of Alcoholic Cirrhosis

  1. Inflammation of space of Disse
    1. Alcohol is solvent to lipid membrane
    2. Alcohol (NAD) ⇒ Acetaldehyde (NADH)
      • High alcohol conversion uses up NAD
      • NAD is used in gluconeogenesis & fatty acid oxidation
      • Low NAD ⇒ fatty acid production + Inc lactate
        •  ⇒ Fatty depositions
        • Lactic acidosis
    3. Acetaldehyde is toxic
    4. Cytochrome p450 CYP2E1 metabolsim
      • produces ROS ⇒ lipid peroxidation of membrances + antioxidant deplettion
    5. Alcohol causes endotoxin release (LPS) from gram -ve bacteria in intestinal flora ⇒ TNF from cells ⇒ inflammation
  2. Stellate cells ⇒ myofibroblasts
    • ROS, GF, cytokines (TNF, IL1), lymphotoxins & +ve feedback
    •  ⇒ Collagen (1,3) & ECM in space of Disse
  3. Loss of fenestrations & villi, dence ECM in Disse, +Kuppfer, -Hepatocytes & SINUSOIDS NARROW

7

Outline the causes of portal hypertension

  1. Compression of sinusoides from perivenular fibrosis
  2. Anastomoses between arterial & portal system in fibrous bands
  3. Reduced clearance of bacterial DNA ⇒ NO production ⇒ vasodilation of splanchnic circulation

8

Outline the pathophysiology of NASH

  • Fat in hepatocytes (steatosis)
  • +/- inflammation (steatohepatitis)

Fatty liver is usually caused by alcohol but NASH can occur.

9

Outline the causes of ascites

  1. Intravascular fluid moves into Disse due to sinusoidal hypertension & hypoalbuminaemia (↓oncotic pressure)
  2. Hepatic interstitial fluices moves into peritoneal cavity
    • ​​Hepatic lymphatic flow exceeds thoracic duct capacity
    • High protein/ low triglycerides in hepatic lymph
  3. Additional sodium & water retention due to 2ndary hyperaldosteronism

10

What are the signs & complications of liver disease & cirrhosis?

THE COPS

  • Telangiectasis
    • ​Spider naevi
    • Terry's nails
  • Hypoalbuminaemia 
    • Leuconychia
    • Oedema
  • Encephalopathy (toxins unremoved)
    • Liver flap
    • Confusion/ coma
    • Constructional apraxia (draw 5 pointed star)
    • Cerebral oedema
  • Coagulapthy
    • ↓F2, 7, 9, 10 ⇒ ↑INR
  • Oestrogen issues
    • Hypogonadism & gynacomastia
    • Palmer erythema (local vasodilation)
  • Portal hypertension & portosystemic shunting
    • Ascites
    • Splenomegaly
    • Varices
    • Caput medusae (umbilical veins)
    • Fetor hepaticus
  • SUN YELLOW! - Jaundice (hyperbilirubinaemia) & SBP/ Sepsis
  • Hepatorenal & Hepatopulmonary Syndrome

11

Outline blood tests you would perform and what each indicate in suspected liver disease

  • Hepatocellular damage
    • ↑ALT - specific to liver (ALT< strong="">, otherway in Hepatitis/ NAFL)<>
    • ↑/- AST - not specific
  • Cholestasis
    • ↑/- ALP
    • ↑/- Bilirubin -  reduced hepatic metabolism by UDP-glucuronyl transferase
    • ↑/- GGT - esp in chronic alcohol
  • Impaired synthetic function
    • ↓Abumin - protein made by liver
    • ↑INR - coagulopathy
  • Hypersplenism
    • ​↓platelets
    • ↓WCC

12

Outline the pathogenesis of oesophageal varices

  • Portal hypertension
    • Compression of sinusoides from perivenular fibrosis
    • Anastomoses between arterial & portal system in fibrous bands
    • Reduced clearance of bacterial DNA ⇒ NO production ⇒ vasodilation of splanchnic circulation
  • Portal pressure >10mmHg ⇒Varices
    • >12 ⇒ Bleeding risk!

13

Outline Hepatorenal Syndrome (HRS)

  • Definition
  • Pathophysiology
  • Types of HRS

Definition

  • Cirrhosis + Ascites + Renal failure = HRS

Pathophysiology

  • Inadequate hepatic breakdown of vasoactive substances
  • ⇒Splanchnic & systemic vasodilation
    • Splanchnic: also caused by BØ translocation, cytokines & mesenteric angiogensis
  • Renal vasoconstriction
    • Altered renal autoregulation
  • ⇒Kidney percieves hypovolaemia → +RAA axis → A2 activated NaK → Water reabsorption & hyperosmolar urine
  • →Worsens portal hypertension

Types

  • HRS1
    • Rapidly progressive deterioration in circulatory & renal function (median survival 2wks)
    • Treatment: Terlipressin replenishes hypovolaemia → Haemodialysis
  • HRS 2
    • Steadier deterioration (survival ~6months)
    • Treatment: Transjugular intrahepatic portosystemic stent shunt

Treatment

  • Other than immediate management for HRS1 & 2, the only definitive treatment for both is liver transplant

14

Outline Hepatopulmonary Syndrome pathophysiology

  • Pulmonary vasoconstriction
  • ⇒Hypertension
  • ⇒Anastomoses & shunting

15

Outline Hepatic Encephalopathy pathophysiology

Pathophysiology

  • Nitrogenous waste (as ammonia) builds up in circulation and passes to the brain
  • Astrocytes clear it (by processes converting glutamate to glutamine)
  • Glutamine causes osmotic imbalance & a shift of fluid into these cells
  • ⇒ Cerebral oedema

16

Outline Hepatic Encephalopathy grading

  • Altered mood/ behaviour; sleep disturbance, dyspraxia (constructional apraxia), poor arithmetic, no liver flap
  • ⇈drowsiness, confusion, slurred speech +/- liver flap, inappropriate behaviour
  • Incoherent; restless; liver flap; stupor, no coma
  • Coma

17

Outline Hepatic Encephalopathy diagnosis

Diagnosis

  • Liver flap
  • GCS
  • Draw 5-pointed star (constructional apraxia)
  • ⇈Ammonia
  • EEG: ⇈Amplitube ⇊Frequency Triphasic waves
  • CT/ MRI exclude other causes

18

Outline Hepatic Encephalopathy treatment

  • Lactulose/ bowel enemas: draws water & nitrogen from gut
  • Antibiotics: Neomycin to reduce ammonia-forming colonic bacteria
  • Flumazenil (benzodiazepine antag)
  • 20º head up tilt

19

Outline differentials of Hepatic Encephalopathy

  • Hypoglycaemia
  • Sepsis
  • Trauma
  • Post-ictal

20

What investigations would you perform in suspected cirrhosis?

  • LFTs
  • Liver ultrasound & duplex
  • Liver biopsy (confirms)
  • Endoscopy for varices

21

What is Spontaneous Bacterial Peritonitis & how do you diagnose it?

Complication of Liver Failure.

Ascitic tap finding Neutrophils >250/mm3

22

Outline King's College Hospital criteria for liver transplantation in Paracetamol induced liver failure

If tha patient has;

  • Aterial pH <7.3 24hr after ingestion

Or all of;

  1. Prothrombin (PT) >100s
  2. Creatinine >300umol/L
  3. Grade 3/4 encephalopathy

23

Outline King's College Hospital criteria for liver transplantation in non-paracetamol liver failure

If the patient has;

  • Prothrombin time (PT) >100s

Or 3/5 of the following;

  1. Drug induced liver failure
  2. Age <10 or >40yrs
  3. >1wk from 1st jaundice to encephalopathy
  4. PT >50s
  5. Bilirubin >300umol/L

24

Outline the indications and contraindications for liver transplant in Chronic Liver Disease

Indications;

  • Advanced cirrhosis
    • ALD, HBV, HCV, autoimune, PBC, PSC, Wilsons, a1-antiT def.
  • Hepatocellular cancer
    • 1 nodule <5cm or 2/3 nodules <3cm

Contraindications

  • Extrahepatic malignancy & multiple tumours
  • Severe cardiorespiratory disease
  • Sepsis
  • HIV
  • Non-compliance with drug therapy

25

How do you manage cerebral oedema in liver failure?

ITU

  • 20% Mannitol IV
  • Hyperventilate

26

How do you manage ascites in liver failure?

  • Restrict fluid
  • Low-salt diet
  • Diuretics

27

How would you manage spontaneous bacterial peritonitis (SBP)?

  • MC&S
  • Cefotaxime or tazocin for 5d/ until sensitivities known
  • +Metronidazole if recent instrumentation to ascites
  • Prophylactic to high risk patients: Norfloxacin