Jaundice & Liver Disease

Question 1

JAUNDICE - QS TO ASK

i) what does dark urine/pale stool indicate?
ii) name two drugs that can cause liver problems
iii) what condition is usually associated with underlying inflammatory bowel disease?

Answer 1

i) dark urine/pale stool indicates obstruction = cholestasis
ii) isosobomononitrate (angina) and simvastatin can cause hepatitis
iii) crohns disease can be associated with primary sclerosing cholangitis (autoimmune liver disease)

Question 2

O/E

i) what does spider naevi strongly imply?
ii) what may be seen on the chest in LD?
iii) what two things may be seen in the hands?
iv) what may be seen on the abdomen?

Answer 2

i) spider naevi strongly implies portal hypertension
ii) see gynaecomastia
iii) may see palmar erythema and leuconichya
iv) see caput medusae

Question 3

LIVER FUNCTION TEST

i) what is the best tets for liver function?
ii) what is cholestasis?
iii) which two things are a marker of hepatocyte inflammation? what happens?
iv) which two markers are associated with the biliary epithelium and cholestatic problems?
v) is AST liver specific? why?

Answer 3

i) INR
ii) cholestasis is decrease in bile flow due to impaired secretion by hepatocytes or obstruction of the bile duct

iii) hepatocyte inflammation = AST and ALT raised
- hepatocyte injury > release these into circulation

iv) cholestatic problem = riased ALP and GGT (assoc with bile duct problems)
v) AST is also contained in RBC and cardiac muscle therefore not liver specific

Question 4

RAISED INR

i) what is INR?
ii) how is vitamin K implicated in clotting? what effect may low vitamin K have on INR?
iii) in what situation would giving vitamin K not correct abnormal INR?

Answer 4

i) time it takes for your blood to clot

ii) Vitamin K is essential for synthesis of clotting proteins 2,7,9,10
- low vit K may increase INR as you cant make those clotting factors

iii) if the raised INR is due to to liver failure where liver cant make clotting proteins then giving IV vit K wont correct it

Question 5

JAUNDICE - PRE HEPATIC CAUSES

i) what is jaundice? what is it due to?
ii) how does hameolytic anaemia cause jaundice? is there increased conjugated or unconjugated bilirubin?
iii) name a congenital condition that causes pre hepatic jaundice
iv) will there be bilirubin in the urine? what levels of urine urobillinogen will be seen?
v) will LDH be raised?

Answer 5

i) jaundice
ii) haemolytic anaemia > increased breakdown of RBC therefore increased haem and bilirubin > increased pressure on liver to conjugate it > overwhelm therefore increased proportion of unconjugated bilirubin in the blood
iii) congenital hyperbilirubinaemia (gilbert syndrome)

iv) no bilirubin in the urine
- high levels of urobillinogen

Question 6

BILIRUBIN I) which cells does it come from? Which cells take it out of the circulation? Ii) why does bilirubin need to be removed? How is it transported to the liver? Ii) what happens to bilirubin in the liver? Iv) how is it excreted v) why do you get dark urine if bilirubin gets into the blood?

Answer 6

I) comes from RBC (haem is iron + bilirubin) - macrophages in the spleen and liver take it out the circulation after 120 days Ii) bili needs to be removed as its toxic > travels to the liver bound to albumin Iii) conjugation occurs in the liver > add glucuronic acid to make it water soluble Iv) conjugated bilirubin is excreted in bile V) if bili gets into blood it is excreted by the kidneys > dark urine

Question 7

CASE HISTORY I) what does a raised ALT imply? Ii) what does normal albumin and INR mean? Iii) why would an US be done? Iv) give three differentials for a very raised ALT and jaundice V) which two things define liver failure

Answer 7

I) raised ALT implies inflamed liver (Acute hepatitis) Ii) normal albumin and iNR means liver synthetic function is normal Iii) US to look for hepatic obstruction or underlying chronic liver disease Iv) raised ALT and jaundice > viral hepatitis, autoimmune hepatitis, drug induced liver injury eg paracetamol V) liver failure = INR >1.5 (coagulopathy) and hepatic encephalopathy (urea cycle not working therefore can’t get rid of ammonia > encephalopathy)

Question 8

HEPATITIS I) what is the incubation period for Hep B? What is a marker of hep B? Ii) what does hep C cause? Iii) what does hep A cause? Iv) how may autoimmune hepatitis be diagnosed? How is it treated?

Answer 8

I) hep B incubation = 6 weeks to 6 months Ii) hep C causes chronic disease = cirrhosis Iii) hep A causes acute severe hepatitis Iv) auto imm hep can be diagnosed by liver biopsy and need to urgently treat with immune suppression

Question 9

PARACETAMOL AND LIVER INJURY I) how many grams of paracetamol sparks concern? Ii) what liver marker will be raised in overdose? What do levels of this marker correlate with?

Answer 9

I) 12g (24 tablets) Ii) raised ALT indicates injury to liver - ALT levels correlate with he size of the hit

Question 10

CASE HISTORY I) what two thing can cause ascites? Ii) what levels of AST and ALT are seen in alcohol related liver disease? Iii) is ALT or AST usually higher in hep c and NAFLD? Iv) what type of enzyme is GGT? What does the liver make more of it in response to? V) what may an elevated INR represent?

Answer 10

i) portal hypertension and malignancy Ii) AST usually higher than ALT in a 2:1 ratio Iii) ALT higher than AST in hep c and NAFLD Iv) GGR is a cholestatic enzyme - liver makes more of it in response to alcohol so can be used as a marker of too much ETOH V) elevated INR - reflect liver failure (global hepatocytes failure so can’t produce clotting factors)

Question 11

CONSEQUENCES OF LIVER CONDITIONS

I) how to hepatitis progress to cirrhosis to liver failure?

Ii) what are the consequences of portal HT? (SAVER)

Iii) how does hepatic encephalopathy develop?

Answer 11

I) hepatitis causes fibrosis (lay down collagen) > cirrhosis (bridging fibrosis between portal triads) > liver fail and PH

Ii) portal HT - splenomegaly, ascites, varices, encephalopathy)

Iii) liver breaks down nitrogen waste products to urea and if there is blockage or PH to liver then ammonia gets to the brain > drowsy and coma

Question 12

CIRRHOSIS

i) what is it? name four causes? name two genetic and two drug causes?
ii) name three things that may be seen in the hands? seen on the face? trunk? abdo?
iii) what score is used to assess severity? name four things included? what is needed for a dx of cirrhosis?
iv) what may be seen on LFT - bili, AST, ALT, GGT, albumin, PT/INR, WCC, plat? what may be seen on US? (3) what does high neutrophils on ascitic tap indicate?
v) what is vital in tx? what should be abstained from? (3) how often should US/AFP be done to screen for HPC carcinoma?
vi) what can be given if ascities? what is the only definitive tx? name three complications

Answer 12

i) Irreversible damage/fibrosis
* Last stage progression of CLD
* Caused by ALD, NAFLD, chronic hep B/C, AI hepatitis
* Genetic causes - haemochromotosis, a1 antitryp defic
* Drug vauses - amiodarone, methyldopa, methotrexate

ii) Hands - palmar erythema, leuconuchia, DC
* Face - jaundice, xanthelasma, parotid enlarge (ETOH excess)
* Trunk - spider naevi, hair loss, GCM
* Abdo - striae, hep/splenmegaly

iii) Child-Pugh grading asseses severity of CLD (espec cirrhosis), can be used to guide mx of hepcell carcinoma
- CP grading Albumin, Bilirubin, Clotting (PT), Distension (ascites), Encephalopathy
- Liver biopsy (cirrhosis is histological dx)

iv) LFT - high bil, AST, ALT, GGT (later see low albumin with raised PT/INR, low WCC/plats dye to loss of synthetic function/hypersplenism)
* US - small liver/hepatomegaly/splenomegaly
* Ascitic tap - high neutrophils indicate bacterial peritonitis

v) Good nutrition is vital
* Abstain from alcohol, NSAIDs, sedatives, opiates
* Do US/AFP every 6 months to scren for HC carcinoma

vi) If ascites, fluid restriction, give spironolactone
* Bacterial peritonitis - Abx
* Liver transplant is the only definitive treatment
- complications > Hepatic failure (fail synth clotting factors > coagulopathy)
* encephalopath, hypoalbumin, sepsis, bacterial peritonitis
* Portal hypertension - ascites, splenomeg, oes varices, caput medusae

Question 13

VIRAL HEPATITIS

i) name four things it can be caused by?
ii) what symptoms may be seen in Hep A/B/C?
iii) name four investigations that should be sent?
iv) name two supportive management? when is anti viral tx indicated? name two

Answer 13

i) Caused by hep A-E
- Can also be caused by CMV, EBV, HSV

ii) Hep A - fever, malaise, then jaundice, hep/splenmegaly, ademp[atju
* Hep B - sim to hep A but more arthalgia/uritcaria
* Hep C - usually asymp

iii) HBV serology
* LFTs, IgM, IgG, Hb surface antigen

iv) Supportive > No EtOH, Avoid hepatotoxic drugs (e.g. aspirin)
- Anti-viral > Indicated in chronic disease
- HBV: PEGinterferon
- HCV: PEGinterferon + ribavarin

Question 14

ACUTE HEPATITIS - DRUG INDUCED

i) what happens?
ii) name three drugs tha tcan cause hepatitis? name three drugs that can cause cholestasis?
iii) name a drug that can cause fibrosis? name two drugs that can cause necrosis?
iv) what is the only definitive tx?

Answer 14

i) Acute liver parenchymal destruction
* Various patterns of liver injury

ii) Hepatitis - statins, ketoconzaole (anti fungal), TB drugs
* Cholestasis - co-amox, fluclox, chlorpromazine, NSAIDs, Sus, COCP

iii) Fibrosis - methotrexate
* Necrosis - paracetamol, NSAIDs

iv) definitive tx > remove offending stim

Question 15

ACUTE HEPATITIS - ETOH INDUCED

i) what is it? what is it usually associated with?
ii) name four symptoms? what indicates a poor prognosis? what may MCV and GGT be?
iii) what score is used - what two things does it use? what needs to be screened for? when may corticosteroids be offered? what WCC, plats, INR, AST may be seen?
iv) what needs to be withdrawn? what needs to be replaced - why? what needs to be supplemented?

Answer 15

i) Liver inflam due to high ETOH consump
* Early stage in alc liver disease, usually assoc with steatosis (fat depos in liver)

ii) Generally unwell - fever and jaundice, Hepatomegaly due to steatosis, D+V, ascites
- Hepatic encephalopathy > poor prognosis
- High MCV & GGT

iii) Maddrey score - assess severity (PT and bilirubin levels) > predicts mortality
* Screen for infection/ascitic tap for bacterial peritonitis
- Offer corticosteroids if DF in MS is >32
* Blood - high WCC, low plats, high INR, AST, MCV, Urea

iv) Alcohol cessation + withdrawal prevention
- Vitamin B1 replacement - pabrinex + oral thiamine to prev Werenickes
- Nutritional supplement

Question 16

AUTOIMMUNE HEPATITIS - CHRONIC

i) what is it? what is present? what are the two age peaks in females? what may trigger it? which two HLA are assoc?
ii) name four vague symptoms that may be seen? what is seen in young women? what do 25% present with? name four other conditions it may be assoc with?
iii) which two autoimmune antibodies may be present? what Ig may be seen in protein electro? what may be seen on FBC aand LFT? what may be seen on biopsy? (2)
iv) how are asymp cases managed? what immunosupp tx may be given?. (2), how is response to tx monitored? (2) what is done if disease is advance?
v) name a complication

Answer 16

i) CHRONIC inflammatory liver disease
* Presence of auto antibodies
* Females - peak in 20s and then perimenopause
* Enviro trigger eg viral illness sets off inflam casvade
* HLA-DR3/DR4 are associated

ii) Vague symptoms - fatigue, nausea, myalgia, upper abdo discomfort
* Amennorhea in younger women
* 25% present with acute hepatitis (high liver enzymes, jaundice, hepatomeg)
* Assoc with hashimoto, RA, Graves, IBD, pleurisy, urticaria, AI haemolytic anaemia

iii) AI profile - anti nuc antibody (ANA) & anti sm musc antibody (SMA)
* Protein electro - hgih titres of IgG
* FBC (anaemia), LFT (deranged - high aminotransferases)
* Biopsy - interface hepatitis & plasma cell infiltration (with or without cirrhosis)

iv) Watch and wait if asymp
* Immunosupp - high dose oral prednisolone, add azathioprine if LT tx req
* Monitor response looking at ALT/AST
* Liver transplant if advanced

v) Increased risk of HC carcinoma

Question 17

LIVER FAILURE

i) what two things characterise it? how are acute and chronic LF charac? what is fulminant hepatic failure? name three things that can cause LF
ii) name four symptoms?
iii) what serology should be done? name three imaging screen that may be done? what may be seen in relation to PT and INR?
iv) what needs to be considered first in tx? what care may pt require? what must be treated? what must be avoided? what should be given prophylactically?
v) name four complications and how to treat each

Answer 17

i) Recog by dev of coagulopathy (INR >1.5) and encephalopathy
* Sudden on healthy liver bground = acute
* Slower onset on bground of cirrhosis = chronic
* Fulminant hepatic fail = massive necrosis of liver cells > severe impair liver func
* Caused by viral hep, paracetamol od - many causes

ii) Jaundice
* hepatic encephalopathy
* smell of pear drops (fetor hepaticus)
* asterixis
* constructional apraxia (cant copy 5 point star)

iii) CMV/EBV serology
* CXR, abdo US, doppler flow of portal vein
- Bloods - infection, increased PT/INR

iv) Think sepsis, hypogly, GI bleed, encephalopathy
* ITU care, intubation, NG
* catheters to assess fluid status
* Give 10% glucose to avoid hypo
* treat the cause eg GI bleed, paracetamol poison, sepsis
* Avoid sedatives/drugs with hepatic metabolism
* PPI prophylaxis

v) Cerebral oedema (due to ammonia etc bup in blood) - give mannitol
* Ascites - restrict fluid
* Bleeding - give Vit K
*Infection - abx
* encephalopathy - avoid sedatives, correct electrolytes

Question 18

ASCITES

i) what is it? what is it a common complication of? why? name three other causes
ii) name four symptoms? what may be seen if severe? why?
iii) what is serum-ascites albumin gradient used for? what is the cause if gradient is high? what is cause if gradient is low?
iv) what dietary advice should be offered? what drugs are givene first? what non pharma therapy can be used? what sx intervention may be done?
v) name a complication and how to tx it?

Answer 18

i) Accumulation of fluid in abdo cavity
* Common complication of CLD due to portal HT exerting increased hydrostatic pressure > transudation of fluid into abdo cavity
* Also exacerbated by low plasma oncotic pressure due to low albumin synthesis
* If not assoc with PTH - caused by nephrotic synd, malig, pancreatitis, TB

ii) Abdominal distention/discomfort
* nausea/vomiting
* Dyspnoea if severe (due to hydrothorax or splinting of diaphragm)

iii) Serum-ascites albumin gradient (SAAG) is used to determine aetiology (serum albumin/albumin in ascites fluid)
- SAAG >1.1 = high gradient = caused by PTH (cirrhosis, heart fail, budd chiari, constric pericarditis)
* SAAG <1.1 = low gradient = not assoc with PTH = peritoneal cause

iv) Dietary advice, reduced salt intake
* Diuretics - spironolactone first line, then loop (furosemide) - risk of hyponatremia
* Drain if large volume
* Consider TIPSS (stent bet portal and hepatic vein > shunt to decompress the portal sys)

v) Spontaneous bacterial peritonitis (usually caused by E coli) - give broad spectrum abx

Question 19

IRON DEFICIENCY ANAEMIA

i) how is it defined in men/preg/non preg women? name three causes? name four symptoms?
ii) what is found on bloods? (3) what will serum iron be? what will total iron binding capacity be? what will transferrin sat and serum ferritin be?
iii) what is first line treatment? what form is this given? what is second line tx?
iv) when should a red cell transfusion be done? what needs to be monitored?
v) what ultimately needs to be done

Answer 19

i) IDA = haemoglobin <130 g/L (13 g/dL) in men aged ≥15 years,
- <120 g/L (12 g/dL) in non-pregnant women aged ≥15 years
- <110 g/L (11 g/dL) in pregnant women
- Causes include decreased iron intake (dietary), increased iron loss (bleeding), impaired absorption (surgery/coeliac) and increased iron requirements (pregnancy/lacttion)
- symptoms > fatigue, pallor, dyspnoea on exertion, and pica.

ii) Blood tests reveal microcytic, hypochromic anaemia; low reticulocyte count.
- low serum iron, increased total iron-binding capacity (TIBC), less than 16% transferrin saturation, and low serum ferritin

iii) first line is oral iron replacement (ferrous sulphate, ferrous gluconate, ferric maltol)
- second line > IV replace by iron dextran/sodium ferric gluconte complex or iron sucrose

iv) transfuse red cells if CV compromise (SOB at rest, chest pain, light headed)
- dont replace red cells too quick > vol overload

v) find and treat underlying cause

Question 20

BILIARY SEPSIS

i) what acute condition can it arise from? what three things will be present? name three other symptoms that may accompany it?
ii) what causes it? what imaging is done? what is the dx if bile duct is dilated and lab evidence of cholestasis?
iii) what tx is given first line? name two possible sources of sepsis that need to be controlled?

Answer 20

i) acute cholangitis
- charcot triad - RUQ pain, fever and jaundice
- may also get hypotension, shock and mental status change

ii) caused by increased intraductal pressure from an obstruction > reflux of bacteria > sepsis
- US of RUQ
- asc cholangitis

iii) abx > piperacillin-tazobactam
- asc cholangitis (do ERCP for biliary decompress)
- cholecystitis (perc drain if not responding to medicl tx)

Question 21

COELIAC DISEASE

i) what is it? what is it ttriggered by? what three things are seen in the small intestine as a result of immune activation? what do these changes led to?
ii) name five symptoms? name four RF? name four investigations that should be ordered? what is seen in each
iii) which MHC do almost all people with CD carry? how does this manifest in CD? what type of immune activtion do peptides trigger in the SI?
iv) what is first line tx? what should be added in? what happens if patient doesnt respond to first line tx?
v) what is coeliac crisis? how does it present (3) how is it treated? (3)

Answer 21

i) systemic autoimmune disease triggered by dietary gluten peptides found in wheat, rye, barley, and related grains.
- Immune activation in the small intestine leads to villous atrophy, hypertrophy of the intestinal crypts, and increased numbers of lymphocytes in the epithelium and lamina propria.
- Locally these changes lead to gastrointestinal symptoms and malabsorption

ii) diarrhoea, abdo discomfort, bloating, osteoporosis, fatigue, weight loss
- RF = FH of coeliac, IgA defic, T1DM, autoimmune thyroid disease
- order FBC and blood smear (low Hb and microcytic hypochromic red cells)
- IgA tissue transglutaminase (IgA-tTG)- above normal levels
- endomysial antibody - elevated
- skin biopsy - granular deppos of IgA in dermal papillae

iii) HLA DQ2 or DQ8 > required to present gluten peptides > ativates T cell response (most with DQ2/DQ8 dont have CD but must have them to have CD)
- both innate and adaptive

iv) gluten free diet is first line + vitamin and mineral supp (ergocalciferol and calcium carbonate) - check pt for common defic and substitute
- if dont respond first line > refer to dietician/gastroenterologisy

v) presents with hypovol, watery diarhoea, acidosis, hypocalc, hypoalbumin
- give rehydrate and correct electrolyte abnorms
- may add in a corticosteroid