liver - jaundice

Question 1

120 days rbc worn out —–> macrophages recognise this ——–> phagocytose them ——-> heam oxgenase converts it into biliverdin (water soluble ) —–> bilirubin reducatse reduces it into bilirubin (water insoluble)

to transport bilirubin to the liver - has to be conjugated - bound to albumin
normally 1 bilirubin to 1 albumin. In high conc - more bilirubin binds to 1 albumin

Bilirubin in the liver conjugated to glucuronic acid to make it more soluble. This is secreted into bile and passes into duodenum via gall bladder.

*

Answer 1

look yp grey baby syndrome.

Question 2

What is Jaundice ?

Answer 2

OTHER NAME :
ICTERUS

Accumulation of bilirubin in the bloodstream which can then deposit into skin causing:

Yellowing of :
0 skin
0eyes - sclera (white of the eye )

eyes often yellow before skin ( elastin the sclera has a high affinity for bilirubin )

NORMAL RANGE OF BILIRUBIN : 3.4 TO 20 micromol / L . (0.2 to 1.3 mg/dl)
might only see jaundice at btw 2 - 3 mg/dl

TYPES :

***Pre - hepatic - HIGH LEVELS OF UNCONJUGATED BILIRUBIN
causes :
0 Haemolysis from :
- Drugs
- any form of haemolytic anaemia (extravascular , autoimmune e.g Hepatocytes cannot cope with increased number of broken down RBC So unconjugated bilirubin not conjugated)

• infectious causes - LOOK FOR FEVER e.g. cytomegalovirus , infectious mononucleosis , toxoplasmosis, leishmaniasis,
  Leptospirosis (people who work outdoors , swin in contaminated lakes at risk)
• Paroxysmal nocturnal haemoglobinuria ( rare - aquired RBC membrane defect )

0 Impaired bilirubin conjugation
- Gilbert’s syndrome (faulty gene means bilirubin builds up in the blood instead of passing into bile at a normal rate. )

*** Hepatic - rise in CONJUGATED
- Hepatitis (Viral , autoimmune, alcoholic),
- HIV
TOXINS
- Alcohol (cirrhosis)
- Drug-induced liver disease (paraceatmol overdose , IV drug usage (HEPT B), infected tatoo needle etc)
- Cancer (metastases, lymphoma , hepatocellular carcinoma ) p destroy healthy liver tissue (reducing liver capacity to conjugate or by compression of intra- bile duct)
- primary billary cholangitis/ cirrhosis
- primary sclerosing cholangitis.
0 Genetic :
-Wilson’s disease (excessive copper in body (liver , brain etc.)

• Hereditary haemochromatosis - excessive iron (this damages liver and can cause jaundice& cirrhosis)
• ** Post hepatic/cholestatic - OFTEN PRESENT WITH PRURITIS (ITCH) - RISE IN CONJUGATED
• Gallstones e.g choledolithiasis
• post operative stricture (can cause obstruction)
• Ascending / acute cholangitis (infection of biliary tree ) - can have underlying cause e.g. gallstone , surgery , chronic pancreatitis, radio / chemo.
• Cancer - pancreatic cancer (head of pancreas - common - will see epigastric pain with radiation to back - can be asymptomatic tho ), metastases , cholangiocarcinoma, lymphoma.

CAUSES

0 increased serum unconjugated or conjugated bilirubin

• ascites
• hepatic encephalopathy
• portal hypertension
• erythema palmar
• gynercomastia

Question 3

Bilirubin pathway and metabolism & excretion?

Answer 3

RBC, phagocytosed by macrophage

2. haemoglobin broken down into heme + globin
3. globin broken down into amino acids . Heme broken down into iron and protoporphyrin.
4. Photoporphyrin coverted into unconjugated bilirubin. (lipid soluble not water)
5. Unconjugated bilirubin binds to albumin an transported to liver.
6. Bilirubin is conjugated (water soluble )by UGT - uridine glucuronic transferase
7. Drains into bile caniculli —–> bile duct ——> gallbladder for storage as bile.
8. Food in GI tract stimulates bile secetion from gallbladder. Bile travels through common bile duct into duodenum.
9. Conjugated Bilirubin converted to —–> Urobilinogen (by intestinal microbes )
10. urobilinogen ——> urobilin ( by spontaneous oxidation)
    0 20 5 of urobilinogen recycled back to blood.
    - 90 % of this goes to liver
    - 10 % goes to kidney - secreted in urine.
11. Urobilin exreted into feaces.

JUST TRY AND REMEMBER THIS.

LOOK HERE FOR BRIEF OVERVIEW ——> RBC broken down ——->unconjugated Bilirubin (waste product produced) ———> hepatocytes conjugate bilirubin with glucornic acid ( conjugated B - water soluble - can pass into bile ) —————> Conjugated B convert to urobilinogen & stercobilinogen by gut bacteria —————> exreted into urine & stool>

Question 4

Causes of jaudice - raised unconjuagated bilirubin ?

Answer 4

THINK PRE -RENAL CAUSES OF JAUDICE - Unconjugated B from broken RBC cannot be conjugated by Hepatocytes bcc too much UB to cope.

0 Extravascular Haemolytic anemia - RBC broken down prematurely .

0 Ineffective hematopoesis - RBC dont form properly in bone marrow so macrophages break them down.

0 Physiological jaundice of the newborn - fetal liver has low level of UGT enzyme ( converts bilirubin from unconjugated to conjugated.
macropahes engulfing and breaking fetal RBC after baby is born —–> release unconjugated B.
- if the liver cannot cope - builds up in blood.

• in severe cases - Kernicterus - Unconjugated bilirubin collects on brain cause damage and death.
• RBC release unconjugated bilirubin . Hepatocytes get overwhelmed as they cannot convert the extra unconjugated bilirubin.

Question 5

What is primary biliary cholangitis (cirrhosis )?

Answer 5

Liver disease - gradually gets worse over time. (form of cholestasis - reduced / blocked flow of bile from liver - build of billirubin.)

CAUSES-

Immune system attacks the bile duct in liver (intra - hepatic bile duct) mistakenly - damaging it —————————-> bile builds up in the liver————————-> can lead to cirrhosis/ scarring ( Arise at end stage ) ——————> progressive so if not treated can lead to liver failure.

Symptoms

o Itchy skin
o Fatigue 
o bone and joint aches
o dry eyes and mouth
o Pain / discomfort in upper right side of tummy. 

Diagnosis

(Raised ALP + rasied anti - mitochondrial antibody - often enough for diagnosis - no need for biopsy )

• Antinuclear antibiody may also be raised
• FBC
• LFT ( rasied ALP , slightly raised GGP - seen on capscule )
• Ultrasound - to rule out other problems with bile duct and assess liver
• Liver biopsy - is sometimes recommended
• Blood test - can find anti - mitochondrial antibodies.
  (serum lipid - often have raised cholesterol levels - Hypercholesterolemia - can causes Xanthelasma (soft yellowish fatty deposit that forms under skin - either side of eyelid )

Complications

o Jaundice develops as disease progresses
o Osteoporosis - linked with liver diseases
o Portal Hypertension
o Ascites - ( liver produces Albumin )
o Vitamin deficiencys - A,D, K
- (Vitamin D precusor - 25 hydroxylcholecaliferol - stored in the liver. )
- Vitamin D, K , A , B12 stored in the liver.
- Vitamin D ,K , A , E - are fat soluble vitamins )
o increased risk of developing liver cancer.

Question 6

Treatment of primary Billary Cholangitis ( Cirrohosis ) ?

Answer 6

Ursodeoxycholic acid - 1 st line

Obeticholic acid - 2nd line - used when response is inadequate to Ursodeoxycholic acid.

Medicine to treat itch
Cholestyramine -
( used to alleviate pruritus
* must be given at least 2 hours apart from ursodeoxycholic acid.)

o Fat soluble vitamin prophylaxis (Vitamin K , A, D, E)

Liver transplant - last resort.

Question 7

Contraindications for liver biospy ?

Answer 7

o Platelets <100 x10⁹/L,
o INR >1.3,
o Hb <100 g/L

all risk factors for biopsy i.e. high risk of bleed or unable to tolerate blood loss.

o Acute confusion - cannot cooperate , give consent

o Acities - should be drained - as increases bleeding risk .

Question 8

Tests for Wilson’s disease ?

Answer 8

Serum Ceruloplasmin (protein made in the liver & stores & carries copper to liver. )
urinary copper excretion.

Question 9

Causes of Conjugated Bilirubin jaundice ?

Answer 9

Hepatocellular injury ( cause damage to hepatocytes - so reduced secretion of conjugated bilirubin into bile duct so remains in the liver & eventually gets into blood stream. 
(HEPATIC)

Cholestasis - Blockage of bile duct - stop flow of bile.
(POST - HEPATIC)

Question 10

What is kerticterus ?

Answer 10

Brain damage & seizures cause by build up of bilirubin in babies (new born jaundice )

• jaundice is normal in babies -usually get better on its own within 24 hrs.

treatment -

1. phototherapy - blue light polymerises bilirubin more easy to pass out.

or

2. Exchange transfusion - blood of baby removed and transfused with donor blood.

pathological hyperbilirubinaemia: unconjugated - medical emergency

1ST LINE

immediate exchange transfusion
+ phototherapy
(Started while preparing for transfusion and continued after)
+ hydration

pathological hyperbilirubinaemia: conjugated

1ST LINE

treatment of underlying cause.

If above 95 percentile for bilirubin level for their age group ( on graph for exchange transfusion)

1ST LINE

ET + PHOTOTHERAPY + HYDRATION

If above 95 percentile for bilirubin level for their age group ( on graph for phototherapy)

1ST LINE

Phototherapy + hydration

Question 11

What is carotenemia ?

Answer 11

Yellow pigmentation of the skin & increased beta - carotene in the skin.

Usually caused by excessive consumption of carotene risch foods e.g. carrots , squash , sweet potatoes.

NEED TO DISTUINGIUSH FROM JAUNDICE (SCLERA ALWAYS SPARED IN CAROTENAEMIA)

• if present reduce amount of beta - carotene rich foods.

Question 12

What examinations would you do if a patient presented with yellow skin ?

Answer 12

if Yellow skin - look to see if sclera are yellow.
- if they are not could be Jaundice or carotenaemia.
(if they are - JAUNDICE)

DO :
Abdominal exam
Neurological exam - (need to exclude hepatic encephalopathy )

Question 13

Investigations for jaundice?

Answer 13

LFT test with fractionation of bilirubin ( Direct = conjugated
indirect = conjugated

0 Urine dipstick - if positive for bilirubin indicated increased levels of conjugated in the serum (can’t determine unconjugated levels with urine dipstick as unconjugated B is not soluble in water)

0 U & E - indentify renal impairment

0 FBC , lactate dehydrogenase , peripheral blood smear , direct / indirect B - Identify haemolysis

0 Clotting screen

e. g.
- Prothrombin time
- INR
-
- - abnormal clotting can occur in biliary obstruction and parenchymal liver disease.

0 Serum Amylase - pancreatitis suspected.

0 Hepatitis A, B, C if suspected

0 serum paracetamol - check for paracetamol overodose. (if suspected overdose)

0 Seum ceruloplasmin & urinary copper excretiion- if Wilson’s disease suspected.
0 ESR , CRP

IMAGING - ALL PATIENTS REQUIRE SOME FORM OF IMAGING TO :EXCLUDE OBSRUCTIVE PICTURE :

0 Abdominal ultrasound or CT scan

Question 14

Red flags of Jaundice ?

Answer 14

Signs of Hepatic encephalopathy :

• confusion
• altered neuromusclar function e.g ataxia , asterixis ,nystagmus , poor - coordination

Signs of severe hepatic dysfunction

• brusing
• purpura
• petechiae

Signs of GI beeding

• Haematemesis (vomiitng bloood)
• melaena (black , tarry stools )

Signs associated with sepsis

• Fever
• hypotension
• tachycardia

Signs associted with ascending cholangitis (inflammation of bile duct)
- Charcot’s triad - fever , RUQ , jaudice.

• Signs / history of paracetamol overdose.
• Vomiting
• Marked abdominal tenderness or pain

Weight loss & Jaundice (URGENT REFFERAL - indicated underlying maligancy or chronic disease e.g. alcoholic cirrhosis)