h e p a t o l o g y Flashcards
what are the causes of liver failure - acute vs chronic
chronic = cirrhosis
acute = Infection: Hep A/B, CMV, EBV, leptospirosis
Toxin: EtOH, paracetamol, isoniazid, halothane
Vasc: Budd-Chiari
Other: Wilson’s, AIH
Obs - eclampsia, acute fatty liver of pregnancy
what are the signs of liver failure
Jaundice
Oedema + ascites
Bruising
Encephalopathy= Aterixis, Constructional apraxia (5-pointed star)
Fetor hepaticus
signs of cirrhosis or chronic liver disease
what investigations are required in liver failure
FBC: infection, GI bleed, ↓ MCV (EtOH) U+E = ↓U, ↑Cr: hepatorenal syndrome Urea synth in liver poor test of renal function LFT AST:ALT > 2 = EtOH AST:ALT < 1 = Viral Albumin: ↓ in chronic liver failure PT: ↑ in acute liver failure Clotting: ↑INR Glucose ABG: metabolic acidosis Cause: Ferritin, α1AT, caeruloplasmin, Abs, paracetamol levels Microbiology Hep, CMV, EBV serology Blood and urine culture Ascites MCS + SAAG Radiology CXR Abdo US + portal vein duplex
what is hepatorenal syndrome
dx of exclusion
renal failure in pt with advanced CLF
describe the pathophysiology of hepatorenal syndrome
- Cirrhosis → splanchnic arterial vasodilatation → effective circulatory volume → RAS activation → renal arterial vasoconstriction.
Persistent underfilling of renal circulation → failure
how is liver failure managed
Manage in ITU
Rx underlying cause: e.g. NAC in paracetamol OD
Good nutrition: e.g. via NGT ̄c high carbs
Thiamine supplements
Prophylactic PPIs vs. stress ulcers
what clinical parameters require monitoring in liver failure
Fluids: urinary and central venous catheters Bloods: daily FBC, U+E, LFT, INR
Glucose: 1-4hrly + 10% dextrose IV 1L/12h
what are the complications of liver failure
Bleeding: Vit K, platelets, FFP, blood
Sepsis: tazocin (avoid gent: nephrotoxicity)
Ascites: fluid and salt restrict, spiro, fruse, tap, daily wt Hypoglycaemia: regular BMs, IV glucose if <2mM
Encephalopathy: avoid sedatives, lactulose ± enemas,
rifaximin
Seizures: lorazepam
Cerebral oedema: mannitol
what are the key points to remember when prescribing in liver failure
void: opiates, oral hypoglycaemics, Na-containing IVI Warfarin effects ↑
Hepatotoxic drugs: paracetamol, methotrexate,
isoniazid, salicylates, tetracycline
what are poor prognostic factors in liver failure
Grade 3/4 hepatic encephalopathy Age >40yrs Albumin <30g/L ↑INR Drug-induced liver failure
what is cirrhosis
permenant scarring/ fibrosis of the liver parenchyma
leading to loss of elasticity of liver and impaired organ architecture
what are the common causes of cirrhosis
Chronic EtOH
Chronic HCV (and HBV)
NAFLD / NASH
what are other causes of cirrhosis
Genetic: Wilson’s, α1ATD, HH, CF
AI: AH, PBC, PSC
Drugs: Methotrexate, amiodarone, methyldopa,
INH
Neoplasm: HCC, mets
Vasc: Budd-Chiari, RHF, constrict. pericarditis
what are the HAND signs on examination seen in pt with cirrhosis
Clubbing (± periostitis) Leuconychia (↓ albumin) Terry’s nails (white proximally, red distally) Palmer erythema Dupuytron’s contracture
what are the FACE signs on examination seen in pt with cirrhosis
Pallor: ACD
Xanthelasma: PBC
Parotid enlargement (esp. ̄c EtOH)
what are the TRUNK signs seen in cirrhosis on examination
Striae
Hepatomegaly (may be small in late disease)
Splenomegaly
Dilated superficial veins (Caput medusa)
Testicular atrophy
what are the complications associated with cirrhosis
- decompensation to hepatic failure
- SBP
- portal HTN
- increased risk of HCC
what are the signs of hepatic failure
Jaundice (conjugated) Encephalopathy Hypoalbuminaemia → oedema + ascites Coagulopathy → bruising Hypoglycaemia
what Lx are required in cirrhosis
FBC: ↓WCC and ↓ plats indicate hypersplenism ↑LFTs ↑INR ↓Albumin Find Cause EtOH: ↑MCV, ↑GGT NASH: hyperlipidaemia, ↑ glucose Infection: Hep, CMV, EBV serology Genetic: Ferritin, α1AT, caeruloplasmin (↓ in Wilson’s) Autoimmune: Abs (there is lots of cross-over) AIH: SMA, SLA, LKM, ANA PBC: AMA PSC: ANCA, ANA Ig: ↑IgG – AIH, ↑IgM – PBC Ca: α-fetoprotein Abdo US + PV Duplex
Ascites Ascitic Tap + MCS
Liver biopsy
describe the general management of cirrhosis
Good nutrition EtOH abstinence: baclofen helps ↓ cravings Colestyramine for pruritus Screening HCC: US and AFP Oesophageal varices: endoscopy
describe specific management of cirrhosis
HCV: Interferon-α
PBC: Ursodeoxycholic acid
Wilson’s: Penicillamine
what score is used to grade cirrhosis
child-pugh grading of cirrhosis
predicts risk of bleeding, mortality and need for Tx Graded A-C using severity of 5 factors Albumin Bilirubin Clotting Distension: Ascites Encephalopathy
score above 8 = significant risk for vatical bleeding
what are the causes of portal HTN
Pre-hepatic: portal vein thrombosis (e.g. pancreatitis)
Hepatic: cirrhosis (80% in UK), schisto (commonest
worldwide), sarcoidosis.
post hepatic = Budd-chiari, RHF, constrictive pericarditis
what are the portosystemic anastomoses and their effect
oesophageal varices = Portal (left and short gastric veins), systemic (inferior oesophageal veins)
caput medusae = (portal) peri umbilical veins, systemic (superficial abdo wall veins)
haemorrhoids = (portal) superficial rectal veins, systemic (inferior and medial rectal veins)
describe the pathophysiology behind encephalopathy
↓ hepatic metabolic function
Diversion of toxins from liver directly into systemic
system.
Ammonia accumulates and pass to brain where
astrocytes clear it causing glutamate → glutamine
↑ glutamine → osmotic imbalance → cerebral oedema
describe how encephalopathy is graded
1: Confused – irritable, mild confusion, sleep inversion
2: Drowsy – ↑ disorientated, slurred speech, asterixis
3: Stupor – rousable, incoherence
4: Coma – unrousable, ± extensor plantars
how do pt with encephalopathy present
Asterixis, ataxia Confusion Dysarthria Constructional apraxia Seizures
what are the precipitant of encepatholopathy
HEPATICS
Haemorrhage: e.g. varices Electrolytes: ↓K, ↓Na Poisons: diuretics, sedatives, anaesthetics Alcohol Tumour: HCC Infection: SBP , pneumonia, UTI, HDV Constipation (commonest cause) Sugar (glucose) ↓: e.g. low calorie diet
what investigation required in encephalopathy
increased plasma NH4
how is encephalopathy managed
lactulose and PO4 enemas to reduce nitrogen forming bowel bacteria = 2-4 soft stool/ d
consider rifaximin PO to kill intestinal microflora
describe the sequelae of portal HTN
SAVE
Splenomegaly
Ascites
Varices
Encephalopathy
what is ascites and what are the sx
Back-pressure → fluid exudation
↓ effective circulating volume → RAS activation
(In cirrhosis: ↓ albumin → ↓ plasma oncotic pressure and aldosterone metabolism impaired)
Distension → abdominal discomfort and anorexia Dyspnoea
↓ venous return
what is used to find ddx for ascites
Serum Ascites Albumin Gradient (SAGG)
what are the causes of SAAG grater than 1.1g/dL
SAAG ≥1.1g/dL = Portal HTN (97% accuracy)
Pre-, hepatic and post
Cirrhosis in 80%
what are the causes of SAAG less than 1.1g/dL
Other Causes
Neoplasia: peritoneal or visceral (e.g. ovarian) Inflammation: e.g. pancreatitis
Nephrotic Syndrome
Infection: TB peritonitis
what ix are required in pt with ascites
Bloods: FBC, U+E, LFTs, INR, chronic hepatitis screen
US: confirm ascites, liver echogenicity, PV duplex
Ascitic tap
MCS and AFB
Cytology
Chemistry: albumin, LDH, glucose, protein SAAG = serum albumin – ascites albumin
Liver biopsy
how to manage pt with ascites
Daily wt. aiming for ≤0.5kg/d reduction
Fluid restrict <1.5L/d and low Na diet
Spironolactone + frusemide (if response poor)
Therapeutic paracentesis ̄c albumin infusion (100ml 20% albumin /L drained)
Respiratory compromise Pain / discomfort
Renal impairment
Refractory: TIPSS
SBP presents with
Pt. ̄c ascites and peritonitic abdomen
most common pathogens causing SBP
E. coli, Klebsiella, Streps
describe the management of SBP
Rx: Tazocin or cefotaxime until sensitivities known
Prophylaxis: high recurrence cipro long-term
what are the systemic effects of alcoholism
Hepatic Fatty liver → hepatitits → cirrhosis AST:ALT >2, ↑ GGT GIT Gastritis, erosions PUD Varices Pancreatitis Carcinoma CNS Poor memory / cognition Peripheral polyneuropathy (mainly sensory) Wernicke’s encephalopathy Confusion Ophthalmoplegia (nystagmus, LR palsy) Ataxia Korsakoff’s: amnesia → confabulation Fits, falls Heart Arrhythmias: e.g. AF Dilated cardiomyopathy ↑BP Blood ↑MCV Folate deficiency → anaemia
how is alcoholism dx
CAGE Cut down? Annoyed by people’s criticisms Guilty about drinking Eye opener?
what are the sx and signs of etoh withdrawal
presenting 10-72h after last drink
signs = increased HR, reduced BP, tremor, confusion, fits, hallucinations esp formication
how is alcohol withdrawal management
tapering regimen of chlordiazepoxide PO / lorazepam IM
Thiamine
describe the long term management of alcoholism
Group therapy or self-help (e.g. AA)
Baclofen: ↓ cravings
Acamprosate: ↓ cravings
Disulfiram: aversion therapy
how does alcoholic hepatitis present
Anorexia D/V Tender hepatomegaly Ascites Severe: Jaundice, bleeding, encephalopathy
what Ix are required in alcoholic hepatitis
Bloods: ↑MCV, ↑GGT, AST:ALT>2
Ascitic tap
Abdo US + PV duplex
management for alcoholic hepatitis
Stop EtOH Rx withdrawal High dose B vitamins: Pabrinex Optimise nutrition Daily wt., LFT, U+E, INR Mx complications of failure
what are the types of viral hepatitis, their spread and cause
a = FO = seafood esp abroad b = IV = blood, body fluids and babies - vertical c = IV = blood, less vertical d = iV dependen on prior HBV e = FO in developing world
what are the different phases of viral hepatitis and how each stage presents
pro dromal phase - seen particularly in HAV and BV. Flu-like, malaise, arthralgia, nausea
icteric phase - Hepatitis
Abdo pain
Hepatomegaly
Cholestasis: dark urine, pale stools
chronic phase - Mainly HCV and childhood HBV
Ix needed in viral hepatitis?
FBC, LFTs, clotting
Hep A/B/C serology
how do you managed viral hepatitis
supportive
No EtOH
Avoid hepatotoxic drugs (e.g. aspirin)
Anti-viral = Indicated in chronic disease
HBV: PEGinterferon
HCV: PEGinterferon + ribavarin
what is NAFLD
Cryptogenic cause of hepatitis and cirrhosis assoc. ̄c insulin resistance and the metabolic syndrome.
(NASH) is most extreme form and → cirrhosis
Rx for NAFLD
Obesity
HTN
T2DM
Hyperlipidaemia
Presentation of NAFLD
Mostly asymptomatic
Hepatomegaly and RUQ discomfort may be present.
what is metabolic syndrome
Central obesity (↑ waist circumference) and two of: ↑ Triglycerides
↓ HDL
HTN
Hyperglycaemia: DM
Lx required in NAFLD
BMI
Glucose, fasting lipids
↑ transaminases: AST:ALT <1 Liver biopsy
Management for NAFLD
Lose wt.
Control HTN, DM and lipids
what is HH, describe the pathophysiology
hereditary haemochromatosis.
Inherited, multisystem disorder resulting from abnormal iron metabolism
↑ intestinal Fe absorption (↑ enterocyte DMT + ↓ hepatocyte hepcidin) → deposition in multiple organs.
what are the clinical features of HH
iron MEALS
Myocardial
Dilated cardiomyopathy Arrhythmias
Endocrine
Pancreas: DM
Pituitary: hypogonadism → amenorrhoea, infertility
Parathyroid: hypocalcaemia, osteoporosis
Arthritis
2nd and 3rd MCP joints, knees and shoulders
Liver
Chronic liver disease → cirrhosis → HCC
Hepatomegaly
Skin = slate grey discolouration
Lx in HH?
Bloods: ↑LFT, ↑ ferritin, ↑Fe, ↓TIBC, glucose, genotype
X-ray: chondrocalcinosis
ECG, ECHO
Liver biopsy: Pearl’s stain to quantify Fe and severity
MRI: can estimate iron loading
how is HH managed
Iron removal Venesection: aim for Hct <0.5 Desferrioxamine is 2nd line General Monitor DM Low Fe diet Screening Se ferritin and genotype Screen 1st degree relatives Transplant in cirrhosis
prognosis of HH
enesection returns life expectancy to normal if non- cirrhotic and non-diabetic
Cirrhotic patients have >10% chance of HCC
describe the pathophysiology behind autoimmune hepatitis
Inflammatory disease of unknown cause characterised by Abs directed vs. hepatocyte surface antigens
Predominantly young and middle-aged women
prevention of AIH
Teens and early 20s (25%) Constitutional: fatigue, fever, malaise Cushingoid: hirsute, acne, striae Hepatitis HSM Fever Amenorrhoea Polyarthritis Pulmonary infiltration Pleurisy
lx in AIH
↑LFTs ↑IgG Auto Abs: SMA, LKM, SLA, ANA ↓WCC and ↓plats = hypersplenism Liver biopsy
management of AIH
Immunosuppression
Prednisolone
Azathioprine as steroid-sparer
Liver transplant (disease may recur)
how do you manage paracetamol overdose? Lx
NAC - N-acetyl cysteine acts as glutathione replacement
paracetamol levels in blood
describe paracetamol overdose
- paracetamol is an antipyretic and analgesic. active ingredient is NAPQI
- NAPQI is toxic to liver if accumulates. oxidises hepatic enzymes and causes necrosis and apoptosis
- if overdose, reduction in glutathione which is used to neutralise the toxin.
describe paracetomol overdose sx
bdominal pain, vomiting in first 24hrs
what tool is used to assess malnutrition
MUST. nutritional tool. 1. calculate BMI. 2. calculate weight loss 3. establish acute disease effect and score. 4. overall risk of malnutrition. 5. use management guidelines to develop care plan.
management based on MUST tool malnutrition
management = refer to dietician if high risk. low risk = no action. medium risk monitor. high risk = manage.
options for nutritional support
- nutritional support = meal times should not be interrupted and high calorie options encouraged.
- some supplements = fortisips to give macro and micro minerals required
- unsafe swallow or non-functiong GI tract = NGT, PEG/RIG/PEGJ/RIGJ, parenteral nutrition.
short term nutritional support and caution
- NGT short term for supplementary feeding or can be used on top pt usual oral intake. need to check pH prior to ensure tip in stomach and not in lungs and this can be used. this can be affected by PPI’s so a CXR may be required.
- NGT can be useful for pt with swallowing difficulty - decrease aspiration on food but pt can still aspirate on saliva.
option for medium to long term nutritional support
- medium or long term feeding - requires puncturing the stomach. PEG, PEGJ, RIGJ, RIG.
- Parenteral nutrition = nutrition and fluids directly into pt veins. indicated if GIT not accessible or not working. given via PICC line (central line). risk of line sepsis and liver dysfunction.
which drugs can cause a hepatocellular picture in drug induced liver disease
paracetamol sodium valproate, phenytoin MAOIs halothane anti-tuberculosis: isoniazid, rifampicin, pyrazinamide statins alcohol amiodarone methyldopa nitrofurantoin
which drugs can cause a cholestatic picture in drug induced liver disease
combined oral contraceptive pill
antibiotics: flucloxacillin, co-amoxiclav, erythromycin*
anabolic steroids, testosterones
phenothiazines: chlorpromazine, prochlorperazine
sulphonylureas
fibrates
rare reported causes: nifedipine
GAMED antibodies in body
G = long life in body, years , and highest amount
A
M = produced in infection initially until IgG has been produced
E
D
what are the 3 antigens of hepatitis B
surface antigen HBsAg
core antigen HBcAg
E antigen HBeAg
what does HbsAg represent
HbsAg = s for sx
this is what the body wants ro get rid of
HBsAg vs IgG-HBsAg
what does HBeAg represent
e = marker of viral replication
marker of infectibility or transmission
how does body produce Ig against Hep b
it takes a while for IgG to be produced about 6 months
so body produces IgM’s and then IgG
Igm-HBCAg and later IgG HbcAg
patient with hep b is cured when
IgG-HBsAg present
if pt has HBsAG is present it means
current infection = acute to chronic
if pt has IgG HBsAg present it means
you have won
either cured or vaccinated
if IgG HBsAg is positive with positive IgG GBcAg it means
cured previous infection
if IgG HBsAg is positive with negative IgG GBcAg it means
vaccinated
