Types Of Jaundice | Causes, Symptoms & Treatment | Dr Najeeb

Today we'll be discussing about pathophysiology of Jes patho physiology of of Jas how do you define jundas yes please what's your concept of Jas it's yellow discoloration of eyes uh for example if someone is taking lot of carrots and lot of beta carotin has gone to the body and some tissue Turns yellow is that jundas that is not jundas uh just increasing BL Rubin level is not generous because sometimes BL Rubin level go slightly above the normal level and we say there's hyper bmia but if it does not impart the yellow color in skin or

mucous membrane or interstitial fluid or scera we don't call that jundas so I think before you tell me new definitions I must tell you what is jundas J there are three terms which you should be clear number One jundas another term is hyper bil rubinia then there's jundas then there's another term is eus then other term is col stasis these are terms which should be differentiated from each other first of all we must know that you know blur Rubin is produced mainly as a during the breakdown of Abes and other hemoproteins and blur Rubin is

highly toxic molecule And because bu Rubin is constantly being produced in our body whenever rbcs are breaking down and whenever hemoproteins are breaking down uh these toxic molecules because they daily produced about2 to3 grams per day so this uh blur Rubin should be pushed out of the body body should have very very efficient mechanism to get rid of bobin but if bobin levels go above normal in the body first of all you should know what is the normal level of Bobin what is the normal level of bobin yeah2 to some people 1.2 mgram per DL

some people take it up to 1.6 anyway if we say this is a normal level of BL rubin2 to 1.2 milligram per DL right and if your level go above that we say there is hyper B nemia so how do we define hyper binia that bin level in the body is more than normal levels is that right now actually what really happens look here this is normal bu Rubin level normal BL Rubin level range right2 to 1.2 if someone BL Rubin level goes up to this level this level this level is not going to develop

yellow coloration of skin or Scara or the mucous membrane or interstitial fluid actually significant concentration of blue Rubin should be there so that that enough yellow coloration of the body tissues occur so that it can be appreciated by the eyes of the examiner usually it happens when blin level is somewhere around 2.5 mgram per De when blin level when it is going up when it reaches around 2.5 mgram per DL then what really happens that Observer can identify the presence of highin level is that right and how the decides because patient shows that there's yellow

coloration of or discoloration of the skin and mucus membranes and scera and when you have especially skin and mucous membrane with yellow coloration due to hyperemia we call the Condition jaundice so what is jaundice jundas is yellow discoloration of the skin mucous membrane and interstitial fluids right due to andera due to to hyperemia due to hyperemia right it means every hyper bmia is not jundas very mild hyperemia is not jundas right hyperemia should be up to a level that it should that Observer people are able to observing people are able to you can say appreciate

the yellow Coloration of the skin or the mucus membrane or the Cera or the inter fluid then we say jundas is there is it right another important thing is what is oteris oteris is the term which is used when especially due to hyper bmia Clea turns yellow when we say I can detect Theus in this patient it means we are a person is specifically referring to Yow discoloration of Cera is that right again what is eus eus is yellow Coloration of C due to hyper bmia remember that Cera shows the yellow coloration very easily as

compared to the rest of the body tissues the reason being number one CA is white so yellow paint yellow color can be appreciated secondly Cal uh certain connective tissue molecules they love to bind the bobin due to these two reasons what really happens thatas is usually appreciable before the full-blown jundas Develops all over the body if the you are really watching your patient uh you can examining your patient serially right again I will repeat what is hyper bmia when your buin level is more than normal what is jundas when hyperemia lead to Yellow coloration of

skin mucous membrane Cera and interstitial fluids right what is AAS when when we are specifically refering to Yellow coloration of Cera due to hyperemia due to hyper bmia because if There's yellow coloration of body tissue due to some other reason that should not be considered jundas then another thing which is there is what is kacis yes have you heard of this term kist stasis what is kist stasis yes please Dr kashf what is kacis right he's very right actually what he is talking about that there's impaired bile outflow right he's right under these circumstances not

only blubins spills Over into blood but other content of bile may also spill into blood you know bile has three many contents but three most important contents of the B should never forget and what are those three most important contents of the bile there bobin the bile acids or salt or salt right and what is the third component of it yes please Cholesterol cholesterol right now when we say this hyperemia it means we are specifically talking about increased concentration of bobin we are not commenting on level of cholesterol or level of bile acids or bile

salt but sometimes it happen that bile outflow from heyes or from the bile ducts stops right and all these substances regurgitate into blood so if someone has raised level of B Rubin along with that Bile salts along and acids and along with that cholesterol all of these substances are raised into blood then we say person is suffering with kist stasis what is chasis kist stasis is that there's impairment of bile outflow of course you know bile is formed from the hepatocytes and thrown into intraa B and Al and from there it goes to the extratic

Builder drainage system you must be knowing there's right atic duct and there's left atic duct the Fus Together to make common tic duct then there is GBL cystic duct and then there's common B duct which fuses with the pancreatic duct in most of the patient is it right and opens at the Dum at temp of V is that right now if there's problem with that system let me draw the diagram let's suppose that here is your liver right uh hypothetically if these are your hepatocytes and these are B canalicular System these are building canalicular system

of course you must be knowing that here is your yes pancreas now what really we see there what we really see there right these are considered intra this point number one intrahepatic Bal Point number one is intrahepatic Bal right then of course you can say From both sides this is right hepatic duct and what is it left hepatic duct and right and left optic duct they fuse together to make what common optic duct and what is this fusing with the common optic duct cytic duct and then common optic duct and cytic duct when they fuse

together they make what is this common common bile duct and common bile duct Fuses with which other duct panc pancreatic duct so pancreatic juices and bile both can come out from this particular RFS what is this amplop V and surrounded by spinter of OD this is called bile out outflow system right if there's obstruction with this bile outflow system at any level then whatever bile was uh draining through this to the G8 their drainage will be impaired and this bile will be regurgitated into Circulation and when this bile will be reated into circulation what really

happens we say not only uh B Rubin will go to circulation but along with B Rubin bile acids will go to circulation even cherol will also go to circulation right and we call this condition chasis is that right but right but sometimes what happen problem is let's suppose at this level that bu Rubin Cannot be conjugated and unconjugated blin go high in the blood under these circumstances bacds are drained well right and cholesterol is drained well so only unconjugated bubin goes high in the blood this kind of hyper buin anemia should not be called col

stasis right now if you really want to have a good concept about the jundas first you should understand the normal physiology of bobin and how bobin is produced in The bodies why bil Rubin should be thrown out of the body how bil Rubin is carried in circulation how it is dealt with by the liver and in which form it appears inal matter and in which form it appears in urinary system right so right now we shall talk about normal physiology of bobin after that we'll talk about the causes of hyperemia or causes of jundas Right

let's suppose here is your suen you know the major source of blin is from where breakdown of hemoglobin is that right hemoglobin and other H protein like cytochrome and other enzymes when they break down right they may release bobin now let's suppose we talk about one RBC you know when rbc's normally they're constantly being produced by the bone marrow they're going to circulation then when they Become you can say around 120 days old right they lose their plasticity and they get stuck into some narrow spaces in circulation like cards of B Roth in suine in

the suen there are some very narrow and torous points in which rbcs which are old right and which are not pliable rbcs because fresh RBC is smart and pliable like fresh people you know like adolescents but as you become old you develop osto arthritis and you also develop some degree of stiffness in your Body and your mind even sometimes unfortunately same is true about RBC when RBC is you know RBC doesn't have a nucleus because RBC doesn't have a nucleus so what really happens with RBC when time passes by rbc's proteins undergo denaturation but because

it doesn't have a nucleus can it resynthesize new proteins it cannot it has kicked out its genetic Machinery so when its proteins become you can say uh denatured shed With the time and less functional with the time then capability of rbcs to be pliable and twist and turn through the narrow capil is lost then that is the time for rbcs to be get lost that rbcs will get stuck into some narrow points most commonly in the suen there are some very narrow circulatory points which are really test point for rbes we call them C bth

when a fresh RBS passes through that that will T turn and move out right but if an old RBC come it will get stuck Over there and when RBC will get stuck into those narrow points in suine or in some other points in bone marrow or in liver then what really happens that neighboring macr fases come into action and they eat up the areses because if arbes go and stuck into suleen do you think they should remain stuck there forever answer is no so when rbcs get stuck over there it activates a neighboring macro fases

and these macres basically fyos those rbcs it means that Rbcs break down within the circulation or within the macro phases yeah that is the point to understand that normally rbes break down within the macres that is why we say normally old rbcs don't undergo intravascular hemolysis they go into extravascular hysis actually intra macras monoy macras system hysis is that right now we'll talk about let's Suppose there is one let's suppose here is your Spain okay In the suine we make here one we just make one macras this is a large macras and in this macras

you know this is RBC which this macras has recently captured right now we are going to see how macro deals with the RBC and how bu Rubin is produced right what really happens that talking about that uh when when a macras captures an RBC what really happens with the RBC and its components right now RBC Basically consist of cytoplasm and its cell membrane that's a major thing and of course within the cytoplasm of uh RBC there's a lot of hemoglobin is that right uh let's see by the breakdown of the important component of RBC what

we really get right RBC is the broken down number one into membranes and their breakdown products number two different types of cytosolic proteins and Enzymes right and then of course you should not forget there is hemog globin is it right membranes you know break down into yes lipids and proteins and proteins lipids will go eventually into free fatty acids and proteins will break down into amino acids and these substances can be utilized by macras for its own purposes right so membranes are Gone With the Wind they're finished we left with the proteins what will happen

with the proteins proteins will be also broken down into yes amino acids and that story is also over now you are left with what hemoglobin first of all we should see what is the normal structure of hemoglobin and then we'll see once it break down what really comes out let me tell you here what is the normal structure of hemoglobin is that right normal structure of hemoglobin when we Are talking about basically this is a pyrole ring the single ring is called pyro ring and if four pyro rings are put together right when four pyro

rings are put together this structure is called protoporphyrin what is it protopore firein this is pyro ring when hemoglobin synthesis start first we have to synthesize he first we have to synthesize he and then we have To fuse the he with the globin chain and we end up with the hemoglobin so what really happens in a hemoglobin synthesis first of all we should synthesize pyro ring Arro blast synthesizes pyro ring then pyro rings are put together to synthesize Proto poin protopore irin then what really happens that within the protop Forin let's suppose I show protopine

like this FL of course these petals are pyal rings and the protop pyin if you put the iron What you put iron now the structure is called yes him what is the structure him and then what really happens that let's suppose this is him and here is iron with that if you bind a globin chain which should be made of what amino acids then this structure is called hemoglobin what is this called hemoglobin one pro one hem with one globin is hemoglobin monomer what is the Structure hemoglobin monomer let's recap attention please you start from

the top pyro ring fused with each other make protoporphyrin protoporphyrin Incorporated with iron becomes him H fused with globin chain is called hemoglobin is that clear to everyone right now this is hemoglobin monomer normally a full molecule of hemoglobin is a tetramer how it is tetramer let me tell you what really happens that let's suppose these are Four what is this protoporphyrin and all of them are having iron so they are for him and let's suppose here is Alpha globin chain here is also Alpha globin chain and here is let's suppose betag globin chain and

there's also betaglobin chain now this whole structure this whole structure is one hemoglobin tetramer one hemoglobin tetramer you must be knowing such kind of hemoglobin is called hemoglobin a which is having two Alpha chains Plus plus two beta chains in the same in place of beta chain if you bring the gamma chains it become hemoglobin F and if there's Delta chain it become hemoglobin A2 right so anyway now you know what is the basic structure of hemoglobin let's suppose we make a hemoglobin here right now of course this hemoglobin should be what it should be

having iron and it should be having what is this structure protor irin and with the Fireing normally should have what is this iron so what is it he with the he if this is a globin chain then what is this hemoglobin now what really happens first of all enzymes break down what is this globin chain when know globin chain will break down it will also become the part of Amo acid pool it will also become the uh part of acid pool after that what is we are left with globin has gone we are left with

the he isn't it with iron and other structure Remaining structure we are left with the H now what really happens the next step is that enzymes will break down and bring the iron out now this iron which is being brought out let's suppose this is iron this iron is highly toxic molecule and it will react with the different substances in the cell it may damage the cell so this iron should be put into a proper container the container is that there's a special type of protein which is synthesized by the Most of the cells which

handle the iron that protein is called yes what is the protein which handles iron EPO fertin this is EPO fertin now what really happens EPO faratin and iron fuses together and when both of them fuse together they convert into a structure and this structure is called fertin so what is the structure fertin now when many fertin are put together let's suppose we put many fertin put together and make a polymer of Fertin there's a polymer of fertin and this polymer of fertin right this is called yes please very good excellent this is called hemo sidin

okay by the way before we really go into detail of jundas what is the difference in hemosiderosis and hemocromatosis who will explain have you heard of these terms hemocromatosis and hosis or never heard you heard of it so Dr rafik would You like to tell what is the difference between the hosis and hemocromatosis okay write it down uh everyone has some normal amount of hemosiderin in the body iron is basically kept into stor storage form and the storage form of iron in our body is mainly hemos when sto storage form of iron become more than

normal but yet it is not damaging the tissue it is called hemosiderosis when hemosin become more Than normal but it is it has yet not started damaging the tissue significantly this is called hitosis but if hemoc level further become high and start damaging the tissue then we call the condition hemocromatosis so what is hemocromatosis hemocromatosis is a condition in which hemosin level is so high in the body that tissues are being damaged for example liver will be damaged in hydrosis pancreas will be damaged in Hydrosis your suine will be enlarge or maybe your yes heart

that may be damaged by hitosis that may produce some right then the hosis may damage interior P Tre this may damage test many tissues in the body so what I'm talking about that hitosis mean simply high level of iron storage form but yet not has started damaging the tissues but if it has started damaging the tissues then it should be called hemocromatosis now let's come back we have solved the Problem of the membranes we have solved the problem of cytosolic proteins we have soled now we are dealing with the problems of hemoglobin that he was

hemoglobin was divided into globin and he and globin was further divided into amino acids then we were left with the he he was this he was divided into yes iron and the leftover material the leftover material is what is this material yes please yeah this is not protor firein That is a ring structure my brother so what should it be this is bin so this is how you produce the bin in your body from where the bin comes right that is breakdown product of hemoglobin and other hemoproteins in the body is that right so it

is not protoporphyrin if it was protoporphyrin it could be recycled right it is not protoporphyrin it's a broken protoporphyrin modified protoporphyrin it is wasted protoporphyrin it's a toxic Protoporphyrin it is actually not protoporphyrin it is bobin do that right right and this Blue Ribbon right what were the enzymes on the way which handled with it first of all actually it was made Billy Worden the first compound which is made is Billy Wen then it goes One Step more and then it convert into yes then it convert into yeah B Robin now the enzymes which are

involved in this game number one him is first of all Converted him it was here converted into this form beli then the enzyme which is involved here is yes which enzyme is here what is the name of this enzyme yeah this is called hem oxygenase what is the name of this enzyme him oxygen is so what is h oxygenase this basically break down the he into B wordin and iron iron is ler Incorporated with EPO faratin becomes fertin and fertin Convert into hemosin does that right then what is there bin bin bin is acted upon

by one more enzyme this is acted upon by one more enzyme and what is the name of this enzyme yes what is the name of this enzyme Mr Abid must tell right but it's not that simple my friend this is called believe word in reductase what is the name of this enzyme the name of this enzyme is blue word In reductase blue word in reductase right and now yeah it is reduced form yeah when bin is reduced bin is reduced it become bin now this blin will come out of from where it will come out

macres macres wherever they are wherever macres they may be in the suine most abundantly or they may be present in the liver or they may be present in the you can say bone marrow so what really happens that Macr phases take up the rbcs and they release the bobin now you are clear that if somewhere it is written that macras take up the rbcs and release the B Rubin you know what are the steps and what is really happening within the macrophases now we have to deal this B Rubin is a highly toxic molecule it's

a dangerous molecule it is constantly being produced in our body and our body must get rid of it so we'll talk about how we really get rid of this molecule I told you that Daily we produce how much BL rubin2 to3 G per day how much blin is daily produced 2 to 3 G per day so somehow body should get rid of it and during the process of getting rid of the substance body should have some special precautions not to injure itself let's see that matter how body deals with it going to talk about physiology

of blin first and then we'll talk about pathology right and related therapeutic aspects and investigations so we were Talking about that let's suppose here is PL and this is a macras and this macras has taken up one RBC it's going to degrade the components of RB's into simpler compounds as we know that membranes of the RVs will degrade into protein and lipids and proteins will eventually degrade into amino acids lipids will break down to free fatty acids and other simple lipids and uh proteins which are from other enzymes you know RBC a lot of enzyme

do you know Any enzyme in RBC yeah any other enzyme you know pyro pyro kyes glucose 6 phosphate dehyrogenase the anemia related with these two enzymes when there's deficiency of pyrovate kyese or glucos phosphate dehyrogenase deficiency patient may become a namec is right these are the minimum two enzymes you are supposed to know about rbes and of course then there are other structural proteins like enrin and Spectran which are uh specially stabilizing the membrane of the Ares anyway all these enzymic proteins and structural proteins they will dink break down into simple amino acids right then

what really happens we are left with the hemoglobin hemoglobin will be broken into H and globin and again you know that globin will degrade into amino acids now we are left with he out of he iron is extracted out right and iron is fused with epop faratin and iron with Epop faratin makes a monomer of fertin and multiple fertin molecules Fus together to make a polymer which is called hosin now we are left with the remaining component of him which is actually this structure and this structure is called yes please this is called initially it

is converted into Bel bden and eventually it is converted into yes B Rubin and this B Rubin is pushed out into yes circulation so this Is a bin which we have to deal with this is very important bin what is the important point about it this bobin number one first point which we have to talk about this bobin that it's highly toxic molecule and because this bin is highly toxic molecule we have to get it out of the body but in a safe Manner and once blur Rubin is released from the monuclear cell into circulation

we should trap it into Circulation so that it does not leak back into other tissues the first principle is that if monuclear cells are releasing this BL Rubin into circulation we should trap this molecule into circulation so that it does not diffuse into many other tissues back to the body because if this is held and trapped into circulation then sooner or later it will pass by the liver where liver will handle it but what is the way to keep and trapped into Circulation answer is it's a small molecule it has a tendency to leak out

so there are special blue ribin trapping proteins which are again synthesized by liver let's come this is a li here's the heyes I've drawn just two pyes this is Builder drainage system you know a pyes have one phase it's a very simple functional diagram if we talk about this hepy this face of the hepy is towards a blood side and this face of The py is towards yeah bery system right it means the pyes have basically two important faces number one some of some part of the membrane of the pite face to each other and

one part of the aptoite membrane should be facing towards the space of Dy and cdal phase and this side of the phas of the aptoite should be towards a yes B canalicular phase so it is just like that there's a Front Road and there's a back road right so Front Road what is moving here blood in the back road there's a drainage system right what is this drainer system yes B system every ocy has a front face right and it has a back face in the front face it is facing with the circulation the back

face it is facing with the B canalicular system and remember one very important thing that functional characteristics of this part of the membrane is very different than function characteristics of this part of the Membrane as we'll go into detail we'll talk in reference to bobin right now what I wanted to tell you that one of the function of hey is that it will secrete special type of you can say proteins and these proteins will go into circulation and once these proteins go into circulation one of the major function of these protein is that they will

immediate as soon as bbin comes out these protein will bind with bobin that is why these proteins are Called bobin binding proteins they part of the protein which are released by The pyes Daily into circulation so we can say that this is the duty of a ptoy to provide the circulat system with such proteins which are bluubin Trappers right once this bluubin bind with this plasma protein once this BL Rubin binds with this plasma protein what really happens that now the whole complex become very large when this become become this Complex become very large do

you think this blur Rubin can go back to the tissues no Okay can now this blur Rubin which is bound with the plasma proteins right can this blur Rubin filter out here and appear into urine answer is no because normally proteins don't filter out if proteins are not going into filtrate how protein bound substances will go into filtrate so it means this newly release B Rubin immediately bind with the B Rubin binding proteins and After that rest of the body will become safe from it now this BL Rubin after mining of the protein has developed

two properties property number one is it cannot diffuse through micro circulation back to your many tissues property number two is it is unable to filter into urine so it means this form of BL ribbon will not produce blur Rubin Uria if you find blur ribin in anyone's urine be sure that BL ribin will not be this form because this form is fused with Proteins normally proteins don't filtrate in heavy amount so protein bound buin also does not this type of buurin is called yes uh yeah no first listen question I know you are in Harin

answer but still I will put a question a decent way you're respectable lady so this BL Rubin molecule once it is bound with the plasma protein what type of blur Rubin is this yes please conjugated or unconjugated It is conjugated B Robin according to Dr tanzilla what about dral it is unconjugated okay then these ladies have to fight with each other it means one lady is saying this is conjugated blin other lady say it is unconjugated bin how would you prove your point how you prove she's wrong ex yet to pass through the liver yes

she's right because thein gets conjugated within the liver within the hepy and it has not yet gone to Hepatocytes listen conjugated buin does not mean that bubin fused with anything is conjugated the term of conjugated bluubin is used when bluubin bind with gluconic acid when bluubin is fused with gluconic acid then we say BL Rubin is conjugated and plasma proteins are not gluconic acids right so it is so when plasma protein bind with this BL Rubin newly released BL Rubin it is yet not fused with gluconic acid so it must be considered unconjugated protoplasma Protein

bound below Rubin is that right here there's one very important technical point so I think just to remind you for next we'll correct this we should write it unconjugated yes bobin unconjugated bobin right so when blin released it is unconjugated BU Rubin initially it is free unconjugated B Rubin then it is plasma prot bound un conjugated bin here is a very important Point especially in the gy of world Doctors are very concerned that if newborn produces excessive amount of unconjugated B Rubin they say there's increased risk of leakage of unconjugated B Rubin to the central

nervous system and may produce a problem called connectors that is called Carras what is Carras if blue Rubin goes into heavy mountain central nervous system of course not only it will morphologically uh impart a yellow color To the cerebral cortex and the basil ganglia but actually it will damage them as well it's a toxic to the central nervous system neurons and that may lead to mental if baby really survives right then baby May develop clinical features related with mental retardation along with that when damages to the basil ganglia there may be motor dysfunctions as well

my question is this that uh if un conjugated BL Rubin is bound with the Plasma protein can plasma protein bound unconjugated build leak into central nervous system what about bloodbend barrier not it should not but it will we'll talk about how first of all look plasma a brain you know in the brain the circulat system right it is very tight in a way that in central nervous system the capillaries which are passing through the central nervous system their endothelial cells are Stitch to each other very tightly plus the estro sites On the outside and there's

something called bloodb brain barrier it is not really a truly physical barrier blood brain barrier mean everything which is present in the blood is not going to spill into interstitial micro environment of central nervous system in which neurons work up right only smaller molecular things or highly lipid soluble things can move from the blood to the micro environment of central nervous system is that clear now our question Goes back that why in new bar if unconjugated BL Rubin level is pathologically high then there's a great risk that unconjugated BL Rubin will go to the central

ofous system how would you answer to this question the blood barrier is okay number one reason is that in the newborn bloodb barrier is not so well developed and number two reason is more important what is That that as unconjugated bin level goes high in the blood there's a shortage of these proteins and as unconjugated bubin level goes high and high all the Trappers of unconjugated bubin will become saturated especially in the new Bond which has a limited supply of plas B Rubin binding proteins so what really happens that the fraction fraction of unconjugated B

Rubin which is not bound to plasma protein progressively increases and that is Which can flood into circulation uh central nervous system micro environment and produce toxicity to the central n system okay then what you will do for these kids there's a kid which is having very high you can say unconjugated bobin and you are very much worried about that uh baby may not go into problems of konic tress what will you do about this baby we could an exchange blood transf okay one way is uh exchange blood transfer in a very Advanced State Excellent what

else you can do phy phototherapy you will show the photo of mother or father to the baby yeah what is phototherapy what is phototherapy you know phototherapy okay there special type of light we expose the baby to that for a long time and then what will happen the baby's color look less yellow in that light or there's some other reason some other reason what is that started passing out rapidly out of The body why because because that particular light can makes the conjugated bu Rubin into special photo isomers special photo isomer which do not need

to be conjugated by liver and can pass out because newborn's liver is also uh you can say relatively immature and not well equipped with all the enzymes and the concentration to handle with the flood of the unconjugated bobin is that right am I clear okay let's Another thing they have recently started there's another thing what they have started giving to the babies is 10 protor firein what is this 10 protor firin there's something coming in the 10 this 10 protor firin what is 10 protoporphyrin they started as a thy of the babies who suffer who

are the risk of conectas yes it is a righted down please it is synthetic Metallo protoporphyrin it is synthetic Metallo protoporphyrin it is 10 protoporphyrin It's the synthetic metall protoporphyrin it is a potent competative Inhibitors of hem oxygenase it a powerful inhibitor of hem oxygenase and now look here if there's a newborn baby and you have given him tin protor firin and Tin protor firin goes into macrophases and inhibits a hem oxygenases the power of the Hem oxygenases to produce bin and eventually bin has been reduced reduced so in this way when we give 10

protor fireing to The newborn baby we reduce the rate of production of unconjugated buin at the same time we expose them to the special wavelength of the light so that whatever unconjugated buin is already produced this should rapidly convert into such photoisomers which can be expelled out of the body very rapidly without depending on the conjugative process of the liver okay let's go ahead so we were talking about this is unug bu Rubin which is bound with the plasma protein Normally it cannot enter into Central of system even it cannot go to many other tissues

it cannot filter into urine so and it is highly toxic but trapped highly toxic but trapped now what really happens that I told you these substances were produced by liver and then they were they are going and binding this once this become fully loaded once plasma protein BL Rubin binding pre- albumin and bl Rubin binding albumin They're fully loaded they will take this BL Rubin through the circulation of course his hepatic artery and portal vein are still going to the liver right and from General circulation these unconjugated B Rubin along with the plasma proteins through

the hepatic artery or through the portal circulation they will go to the LI you know hepatic artery blood and portal circulation vein blood mix with each other in the uh hepatic cyes So eventually this will be Taken to the hepatic cyes when the these are passing by the hepatic cide this was what yes unconjugated bobin as along with the plasma protein as they passing by this there is a very special type of molecule which is present over here and it will love to bind yes it will love to bind what conjugated there's a special receptor

an uptick mechanism which is present on the con Present on the cidal face of the htide right as soon as unconjugated bobin along with the plasma protein come near to it it will transfer this blur Rubin into yes hepatocytes so hepatic uptake has been done and here you must know there are few things which interfere with the hepatic uptake can you tell me some substance which can interfere with the hepatic uptake any substance you have ever heard of it the many drugs which bind here and Reduce the hepatic uptake okay from the drugs I remember

some drugs can displace the BL Rubin from this point some drugs can interfere with the BL Rubin handling here uptake some drugs May impair the conjugation of the bin some drugs May impair the secretion of bobin now you have to tell me few drugs which can displace the what is this you have to tell me few drugs which can displace the unconjugated bbin from plasma protein and at least one drug Does not allow the uptake of it or interferes with the up yeah do you know any drug which will displace it because clinically important because

if you're taking giving those drugs to a person who is J us for one or the other reason you are giving those drugs bobin level will go up free bobin especially if you give those drugs to babies right newborn babies you give those drugs unconjugated BL will be displaced and now you know where it is Headed for to the central nervous system is that right do you know any drug like that at least one drug which may be used for one or the other reason in the newborn even yeah why don't you tell me sulphonamides

write it down please these are the displacers of unconjugated B Rubin from plasma proteins displacers of unconjugated B Rubin from the plasma proteins the drug which displace BL Rubin from this side especially in the newborn increase the Risk of kust good doctors should know the name of those drugs sulphonamides you know in newborn sometimes there are infections and we have a tendency to use solomides be careful sulphonamides in the newborn especially we use for which purpose for which purpose we use solomides please tell me manius have you heard of it Neal menitis then pencin derivatives

sometimes if you're giving some babies heavy amount of penins for Some other reason but derivatives of penin May displace the unconjugated BL Rubin from the plasma protein and produce trouble to the person then of course not in babies but uh in adult people even fide and radio graphic contrast material can also displace the B Rubin from the B Rubin binding proteins anyway once blin has been in the bound form has been taken to the he Liver circulation and from the cocal side it will go to space of dis from there it should be taken up

into hepto side there's some drugs which interfere at this point at least one drug you must tell me because these drugs will produce unconjugated hyper vinia the classical drug here is I will give you an idea uh that drug is usually used in anti-tuberculous Therapy then another thing I will tell you about that drug yes that produces your all secretions orange color even ladies lens will become orange color you remember it from ladies lens isn't it R yeah all the secretions will become pink not truly red right patient will sweat pink he will have the

truly pinkish uh bloody type of what these tears even slal will become pink and even even after taking the fusin your Lens which lens artificial lens right they may become permanently stained pink color right so that also reasin loves to bind here and it reduces the uptake of bobin sometimes in some patients clear anyway let's go ahead once Belin has gone in this is conjugated or unconjugated bobin unconjugated it is unconjugated bobin it has come in it will enter into endoplasmic reticulum it will enter into a Endoplasmic reticulum it will enter into endoplasmic reticulum and

within the endoplasmic reticulum there's a very important enzyme and name of this enzyme is yes what is the name of this enzyme glucon transferase now I want to highlight one thing look to get this BL Rubin out of the body we have to make it more polar we have to make it more polar we have to make it more charged so that it become water soluble and it is no more lepid soluble now when you want to Make a substance more polar or less lipid soluble or more water soluble one way to do so is

that make the substance more charged right and one way to make a substance more charges that you take the substance to the liver hepatocytes and hepatocytes produce highly charged molecule for example hosy convert glucose into gluconic acid into glucaric acid and that into glucuronic acid what hepatocytes are doing hepatocytes are Able to convert glucose into glucuronic acid gluconic acid is highly polar compound right then aptoides once they synthesize the glucuronic acid they're having a special enzyme which is called UDP glucon transferase right you just call it GT GT is glucon transas transferase so this is

our enzyme we should be called glucon trans phrase is that right now this glucon Trans phrase this enzyme is normally abundantly present in the liver especially in the endoplasmic reticulum and its duty is that it will fuse the gluconic acid with unconjugated bobin and now bluubin become conjugated with gluconic acid now blin should be called conjugated bobin so this unconjugated bobin is now what is happening to this it is fused with yeah gluconic acid glucuronic acid and after it is bound with the glucuronic acid we call it yes Conjugated conjugated bobin this is now conjugated

bobin now it is called conjugated BL Rubin now this conjugated BL Rubin this conjugated BL Rubin okay I'll make it black some people like the black things too much this is now conjugated BL Rubin right this conjugated bbin is highly it is conjugated with gluconic acid So This is highly what Polar Polar once it is polar can it dissolve into lipid membrane of hocy no so it means Now conjugated bobin is trapped within the heyes now it is trapped within the Hite if it is trapped within the Hite now up to the it is up

to the hpto side attention play that hpy will throw it to the blood or to the B canalicular system now it is up to hepy actually Ayes have already planted in the honor of this molecule special type of Transporters yeah on which side these are active Transporters and these substance these special Transporting molecules which are present on the canalicular canalicular pH of aite they're expressed over there they're capable of catching the conjugated bobin from the pyes and expel into where B alas so they are responsible these pumps they will throw it into bicular system and

this conjugated bobin has now gone into the system as I showed you that this was a pump system and this pump system is actively Transporting the conjugated BL Rubin from intrahepatic site to the B canalicular system now this B Robin which is now conjugated B Robin it will pass through the B dra drainage system there's no fun in telling that there is B canalicular system which go into B ductules then there is right hepatic duct there's left atic duct they fuse together make a common atic duct and of course bile also comes to to galb

where what major thing happens to bile in the Galb yes what GB is doing with the bile number one concentrating right and many other things as well but anyway it will come here for the storage and concentrating eventually bile along with conjugated blin of course with the conjugated buin bile will have bile salts and isds what are bile acids can you name B salt of B acids acid and Chino deoxycholic acid deoxycholic acid and Chino deoxycholic Acid they are fused with toine and other amino acids to convert into salt anyway bile salt and bile acids

along with the conjugated B Rubin along with cholesterol and letin they of course many other subst inorganic material as well especially b car they are taken down through bery system in this way conjugated blue Rubin is now headed towards your yes to your git eventually the final destination is Your git from here conjugated blin will come over yeah this is conjugated bobin it has been released to git of course this point is called emplo of ver and it is having a sphincter which is called sphincter of OD once the conjugated B Rubin comes here once

the conjugated BL Rubin comes to the git now eventually what will happen to this conjugated bin it will undergo Further modifications there are lot of enzymes which are present in git plus lot of microbes which are present in your git right and this conjugated bow Robin conjugated B Rubin as it is passing through Git it is acted upon by yeah bacteria and enzymes different bacteria and different enzymes and they may convert this uh conjugated bin into another compound which is called Urobilinogen what is it called Euro binen now listen you know from G the portal

blood is taking the some absorbed material to the liver right now what really happens you know portal blood take a lot of sub blood you know from the git and this blood is going to the liver and of course portal Blood also passes from where it passes portal blood is going to the liver and eventually Drain into cocal system and sinal right now what really happens there actually this eurobin noen eurobin noen right this is a small part of that is taken up by yes taken up by G it is reabsorbed small part but major

part is more destined to the last part of the gut where it will convert into yes stco Bogen and eventually it will pass into FAL matter and this Turco Bogen is responsible to giving a characteristics yellowish brown color to the fecal Matter normally is that right stob Bogen but the urob balen which has been absorbed from here right it will pass through the portal circulation and as portal circulation will be passing through the pite part of eurogen may be taken up by against cocal side of the hepatocytes and recycled from here right but real problem

is that a very small percentage of it may Escape into yeah urob Bogen into Circulation this eurogen it is a polar compound and it does not bind with the plasma protein it's a charge compound compound so this eurogen yeah Euro Bogen it's a polar compound but not bound with the plasma protein because it is not bound with the plasma protein it will easily filter into urine urine and because it is what is it it is polar it cannot dissolve into nephrons epithelial cells so it cannot Come back so this urob Bogen is headed to be

part of your urinary output so in this way every normal person should pass at least small amount of urob Bogen and urine is that clear any question here now this finding should tell you one thing if a patient comes to you and patient is having jundas if you take the urine of the patient and with di stick you check is Euro Bogen there or not if eurogen is not there if urogen is not into urine it Means it is not present in the blood if it is not in the present in the blood it means

it was not present in git Ur Bogen was not present in Git it means conjugated buin never came here it means where is the problem outflow if your blood has lot of conjugated bin listen now carefully if someone has hyper binia and lot of conjugated B ubin is spilling into blood but there's no urogen into urine it me problem is somewhere between this point To this point so it's very simple that whenever a patient come with conjugated hyperemia and you just check with dip stick and there's no eurogen you must think there is some catic

problem there's some bile outflow problem right now what I was talking about that this eurell enery which was retained within here it may convert into stco Bogen which will be passed into FAL matter and if FAL matter is left into Open air oxygen will react with that and convert stco Bogen into stoin which is more darker color right right now we'll be talking about once we have done with the physiology of bluin handling now we'll talk about that under what circumstances hyper binia develops which may eventually become a cause of jundas as you know that

normal buurin level are your normal blin levels are considered 2 to 1.2 mg per DL this is total plasma B Rubin total plasma B Rubin of course this total plasma B Rubin should be divided into two parts that is unconjugated B Rubin and conjugated B Rubin right so normally B Rubin level is this much due to any reason the B Rubin level in the blood start going up right we say patient is developing hyperemia but when hyperemia is sufficient enough to impart the yellowish coloration to your skin and mucous membrane and scera and intertial Fluids

or tissues we say patient is jaust is that right now whenever a patient come with jundas of course a patient will will have total blin very high but as a good doctor you must determine that the major component of high total B Rubin is unconjugated B Rubin or conjugated B Rubin in some patient with jundas the dominant component of accessible Rubin is unconjugated in other patients the dominant component of accessible Rubin Is conjugated buin so it means that whenever you have a patient with jundas you have thing in the term of that patient is having

unconjugated hyper bmia or patient is having conjugated hyperb rmia dominantly now let's talk about why hyperb rubinia develops and what are the causes which lead to unconjugated hyperemia and what are the causes which lead to conjugated hyperemia we start from this side one mechanism may be that there's Excessive release of unconjugated B into circulation due to any reason if your body starts producing excessive amount of unconjugated B Rubin to circulation is that right it's quite possible that the total B Rubin is released in such a rapid rate that liver cannot handle that well and then

unconjugated B Rubin start dming up into blood this is one mechanism second mechanism is that buurin production is normal But there's interference or problem in the bu Rubin uptake mechanism number two mechanism number three may be the buin production is normal buin uptake by the heite is normal problem is with yes conjugation that bu Rubin once it is taken up it is not conjugated properly now the group of patients would have problem either at level number one that is accessive B Rubin production or problem number two poor hepatic uptake Of the B Rubin or problem

at level number three that poor conjugation these three groups of patient tend to develop unconjugated hyperemia right then after that if someone has a problem Beyond or dist to this point for example a person who is developing normal levels of blin daily producing normal level of blin hepatic uptake of the blin is almost normal conjugation is also normal so it means Whatever BL Rubin is entering into a ptoy it is nor in a normal fashion it is conjugated with glucuronic acid sometimes with bin molecule we bind with one gluconic acid sometimes we bind with one

buin molecule to gluconic acid so it means liver is responsible to produce monoglucuronides and D glucuronides of bobin normally right after that if person has problem at level number four what is the level number four problem is with A active transport of blur Rubin and other substances from the heite to the B canalicular system it means dysfunction is on which side of the hepatic membrane hepy membrane canalicular face of the hepy membrane right under now in mechanism number four bbin is getting conjugated but not getting to the B system so it will spill back to

circulation so it will become what kind of hyperemia conjugated hyperemia then Another cause of conjugated hyperemia may be yeah intrahepatic obstruction to the outflow and then there may be yes extra hepatic obstruction to the bile outf flow now cause number four five and six they will produce what kind of hyperemia conjugated hyperemia so first you should be able to determine your patient is really their jundas is there or not it means total bubin should be high and right once you know there's Jundas or you know there's hyper binia the next step is to determine is

it unconjugated hyper bmia dominantly or is it conjug conjugated hyperemia dominantly if it is unconjugated Hy bmia problem is at level number one or two or three it means either patient is producing excessive amount of B Rubin or there's reduced hocy uptake of the B Rubin or there reduced conjugation by The Hite and if patient has conjugated Hyperemia then causes may be either problem is with the hey to transfer the bu Rubin from interior of hey to the building Al system a problem is there is bicular system within the liver is dysfunctional intra petic yesu

obstruction or colis and there is some other outflow obstruction outside the lever which may be in the right and left hepatic duct or it may be in the common bile duct or it may be at templ wet right these are called extra Extratic bile outflow obstructions that's is that right all of these mechanism four five and six they will lead to conjugated hyperb now let's start working Upon Our patient let's suppose you are in charge of the jundas clinic and patients are coming over there right so diagnosis of jundas is not enough if you're making

the diagnosis and the patient the patient is having jundas it is no diagnoses in fact because you Should you have to look for the cause always different patients may have jundas different reasons which need to be managed in a different way so Jos say no diagnosis right a good doctor will always look beyond that is there jundas or not if jundas is there what type of hyperemia is there or not what is the underlying mechanism and cause of that and how to manage that now we'll talk one by one let's start with the mechanism number

one the patients in Which there's excessive production of bobin so first of all we talk about what could be the causes of excessive production of BL Rubin yes please patient who come into group number one and patient pent who are coming to the group number one are those patients who are having excessive production of bobin in their body now we have to think over why some people may have excessive production of bobin right can you tell me any reason yes hemolysis do you think Hemolysis will always produce excessive hog accessible Rubin answer is no because

daily we have physiological hysis you know normally rbcs uh after about 120 days undergo physiological hemolysis they are taken up by the macrophases and these rbcs are rapidly destroyed within the macrophases it means that holes is within the circulation or within the cells cell within the cells so that physiological holes which occur within the cells we Call it uh extravascular hemalis because it is not within the vessels it is outside the vessels into cells macrophases right so number one thing is that hemolysis occurs physiologically right so and we don't develop jundas with that usually so

then my question is that what are the condition in which there is excessive production of BU Rubin you will say excessive Himalayas answer is not hysis answer is excessive hysis all Hemolytic conditions right which break down RB's excessively and they produce so much BL Rubin which liver cannot handle that what will happen what will happen unconjugated buin level will go up into blood is that right now remember here if the cause of hyper unconjugated hyper bmia is just excessive production usually buurin level in the blood does not go more than 5 to six milligram per

D again let me tell you if you have a problem due to Which you are producing excessive BL Rubin whatever excessive BL Rubin you produce if your liver is functional liver is capable of handling extra blur Rubin that it won't allow yes it won't allow unconjugated BL Rubin to Dam up into blood more than 5 to six milligram per DL what does it really mean it means if a patient come who has unconjugated hyperemia and his level is 10 milligram it means problem is not with excessive production probably problem is also with The uptake or

conjugation this is a mixed problem am I clear to you yes is it clear now we were talking about what are the conditions in which there is excessive production of bluin of course when there's excessive hemolysis now excessive hemolysis may be certain sere excessive hemolysis number one in hemolytic anemias hemolytic anemias where breakdown of rbcs will be Very rapid and bone marrow is trying to compensate but it cannot compensate so hemoglobin levels start going down into blood number two absorption of large hematomas absorption of large hematomas if you have a large bleeding within the body

and rbc's rupture within the body for example you may have uh intraperitonial Hemorrhage or in the G there are some reason G OB that there may be large hematoma formed Or then later on yeah very good very right ectopic pregnancy or if person survives right then patient will dwop jundas otherwise not right if there's ropic pregnancy or there's ovarian cyst or intraabdominal Hemorrhage right what really happens that if patient survives the acute collapse you have been there and managing it well then what really happens a lot of arbes which are present in the body they

rupture rapidly a lot Of macres go over there and try to convert that hemoglobin into bobin and so much unconjugated bobin will flood into your Circ system that liver cannot deal with it that efficiently that may translate into unconjugated hyperemia then of course we can talk about abruptio placenta which has which one revealed revealed Hemorrhage is responsible for jundas later on or concealed Hemorrhage concealed of course in abrupt placenta when placental Attachment partially abrupt from the uterine attachment and some hemotoma may be having concealed blood collection between the placenta and the uine uterine wall or

even RV's infiltrated into myometrium which make it board like rigidity and painful right so that rbcs will also absorb and later on they may increase the load of blin to the liver and if lady is unable to handle that excessive amount of not lady ladi's liver is unable to handle the excessive Amount of Bin shop conjugated hyperemia so I'm talking about that different type of hemolytic anemia as or absorption of large amount of holis hematomas that may lead to transient unconjugated hyper bmia sometimes that will produce mild jaundice then any other condition yeah physiological hysis

occur at two stages of ropes who will tell me what some himalis occur during the Arthrosis you know when ladies are cooking things in the kitchen there are some intra kitchen losses which never reported on the dining table is that right in the same way when bone marrow is cooking the rbcs intra bone losses of rbcs occur that is called pysis yes phis duris okay she has given a big statement physiological hysis occuring during arthrosis that is about 10 to 15% Of normal eotic process is that right and in some diseases this is one hemolysis

physiological secondly when RBC jump into circulation they will complete their circulat time and then they undergo terminal hemolysis so there can be hemolysis during the rosis and hemolysis after the rbcs have completed the circulatory time both can be physiological now in some conditions intram medary hemolysis we don't call we call that intra medary hysis Physiologically intram hysis is 10 to 15 to 20% 10 to 20 % right it means for every five rbcs intact one RBC is destroyed before it appears into circulation right of course those rbcs are also taken up by macras and then

what happens they are also responsible to add to the unconjugated blin pool of the body is that right in some conditions intramed H intramed homolysis become very excessive for example in Some conditions 80% of the bces which are being produced during the arotic process are destroyed within the bone marrow before they appear into circulation it's excessive can you tell me some conditions like that you understand my question it's in English I'm talking about that sometimes ropes is going on very rapidly in bone marrow and due to some dysfunction intra bone marrow losses become percentage wise

very heavy that for every RBC one RBC spilled into C ction four may be destroyed within the bone marrow during the synoptic process we call it that there's pathologically excessive what inary hysis so what could be the reason for that please tell me any any proding abnormal type of any severe condition in which bone marrow is doing its best it has accelerated rrop pois especially in Pernicious B12 deficiency and then in every you know every B12 deficiency is considered pish nemia or not how do you define pish nemia of the in okay you remove my

stomach for example you become angry with me you remove my stomach and throw it to some birds and you connect my esophagus with the judum do you think I will develop pernicious anemia answer is no but I won't have an intrinsic factor so this is not enough to say that Deficiency of intrinsic factor is just pish anemia very good doctor you have given an answer from a good doctor but a very good doctor will say pernicious anemia is megaloblastic macrocytic anemia produced due to deficiency of intrinsic factor which must be due to autoimmune process directed

against parial cells and intrinsic factor itself look whenever you have deficiency of intrinsic factor if deficiency is due to autoimmune process then it is Pricious anemia otherwise it is not is it clear so postgastrectomy right intrinsic factor deficiency should not be labeled as pernicious anemia anyway if someone has pernicious anemia or folic acid deficiency anemia and bone marrow is really accelerating its arthropo and lot of abnormal rbcs are made and they before those rbcs spell into Circ spill into circulation that destroyed within the inary cavities where that may Produce heavy load of unconjugated build to

the circulation liver cannot handle that and that may end up into unconjugated hyper bmia so we can say that excessive yes what is this excessive intra medary himalis so all these conditions have a tendency to load the body with excessive amount of Bin and if liver cannot handle All that bin unconjugated hyperemia will be there now with all these things there's some other features as well this is called prehepatic you can say prehepatic jaundice because problems of the problem of the jaundice is not due toet Builder dysfunction problem is that normal pilder system is overloaded

with the unconjugated bin now how you really know that let's suppose a patient come with jundas how You really know that problem is prehepatic let's talk about the parameters related with that okay this is the investigations or some important pointers right if a patient has okay I will make these scenarios later right we'll talk about the clinical scenarios later in the lecture I will continue first with the basic concepts causes and Concepts then we'll go to the clinical Scenarios and laboratory interpretations of abnormal results of liver function test and hematological and serological results now we

have talked about this here you have to remember excessive impales then if there's excessive displacement from the B Rubin here you remember at least one drug what is that sulphonamides then I told you there are some mechanisms in which uptake of bobin by the liver is reduced for example I told You right after that we come to the conditions in which problem is with the conjugation that conjugating power of liver is R reduced it means that there is poor conjugating power of the liver now when we talk about that impaired BL Rubin conjugation at the

top must be physiological jundas of newborn right in physiological Jas of newborn the one of the major reason is That hob system is immature hepatocytes have not yet expressed the genes related with formation of glucon transas with full power so baby's liver newborn's liver has you can say pyes have under supply of glucon glucon trans phase number one problem secondly you know when baby is bornn fetal hemoglobin is breaking down so slightly extra load of unconjugated blin to the liver and significant impairment in the B conjugating power of The new bonds lever so both of

these are combined together to produce slight elevation and unconjugated Bel Rubin in the blood so new bonds usually develop what kind of hyper bmia unug unconjugated hyper bmia they produce unconjugated hyper bmia right okay so this is one cause that there's problem with the conjugation there's decreased enzyme activity in the secondly not only their hepy is Hep both systems are Disturbed in newborn not Only the poorly conjugate the bu Rubin rather they have one more problem that whatever they conjugate they do not effectively throw here right but main problem is poor conjugation is that right

after that we come to another there's another term used breast milk jaundice what is breast milk jaundice what is breast milk jundas I think someone put music with this information so yes what Is breast milk Jas no one knows about it you should know it isn't it okay let me tell you that uh actually in the breast milk there are some enzymes which are which break down the conjugated conjugation between the bobin and gluconic gluconic acid so we call them breast milk D glucuronidases or simply Glucuronidases now in the normally physiologically in the breast Mill

there is significant amount of glucuronide disas enzyme now if baby is heavily fed through breast and not on other sources what will happen that breast milk when it will go to the G the baby's git whatever conjugated bu Rubin is coming it will deconjugate that whatever conjugated bu Rubin is coming breast milk enzymes will break down that conjugation process is That right and what will happen un bin will be again take up into circulation and that may become unconjugated hyper bmia is that right so this is one problem more right breast we call it breast

milk jundas right then we come to some more causes there are some syndromes now we are entering into the valy of syndromes okay this is which enzyme please name it glucon transferase of course this is a protein So proteins are synthesized by the expression of genes now if we do something wrong with the genes concerned with the synthesis of this enzyme it is quite possible synthesis of this enzyme become impaired is that right now let's talk about inherited disorder in which you inherit the defective genes where you are inheriting defective genes which are supposed to

synthesize glucon transferase now it's very easy to talk about this That in these heriditary conditions there may be mild deficiency of glucon transfer yeah or there may be moderate deficiency of glucon trans phrase or there may be severe deficiency of glucon transfer of course there are how many genes which are making this enzyme at least there should be how many gen means to make the you never counted it too busy in your life yes have you been counting it it's Too easy one gen should come from Mother and another should come from father so minimum

for everything you should have two two gen except Y chromosome which only come from the father right most of the Gen are present as double copy one maternal and another paternal is that right so it means that problem may maybe with the genes right with one gene or both genes and problem may be producing mild deficiency of this enzyme activity or moderate Deficiency of this enzyme activity or severe deficiency of this enzyme activity is that right now in about 2 to 7% of the population 2 to 7% of the population there's mild deficiency of this

enzyme activity in 2 to 7% of the population there is deficiency of this enzyme so in these people in these people there's a tendency to keep all the time slightly high level of what unconjugated bobin But usually it is not enough to produce Jas but if these people undergo some sort of stress they may undergo fasting especially more than 24h hour or they undergo dehydration or they undergo excessive physical activity under all these circumstances these people tend to do mild jundas due to unconjugated hyper bobamia and in these patients all other things are normal in

their body now here I want to highlight one Thing you know before I really go to the function of this enzyme I will go to discuss about the height of the human beings you know the people for example if we say that human female what is the average height of human female yeah I think you have been meeting with including the Western and Eastern both World it must be five one okay uh I think it's around 54 or 53 depends on uh what kind of female you Are coming across okay we keep with this young

man's idea that average height is most of the females have height around 5'4 is that right their number is very high such females then females who have a height of 52 they are less females with the 51 are less having only five is less and of course having four is extremely less and of course there are females which are taller than the average female so the females who are 5'6 they are also Less in number there's A percentage and females which are 5'8 are less and than God females with 51 are very less and female

with six are alhamdulillah very rare now what we really find that this is normal characteristics do you think if we say that normally female has a height of five on average 5 four POS if you come across a female which has a height of five do you think she's abnormal or if you come across a female which is 58 is it aboral no we say this Character of height is distributed in a goian fashion gosan curve bell shaped curve in human population this concept is clear and these females in the very beginning too short and

too not long actually tall females just present what ends of the goian curve is that right same is true about many other functions including your efficiency of glucon transfer that people there are a lot of people who have average activity of Glucon transfer some have really very excessive activity of glucon transfer some people have relatively less power of glucon transr so people who come at the end of if this curve is for the glucon transfer activity right then the people who come to this end of the curve they are 2 to 7% these are not

significantly diseased people rather they're not diseased people these people have some mutations in their Gene which are especially Mutations in the promotor boxes their Gene does not express fully in 2 to 7% of the population the gene does not express glucon transfer genes do not express fully but whatever messenger RNA they make their normal right so they do make glucon transfer enzyme but in slightly less concentration in their heyes due to that reason whenever there's extra challenge to the liver with unconjugated bobin they cannot handle and they develop Unconjugated hyper bmia now this population is

extremely important to diagnose you know why extremely important because number one the number is very high two to 7% or on average 5% of population number two these people develop mild jundas many times in their lifetime they they all the time they are keeping unconjugated hyperemia and as I told you when these people have stress They may tend to develop mild junders but the liver enzymes are normal there are no features of excessive meses liver enzymes are normal no features of outflow obstruction B obstruction right why they so important because you diagnose them and tell

them that this hereditary problem is not dangerous so that they don't undergo undue excessive repeated investigations for their jordas it is just the end of the normal gosan curve is that right so whatever Unconjugated buin goes up in the blood that usually does not produce any sign disease problem to them that does not produces any disease the only disease is created by the doctors which do not diagnose this condition and even they don't know this condition so they keep on sending them okay this time I could not find anything next time when you develop this

thing please come to me again so I want to know what is the name of this condition yes Dr an Dr tanzilla At least we should know the name of this condition isn't it this is called Gilbert Syndrome you heard of Gilbert Syndrome that is that thing Gilbert Syndrome so what is the this yes please the smile problem is yeah gome Gilbert Syndrome so today onward what is Gilbert Syndrome not a dangerous thing very common thing to be diagnosed only to reassure the patient so that patient does not go undergo Repeated undue investigations is that

right these patients have you can say a lower end of normal rate of enzymes enzyme is just too low but not so low to produce dangerous pathologies is that right am I clear no now we come to the problem who have moderate and severe deficiency the people who have moderate or sere deficiency of this enzymes they are labeled as y kular Nar syndrome cular Nar Syndrome right now this cular Nar Syndrome again is of two types yeah regular Nar syndrome is again of two types in one type of cular Nar syndrome what really happen that

there is severe deficiency of what glucon transfer and in other type there is moderate deficiency of glucal trans phrase right so what really happens that this is which is having a severe problem this is called kular naar type One and this which has moderate problem is called kular Nar type two is that right again let me repeat it we have put Gilbert Syndrome and G Nar syndrome as the syndromes in which problems with gluc transfer if you really love someone always pray if problem has to be there it should be Gilbert not cular because in

kular there's very mild deficiency so there's un asymptomatic unconjugated hyper binmas not a big deal Problem really start when there's moderate deficiency and moderate deficiency it is autosomal dominant disorder in which there is significant reduction in what glucon transfer is activity and these babies develop very SAR unconjugated hyper bmia of course they have a higher risk of developing caric tress right how would you treat these patients there are two things number one how would you treat them and number two How do you cure them yes how do you treat them you give some drug which

can induce the enzymes treatment is phenobarbitol you know phenobarbitol induces hepatic enzymes it forces the genes to overexpress do you know that or not so we give these babies C jaru inob barbital which keep on forcing the ocytes to overexpress the Gen genes and glucal transfer should be more so that build Rubin handling should be at least somewhat better and if you really want To cure you cannot cure it short of liver transplant we don't have any other treatment right then we come to C Nar one I don't know it's really how bad condition it's

bad for mother actually because baby never really suffers so much because baby dies very early sometimes in intrauterine death or just after the birth in C N jar one baby never sees first birthday you know Why jaran because there's severe very very severe deficiency or almost in some cases absence of glucon transfer activity so un conjugate buin becomes so high that it cannot be kept fused with all of it fused with plasma protein so all excessive bobin will flood into tissues including central nervous system and such a higher toxic level of this uh substance will

damage the central nervous system so much that it won't remain compatible with the life is that Right talking about that unconjugated hyperb rubinia is either due to over production and over representation of the unconjugated B Rubin to the liever or it is due to reduced uptake or it is due to impaired conjugation in impaired conjugation we were talking about inherited disorders and acquired disorder in inherited disorder we talk about Gilbert Syndrome and which there's a mild impairment very mild impairment no consequences on the patient's life Then there is moderate impairment in case of cular Nar

syndrome type two and of course cular Nar type one very very sphere deficiency or almost absence of glucon trans right glucon transferase and that will end up into very high levels of unconjugated BU in infant or in the newborn and almost all cases are fatal then we are talking about acquired causes of impaired glucon isation function by the ocytes here I would say all the Mechanisms which prod produce inflammation of heyes anything which produces hepatitis anything which produces hepatitis that produces of course hepatocellular dysfunction and when you have hepatitis or there's hepatocellular dysfunction bobin handling

will become impaired in two mechanism why when you have inflamed and dysfunctional cells number one they will conjugate poorly number two these membranes will become defective in Inflam FL cells and they will not secrete the conjugated bu Rubin properly even inflamed cell will swell up and when they will swell up they will compress the B aluli and there will be intra hepatic K stasis let me repeat it again that anything which produces hepatitis it means that will lead to dysfunction and swelling of heyes and when hepatocytes are having impaired function number one they have impaired

conjugating function number two they Will have impaired secretory function to the bile side due to that reason in hepat cellular injury or due to hepatitis patient develops jundas in which not only unconjugated buin goes up but also B Rubin which is getting conjugated may not be able to clear or pass through b outflow system so that will also spill back to circulation and patient may develop conjugated hyperemia as well right so in a nutshell we can say in a Nutshell we can say that in patients with hepatitis right there's a Pell dysfunction and that will

produce impaired conjugation function as well as impaired secretory functions when both functions are impaired that will lead to unconjugated hyperemia as well as conjugated hyperemia right now what could be the causes of hepatitis okay first of all I want to know how do you define hepatitis who will Define hepatitis for me Dr Kashf what is hepatitis don't give me a definition which no one knows in the world okay this is one way to say hepatitis is inflammation of the liver listen one thing attention please for example you take a liver biopsy of course you damage

few cells and they are inflamed is that right few cells are damaged and small amount of liver inflamed do you call hepatitis inflammation what is the simple Definition of hepatitis hepatitis is inflammation of liver characterized by characterized by spilling of inflammatory cells from Portal tracts into liver parenchima is that right will you remember that please write it down what is hepatitis in a simple term hepatitis mean inflammation he's right but when you're talking about histopathology how we really know there's hepatitis or not when a patient Is suffering with hepatitis actually from the portal tracks inflammatory

cells are spilling in big number to liver parena right so what is hepatitis inflammation of liver characterized by spilling of inflammatory cells of course in acute hepatitis neutrophil and chronic hepatitis lymphocytes and acute viral also Lymphocytes right spillage of inflammatory cells from the portal Triad to the liver parenchima clear now what are the causes of hepatitis now this is let suppose this is liver lobule and if it is injured by any mechanism that will produce hepatitis right so can you tell me some important causes of hepatitis you viral okay viral we should divide it into

infectious and non-infectious Hepatitis hepatitis is infectious and non-infectious so first of all we should write here infectious hepatitis and hepatitis due to without infection that is non-infectious hepatitis now infectious hepatitis may be viral is that right and which virus you will tell me don't tell me just a b c d e tell me something more than that viral hepatitis Virus hpna virus is actually Hepatitis B virus right again B what I'm talking about look when we say there is viral hepatitis okay viral atitis may be that some vir virus is damaging the liver some viruses

predominantly involved the liver and other viruses involve the liver as well as many other tissues the viruses which specifically involve the liver are more prominently involve the liver they are called hepatotropic viruses the other viruses which may Involve many organs liver is only one of those organ those viruses also produce hepatitis but they are not called hepatotropic viruses so when we talk about hepatitis viral hepatitis we should talk about viral hepatus due to yes hop tropic viruses and non Tropic viruses in hepatotropic viruses of course we specifically love to produce problem dominantly in the liver

hepatus a hepatus b hepatus c and You know Delta or D which produces problem when it is co-infected or superimposed on B infection and then hepatus e e we'll go not go into detail of these uh viral hepatitises but what I'm talking about viral hepatitus may be due to aat Tropic viruses which are a b c Delta and E then there are some viruses which are not hepatotropic can you tell me few viruses which are not atropic but can produce hepatitus it Means they of course they do bind with the in a very strict sense

they are also hepatotropic but along with that they also involve many other tissues right so they're not specifically hepatotropic of course you must be able to tell me if stin bar virus right you must be able to tell me yellow fever virus you must be able to tell me cyto magalo virus this is the minimum three you are supposed to know when you go for your International Career right so viral hepatitis there can be bacterial hepatitis also and you tell me some bacteria which can produce hepatitis of course one of the Spyro Spyro spirochetal bacteria

are basically spring shaped Quil bacteria out of Spyro there write which one produces hepatitis I will give you a scenario there's a person who is seage worker and he has developed hepatitis with Rees and bleeding Tendencies what Do you which what could be wrong with him there's something related with seage worker you know there are in the large cage pipes there are rats or their wife's Mouse and male female all of them some of them pass in their urine a special type of bacteria which is called yeah excellent lepos spiry EO hemr lepos spiry EO

hemr and this bacteria when it enters in your body not only it produces Leptospiremia it is spreading in the blood but it also localizes in liver and produces sphere hepatitis right and many other problems right especially bleeding Tendencies and many other bacteria as well so viral atius bacterial atitis can there be protozoal hepatitis can there be Proto hepatitis can you tell me some name of the Proto which can produce hepatitis yes amiba can produce hepatitis right when it is white spread In the liver usually it produces a localized obsess any other Toxoplasma gandi that can

produce hepatitus Toxoplasma gundi also produces sere problem in the central of system of a patient from where the Toxoplasma gondi come at least you should know cats people who are cat lovers or they raise the cats or they keep the cats they may get Toxoplasma go Under what circumstances you you should not keep the cats in your home preferably any autoimmune deficien no when the family some female in the family is pregnant because in pregnant females if they get Toxoplasma gandi from the cats they can pass it translucently to the baby and the severe damage

to the baby right so I think you must be knowing that isn't it you're working in gyob uh what Toxoplasma gondi does to the baby It is one of the torch infections isn't it it's the first one of the torch infection right it comes from the cats and many other uh pets also but dominantly from the cats what it is doing to the baby you no idea but actually when baby develops transplacental acquisition of the Toxoplasma it produces ear problem ear development is defective eyes development is defective and cardiac development is defective and many other

Combinations can occur as well right anyway let's come back so we are talking about there can be viral there can be bacterial there can be protozoal hepatitis okay let's come to the non-infectious causes of hepatitis can you tell me some non sub first of all toxins chemical toxins can you tell me some chemical toxin which can produce Stites even kill the person okay very good alcohol is also uh it should be considered chemical toxin When it is producing severe damage to your liver you is not classified as chemical toxin but theoretically you are right even

though many alcohol lovers may not agree with you right so why don't you tell me something more dangerous and less loved carbon tetrachloride carbon tetrachloride is present in bleaching powders and other and if you really get fumes of this it will lead to a Pell failure as well as Reno failure and very SAR damage okay don't that is related with the fungus right there biological toxin toxin I'm talking about chemical toxin okay uh just your honor I will make here okay alcohol can produce also hepatitis is that right alcohol can also produce hepatitis carbon tetrachloride

is less common cause but drastic cause alcohol is a common cause of hepatitis or chronic liver damage and remember one thing that in Jas when you're taking the History of alcohol intake most of the people unknowingly understate their consumption does right not only to the wives but also to the doctors right then toxins alcohol yes okay why don't you we forget here fungi fungi can also produce uh problems have you heard of amonita fidus this is a fungus mushroom yes mushroom that can also produce problem right then of course Alpha toxin or Al toxin e

toxin that is Toxic to the liver that's very good and any other non-infectious drugs there so many drugs which produce hepatitis so many drugs which may react with the liver substance and produce of course you should not forget heloan which is very notorious and less dangerous uh but more dangerous is like parasitol overdosage right that can produce sere hepatitis and there's a long list yeah any other cause of Non-infectious hepatitis yeah Auto autoimmune yes autoimmune hepatitis autoimmune hepatitis is more common in males or females I don't know females suffer with a lot of gyo problem

as well as autoimmune diseases but still they outli The Men We have to sort out this mystery one day right now so toxins may be chemical toxins or alcohol may be there or drugs may be there autoimmunity may be there what Else yes tell me just one more cause of non-infectious hepatitis very important cause swear yes fill in the blanks please swear hypo profusion to the liver when this prolonged sphere hypo profusion to the liver prolonged scheme of the liver and shocked patient sometimes right what will happen many Cells of the become necrotic and to

eat up those necrotic cells and handle those necrotic cells inflammatory cells will spill over into liver parena so that may be responsible for hepatitis can you tell me some more graceful but rare causes of hepatitis why don't you tell me some metabolic disorders yeah Wilson's disease hemocromatosis Alpha 1 antipin deficiency say these are very graceful causes to mention but less often seen of course hemocromatosis is bit more common so that can also produce metabolic disorders metabolic disorders there's so many of them but at least you know three of them what are those three Wilson disease

especially in which you make a special type of ring coer deposition ring in the yeah in the At the junction of Cera and the cornea at the limbus that is called no that's the only thing my pronunciation is very right Kaiser flesh ring Kaiser fleshner ring right Kaiser fleshner ring right you develop a brownish ring and uh and what type of visual problem it produces usually does not it is main importance is diagnostic Kaiser flaring Wilson disease you know copper overloading condition in liver as well as basil gangli right that is why People develop motor

dysfunction extra peramal signs along with therosis right okay wion these hemocromatosis that also produces hepatitus and jundas and with that of course Greek coloration of the skin what is the most common what are the common causes of death of hemocromatosis no what do you think iron is trying to go out of kidney what are the important causes of death in patient with hemocromatosis It is one of the most common inh herited disorder in the Western World so you must know that one of the most common very common at least tell mosis we are talking about

liver many patient with hemocromatosis go into repeated damage due to iron loading to the pyes and thoses occur any chronic inflammation of liver will lead to therosis so tell me many patient people many patient die of complications of therosis many patient Die complic Another important cause of death is yes please in hemocromatosis patient is we call this bronze diabetes also isn't it yes so what should be don't tell me bronze color of skin kill the patient diabetes yeah it damages the you can say pancreas pancreas and diabetes if you don't manage person may die of

complication to diabetes but more pathetic death comes due to hosin getting deposited and yes Deposited in myocardium and that is the major cause of death the only treatment for that problem is cardiac transplant right so anyway what I was trying to tell you anything which produces hepatitis has a capability to produce jundas and that hyperemia partially unconjugated and partially conjugated let's move forward so we have discussed the causes of unconjugated hyper bmia which may be either over production of bobin or Displacement of bobin from the proteins by the drugs or it may be reduced uptake

or then there may be poor conjugation conjugation now let's come to the causes of what conjug we talk about the causes of conjugated hyper bmia right and in case of causes of conjugated hyperemia we can divide rather into two mechanism four mechanism is here Intrahepatic outflow problem intrahepatic stasis you write it here five and this is extratic colis four and five have made one group right the group in which there is impaired conjugation is going on either cell cannot push the conjugated material here or conjugated material which is pushed over here it cannot go out

of liver is that right so we say four and five causes previously previously have made them As intra petic kist stasis and this was the sixth which is now called fifth this is extratic col stasis is that right now first we'll talk about the causes of intraa stasis that what's wrong with the liver that once bu Rubin is conjugated either it can not somehow it cannot be properly drained through intrahepatic canalicular system right now let's come to the causes of that first of all we'll talk about impaired canalicular transport of Blur Rubin gluc coronoids here

these Transporters are not working what could be the causes of impaired function of these Transporters this is one uh let's talk first inherited disorder and then acquired as we reduce GL glucon transfer activity we divided into what inherited disorder and acquired now we are talking about that if intra hepatic kis stresses occur B bile or you can say bu Rubin Cannot be pushed through then causes which are inherited and causes which are acquired right inherited causes one is duban Johnson and other is rter right one is dubben Johnson another is rter rotor syndrome the good

news is that both of them are innocent patient does develop un conjugated hyper anemia but not a big complication to his life so duban Johnson syndrome and rter syndrome both Of them have a problem that there is poor B conjugated B Rubin transport from the cell to the B alular system right but what really happens that usually this conjugated hyperemia does not have any other marker of injury so usually it is not toxic to the patient right of course now in this condition dubben Johnson and rter syndrome what is the real difference in them these

are two different conditions just tell me one point how they can be differentiated of Course other than spellings how do you differentiate them duban Johnson Johnson was the white person or black person black there's one very famous Johnson who was black why the Johnson was famous johon Michael Johnson yes M anyway there are many you can say black colored Johnson so you can remember that in case of dub and Johnson liver becomes black when you take the biopsy liver is black because lot of Metabolites which are supposed to be secreted by the ptoy into build

they accumulated within the liver especially metabolites of Breakdown off what is retained in the ptoy which produces black color yes please don't tell me conjugated blin because conjugated blur Rubin is poorly secreted in dubben Johnson as well as in rter but roter is rter liver is not black jupin Johnson liver is black what could be the reason Because juben Johnson has one more problem not only conjugated buin cannot come out rather plus there is another problem and to another transport system which is supposed to secrate what metabolites of cacola means right and when the metabolites

of cacola means the retained here imparted black staining is that right not melanin now everything black is not due to malan right anyway so let's come back So I was talking about these are two innocent so if you really want to know about three innocent one is Gilbert with unconjugated hyperemia and dubben Johnson and rter conjugated hyper binmas but in between is a Crigler in a jar which is very very bad right type two you do survive but very sere problem or type one you simply don't survive it's not compatible with Life is that clear

then we come to other Causes right that is hepatocellular damage and toxicity I told you hepatocellular damage should be classified as a cause of unconjugated hyperemia as well as hepatocellular damage should be classified as a cause of conjugated hyperemia now conjugated hyperemia again can be caused by hepatitis hepatocellular damage mean there is hepatitis so no need to go into big discussion again come up all these Things all types of hepatitis will produce some impairment in Hell function in conjugation and some imp impairment Inc capability of heaty to secrete the blin and some impairment in the

drainage system am I right what will be the causes again infectious hepatitis which is viral bacterial protal fungal or you will talk about non-infectious hepatitis noninfectious hepatitis may be due to alcohol it may be due to chemical toxins it may be due to drugs it may be due to Esic deficiency it may be due to metabolic inherited disorders is it right or prolonged esia whatever after that there are some other special causes in which intraa B canalicular system may not be functional right can you tell me a disease in which autoimmune process specifically specifically attacks

Buri alular system and destroys it this problems usually occur more commonly in females there typically a female is in her 30s her own 30s and she Develops severe jundas progressively building up conjugated hyperemia and she developed lot of excoriations why esor all over her body itching itching itching what do you think what's wrong with that female don't tell me scabies scabies is possible with jundas but let's suppose in this case it's not scabies there's a female you should call her still young she will be angry if you don't tell her she's in 30s and uh

she Has one husband and two three kids all of them need her these days but suddenly she turned jundas conjugated hyperemia along with that she develops SAR itching yeah what could be the cause there's an autoimmune process which is rapidly destroying build canalicular system and if you this process goes relentlessly this will eliminate really virtually most destroy most of the build alular system right initially will find around the build Alular system lot of lymphocytes and plasma cells then fibrosis and elimination right okay I'll give you one more pointer to the disease another pointer to the

disease is if you're really going to look for what is the autoimmune process you must check autoimmune profile including anti mitochondrial antibodies these females are usually positive in antim mitochondrial antibodies yeah what is this disease Called primary bosis this young man knows primary bellary ceris what is primary bosis bile cannot be drained so retained bile produces sere damage to the liver on chronic basis and that chronic injury produces therosis and because it was not secondary to any stones or carcinoma so doctor never knew what is the cause they thought it is primary but now we

know it is autoimmune is that right primary building So when you see a female in her 30s right of course younger and older females are not immune to this problem but most commonly and classically it appears in 30s right and what really happens that she develops why she was scorting and itching all the time you don't know because not only B Rubin is conjugated B Rubin is going spilling to the blood but along with that BDS are also going and BDS are irritant to the m cells and low level of Histamine produces spere a chain

is that right is that clear so primary bues is one autoimmune process which can produce a trouble like that then there can be autoimmune hepatitis also please don't confuse primary build sources with autoimmune hepatitis and autoimmune hepatitis autoimmune processes are directed against hytes primary bildes autoimmune processes are directed against B Canalicular system is that right so what we can say that these patient may develop intraa bile duct problem and in this case there may primary Bild sources can you tell me an duly autoimmune diseas are more common in females or there are some autoimmune diseases

which could be more common in males drol you don't know any disease autoimmune disease which is more common in males or do you know any autoimmune Disease which is more common in males any idea just uh use the bank of your knowledge right in knowledge Bank in your knowledge Bank do you think all autoimune diseases are more common in females or are there some Auto diseases which are more common in males more common than in the males than females Dr tanzilla I write it down there's a basic principle all the autoimmune diseases which are associated

with m MHC Class 2 Molecules are more common in females I will explain the cinemology all the autoimmune diseases which are associated with MHC class two are associated in more common in females like HLA Dr group all the diseases which are ass with hlr four 5 2 the more common in females and right and all the autoimmune diseases which are associated with MHC class one are more common in males thank God that those diseases are less right automine diseases which are Associated with class two molecules are very common and auto diseases which are associated with

class one molecules are less common right they are usually HLA a or h b or HC you have heard of diseases which actually B27 for example and losing spondilitis right that is more common in male the females M yeah that is the most important cause of chronic back ache in male females do have back ache commonly but if a male develops young male Develops chronic back ache you have to rule out yes an enyoing spondilitis and another disease which is H B27 Associated and in that case bery canalicular system is not destroyed rather it is

filled up by the fibrotic tissue I told you in primary B roses B system is attacked by the autoimmune system and then it is destroyed and disappears but in case of the condition which I'm talking now it is more common in males and then this Case autoimmune process specially attack the buildy drainage system and eventually produces chronic inflammation and all the system become fibrotic of course when it become fibrotic it cannot drain the things well we call it closin colangitis have you heard of it closin colitis which is actually B27 Associated more common in and

males males of course it would be the cause of jundas as well right there's a G8 condition with which the closin colitis is associated what is That g condition yeah alera excellent I think you have it ulcerative colius yes he knows a lot about alternative K he have the knowledge about that now so what we are talking about that there can be okay another cause of bilder immune system especially attack the bilder drainage system I told you and young females immune system May attack the B system and destroy it primary B sosis and young men

immune system May attack the B train System and make it fibrotic that is called cing colangitis and then we can talk about and then we can talk about another immunological process in which immune system attack the buildy system okay I'll give you a condition you have to tell me the name of the condition there's a patient who received a transplant after receiving a particular tissue transplant within few days patient developed Rous bloody diarrhea And obstructive Jas this triangle you must know patient who received a graft and what did he develop what did he develop rashes

bloody diarrhea with with obstructive junders what is that condition Mr kashf the transplanted tissue has attacked the host this is called graft versus host reaction when you transplant imuno Competent tissue like bone marrow transplant when you transplant imuno competent tissue to a imuno supressed recipient when you transplant amuno competent tissue to the amuno supressed recipient amuno competent tissue May attack skin of the person mucosa of the git and Bild nocular system this is very classical triangle of graft versus host attack which is called yes patient develop Precious Blood di bloody diarrhea andru obstructive jundas is

That right so of course that will also become a cause of what cause of Jas okay please tell me some drug at least one drug which can reduce the bile flow now this is the time to be impressed do you know one single drug Group which can reduce the okay I will give you a hint similar mechanism is involved gyo people know it a lot s similar mechanism is involved in pregnancy related col stes you know There is pregnancy related colis something like that what is the mechanism okay look at this young man and his

IQ he's saying if there's pregnancy related kis which occur at the advanced stage of pregnancy is contraceptive PS I think you don't know what is the function of contraceptive pells they are not sweeteners in the mouth you are thinking about what the lady who is not pregnant let's come back to the lecture now right Yes what is the reason anyone who want to tell me high level of estrogen and that young boy was is not very wrong when female have very high level of estrogen now they know that sometimes estrogen levels if they become very

high they distur the bery drainage system right in the same way female is not pregnant and taking oral contraceptives again estrogen level is high that can also produce chasis so if I say which drug can produce chasis please tell me Or contraceptive but not in a female who is pregnant right then we can come to extratic B obstruction right extratic B obstruction that's the easiest part of the lecture which I love to talk about what can be wrong with this system from here up to here it's so simple first of all gall stones G Stones

can produce obstructive jundas usually it is fluctuating right associated with upper quadrant pain G Stones then there can be malignancies Yes malignancy of common bile duct a malignance of the head of the pancreas of malignancy of amp of v a malignancy of so there can be malignancies again there may be common B duct malignancy malignancy of the head of the pancreas or malignancy of imp of is that right then there can be structures what are structures and atras and how do they differ from each other common B duct structure have you heard of this term

common B duct traas in Traas the conal defect and common B duct is not developed properly and it cannot drain well structure is usually acquired problem for example you have produce a cut in common B duct removed a stone and later on a stenotic fibrotic band is formed there right so what could be the causes there may be Stones there may be cancers there may be atas there may be structures there may be col K doco doal cyst right there may be a cyst from this area developing and then pressing this Right kocal Cy and

of course do you know some flukes which love to accumulate into drainage system you don't know any flukes you know what is fluke what is fluke please don't tell me ca ca involves the liver but does not produce his problem here yeah or is it s I don't know something you should Should tell I've told you so many things there's one fluke parasite which involves the liver and then it produce sometimes obstructive Jas how many flukes Nam you know just one you know only one okay that's good I also know only one right I'm happy

to see you so I know others also but I'm not uh willing to share my knowledge right now with you right so anyway so some flukes liver flukes they can produce trouble here right one of that Fluke is also related okay let me tell you one of those fluke is also related with causes of malignancy in the liver yeah yeah oh no you are going for far off places okay you tell me tomorrow the name of that right okay now we come okay there's another very funny type of I should say worm it's really like

worm there's a worm which may be present in your G and sometimes I don't know somehow it navigates it tip into Sphincter of 4 and sphincter of 4 become tight around it and then person develops what obstructive Jas you just tell me the name of that parasite that's round yes she knows it escar escaras Lum quets how you know that you read it somewhere or heard it read it okay so she has read it at least about this thing that there is a worm called here scarus lumoid which is present in git and sometimes it

navigates it one End into impl vet and then it irritates that area and what will come yeah spinter 4 will become tightened around it and there will be obstructive Jers is that right of course to diagnose this you don't need to do ER CP fine talking about that if you have let's suppose you are running a center for the patients of jundas and many patients turn up to you now just Diagnosing jundas is no diagnosis right it is just a state and you have to find what is the underlying cause what is the underlying mechanism

right it's quite possible one person has jaas due to mild hysis another person has jundas due to cancer right so so as a good doctor you must know that you must be able to differentiate the people who have Jus due to hysis or people have jundas due to decreased uptake of B Rubin or who have jundas due to impaired conjugation Or the patient who have who have jundas due to intraa colis or the patients who have jundas due to extratic chasis is that right so let's talk about this thing the basically there are three things

which are important in regard to this thing number one that in these patients of course you have to have some points from history you have to pick up some points from physical Examination and in these patients of course are very important is your D laboratory work lab work is that right right laboratory results in which you have to talk about so this is going to tell you about the diagnosis of a jundas person right now when we talk about the diagnosis of jundas I will let's do a little bit practice first of all suppose we

talk about a person who has hysis right what will be the findings in him different type of indicators or Pointers which will Point towards the diagnosis this person has hysis or he has Jas due to excessive hysis right what will be the finding number one in a patient who has hysis what will be the real finding first of all we have to determine is there any evidence of hysis or not is there evidence of himalis or not if someone has sere himalis then naturally his hemoglobin may go down especially if bone marrow cannot Compensate that

loss of rbcs usually what happen if someone has himalis and if bone marrow is very very effective inois it tend to try it's best to compensate but let's suppose we have a patient who has severe hemolysis is that right and due to sere hemolysis what really happens that bone marrow has increased its thop potic activity but still it cannot cope up or compensate for all the rapid losses right so his hemoglobin level will be yes hemoglobin Level will be down in this person number one this is evidence of that rbcs are being destroyed or there's

something wrong with the hemoglobin number two in these patients who have hemolysis right naturally then we can talk about there are two types of hysis excessive hysis may be occurring within the macrophases or homolysis may be occurring within the circulation when homolysis is occurring excessive rbc's destruction within the macr fases we Call it extravascular hysis we call it extravascular es and if arbit is break down within the circulation then what we call it intravascular hysis is that right so another thing which is there that hemoglobin is low and if there is spinali what do you

think spinali points tot that points to extravascular hysis right opposite to that if right this is a feature of extravascular hysis But if there's intra V hysis can you give me an example of intas hysis autoimmune hemolysis may be vular or extravascular for example in some autoimmune diseases Auto antibodies are uh you can say coating the rbcs and these rbcs which are IGG coed they're trapped in the suen and then mcroof take them up then it will become an example of extra extra vysis but in some cases like Avion compatibility of course rbcs May undergo

massive destruction within the circulation that is an example of intravascular hysis and when you have intravascular hysis what will be the feature there number one you will have hemoglobinemia free hemoglobin in the blood we call it hemoglobinemia number two when free hemoglobin is released in blood normal hemoglobin is not present in free form in the blood hemoglobin is packed within Rves free hemoglobin is present in the blood right then naturally what will happen it will bind with certain proteins the protein which is released by the liver to bind with the free hemoglobin which is a

toxic molecule right that protein is called hpog globin what is the name of that protein hepto globin so what really happen in these patients who have intravascular hemolysis that number one there will be hemoglobinemia number two heog globin Level Free apoglobin level will be down heog globin is a protein which is released by the liver and usually it is present in circulation the main function of the EPT globin is if there is whenever there is intravascular hysis it will bind the hemoglobin molecules and naturally when haptoglobin become loaded with the hemoglobin molecule free apoglobin levels

go down so whenever your blood free apoglobin levels are down it means there is intravascular Hysis then if intravascular hysis may be acute or maybe chronic it may be acute or it may be chronic there many ways to differentiate them one of the way to differentiate them is that if there's a cute intas hysis then naturally when RBC will break down what will happen hemoglobin molecules will come out hemoglobin is a trammer right but it breaks down into free form into diers and these diers can Easily yeah going to filtrate and they very small so

as the are passing down they will make number one these ders may be taken up by proximal convulated tubular cells right and if proximal con tub cells if they take up this hemoglobin they may be acute tubular necrosis because toxic to these cells they may be acute tubular necroses because this these molecules may be toxic to proximal convol tubular cells this is Number one number two what really happens that if there's a lot of hemoglobin coming down then there may be yeah there will be hemoglobin UA Ura excellent so acute hemolysis may lead to of

course clinically it may lead to cute tubular necrosis and on Investigation you may find hemoglobin hemo globin Uria and another thing This is acute hemolysis but if there's chronic hemolysis this's chronic intravascular hemolysis right if there's chronically hemolysis is occurring within the blood vessel what will happen of course other things are same hemoglobin emia reduced seog globin level with that there will be hemoglobin Ura but listen hemoglobin Ura will be also there hemoglobin Uria but there will be One special feature what is is that that if there is chronic intravasal hysis and proximal con tubular

cells are chronically taking up the hemoglobin then they will develop the capacity to find the to synthesize epop faratin and fuse EPO faratin with the iron released from hemoglobin hemoglobin in this way these cells develop a capacity to synthesize fertin and polymerize the fertin to make hemosin so whenever someone has chronic hemolysis he will Develop he will develop a lot of hemosin formation within the proximal convulated tubular cells and then these cells which are loaded with hemosiderin May shed into tube and then they appear into urine and we say that there is hemosiderin Ura excellent

there is hemo sidin UA in acute cases again let's compare first of all that hemolysis may be within the circulation or within the Macrophases if hysis within the macras we call it extravascular hysis if it is within the circulation we call it intas hemolysis the major feature of extravascular hemolysis is suino magal in case of intas hysis what really happens number one free hemoglobin is present in the blood number two hpog globin level will go down along with that if it is acute case there may feature of acute tubular necrosis and hemoglobin Ura even there

may Be cost hemoglobin cost right but if this is chronic intravascular hemolysis patient may develop not only hemoglobin Uria but with that patient may have hemosin Ura as well right now in this particular patient let's suppose person who has hysis number one in hysis what happen hemoglobin number go down number two RBC count Goes down number three in these patients what really happens unconjugated B Rubin will go RBC is a breaking down now so total BL Rubin will go up first of all total B Rubin will go up and out of the total B Rubin

which will go really up unconjugated BL Rubin will go up and conjugated BL Rubin will be normal is that right total Rubin right they high and usually this unconjugated hyper rubinia in case of if your liver is functioning well if Your liver is functioning well then unconjugated hyper rubinia usually does not exceed above the levels of five to 6 migr per de again let me repeat it if there's excessive hemolysis right but if liver is functioning well herob system is functioning well then uh usually this type of hemolysis which is resulting due to unconjugated hyperemia

this usually does not exceed the levels of 5 to 6 milligram per DL it means it is almost always mild jaundice It is almost always mild jundas but if someone has uh under these circumstances having uh sphere himalis along with with that if hemoglobin unconjugated blin level has gone above six six G milligram per DL you must think of probably there's something wrong with the liver as well is that clear now bu Rubin is high then these patients have more problems what will happen that there may be features of that bone marrow is trying to

compensate for Example reticulite count may be retic count is High it means this is a feature of bone marrow compensation and when bone marrow is rapidly producing rvcs the fresh rves which are released in hurry they're slightly larger and slightly blue strange so when they're slightly larger we say there may be mild macrocytosis macro cytosis and if rbcs are having unusually blue shade we call it polymorphic uh Polychromasia poly chromia so macrocytosis and polychromasia occurs with the long with high rtic count when bone marrow is trying to compensate for the rbcs which are rapidly being

destroyed right so we have seen a person who has low hemoglobin low RBC count total blin has gone up dominantly unconjugated buin has gone up with that if patient has hemoglobinemia with low hpog globin Is that right hemoglobin jua right it is showing which type of hemolysis acute acute hemolysis and it is also showing that bone marrow is trying to compensate the reticulite count is going up macrocytosis slight macrocytosis macrocytosis slight polychromes is present as well is that clear now in this particular patient there will be no evidence of liver damage there will be no

evidence of liver damage if person hepatobil system is perfectly okay for Example you know whenever hepatocytes are injured listen carefully whenever heyes are injured hytes are very rich in a special group of enzymes what is the name of these enzymes these are trans phrases or trans Ames right one is a EST stand for spared trans phrases or Mino trans phrases and other group is yes a t alanine trans phases or transaminases some people call them transes some People call them transes in this diagram you must remember a and ALT are present in the Hep hepatocytes

because these are present within the heyes so we also call them hepatocellular enzymes actually these enzymes are marker of hpto cellular injury these enzymes are markers of HP cellular injury what is really meant by that that these enzymes are the marker of Pell injury it means that whenever hepatocytes are Injured whenever a pyes are heavily injured these a and ALT a and Al they will spill into circulation as and Al out of them remember Al LT l for liver it means it is more specific for liver diseases EST is not as specific for the liver

diseases so whenever there is significant acute hepatocellular damage then hepatocellular enzyme will spill into C you can say circulation and we say that serum trans mines or a ALT Level has gone up here it is very important to understand that if there is a cute H cellular if there is a cute HP cellular necrosis then as levels and ALT levels are usually above the yes they are they have gone so high that usually they are more than 10 times the normal value again let me tell you if you find EST and ALT levels in a

patient more than the 10 times value of the normal values right you must think in terms of acute Hepat cellular necrosis for example it may occur in vir hepatitis when it is really sever one right so this was one point which is very important so we can say that Rising a alt especially when it is more than 10 times it points towards the acellular injury right another thing which is important here some other you see there are some other enzymes which are present over here these are called alkaline phosphatases these are called Alkaline phosphatases these

are present on the canalicular side of the hocy membrane or in the build canalicular right when there's obstruction to look if whenever there's obstruction to bile outflow bile salts will accumulate and they will interact with these alkaline phosphatases and these alkaline phosphatases will get detached and they will also go to circulation right so it means alkaline phosph is especially regurgitate to Circulation from B and Al system when the buildy outflow is blocked because whenever uh there's buildy outflow blocked cause may be mechanism number four or mechanism number five right there's intra petic or extratic col

stasis whenever intra petic or extratic col stases is present what really happens these alkaline phosphatases right they are you can see acted upon by the B salts and they get detached and from these uh areas membranes and the Spill into circulation even these membrane decrease the synthesis of alkaline phosphates usually with alkaline phosphates uh there's also another enzyme which is normally secreted by liver cell this is called gamma gluty trans transpeptidases gamma gluty transpeptidases so gamma gluty transpeptidases another enzyme which is released by this is five nucleotidases nucleo TI Days is now look if there

is Col stasis if there is obstructive jundas what really happens not only alkaline phosphor will go to the blood even gamma glutamil transfer will also spill to the circulation even five nucleotidases nucleopeptide ases nucleo again let me repeat it first was what was this alkaline phosphates so whenever there's obstructive Jas so there's any degree of col stasis alkaline phosphor will spill to the circulation number two after that what Will spill gamma glutamide transpeptidases and along with that even five nucleotidases may also spill into circulation it means these three serum alkaline phosphates along with that yes

what was the second enzyme gut gamma gluty transpeptidase along with that five nucleo ties these three are the markers of p b obstruction markers of yeah bilary canalicular problem right markers of canalicular injury Canalicular obstructive problem obstructive problems now we can see if someone has injury to the liver cell what will spill into circulation EST alt trans Ames and if someone has injury to build alular system what will spill into circulation alkaline phosphatases mogile transferases and along with that there may be five nucleotide ases is that clear having said all of this I would like

to introduce One More Concept that alkaline Phosphatase enzyme is released by other tissues as well alkaline phosphatase can be released by the liver the sources of alkaline phosphatases may be liver or it may be bone it may be bone or it may be git or alkaline phosphates Source may be yeah it may be placenta is that right now so alkine phosph may go up when there is obstructive or infiltrative diseases of liver or when there are bone turnover is very fast or postally after The food or from the placenta but all these enzymes which spill

into circulation they have different isotypes they can be differentiated from the electris these alkaline phosphatases which come from different sources right this is these can be electrooptically separated from each other due to that reason it's very important to know that if a person has raised serum Aline phosphatase what is the source one of the simple way to know that source is Liver or not that if only serum alkaline phosphates goes up but ggt and five nucleotide does not go up it means probably the sources other than liver but if someone has rais serum alkaline phases

along with ggt along with five nule disas of course uh this must be coming from mainly from liver right another point which I want to specify about the ggt I told you ggt level goes up whenever there's some degree of Obstruction or canalicular damage Whenever there is B canalicular damage ggt levels in the blood go up in another condition also one condition is when there is Billy canalicular injury canalicular injury another reason of raised gam gluty transfer is alcohol intake the people who take lot of alcohol right G in their liver in their liver gamma

gluty transferases are induced right alcohol intake in Increases the concentration of and production of Gile transferases and then Gile transferases appears into circulation now listen if you end up with a patient who has a lot of gmog gluty trans phrase but not other liver markers it means he's taking alcohol right or some other liver drug which is enzyme inducer or if someone has gamma glutamil transfer along with other enzymes as well it means gamma gluty transfer has gone up due to Obstructive reasons or canalicular injury reason is that right after what in a nutshell what

we can say that marker of H cellular injury is yeah EST alt out of that alt is more specific because EST is released by other tissues not only from the not only from the lver and marker of canalicular injuries mainly serum alkaline phosphates but along with that there's serum level of gamma glut transfer and five uh gamma glutamil trans peptide is and five Nucleotides levels also go up is that right then another thing which I want to introduce here that if your liver has lost its synthetic functions liver has lost its synthetic function for a

short time right it will not produce you can say yeah what it will not produce Co coagulation factors and proant time will be prolonged so prolonged proin time uh is a marker of synthetic failure of liver and if your liver function synthetic function is fluctuating Rapidly proin time in the patient will also fluctuate but remember proin time depends on vitamin K dependent factors and if you have obstructive jundas it mean b AER and salts are not going to Git it is quite possible but that fat is not getting digested and you are not getting back

Vitamin K is not being absorbed because it it is lipid soluble and if Vitamin K is not being absorbed simply Reduced supply of vitamin K to liver can also lead to prolonged Pro time so if a patient has liver disease you are not sure that proin time is prolonged either due to synthetic failure of liver cell or it is due to obstructive problem very easy way to rule out what you do what you do that you inject the person with vitamin K you inject the person with vitamin K and wait for 24 hours and again

check the pro time if it Is normalized then it was due to deficiency of vamin K right and if it is yet still prolong it means synthetic functions of the liver have gone down right another point which I want to highlight at this very moment is that coagulation factors have a short half life due to that reason uh whenever liver function is fluctuating hour by hour or day by day proin time also fluctuate along with that then another marker of liver fun synthetic capability Is serum Albin but serum Albin protein a very long half life

about 20 to 25 days is the half life of serum Alban it means if my liver stop working today if my liver start stop working today of course after within 72 hours my Pro thring time will be prolonged but my but my serum be level will not go down but my serum wom level will not go down but so if someone has really low serumal bment due to reduced synthetic function of the liver the liver should be having Problem acute or chronic chronic chronic is that right so we can say shortterm marker of synthetic capability

of liver shortterm marker of marker of yes synthetic capability of synthetic capability of Ayes what is that Pro proin time once you have ruled out the vitamin K deficiency and longterm yes longterm what is that marker of synthetic capabilities of uh hey is serum albumin level is that clear now let's Recap we have one patient he has sere hepatocellular injury what what markers will rise in the blood EST alt we have another patient who has sphere obstruction to the Builder system what main markers will go up along with its friends like five nucleotide and Gile

transpeptidase is that right and if someone has hocy dysfunction and this synthetic ability of ptoy is reduced for a short time what will really prolong Incre proant time if someone has uh his synthetic capability of ptoy significantly reduced for many months he will have prolonged proant time yes along with that he will also have hypol bmia you'll have hypo albuminemia is that right now about the liver you should know four things very clearly number one a to the marker of H cellular injury they should be considered significant when their levels are more than 10 times

Of their normal upper values number one number two if EST level is double than the alt and both are raised this is considered a marker of alcoholic injury to the liver write it down when as level has gone EST LT both are elevated but EST level is double than the double than the double or more than the ALT level it should be considered aloh alcohol mediated injury To the liver right so whenever you damage the liver cell what spills out serum trans Ames estt and if buildy obstruction occur what spills out Aline alkaline phosphatase and

its friends ggt and five nucleotidases and whenever there's shortterm only short-term synthetic failure of the hepatocytes what is that prolonged proin time once you have ruled out vitamin K deficiency and if someone has prolonged synthetic function failure Of the liver he will develop not only prolonged Pro froment time but he will also have hypol bmia that is why lbum is considered a bad prognostic uh indicator of cerotic patients it is considered a bad prognostic indicator of serotic patient now having said all of this let's come back patient who has just hysis but he does not

have you can say yes he does not have hell injury serum trans minis will be serum trans mines mean a and Al will Be normal then what about uh markers of P injury yes serum alkaline phosphatase will be normal ggt will be normal normal five nucleotide is will be normal right but the total amount of blur Rubin which is loaded to his liver is normal or more than normal more than so when it is conjugating more than normal amount of bobin it means that more bobin is going conjugated bobin is going to the urine more

conjugated BL Rubin is going to the sorry to the git more conjugated is going to the git so production of strogen is more so stool may become dark color and even eurogen production is also increased and urinary eurobin levels also go up is it clear urinary urobilinogen also goes up but because the B Rubin which is raised is unconjugated bin which bin is raised unconjugated bobin and because this bin is plasma protein bound so can it into urine no so it means uh there is no C Uria C Uria mean bin coming into urine so

this type of problem is called AIC jundas as well this type of jundas is called AIC jundas as well ealu jundas as well is it clear right now again let's come back to our first group of patient what was wrong with him this's evidence of hemolysis right hemoglobin is going down RBC count is down total buildin is high dominantly it is unconjugated BU Rubin bone marrow is Compensating for example reticulite count is high slight macrocytosis seen polychromes has seen no evidence of Pell injury EST alt normal no evidence of bicular obstruction because alkaline phosphatase gamut

transas and five nucleotid are normal proin time is why it is prolonged proin time is normal even serum albumin level is normal serum albumin is also normal serumal Women is also normal right now with that urinary bobin is absent urinary bil Rubin because unconjugated bin does not appear into urine because it is complex with plasma proteins so urinary bbin is absent that is why we call it audic jundas jundas is there but blin is not appearing into urine but Euro Bogen is Euro bino gen is more than normal is that clear so this is a

case we can say a sort of pre preh hepatic jundas prehepatic jundas in Which liver function test are absolutely normal except that unconjugated hyper binia was there but that was due to excessive production of B Rubin unconjugated B Rubin due to hysis now we go to another patient let's go to the extreme after having said discussed about case number one now we go to the case number four and five is that right we we are going to now discuss a patient who has obstructive jundas right or if you really want we Can go to case

number three what do you think it is very easy case number two is reduced uptake you can understand no no features of hysis no features of pil injury simply unconjugated buin is high right case number three case number three is the patient who has sere hoc cellular injury dominant injuries toat cellular area with some degree of intra hepatic stasis so what will happen in case number three this this case will be a typical case Of acute viral hepatitis right now when we talk about this case that in this case either some drug or Auto antibodies

or you can say some toxin as damage the hepatocytes significantly right then what really happens number one what will happen to Total buildin this is case number two this was your case number one case number two yes for example he has SP viral hepatitis or due to any Reason he has Sarat cellular injury number one no features of no features of hemolysis features of excessive hysis I must say what hysis yes excessive hysis another thing in this patient of course no features of increased arthropo for example there's no increased rtic count of macrocytosis of polychromasia

is that right but when you do liver function test you find Total Vin Is total bluin is increased increased out of this unconjugated BL Rubin is mildly increased but conjugated bu Rubin is more increased but the real marker of FOC cellular injury is level of enzy Minot transferases so what you really find there's a very high levels of EST Amo aspart trans phrases and ALT alanin trans phrases they're very Very high so this point towards the real diagnosis that there's something wrong with the herp cellular system with that if there's too much damage to the

Hite but short term then Pro thring time may be may be prolonged and if unfortunately hepatocellular injuries for very long time and hocy mass has gone too much down right and if hocy count cell count is very much down and mass is very much down and then what really happens even Albumin level will come down but in atitis human levels remain normal is that right then we can say that in these patients the features of buity obstruction are not there there's slight increase in serum alkaline phosphatases slightly increased gamma glutamide transferases slightly increased yeah what

was that third five nucleotidases slightly increased so there's a heavy increase in uh a alt and Mild to moderate increase in canalicular enzymes so we can say primary target of the injury is hytes not the buildi bu buildi may be suffering secondary to Pell injury due to dysfunction of this pH of the ptoy or due to swelling of the pite compressing the B Canal coli then in these patients what really happens that about Euro Bogen maybe Euro Bogen may Be normal or decreased or slightly decreased but it is usually present uh if there's not full

scale Coles right so again when you come to the group number one and two you don't find you find that markers of liver cell injury are normal and markers of canalicular injury are normal but when you come to the case number three right what really happens that Markers of H cellular injury are very high 10 times the normal value and There is mild to moderate uh elevation and markers of canalicular injury but we come to the case number five four four was what obstr obstructive jundas especially intra hepatic colist stasis right first I will talk

about that intraa or extratic kolasis what are the findings which are present in B obstruction then I will tell you how to Differentiate basically problem with intop petic or extratic first of all it's a very simple thing when a patient come and you want to know is it obstructive jundas or not what is the simplest test who will tell me if a patient comes patient is jundas if your senior says please confirm is it obstructive or not what is the immediate test you can do in 10 minutes in the world if patient is cooperative and

if patient is cooperative enough to provide Few drops of urine you just di stick and see if euro eurogen is absent it is colis it is obstruction because if there's sphere obstruction intraa or extratic it means nothing is going to G to be converted into Euro Bogen so the simplest and very uh you can say rapid determinant of what of OB obstructive juses that simply on di sticks you check the patient's urine and what will be the marker there If it is obstructive jundas urobilinogen will be absent and if eurogen is there obstructive Jas is

ruled out is that right then obstructive jundas is ruled out now let's talk about obstructive Jas and its related parameters what will be the features of obstructive jundas in case of obstructive jundas number one total bobin will be yeah high is that right out of that unconjugated bin may be slightly high But conjugated bin will be very very high high is that right number two in these patients yeah uh markers of P cellular injury a and ALT will be slightly high right but markers of canalicular injury that is serum alkaline phosphates gamma glutamide transferase five

nucle transpeptidase five nucleotide days all of them will be strongly elevated so you see in case number three And four and five in all these cases there may be elevation of hos enzyme as well as canalicular enzyme but if pular enzymes are very high or canalicular enzymes are slightly high it must be pular injury or if canel enzymes are very high and Pell mild to moderately High it must be dominantly obstructive obstructive problem colist static is that right another way to look the situation is that if there's obstructive problem then What really happens in early

course of the disease canalicular markers go go up and later on if obstruction remain for a long time then cell damage start and trans mineses also appear so if a patient of jundas come and you repeat his liver function text over a few days or weeks you find initially alkaline phosphates and its friends go up and later on gradually trans manes go up problem started as obstruction but if Another patient comes to you and in his blood initially there's very high level of estt and gradually then uh canalicular marker like alkaline phosph and it friends

go up then we call this hell injury to begin with leading to colist stasis due to swelling of the blood and due to the membrane canalicular uh membrane dysfunction is that right no then in these patients if there's full obstruction of course a very Important thing there is no Euro Bogen and urine but in the urine conjugated BL Rubin which goes to blood it is water soluble so it can appear into urine so there will be C Uric jundas or there will be urinary bil Rubin is present bil Rubin is very high now look here

again whenever there is obstruction urin urinary you can say eurogen become absent because no conjugated B Rubin is Going to the G to be converted into eurogen but conjugated buin spill into circulation and that also spilled into urinary system because conjugate buin is not plasma protein bound so it easily spills into circulation and it water soluble so it appears into urine so we can say urine will turn which color dark color urine will turn due to presence of the uh you can say conjugated B Rubin urine will turn dark color opposite to that what will

happens to G Because conjugate buin is not coming to g g is not making zuro B Energy stco balen so stool will become clay colored or light colored or pale colored right so dark colored jurine and light colored stool with urinary absence of eurogen and elevation of level of of bobin in the urine right it all indicates what type of obstruction is there it only tells that there is Obstruction obstructive Jas it does not tell the type of obstruction it just tell that obstruction is there really want to know that again what what I've said

that urine in these patients urine will be yes will be dark colored and stool will be light colored with that because there is co Le stes bile acids also go to the circul circulation and bile salt and they produce sere itching so there's lot of excoriations or itching so when Jas patient with itching And dark colored urine and light colored stool it is definitely a case of K stasis and usually in chasis if it become prolonged lot of cholesterol is retained in the body and this cholesterol May produce special yellowish plaque Under the Skin we

call them zenoa zentil ASAS zenas so what did we learn that in four and five cases when there's obstructive jundas most Important finding is eurobin absent from urine and conjugated buin present in urine and conjugated hyperia and markers of canalicular injury appear first in the blood and very high amount and markers of Hell injury appear late and less in amount am I clear now after having said all of this now how do you differentiate really cases of four and five is it intra optic obstruction or extratic obstruction very easy what will you do just do

Ultrasound if you do the ultrasound and you find common B duct dilated it is ex extratic obstruction in this case right you go for ultrasound and ultrasound can tell you if common bile duct dilated then it is extra hepatic K stasis but if common bile duct is common bile duct is normal diameter then it is intra hepatic obstruction if there's intra hepatic obstruction then bile is not going to common bile duct so it will not be Dilated but if there is if there is suppose what is here P carcinoma or there is carcinoma head of

the pancreas or the common B carcinoma or there's a gall stone or structure or traia all these things will produce what type of problem dilated what common B duct is that right so extratic buery system if it is dilated you must think of extratic Coles if they're not dilated we must think of intra petic colesis the Next investigation which is important that if you find that there is extratic what is there if there is extratic colist stasis the next investigation should be ercp ER CP what is ercp endoscopic retrograde colio pancreato gra graphy what you

really do it that to pass a catheter from here endoscope from here and this endoscope is going and it is side viewing endoscope through this endoscope you Have taken the endoscope through the oral cavity to the esophagus feren esophagus and then to the dudum through the stomach and dudum then this is a mirror you can say which can view on the GL side viewing dudos scope we call it and it will locate emplo water when it will emplate then we bring a catheter out of it what we bring out of it a catheter and we

engage the catheter into P of v and then with uh put a radioa material so it can lead to and then we Take up the X-ray so it it can show the pancreatic duct as well as it can show the common bile duct and not only it can uh show the anatomy of that area but it can show the level of obstruction as well is that right we call it ercp endoscopic retrograde we are going retro this is going retrograde endoscopic retrograde P kenio pancreatography endoscopic then retrograde it's going in retrograde fashion right is pushing

the D in Retrograde fashion uh kenio pancreat graphy is that right and another advanced form which has come here and that is replacing the ercp as uh you can say investigative tool that is MRCP MRCP test what is MRCP magnetic resonance magnetic it is something like Mr MRI MRI taking the information about the common bile duct and the ductal system so we call it magnetic resonance Ceno pancreatography these days this Investigation is replacing wherever it is available ercp for diagnostic functions but not for it therapeutic functions now we come to this patient who has common

bile duct problem what will go what you will do with this patient who has common B duct problem uh sorry common B duct is normal it means there is problem inic if there inic obstruction what type of investigation will you do the Next yes what is that PTC PTC what is p TC percutaneous transoptic colio graphy percutaneous transoptic colography what you really do in this case that in the mid exil line first you par out the border of lior right in the mid exil line uh Guided by ultrasound you push a needle which should end

up into some dilated radical of buildy collecting system and there you inject the D to Visualize it if all these things fail you you are left with only to do liver biopsy you're supposed to do liver biopsy again let's come back now I'll ask you a question if a patient come to you there's a patient who comes to you and patient is having right patient is having sere itching there young female sere itching some zenas conjugated hyperemia right no urobilinogen lot of bbin Uria Dark urine light stool what type of jundas is this obstructive jundas

as alt are mildly raised and alkaline phosphates five nucleotide a and Gamma glut transfer are severely raised so what is this obstructive jundas now in this patient obstructive jundas when you do ultrasound in this lady common bile duct is not dilated is that right if you do some autoimmunity profile you find anti mitocondrial antibodies very high what do you think anti mitochondrial Antibodies are associated with primary build SES autoimmune process which attack the B system is that right another case patient come and patient is very much pale and jundas pale mean hemoglobin is low and

eus mean yellow color is there right and patient has strong history of blood transfusions previously due to he has been receiving blood transfusion due to Sphere sphere anemia is that right his spine is a light kum's test is positive against the obes it means obes are qued with ATI bodies is that right unconjugated buin is 5 .5 mgram per DL right with little increase in total eurogen in the urine is more than normal stool is dark colored EST alt normal proin time normal serum Al normal alkaline phosphat is normal ultrasound shows normal ductal system and

ductal Anatomy what do you Think this a extravascular hysis because spinali was there it was extravascular hysis now I will ask one more question if a patient has come to you and patient has complained of listen carefully patient has sphere anorexia nausea low gr fever with upper hypochondria pain for many days patient has developed jundas in which total blin is high conjugated is also High un conjugated is also High there's mild to Moderate increase in alkaline phosphates serum Aline phosphatase and Gamma gluty transferase and ggt and five nucleotide is and there's very high stlt what's

wrong with ittis there's hepatitis and in this patient uh you find that hepatitis B B surface antigen is positive as well as hepatitus b e antigen the Positive what is what is diagnosis by now very clear acute we cannot say is it acute chronic if it is less than 6 months it must be considered acute if it is more than 6 months then it must be considered chronic is that right because in hepatitus cut of point is that evidence of liver injury is less than 6 months or more than 6 months if it is less

than 6 months it should be considered acute and if markers of liver injury or history is Showing problem related with the LI is more than 6 months then it is chronic is that clear okay I'll give you one more case patient is brought to you and patient has severe weight loss severe anemia the severe abdominal pain right especially radiating backward patient has pale color strw Andoria dark colored urine no eurogen there a alt slightly raised caline phosph is very much raised conjugated blin very much raised now what it is obstructive but there are special things

I've said there's old man in this case there's old man number one number two this very significant weight loss number three there's severe pain in the abdomen radiating backward very good carcinoma of head of Pancreas cancer of head of pancreas but if same patient having lot of ult blood appearing into into feal matter then it is probably carcinoma of empl is that clear any question here any question no question CL