Liver Flashcards
NAFLD risk factors
T2DM, Metabolic syndrome, BMI >30, age, sedentary lifestyle
PCOS, OSA, hypothyroid, NSAIDs, tamoxifen, steroids, amiodarone
NAFLD
Excess triglycerides accumulate in liver causing steatosis often asymptomatic until late stages. Alcohol consumption of over 25ml ethanol daily excludes
Causes of cirrhosis
Alcoholic liver disease - alcohol Hx NAFLD - DM, obesity, HTN Hep B/C - IVDU, transfusions, immigrants Wilsons, Haemochromatosis - FHx Drugs - paracetamol, methotrexate, steriods AI conditions - PBC, PSC, AIH
PC chronic liver disease
malaise, wt loss, lethargy jaundice, oedema, puritis, encephalopathy, ascites abnormal LFTs, hepatosplenomegaly, ? SOB/empysema - a1antitrypsin bloody diarrhoea - PSC
Pathophysiology of liver failure
Steatosis - accumulation of fat in hepatocytes, altered fat metabolism leads to increased liver size
Steatohepatitis - accelerated by alcohol, HBV,HVC, obesity early fibrosis, disrupted architecture and angiogenesis
Cirrhosis - hyperplastic nodules, stellate cells prevent exchange, mass fibrotic tissue leads to impairment of function. Portal HTN, varices
Imaging in hepatology
USS - detect liver lesions and metastasis, dilated bile ducts and gallstones. Quick and non invasive. Can be used to guide biopsy and doppler to assess blood flow
CT - higher sensitivity shows focal liver lesions, contrast for vasculature
MRI - good for biliary tree imagine. MRCP is gold standard. No radiation but pt has to be well and able to lie still in claustrophobic environment for 30 mins
Indications for biopsy
chronic liver disease staging
post transplant rejection
Non invasive liver disease staging
AST:ALT > 0.8 indicative of advanced fibrosis
transient elastography
FIB-4 score
Fibrosis
Extravasation of blood components leads to haemostasis, vasodilation and increased permeability allow immune mediators to enter tissues clotting factors cleave fibrinogen to fibrin forming platelet plug. Active innate and fibroblast activation cause mass inflammation and cell recruitment. Matrix deposition, SM and collagen synthesis = repair. Repeated insults or failure to remove the irritant lead to fibrosis. This disrupts normal tissue architecture and impairs function
Primary biliary cholangitis
AI disease 40-60y/o women. Chronic progressive cholestatic liver disease
Destruction of small and medium intra hepatic ducts leading to disrupted bile flow. Bile irritates hepatic tissue leading to further inflammation and damage
PC PBC
asymptomatic
fatigue, itching due to bile salts
xanthomas - due to increased blood cholesterol
Coexisting AI conditions - Sjorgrens, arthropathy
Advanced liver disease
Inv PBC
AMA +ve, high IgM
increased ALP and GGT
USS to exclude reversible causes of binary obstruction
biopsy granulomatous deposits of inflammation around bile ducts
Complications and Mx PBC
Osteoporosis, hypercholestrolemia, HCC
Monitor yearly USS for HCC and osteoporosis
UDCA - ursodeoxycholic acid hydrophilic synthetic bile acid that improve cholestasis and LFT’s, reduces cholesterol uptake from gut to liver
Fibrates - reduce hypercholestrolemia, cholestryamine - reduce itch
AIH
Continual hepatocellular inflammation and necrosis. Genetic links with HLAD8, DR3. Environmental triggers ; Hep a,b,c, statins and nitrofurantoin
PC AIH
non specific fever, malaise, anorexia, arthralgia
1/3rd present with acute hepatitis - RUQ, fever
Acute liver failure
Links to other AI conditions - Graves, pernicious anaemia, Hashimotos, Sjogrens
Types of AIH
type 1 - 75% all ages ANA and AMSA +ve
type 2 - 15% 10:1 female to male ratio, presents in young adults, LKM1 +ve
Inv AIH
ANA, ASMA +ve
IgG, high ALT due to hepatocyte damage
biopsy shows widespread lymphocytic infiltrate
Mx AIH
Steroids + azathioprine to induce remission
Primary sclerosing cholangitis
Chronic condition that can progress to cirrhosis. Inflammation and fibrosis of the intra and extra hepatic ducts
90% of pt will suffer from IBD
PC PSC
fatigue, jaundice, puritis
can present acutely as ascending cholangitis
progressive leading to chronic liver disease
Inv PSC
pANCA +ve, high ALP
MRCP shows beading of bile ducts and annular strictures
biopsy - onion skin fibrosis. T cell mediated destruction leading to concentric rings of fibrosis.
Complications and Mx of PSC
increased risk of CRC and cholangiocarcinoma
replacement of fat soluble vitamins ADEK
stenting for strictures to prevent cholangitis
regular screening
Acute liver failure
PT increase 4-6 seconds ( INR >1.5)
hepatic enchalopathy
without pre-existing cirrhosis
Causes of acute liver failure
hepatitis A,E,B drugs - paracetamol, isoniazid, halothane, tetracycline, anti epileptics, statins, aspirin Acute fatty liver of pregnancy excess alcohol budd chiari AI hepatitis
Stages of acute liver failure
hyper acute (0-7days) = early renal failure, not often ascites prolonged PT, low bilirubin. high risk of cerebral oedema
acute (8-28) = rare renal failure or ascites, marked coagulopathy
subacute = poor prognosis, cerebral oedema and prolonged PT rare. high bilirubin and risk of ascites
Paracetamol OD
widespread hepatocellular necrosis beginning centrally and spreading towards ports hepatis. Paracetamol metabolised via CYP450 to NAPQI. NAPQI is toxic and requires glutathione to break it down, in overdose glutathione is depleted.
Mx paracetamol OD
N-acetyl cystine @ presentation if paracetamol levels >100g/l
Pt @ high risk are those who are malnourished, and on enzyme inducing drugs
PC acute liver failure
jaundice, RUQ pain, ascites,
encephalopathy - asterixsis, apraxia
N/V, anorexia and malaise
Inv acute liver failure
increased PT, INR
high bilirubin, ALT often in 1000/s
?acidosis
paracetamol levels, U+e’s, ABG, ferritin, hep serology, AIH markers
MRI allows calculation of liver volume if below 1000ml = poor prognosis
Complications of acute liver failure
Coagulopathy - necrosis leads to inadequate synthesis of coagulation factors. progressive thrombocytopenia = increased risk of DIC or cerebral bleed
Renal failure - ATN or due to hyperdynamic circulation leading to hepatorenal syndrome
Infection risk - mass systemic inflammatory response leading to organ failure, reduce leukocyte function
Cardiac - high output state with peripheral vasodilation leads to hypotension, increased CO and adrenal insufficiency lead to reduced PR - ARDS/ pul oedema
Hypoglycaemia and hyperammonia
Pathogenesis of hepatic encephalopathy
cerebral vasomotor dysfunction leads to vasodilation of cerebral blood vessels to increase blood flow. SIRS = increased capillary permeability - cerebral oedema. Astrocytes swell converting excess ammonia to glutamine. Glutamine = osmotic effect drawing h20 into cells
PC encephalopathy
Personality changes, reduced GCS, asterixis, increased ICP - papilloedema, vomiting.
Grade I GCS 14-15 slurred speech, inverted sleep wake
Grade II = 11-13 drowsiness, confusion
Grade 3 = 8-11 somnolence, inability to perform tasks
Grade IV < 8 coma
Mx of increased ICP
20% mannitol, target Na+ <150, hypothermia, burr hole if due to bleed.
Urgent transplant for acute liver failure
i) Paracetamol = pH < 7.25 or all of the following PT >100, lactate >3.5, HE grade III/ IV
ii) Non paracetamol = PT >100 or 3/5 drug induced, 40+, jaundice 1 wk prior, bilirubin >300, PT >50
Mx acute liver failure
ITU - NAC stat for paracetamol OD, withdraw hepatic drugs . Glucose and vit K
prophylactic anti fungal and ABx
steroids for AIH
Causes of hepatic encephalopathy
GI bleed, renal failure, acute liver injury
diuretic use
constipation
infections
Mx hepatic encephalopathy
protect airway, treat underlying
lactulose to reduce generation of NH3 by gut bacteria by reducing gut transit time
HCC monitoring
@ risk pt get 6 monthly USS and aFP monitoring. These include hep B,C, alcoholic with cirrhosis, AI - PSC, haemochromatosis.
CT scans and HCC
Contrast used to identify tumor, should glow white on injection due to vascularisation and show venous washout due to extensive venous network
Prevention of HCC
1 - vaccinate HBV avoid alcohol
2 - venesect haemochromatosis pt, lose wt/control DM for NAFLD, abstain from alcohol cirrhotics
PC HCC
Hard to distinguish from CLD hence why screening is used.
wt loss, malaise, RUQ pain moving to back
jaundice - early in cholangiocarcioma
hepatomegaly +/- bruit
Childs Pugh
Used to assess grade of cirrhosis and risk of vatical bleed
Mx HCC
Dependent on scoring
A - carcinoma in situ, normal portal pressures resection
B-C early stages 3 nodules max possible transplant
D - palliative care
TACE
transarterial chemoembolisation aims to occlude main blood supply of tumour. Lesions must be <5cm for transplant
Sofrafenib
tyrosine kinase inhibitor aims to prevent angiogenesis and growth.
Oestrogenic stigmata of CLD
spider naevi - 5+ occur on upper trunk when compressed will blanche caused by high oestrogen. In distribution of SVC
palmar erythema - reddening of thenar and hypothenar eminence due to high oestrogen
gynecomastia - palpable glandular tissue esp around areolar
testicular atrophy
All due to impaired liver function reducing the catabolism of androstiendione leading to increased estradiol. (spironolactone can = due to inhibiting testosterone)
Causes of acute decompensation
SBP, variceal bleed, alcoholic hepatitis, infection, constipation, dehydration, HCC, AKI, drug SE
Clotting abnormalities in CLD
High PT - due to reduced production of fat soluble clothing factors can = easy bruising
thrombocytopenia - hypersplenism = increased platelet destruction, reduced production due to low production of TPO and myelosupression
Wernickes encephalopathy
Triad of opthalmaplegia, confusion and ataxia due to B1 ( thiamine) deficiency
Stigmata of portal HTN
Splenomegaly - abnormal congested blood flow leads to splenic pooling and enlargement. Can be due to increased function - sickle cell, SLE, sarcoid, myelodysplasis, mononucleosis
Ascites - pHTN and hypoalbuminemia leads to reduced oncotic and increased hydrostatic pressure forcing fluid into the peritoneal cavity. O/E - shifting dullness, bullying flanks, inverted umbilicus
Caput medusa, varices and haemorroids - due to hepatic congestion collateral veins are used to return blood to the IVC. Caput - engorged superficial epigastric veins
SAAG
Serum ascites to albumin gradient
> 11g/l = portal hypertension - high hydrostatic
< 11g/l = nephrotic syndrome, TB, infections, peritoneal cancer
SBP diagnosis
PMN cells > 250mm3
leukconhyia
white nails due to hypoalbuminemia
Follow up for pt with severe cirrhosis
HCC surveillance - USS and aFP 6 monthly
2 yearly endoscope for varies - propanolol for prevention
vit B and thiamine
treat osteoporosis
Ascites - poor prognosis approx 2 yr mortality fluid restrict low Na+ diet, diuretics if needed
Metabolic syndrome
3/5 = HTN, hyperlipidemia, hypertriglyceridemia, low HDL, obesity +/- PCOS, acanthosis nigricans
NAFLD pathogensis
Insulin resistance leads to reduced responsiveness and fat storage in the liver parenchyma. HDL secretion reduced and increased uptake and synthesis of fatty acids. Hepatocytes swell with fat globules = widespread steatosis, fat degradation due to free radicals leads to mass inflammation and stellate cells lay down fibrotic material
Inv NAFLD
bright liver on USS
AST:ALT < 1
high lipid, triglyceride and low HDL levels
Mx NAFLD
increase exercise, lose wt
control HTN, statins
dietician
DM - 1st lifestyle, 2nd - metformin, 3rd pioglitazone
Hepatitis
Inflammation of the liver
acute <6 months
chronic 6months+ leads to fibrosis and cirrhosis
Causes of hepatitis
Viral A-E, immunosuppressed - EBV,CMV, AI, alcoholic, drug induced, non alcoholic steatohepatitis
PC acute hepatitis
prodromal - N/V, fatigue, headache, anorexia, fever
acute - RUQ pain, hepatomegaly, jaundice
recovery - resolution of LFT’s
Inv hepatitis
Hepatitis serology,
IgG - AIH, IgM - PBC, IgA - alcoholic liver disease
AMA +e = PBC, ANA, ASMA +ve = AIH, p-anca = PSC
Candidate for liver transplant
refractory ascites
frequent encephalopathy
HCC < 5cm
Hepatitis E
type 1/2 = faecal oral in asia, middle east
type 3/4 = increasing incidence with undercooked meat esp pork seen in western world
single stranded RNA virus. 20% mortality for pregnant women in 3rd trimester
Extrahepatic manifestations hep E
Guillan Barre, encephalitis, glomerulonephritis
Chronic hep E
seen in immunocompromised pt approx 60% of transplant pt with acute hep E will develop chronic hep E. usually asymptomatic can progress to cirrhosis in 10% of pt
Mx - ribavarin
Diagnosis of hep E
serum IgM high for 3-4wks, IgG peaks as IgM falls and remains for 4 years. Present in stool before blood
Hepatitis B
Only 5% of adults develop chronic infection 20-40% of pt with chronic hep B will develop cirrhosis and HCC. Accounts for 50% of HCC
Blood bourne transmitted via sexual contact, transfusions, IVDU and perinatally
Hep B transmission baby
90% develop chronic due to inability to clear infection
Extrahepatic manifestation hep E
membraneous glomerulonephritis, polyarteritis nodosa, serum like sickness
HBsAg
Antigen on surface of hep B virus indicates acute infection
Anti-HBc
Presence indicates previous or ongoing hep B infection
Mx chronic hep B
Tenofovir to reduce VL
6 monthly USS and aFP for HCC surveillance
Anti-HBs
Immunity or vaccination
Hepatitis C
80% of pt infected with hep C develop chronic infection. Of these 20% develop cirrhosis - this is accelerated 100x if alcohol abuse is coexistent.
Extrahepatic manifestation hep C
Sjogrens syndrome, cryoglobulinaemia
Transmission hep C
90% IVDU contamination of needles. HCV ab +ve
Mx Hep C
direct acting antivirals + peg interferon
Choleostatic drug injury (high bili/ALP)
steroids, COCP, co-amoxiclav, flucloxicillin,erthryomycin
Hepatocellular drug injury (high ALT)
paracetamol, statins, methotrexate, valproate, rifampicin, NSAIDs, lisinopril, TCA’s, omeprazole
Charcot’s triad
fever, RUQ pain and jaundice
Pathogenesis of cirrhosis
Activation of stellate cells due to damage to hepatocytes leads to myelofibroblast proliferation. TGFb1 potentiates this and inhibits metalloproteinases to breakdown fibrotic tissue. These fibrotic bands disrupt the architecture of the liver reducing synthetic function and increasing the resistance to blood flow - portal HTN
Mx Ascites
Na+ restricted diet, fluid restrict
spironolactone
Ascites drain
TIPPS shunting if severe - refractory ascites carries a prognosis of 6 months
SBP PC
PC - abdo pain, fever often asymptomatic
Gram -ve ie e.coli, klebsiella. Ascites tap > 250mm3 diagnostic
Mx = IV co-amox/ oral ciprofloxacin
Side effects of portal HTN
Severe pHTN leads to compensationery splanchnic dilation this splenic pooling reduces arterial volume so CO increases. Compensatory RAS activation leads to Na+ retention hence ascites. Peripheral vasoconstriction can precipitate hepatorenal syndrome.
Hepatorenal syndrome
On the background of ascites in pt with severe cirrhosis. vasoconstriction of renal arteries and dilation off splanic vessels
Type 1 Hepatorenal
2ndary to precipitate usually SBP, sepsis, peritonitis or GI bleed poor prognosis 50% at 1 month. Doubling of creatinine to over 221. Rapidly progressing may need terlipressin or ionotropes
Type 2 Hepatorenal
Slowly progressive decline in renal function with refractory ascites creatine rises above 133. Prognosis 6 months without renal transplant
Mx hepatorenal syndrome
look for infection/GI bleed as cause! stop nephrotoxic drugs
terlipressin 05mg QDS - acts to vasoconstrict splanchnic vessels
IV albumin
Oesophageal varices
Collaterals from portoepiploic anastomoses develop particularly around L gastric vein. 50% of pt with cirrhosis have varices at diagnosis
Primary prevention of varices
B-blockers 2/3 yearly endoscope
Mx acute variceal bleed
ABCDE approach - protection of airway if needed.
Terlipressin
Band ligation/acid injection @ endoscopy
Antibiotics
Secondary prevention
Endoscopic banding of varices
TIPS - transjugular intrahepatic portosystemic shunt
- This bypasses the liver reducing development of varies developing but can lead to hypoxic liver injury.
Unconjugated hyperbilirubinemia
Gilberts, Criggler-Nijjar
Increased production - haemolysis
Functions of the liver
Protein synthesis - Albumin -crucial to maintain oncotic pressure and to transport water insoluble substances such as hormones, fatty acids and drugs. Synthesis of all coagulation factors and complement
Synthetic markers of liver function
PT, albumin, bilirubin
Ultrasound Scan uses
Gallstones, hepatosplenmegly, HCC, Budd-Chairi, portal HTN, exclude post hepatic obstruction, NAFLD - bright fatty liver, guided biopsy
Haemolytic Jaundice
Increased breakdown of RBC. raised unconjugated bilirubin, high urobilinogen . Due to causes of haemolytic anaemia - sickle cell, malaria, hypersplenism
Investigation of a liver mass
If mass <1cm repeat USS in 4 months,
if >1cm an IV contrast CT scan/MRI scan
ALT Rise
1000 = ischemia, viral hepatitis, drugs 300-500 = AIH, chronic alcohol <300 = NAFLD, cirrhosis, wilsons, haemochromatosis
AST:ALT
> 2 = alcoholic liver disease
Gamma GT
Enzyme present in liver and other tissue.
Isolated ggt rise = alcohol or enzyme inducing drugs
- phenytoin, rifampicin, carbamazepine,
ALP
Present in hepatic canalicular and sinusoids, bone and intestine.
Isolated ALP rise = bone disorders Pagets, bony mets, osteomalacia, fractures
Cholestasis = high ALP and ggt > AST and ALT
Causes of cholestatic LFTS
Intrahepatic - PBC, PSC, drugs - erythromycin, flucloxicillin, COCP
Extrahepatic - gallstones, carcinoma head of pancreas
Acute Hep B infection
HBsAg antiHBc +ve
Chronic Hep B carriage
HBsAg antiHBc +ve
Immunisation
anti-HBs +ve
Immune from natural infection
antiHBs and antiHBc +ve
High conjugated bilirubin
Blockage of bile outflow - gallstones, PBC, strictures, PSC and carcinoma of head of pancreas
Liver dysfunction - viruses (HBV, HCV), liver mets, cirrhosis
