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Year 3 - Medicine and Surgery book > Jaundice > Flashcards

Jaundice Flashcards

1
Q

Describe how bilirubin is metabolised

A
  1. Production of unconjugated (i.e. water insoluble) bilirubin - RBC broken down into unconjugated bilirubin and iron by macrophages (mainly in spleen though can also occur intravascularly if pathology). Iron stored in transferrin proteins. Unconjugated bilirubin travels to liver bound to albumin.
  2. Conjugation of bilirubin - unconjugated bilirubin is uptaken by hepatocytes and conjugate it to glucuronate. Hence, bilirubin is conjugated to glucuronate and is now water soluble.
  3. Excretion of bilirubin - conjugated bilirubin is secreted into bile canaliculi - flows down bile duct into duodenum. Here, bilirubin metabolised by bacteria into urobilinogen and stercobilinogen (colourless). Some urobilinogen and stercobilinogen reabsorbed by the gut and excreted by kidneys - but majority is oxidised into stercobilin and urobilin (brown). Hence, complete obstruction of the bile duct = no flow of conjugated bilirubin into gut, no conversion into urobilinogen —> so NO trace of urobilinogen in urine
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2
Q

What is meant by pre hepatic jaundice

A

Excessive production of bilirubin (i.e. before bilirubin reaches the liver). This refers to the breakdown of RBC into Fe and bilirubin in spleen (+ vasculature).

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3
Q

What is meant by hepatic jaundice

A

Jaundice due to pathology of the liver. e.g. reduced uptake of bilirubin into liver, enzyme defects in conjugating bilirubin, hepatocyte damage preventing conjugated bilirubin moving into bile canaliculi.

Problems with bile canaliculi e.g. PSC (primary sclerosing cholangitis)

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4
Q

What is meant by post hepatic jaundice

A

Jaundice caused by problem with biliary flow e.g. bile flow obstruction.

some people class PSC in this category

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5
Q

What is meant by obstructive jaundice

A

Jaundice caused by lack of bile flow into gut –> manifests as pale faeces (due to lack of urobilin and stercobilin) and dark urine (conjugated bilirubin in urine)

May be a problem in bile canaliculi or CBD

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6
Q

What is meant by cholestatic jaundice

A

Jaundice due to bilirubin not flowing out via CBD. May be due to obstruction (e.g. gallstone) or paralysis (ileus) of CBD peristalsis

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7
Q

What is meant by unconjugated jaundice

A

Jaundice caused by buildup of unconjugated (i.e. water insoluble) bilirubin. May be due to increased breakdown of RBC (so increased production of unconjugated bilirubin) or decreased conjugation of unconjugated bilirubin (e.g. due to hepatocyte pathology/enzyme defect).

By definition, all prehepatic jaundice is also unconjugated jaundice.

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8
Q

What is meant by conjugated jaundice

A

Jaundice due to accumulation of conjugated bilirubin,

Posthepatic jaundice is always conjugated jaundice

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9
Q

When formulating ddx for jaundice, always break it down into problems in either:

  1. Bilirubin production
  2. Bilirubin conjugation
  3. Bilirubin excretion

What are the ddx for problems with bilirubin production (i.e. increased production of bilirubin)

A
  1. Intravascular haemolysis - may present with black urine as the degradation produces haemosiderin (v dark but water soluble) and schistocytes on a blood film.
    - Congenital causes: G6PDH deficiency, PK deficiency, SCD, thalassaemia
    - Acquired causes: artificial heart valves, DIC, malaria, HELLP syndrome in pregnant women, medications, blood group mismatch
  2. Extravascular haemolysis - may present with splenomegaly and spherocytes on blood film.
    - Congenital causes: hereditary spherocytosis
    - Acquired causes: autoimmune haemolysis
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10
Q

What are the ddx/causes for decreased conjugation of bilirubin?

A

Decreased conjugation of bilirubin can be caused by decreased uptake of bilirubin- e.g. due to hepatocyte damage (rare cos hepatocytes have to be veryyyy damaged where jaundice is the least of your worries) or due to enzyme problems with conjugation.

Ddx/causes:

  1. Reduced hepatocyte uptake - cholecystographic contrast agents, portosystemic shunts to bypass a cirrhotic liver
  2. Congenital enzymatic problems - Gilbert’s syndrome (common), Crigler-Najjar syndrome (rare)
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11
Q

What signs may indicate that there is a problem due to decreased excretion of bilirubin?

A

Remember that, at the excretion of bilirubin stage, the bilirubin is conjugated.

Means that the conjugated bilirubin cannot make it out of the hepatocytes (e.g. due to bilirubin active exporter being highly sensitive to damage) or cannot make it into bowel due to obstruction.

Signs include: pale (due to decreased stercobilin), foul smelling, and floating (steatorrhoea - as lack of bile salts means that fat is not solubilised) faeces, dark urine (due to water-soluble conjugated bilirubin excreted by kidneys)

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12
Q

What are the causes of decreased bilirubin excretion from hepatocytes into duodenum? (INVITED MD)

A

Infection: viral/bacterial hepatitis, ascending cholangitis, liver abscess, tapeworm infection
Neoplasia: metastatic liver cancer, hepatocellular carcinoma, pancreatic cancer, cholangiocarcinoma
Vascular: Budd-Chiari syndrome (thrombosis in hepatic vein)
Inflammation: Primary biliary cirrhosis (PBC), PSC, autoimmune hepatitis, pancreatitis
Trauma: gallstones, stricture (e.g. after ERCP or cholecystectomy)
Endocrine: intrahepatic cholestasis of pregnancy
Drugs: alcohol, paracetamol, valproate, rifampicin
Metabolic: Wilson’s disease, haemochromatosis
Degenerative: N/A

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13
Q

Sickle cell disease affects mainly what background?

Thalassaemias and G6PDH deficiency affects what background?

A

SCD = west African and afro-caribbean

Thalassaemia/G6PDH deficiency = mediterranean, east asian, african

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14
Q

RUQ pain/discomfort, N+V, pruritus (itching) indicate what cause of jaundice?

A

Hepatitis of any cause (i.e. virus, autoimmune, drugs, alcohol)

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15
Q

Fever or diarrhoea may indicate what cause of jaundice?

A

Viral hepatitis, liver abscess

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16
Q

Steatorrhoea, dark urine and pruritus indicate what type of jaundice?

A

Obstructive jaundice - caused by obstruction to biliary flow

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17
Q

Weight loss, fever, night sweats indicate what cause of jaundice?

A

Malignancy - of liver/BD/Pancreas

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18
Q

Bronzed skin and signs of DM (polyuria/weight loss/infections) suggest what cause of jaundice?

A

Haemochromatosis - hereditary condition so check family history

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19
Q

Exposure to outdoor water/sewage may indicate what cause of jaundice?

A

Leptospirosis

20
Q

Gallstones in PMH may indicate what cause of jaundice?

A

Obstructive jaundice due to gallstones or ascending cholangitis

21
Q

PMH of liver disease/cirrhosis may indicate several causes of jaundice such as?

A

Alcoholic liver disease, NAFLD, Hep B/C, haemochromatosis, Wilsons disease, a1-antitrypsin deficiency, PBC, PSC

22
Q

Ulcerative colitis makes what more likely as a cause of jaundice?

A

PSC (strong association between these two conditions)

23
Q

What might emphysema in the PMH suggest?

A

alpa 1 antitrypsin deficiency

24
Q

Describe 4 ways in which medications can cause haemolysis?

A
  1. Intravascular haemolysis - e.g. sulphonamides/aspirin
  2. Autoimmune extravascular haemolysis - methyldopa
  3. Hepatitis - paracetamol overdose
  4. Cholestasis - co-amoxiclav
25
Q

What are spider naevi, palmar erythema, clubbing, bruising and gynaecomastia a sign of?

A

Chronic liver disease

26
Q

What do Kayser-Fleischer (green) rings suggest

A

Wilsons disease

27
Q

Hepatomegaly may indicate malignancy or?

A

Acute hepatitis

28
Q

What are ascites a sign of?

A

Chronic liver disease

29
Q

In the initial screen for jaundice, which bloods must be done?

A
  1. FBC with reticulocytes - low RBC count with high reticulocyte = increased RBC turnover and haemolysis/recent blood. Microcytosis would be consistent with thalassaemia or iron deficiency anaemia
  2. Bilirubin - ?hyperbilirubinaemia. If conjugated bilirubin > 20% total bilirubin, obstruction to bile flow likely. (In Gilberts disease, total bilirubin won’t be >100uM)
  3. Liver enzymes - ALT & AST raised if hepatocyte damage (raised in acute hepatitis). AST > ALT = excess ETOH. ALT > AST = viral hepatitis. AST/ALT in the 1000s indicates viral hepatitis, paracetamol overdose and ischaemic hepatitis.
  4. ALP and GGT - GGT expressed exclusively by biliary epithelial cells. Raised ALP & GGT = bile duct pathology (e.g. obstruction). Raised ALP but normal GGT suggests bone pathology or pregnancy. Hepatitis may cause rised GGT and ALP (element of intrahepatic obstruction). Isolated rise in GGT = alcohol consumption
  5. Serum amylase/lipase - elevated in pancreatic pathology (e.g. pancreatitis)
30
Q

What causes raised ALP?

A

Biliary epithelial cell damage, high bone turnover, placenta

31
Q

In the initial screen for jaundice, which urine tests must be done?

A

Urinalysis - bilirubin in urine indicates post hepatic obstruction (may manifest as brown urine)

Pregnancy - ?intrahepatic cholestasis of pregnancy, pre-eclampsia with HELPP syndrome, acute fatty liver of pregnancy?

32
Q

What are the second line investigations that are done for jaundice?

A
  1. Haemolysis screen (e.g. if jaundice due to anaemia/elevated unconjugated bilirubin) - check haptoglobins, LDH, direct anti globulin test, blood film
  2. Viral screen - elevated liver enzymes suggests hep A/B/C? Also could be EBV/CMV.
  3. Autoimmune screen - check ANA, ASMA, AMA, especially if initial screen shows elevated liver enzymes. AMA elevated in most patients with PBC
  4. Congenital screen - check for haemochromatosis, a1-antitrypsin deficiency
  5. USS abdomen - will show liver cirrhosis/carcinoma.
33
Q

Pale faeces, dark urine, high ALP and GGT indicate a problem with?

A

Biliary outflow

If CBD dilated - mechanical obstruction
If CBD undilated - PBC/PSC/drugs

34
Q

Albumin levels take about 20 days to fall. What may be the causes of albumin levels to decrease?

A

Reduced synthesis: liver damage, severe malnutrition

Increased albumin loss: nephrotic syndrome

35
Q

What do very high ALT and AST levels indicate? (>1000)

A

Viral hepatitis

36
Q

Gilberts disease is a disease of exclusion. What criteria must be met for Gilberts to be considered?

A

Normal liver enzymes
Normal Hb levels
Serum bilirubin < 100
No bilirubin on urine dipstick

NB Gilberts is an autosomal recessive condition resulting in the liver not being able to conjugate bilirubin at a sufficient rate during times of stress (e.g. acute infection/alcohol excess/pregnancy)

Gilberts may present as occasional episodes of icterus

37
Q

A presentation of jaundice, steatorrhoea and dark urine indicates what cause of jaundice?

A

Reduced excretion of conjugated bilirubin due to obstruction - OBSTRUCTIVE JAUNDICE

This combined with waves of RUQ pain and nausea = ?gallstone

38
Q

Gallstones that do not pass by themselves may require what?

A

ERCP

39
Q

Which 2 surgical emergencies have to be ruled out if a patient presents with an acute gallstone pathology

A
  1. Cholecystitis - constant fever, tender (/distended) abdomen, N+V. Requires antibiotics, analgesia, nil by mouth, IV fluids + cholecystectomy
  2. Ascending cholangitis - present with Charcots triad (febrile rigors, jaundice, RUQ pain). Requires blood cultures, broad spectrum antibiotics, ERCP to drain bile duct of pus
40
Q

Elevated GGT and ALP, bilirubin in urine and steatorrhoea suggests what?

A

Damage to biliary epithelial cells - posthepatic (obstructive jaundice).

Positive AMA = PBC (autoimmune disorder - T cells destroy biliary ducts)

PBC would explain pale faeces due to lack of urobilin and stercobilin and offensive smell (undissolved fats due to lack of bile salts), itch (bile salt buildup in skin) and jaundice

41
Q

How is PBC managed?

A

Immunosuppression - corticosteroids, methotrexate, cyclosporin
Referral to hepatologist, confirming diagnosis - via MRCP and liver biopsy
Bile salt replacement - use ursodeoxycholic acid
ADEK fat soluble vitamin replacement

42
Q

How can choestyramine be used as pruritus (itch) management

A

Sequesters bile salts in gut lumen - prevents them from being reabsorbed

43
Q

Patients with UC are at increased risk of getting which jaundice causing condition?

A

PSC - may also involve many regions of multiple strictures

PSC patients may also have elevated perinuclear antineutrophil cytoplasmic autoantibodies (pANCA)

44
Q

What should the initial initial investigations for suspected pancreatic cancer be?

A

FBC - ?anaemia
Serum amylase - raised in any pancreatic disease
Liver enzymes - ?liver pathology secondary to obstruction
Imaging - CT abdo

45
Q

Elevated bilirubin and spherocytes indicate what cause of jaundice?

A

Extravascular haemolysis

Year 3 - Medicine and Surgery book (29 decks)

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