jaundice Flashcards

(43 cards)

1
Q

what are the components of hemoglobin ?

A

Protein part —> globin ( amino acids )

Non-protein part —> Heme ( porphyrin + iron )

heme act as prosthetic group ( permanent non amino acid group associated with proteins )

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2
Q

what is porphyrin ?

A

cyclic molecule formed by Linkage of :

4 pyrrole rings through METHENYL BRIDGES (-CH )

with iron atom in the middle

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3
Q

what are 2 states of heme?

A

oxidized or reduced

Oxidized —-> Ferric

Reduced —> ferrous

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4
Q

examples of molecules containing hemes?

A

Hemoglobin and myoglobin —> transport O

Cytochrome C –> electron transport

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5
Q

Describe heme structures?

A

porphyrin + iron

4 Pyrrole rings

each ring has :

Acetyl Group
Propionyl Group

Methenyl Bridges connect the 4 PYRROLE RINGS —> porphobilinogen

All of these are involved in the synthesis of porphyrins and porphyria disorders

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6
Q

describe the degradation of hemoglobin ?

A

After about 120 days the RBCS will be degraded by RETICULOENDOTHELIAL SYSTEM ( THE LIVER AND SPLEEN )

Globin —> protein part —> will be recycled for making other proteins in the body or for energy production

Heme –> Non protein –> will metabolized into several intermediates which the body will get rid of it

85% of degrade heme comes from the hemoglobin while the rest comes from other heme containing proteins

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7
Q

what is the first step of degradation of heme?

A

Porphyrin ring is opened by OXIDATION REACTION

Catalysed by the MICROSOMAL HEME OXYGENASE

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8
Q

what does microsomal heme oxygenase require ?

A

NADPH

O2

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9
Q

what is the result of the oxidation reaction of the porphyrin rings?

A

Linear biliverdin

Carbon monoxide (CO)

Release of iron —> recycled

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10
Q

describe the 2nd step of degradation of heme?

A

GREEN BILIVERDIN IS REDUCED TO RED/ORANGE BILIRUBIN

via biliverdin reductase ( Require NADPH )

Bilirubin is relatively insoluble

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11
Q

What does bilirubin bind to transport to the liver?

A

ALBUMIN

non covalently

it binds to bilirubin cuz its relatively insoluble

( WHEN ITS BOUND TO ALBUMIN ITS NOT DANGEORUS BUT UNBOUND BILIRUBIN WHICH IS DANGEROUS TO THE BRAIN )

some drugs like SULPHONAMIDES DISPLACES BILIRUBIN FROM ALBUMIN —> UNBOUND BILIRUBIN —> NEURAL DAMAGE

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12
Q

Describe conjugation of bilirubin?

A

In the hepatocytes :

Bilirubin dissociate from ALBUMIN and binds to INTRACEULLULAR PROTEIN LIGANDIN

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13
Q

What enzymes responsible for conjugating bilirubin ?

A

Microsomal bilirubin UDP glucuronosyltransferase / bilirubin UGT

Conjugate bilirubin to two molecules of GLUCURONIC ACID

Bilirubin + Glucuronic acid = Bilirubin diglucuronide / conjugated bilirubin

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14
Q

what is the importance of conjugation ?

A

mechanism in the liver to INCREASE SOLUBILITY OF METABOLITES to FACILITATE EXCRETION

done by covalent bonding with another group

in this case bilirubin + glucuronic acid = more water soluble= easy excretion

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15
Q

what is crigler-najjar 1 and 2 and Gilbert syndrome ?

A

Deficiency in Bilirubin UG transferase enzyme

cant conjugate bilirubin

gilbert syndrome —> benign
Crigler najjar 1 and 2 - more serious

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16
Q

where does glucuronic acid come from?

A

UDP glucuronic acid is a donor of glucuronic acid

UDP glucose is converted to glucuronic acid by oxidation reaction that is CATALYSED BY UDP GLUCOSE DEHYDRODENASE

Glucuronic acid can obtained via various ways :

From lysosomal degradation of glycosaminoglycans ( GAGS

Diet

From glucose 6 phosphate via The uronic acid pathway

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17
Q

what is the end product of glucuronic metabolism?

A

Xylulose 5 phosphate that feeds PPP

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18
Q

What are the uses of UDP glucuronic acid ?

A

Glycosylation of GAGS

other gulcuronidation reactions

19
Q

how does conjugated bilirubin transported?

A

ACTIVELY transported against concentration gradient into BILE CANALIUCILI and then into the BILE

Bile canaliculi ——–> Bile

20
Q

what happens in liver disease ?

A

the energy dependent active transport is disturbed

Unconjugated bilirubin UCB is normally not secreted in the BILE

21
Q

what is DUBIN JOHNON SYNDROME?

A

Deficiency in the transporter of conjugated bilirubin

22
Q

what happens to conjugated bilirubin when it leaves the liver?

A

Hydrolysed and reduced by bacteria in the gut

YIELDING UROBILINOGEN —> colorless compound

23
Q

what happens to Urobilinogen?

A

In intestines :

Urobilinogen is oxidized by the intestinal BACTERIA ———-> STEROCOBILIN

which gives feces brown color

24
Q

what happens to some urobilinogen that doesnt get converted to stercobilin ?

A

Re-absorbed into the gut and enter the portal blood :

Re secreted into the bile

Urobilinogen reach the kidney —> converted to yellow urobilin

25
describe the whole process of metabolism of rbc?
1-Hemoglobin comes from RBC 2- Breakdown of heme to bilirubin occur in macrophages of reticuloendothelial system ( tissue macrophages, spleen , liver ) 3- Unconjugated bilirubin is transported through the blood ( complexed with albumin ) to the liver 4- Bilirubin is taken up via FACILITATED DIFFUSION by liver and conjugated with glucuronic acid 5- Conjugated bilirubin is actively secreted into bile and then intestines 6- in intestines glucuronic acid is removed by bacteria , the resulting bilirubin is converted to UROBILINOGEN 7- Some of the urobilinogen is reabsorbed from the gut and enters portal blood 8- Portion of urobilinogen participates in the enterohepatic urobilinogen cycle 9- the remainder of urobilinogen is transported by the blood to kidney and is converted to YELLOW urobilin and excreted in urine giving it yellow color 10- Urobilinogen is oxidized by intestinal bacteria to the brown stercobilin ( give feces brown color )
26
can we see bilirubin itself in ruine?
No cuz its nots easily soluble only the urobilin IF we see bilirubin in the urine its needs to be conjugated form as its water soluble --> always pathological
27
what is jaundice ?
yellowish discoloration of sclera, skin, nail beds caused by deposition of bilirubin it is a symptom of underlying disease normal bilirubin level are normally is about 1 mg bilirubin level at 2-3 mg is considered jaundice
28
what are the 3 types of jaundice ?
Hemolytic jaundice --> PRE HEPATIC ( production problem ) hepatocellular jaundice ---> HEPATIC( conjugation problem ) Obstruction jaundice ---> post hepatic ( excretion problem )
29
describe hemolytic jaundice / prehepatic jaundice?
Normal production of bilirubin is 300 mg /day Liver has capacity to conjugate and excrete up to 3000 mg of bilirubin/day In hemolytic anemia SUCH AS sickle cell anemia, pyruvate kinase or glucose 6 phosphate dehydrogenase deficiency Results in HIGH RATE OF BILIRUBIN PRODUCTION ( in macrophages) THAT EXCEED THE RATE OF CONJUGATES
30
what is the result of hemolytic jaundice/prehepatic jaundice?
Increased Unconjugated bilirubin Normal or increased Conjugated bilirubin ( CUZ THE CONJUGATION ABILITY OF LIVER THE SAME ) Urine and blood urobilinogen WILL INCREASED ( cuz soo much bilirubin is being conjugated ) no bilirubin urea
31
describe hepatocellular jaundice/ intrahepatic ?
Reduced ability of bilirubin conjugation as a result of DAMAGED hepatocytes LIVER CANNOT CONJUGATE BILIRUBIN TO MAKE IT WATER SOLUBLE
32
What causes hepatocellular jaundice ?
Crigler najjar 1 and 2 ( lack of UGT bilirubin ) Gilbert syndrome ( lack of UGT bilirubin ) Hepatitis Cirrhosis any liver disorder
33
what is the result of hepatocellular jaundice?
Increased in unconjugated BILIRUBIN ( cuz liver cant no more ) Increase in UROBILINOGEN IN THE URINE AND IN THE BLOOD BECAUSE HEPATIC DAMAGE DECREASE THE ENTEROHEPATIC CIRCULATION OF UROBILINOGEN ( gets reabsorbed and not converted to stercobilin ) Dark urine Pale stool ( cuz less conjugated bilirubin , less stercobilin ) INCREASED AST AND ALT Conjugated bilirubin ( CB )---> might increases ( bile secretion is not efficient which causes intrahepatic cholestasis , bile cant move inside the liver ) IT can diffuse to the blood ( SINCE IT CANT GO THE INTESTINE CUZ CHOLESTASIS IT GOES TO BLOOD ) Cholestasis : reduced flow of bile from the liver ( bile retention ) ---> retention of bilirubin , cholesterol , bile salts ----> SKIN IRRITATION AND ITCHING ---> PRUTITIS
34
describe obstructive jaundice/ post hepatic jaundice ?
Obstruction in bile secretion that might be cause of tumor or gall stone Associated symptoms : GI pain and nausea and pale stools Conjugated bilirubin increases in blood cuz EXTRA HEPATIC CHOLESTASIS ( bile cant move outside the liver, in the ducts so it goes to blood) Conjugated bilirubin is excreted in the urine ( As it is water soluble ) ---> dark urine ---> URINARY BILIRUBIN --> always pathological IN COMPLETE BILARY OBSTRUCTIONS ---> NO BILIRUBIN REACHES THE GUT ---> NO UROBILIN IS FORMED ( LOW UROBILIN ) ---> STOOL ARE PALE
35
describe neonatal jaundice?
Could physiological ( Appear in2-3 days ) or pathological ( appear on day 1 ) Physiological : rise in UnCB due to immature bilirubin UGT at birth Pathological jaundice : Inherited disorder ---> rhesus incompatibility If unconjugated bilirubin increases and EXCEED IS ALBUMIN binding capacity --> diffuse to BASAL GANGLIA ---> TOXIC ENCEPHALOPATHY/KERNICETRUS This condition is treated by phototherapy : Converts unconjugated to water soluble isomers ( LUMIRUBIN )
36
how is bilirubin measured?
van den bergh reaction
37
describe van den bergh reaction ?
principle of this reaction is dependent on the SOLUBILITY OF BILIRUBIN unconjugated bilirubin ----> less water soluble Conjugated bilirubin ---> water soluble When WATER is used as solvent in the reaction , The reagent reacts : Rapidly with Conjugated bilirubin as its soluble forming color VERY SLOW with unconjugated bilirubin as it is less soluble so Conjugated concentration will be there with the dye ( direct bilirubin CB only in the dye) When methanol is used as a solvent of the reaction , the reagent interacts with UCB and CB similarly ---> BOTH CB + UCB = TOTAL ( the dye will has both CB AND UCB ) to calculate indirect bilirubin ( UCB ) you have to : Total ( From methanol ) - CB ( Direct from water ) = Indirect UCB
38
what does high AST AND ALT signifies ?
intrahepatic cholestasis as in intrahepatic jaundice
39
what does ALP signifies?
Post hepatic cholestasis as in obstructive jaundice
40
what are the features of cholestasis ?
Hypercholesteremia and itching
41
what are the features of prehepatic jaundice?
Increased unconjugated bilirubin Normal/increase CONJUGATED BILIRUBIN Normal AST/ALT ( cuz no cholestasis ) NORMAL ALP ( cuz no cholestasis ) NO URINE BILIRUBIN ( cuz unconjugated bilirubin is not water soluble ) HIGH UROBILINOGEN ( cuz increased CB going to intestine )
42
what are the features of intrahepatic jaundice?
Increased UNCONJUGATED BILIRUBIN Increased CONJUGATED BILIRUBIN (it gets to the blood cuz intrahepatic cholestasis ) Increased ASLT/ALT due to intrahepatic cholestasis Normal ALP ( no extra hepatic cholestasis ) Urine bilirubin ( cuz conjugated escape to kidney from blood ) Urobilinogen ( normal ) ( but increase cuz it doesnt get converted to stercobilin and goes to enterohepatic cycle )
43
what are the features of post hepatic jaundice?
Normal Unconjugated bilirubin ( liver work normally ) Increased conjugated bilirubin ( cuz extrahepatic cholestasis and it escape to blood ) Normal AST/ALT ( no intra hepatic cholestasis ) increased ALP --> cuz extra hepatic cholestasis Urine in bilirubin --> cuz CB escape to blood and from blood to kidney Absent UROBILINOGEN ( Cuz of obstruction bilirubin cant go to intestine )