HPB / hepatology Flashcards
1
Q
What is the normal metabolism of ammonia?
A
Liver normally metabolises ammonia.
- 50% of ammonia arises from endogenous glutamine conversion in enterocytes. 50% is from the gut lumen by degradation of nitrogen substrate from diet or gut bacteria.
In hepatocytes ammonia is converted yo urea or glutamine.
2
Q
Why does ammonia rise in liver failure?
A
The loss of viable hepatocytes leads to impaired metabolism of ammonia
3
Q
What effects do raised ammonia have?
A
- It accumulates in astrocytes which can lead to hepatic encephalopathy, cerebral oedema, intracranial hypertension and brain herniation.
- It also contributes to immune dysfunction and infection
4
Q
What’s the prognostic value of ammonia?
A
> 150 in ALF is associated with increased complications
In ACLF the risk of cerebral oedema is lower but raised ammonia is a/w increased risk of extra-hepatic organ failure and death.
5
Q
How to measure ammonia?
A
Arterial samples better reflect acute changes in nitrogen metabolism.
Sample needs to be fresh.
Serial measurements are more useful that a single time point
6
Q
What are the potential therapeutic strategies to modulate serum ammonia?
A
- Lactulose
- Rifaximin
- Metabolic scavengers e.g. LOLA
- RRT
- Liver support dialysis e.g MARS
- Plasma exchange
7
Q
What are the mechanisms of action of lactulose in managing ammonia?
A
- Colonic acidification promotes conversion of NH3 (ammonia) to non-absorbable NH4+ (ammonium)
- Inhibits ammoniagenic bacteria growth
- Inhibition of intestinal glutamine absorption
- Decreased ammonia absorption time and increased nitrogen excretion
8
Q
What is the pathophysiology of portal hypertension?
A
- Developes due to resistance in the portal venous system due to functional and structural alterations
- In response to injury liver sinusoidal cells become capillarised
- extracellular matrix gets formed and fibrogenesis occurs
- Myofibroblast contraction and decreased vasodilators e.g. NO
- These all result in increased resistance
9
Q
What circulatory changes does PH lead to?
A
- splanchnic vasodilatation
- neurohormonal disturbances
- systemic vasodilatation
- reduced MAP
=hyperdynamic state
In addition alterations to the gut microbiome, increased gut permeability and systemic infl act as both perpetrators and precipitants of worsening portal hypertension
10
Q
What is the splanchnic circulation?
A
The flow of blood to the abdominal organs including stomach, liver, pancreas and intestines
11
Q
How do varices develop?
A
- PH results in reversal of flow and formation of alternative blood flow channels between the portal and systemic circulation
12
Q
What do varices indicate about portal hypertension?
A
Signify clinically significant portal hypertension
13
Q
What is the surrogate marker for PH?
A
HVPG >5mmHg
14
Q
What HVPG signifies CSPH?
A
> 10mmHg
15
Q
What are the risk factors for variceal haemorrhage?
A
- Larger varices ->5mm
- higher HVPG
- high grade of child class
- presence of red colour signs marking
- active alcohol consumption
- sepsis
16
Q
How is variceal haemorrhage managed?
A
- judicious resus
- aim Hb 7-9
- correcting INR not warranted
- adequate purging of stomach to remove blood as a culture medium
- antibiotics and post bleed sepsis increases mortality and risk os high
- PPI
- Teripressin / octreotide for at least 2-5 days
- OGD and band ligation
17
Q
What is the primary prevention of variceal haemorrhage?
A
Non-selective beta-blockers e.g. carvediolol
18
Q
Why does ascites form in portal hypertension?
A
- PH results in backflow and accumulation of vasodilatory substances
- This results in intrahepatic vasoconstriction, peripheral dilatation and splanchnic vasodilation
- This circulatory changes result in hypoperfusion of the renal system
- State of relative hypovolaemia activates RAAS and SNS leading to salt and fluid retention - which causes an increased blood volume leading to filtration from the liver surfaces and mesenteric vessels
- increased hydrostatic pressure, decreased oncotic pressure and increased vasc permeability contribute to increased filtrations through mesenteric blood vessels which exceed the resorptive capacity of the peritoneum and lymphatics can’t counteract these mechanisms
19
Q
How is ascites manages?
A
Salt restriction
Adequate calories and protein
Diuresis - furosemide and spiro
Terlipressin
Drainage
TIPSS
20
Q
How does terlipressin help reduce ascites?
A
- increases renal perfusion, increases GFR and Na excretion, mobilises ascites
21
Q
What raises AST?
A
Raised in hepatocellular injury and is also found in skeletal muscle and myocardium
22
Q
What raises ALT?
A
Raised in hepatocellular injury.
23
Q
What raises ALP?
A
Hepatobiliary -> biliary obstruction,nintrahepatic cholestasis, primary biliary cirrhosis, hepatocellular damage.
Bone -> healing #, metastatic tumour, Pagets, osteomalacia, physiological bone growth
Intestine -> intestinal infarction
Placenta -> normal pregnancy
Other -> sepsis, renal failure
24
Q
What causes raised GGT?
A
- cholestatic, hepatocellular or infiltrative liver disorders
- chronic etoh
- prostate cancer
25
What is bilirubin?
By product og haem breakdown which is taken up by hepatocytes, conjugated and excreted by the kidneys
- May be raised in haemolysis, hepatic disease or biliary obstruction
26
What is the cause of a type A lactic acidosis?
- tissue hypoxia
27
What are the causes of type B lactic acidosis?
Liver failure
Diabetes mellitus
Renal failure
Drugs e.g. metformin
Haematological malignancy
Pancreatitis
Thiamine deficiency
G6DP deficiency
Short bowel syndrome
28
How is pancreatitis diagnosed?
Requires 2 out of 3 criteria:
1. Typical epigastric pain radiating to back
2. Lipase or amylase more than 3 x the upper limit of normal
3. Characteristic imaging findings
29
How is the severity of pancreatitis graded as per the Atlanta classification?
Mild -> no organ failure, no local or systemic complications
Moderate -> Organ failure that resolves within 48 hours +/or local or systemic complications without persistent organ failure
Severe -> Persistent organ failure more than 48 hours
30
What conditions can result in raised amylase?
- Pancreatic disease / trauma
- GI disease e.g. ulcer, appendicitis, perf, IBD, acute mesenteric ischaemia
- Gynae disease
- Renal failure
- Liver failure
- Pulmonary disease e.g. ARDS, pnuemonia, PE, cancer
- T2DM / DKA
- Surgery
- Shock
- Skin injuries e.g. TENS / burns
- Infections - HIV, covid
- Transplants
- Tumours
- Drugs
- Anorexia
- ETOH
31
What fluid is recommended in the management of pancreatitis?
- Balance crystalloid
- If not hypovolaemic 1.5mls/kg/hr
- If hypovolaemic then a 10mls/kg bolus over 2 hours before maintenance.
32
What are the possible aetiologies of pancreatitis?
Gallstones
Alcohol
Raised triglycerides
Drugs e.g. thiopyrines, valopric acid
Post ERCP
Post trauma or surgery
Autoimmune pancreatitis
Infections e.g. mumps, CMV, EBV, toxoplasmosis
Raised calcium e.g. primary hyperparathyroidism
Anatomical abnormalities
Obstructive
Toxins e.g. scorpion bites
Sphincter of oddi dysfunction
Associated conditions e.g. DM, obesity, smoking
33
What's the mortality in SAP?
Up to 30%
34
What is the ICU management of SAP?
Fluid
Nutrition
Organ support
Abx if needed
35
Discuss nutrition in pancreatitis
- Nutrition within 24-72 hours decreases bacterial translocation
- Evidence shows benefit of early enteral nutrition for decreased infections, organ failure and decreased LOS
- ESPEN guidelines recommend starting within 24-72 hours
- EN should be trialled immediately in a conscious patient with minimal N+V and no signs of ileus or obstruction
- NG/NJ are safe if po isn't feasible
- Use NJ route if delayed gastric emptying or large vol aspiration
- TPN if enteral route isn't feasible
36
How can PCT be used to guide antibiotics in SAP?
Measure on admission and at days 4 and 7 and then weekly
A cut off of 1 has been suggested as a threshold
37
What are the local complications from SAP?
1. Acute peripancreatic fluid collections
2. Acute necrotic collections
3. Pancreatic pseudocyst
4. Walled off necrosis
38
What are the vascular complications of SAP?
1. Sphlanchnic vein thrombosis
2. Pseudoaneurysm
3. Abdominal compartment syndrome
39
How is bilirubin metabolised?
1. Haem breakdown. Initially into biliverdin and then into bilirubin. At this stage it's unconjugated and non-water soluble.
2. Transported to liver bound to albumin where it's conjugated
3. It's then excreted into the bile
4. In the intestines conjugated bilirubin gets metabolised by intestinal bacteria into urobilinogen. Some is reabsorbed into the bloodstream and the majority is converted to stercobilin, giving faeces its characteristic brown colour. Urobilin is excreted in the urine.
40
What are the prehepatic causes of jaundice?
Occurs when the livers capacity ot process bilirubin is exceeded either due to excess Hb breakdown or congenital abnormalities in the bilirubin conjugation pathway.
- haemoglobinopathoes
- RBC memebrane defects
- MAHAs
- Drugs
- Sepsis
- Gilberts
41
What causes intrahepatic jaundice?
- Hepatocellular dysfunction or intraheptatic cholestasis
- Any cause of acute or chronic jaundice
- Most commonly Hep A, CMV, EBV, Hep B, hep C, drug reactions
42
What defines a hepatocellular injury?
ALT > 3x upper limit of normal
43
What defines a cholestatic injury?
ALP > 2 x upper limit of normal
44
What drugs are commonly a/w hepatocellular injury?
Isoniazind
Rifpamipcin
Tetracycline
Diclofenac
Paracetamol
Sulfonylureas
Statins
Sodium valporate
Halothane
Ketoconazole
45
What drugs commonly cause cholestatic injury?
Co-amoxiclav
Flucloxacillin
Erythromycin
Oetrogens
Anabolic steroids
Chlorpromazine
Ethanol
Terbinafine
46
What drugs can cause a mixed hepatocellular / cholestatic injury?
Carbamazepine
Phenytoin
Phenobarbitol
Nitrofurantoin
Clindamycin
Ibuprofen
Verapamil
47
What are the causes of extrahepatic jaundice?
- Occurs secondary to biliary tree obstruction distal to the biliary canaliculi
- Gallstones -> CBD stone, cystic duct stones
- Biliary strictures - cholangiocarcinoma, benign biliary stricture, primary sclerosing cholangitis
- Extrinsic compression - pancreatic carcinoma, pamcreatitis, hilar lymphadenopathy
48
What is acute liver failure?
Rare, life-threatening
Characterised by abnormal LFTS, INR > 1.5 and hepatic encephalopathy
No pre-existing liver disease
49
What mechanisms can cause liver injury?
1. Acute hep B -> massive lysis of infected hepatocytes
2. Paracetamol -> toxic metabolism
3. Amanita phalloides -> RNA synthesis blockage
4. Shock -> ischaemic necrosis
5. Acute fatty liver of pregnancy -> mitochondrial dysfunction
50
Why do patients with acute liver failure get vasodilatory shock?
Liver necrosis results in release of DAMPS which cause a significant immune reaction with the release of both pro- and anti-inflammatory cytokines
51
What are the main categories of causes of acute liver failure?
- drugs
- viruses
- toxics
- vascular
- other e.g AI
52
What are the viral causes of acute liver failure?
HAV
HBV
HVC
HDV
HEV
HSV 1+2
VZV
CMV
EBV
Herpes type 6
Parvovirus B19
Adenovirus
Haemorrhagic fever
Coxsackie B virus
53
What drugs can cause acute liver failure?
1. Paracetamol
2. Antibiotics - isoniazid, tetracyclines, augmentin
3. Halothane, sevoflurane
4. Antidepressants e.g. MAOId
5. NSAIDS
6. Antithyroid meds
7. Amphetamines
8. Methyldopa
9. Ketoconazole
54
What toxins can cause liver failure?
1. Amanita mushrooms
2. Industrial solvents
3. Cocaine
4. Ecstasy
55
What vascular issues can cause acute liver failure?
Ischaemic hepatitis - shock, heart failure
Acute budd-chiari (hepatic vein blood clots)
Ligation of hepatic artery
56
What non toxic, non-viral, non-drug, non-vascular causes of acute liver failure are there?
Autoimmune hepatitis
Wilson's disease
Pregnancy - acute fatty liver, HELLP
Hyperthermia
Heat stroke
Massive tumour infiltration
Reye syndrome - liver and brain swelling linked to salicylates
Urea cycle disorders
Partial hepatectomy
57
When would you suspect HEV as a cause for ALF?
When there is associated neuro abnormalities including GBS
58
When would you suspect AIH as a cause for ALF?
Young women
High transaminase and bili
High IgG
Autoantibodies - e.g. smooth muscle antibody and antinuclear antibody
Antibodies are negative in 50%
59
When would you suspect disseminated herpes simplex as a cause for ALF?
Young
High fever
Very high transaminases and LDH
Rapid progression to MOF
60
When would you suspect Wilsons disease as a cause for ALF?
Young
Family history of liver disease
A/w psych conditions
Mild increase in transaminases
ALP/bili ratio < 2
Coombs negative haemolysis
61
What is the work up for someone with ALF?
1. History
2. Toxicology screening
3. Hep A/B/C/D/E
CMV / herpes 1,2,6 + zoster / EBV / parvovirus
4. ANA, SMA
5. Copper metabolism
6. FBC / u+es / coag / ammonia
7. Blood cultures
8. Urine sediment and culture
9. CXR
10. Abdominal doppler US
11. CT
62
What is the initial management of ALF?
NAC
Support electrolytes
Aetiological management if available
Correct coag only if bleeding / before high risk procedure
Antibiotics
I+V if grade 3/4 HE
Deep sedation and alagesia
Nurse 30 degrees head up
Support BP with norad
If intracranial hypertension - hypertonic saline / RRT to keep ammonia < 100
63
When should you refer someone with ALF to a transplant centre?
Consider in anyone with HE, INR > 1.5, low BM or metabolic acidosis -> ALF can deteriorate rapidly
64
What is the general management of the CNS in ALF?
I+V if HE 3/4
Deep sedation
Avoid painful stimuli
Nurse 30 degrees head up
Temp < 37
Avoid hyponatraemia
RRT if raised ICP
65
What is the general management of CVS in ALF?
Avoid hypotension
Volume resus if needed
Use 0.9% saline
Norad 1st line VP
Hydrocortisone in refractory shock
Avoid flui overload as worsens intracranial hypertension
66
What is the general metabolic management in ALF?
10-20% glucose (avoid hypotonic)
BM 6.1 - 10
PPI
Early enteral nutrition -but stop if worsening HE/ammonia until ammonia controlled
67
What are the aetiological treatments in ALF?
1. Paracetamol - NAC
2. Amanita - pen G
3. AIH without severe HE- steroids. Once HE 3/4 steroids worsen outcome
4. Herpes - aciclovir
5. HBV - entecavir, tenofovir
6. HELLP - delivery
7. Wilsons - plasma exchange
68
Who is most at risk of intracranial hypertension in ALF?
Young
Ammonia > 150
AKI
Norad > 0.1micg/kg/min
69
What is the most effective liver support system available?
Plasma exchange
Detoxing and immunomodulatory effects
Improves transplant free survival
70
What are the Kings college criteria for transplant in non-paracetamol ALF?
HE + INR > 6.7
OR any 3 of:
- unfavourable aetiology (non APAP DILI, indeterminate)
- acute/ sub-acute
- bili > 300
INR > 3.5
71
What are the Kings college criteria for transplant in paracetamol ALF?
pH < 7.3 after IV resus
or
HE 3+, Cr > 300, INR > 6.5
72
What are the contraindications for emergency liver transplant?
- > 50 years survival is poor
- Sepsis
- Irreversible brain injury
- Overwhelming MOF
