⭐⭐JAUNDICE ⭐⭐

               ⭐⭐ JAUNDICE ⭐⭐

1) DEFINITION OF JAUNDICE :

    # Jaundice is yellowish discoloration of

      skin, mucous membrane and sclera 

      due to increased bilirubin.

    # Sclera is yellow because it contains

       large amount of elastin which has high

       affinity for bilirubin.

    # Normal bilirubin = 0.5 - 1.2 mg/dl

       Clinically evident jaundice -

       when bilirubin > 2.5 mg/dl

 ⭐ NOTE ⭐- 

           # Urobilinogen is colourless. It gets

            converted to urobilin which is 

            yellow coloured.

           # Bilirubin - yellow

            coloured

           # Conjugated bilirubin - water 

            soluble

           # Unconjugated bilirubin - not water

             soluble.

                           ⭐⭐⭐⭐

2) NORMAL BILIRUBIN METABOLISM :-

                    Red cell lysis

                             |

                        Haeme

                             |

         Bilirubin ( indirect or unconjugated)

                             |

                 Binds to albumin

                             |

                   Goes to liver

                             |

         Bilirubin is separated from albumin

                             |

                  Conjugation

                             |

           Bilirubin glucuronide 

         ( Conjugated or direct bilirubin)

                             |

     Goes to intestine through bile duct

                             |

     In the colon, colonic bacteria                         deconjugate the bilirubin and convert

     it into urobilinogen

                            |

     A part of urobilinogen is reabsorbed 

     into blood and carried to liver through

     portal vein ( enterohepatic circulation)

     Some amount of it is recycled for bile

     production ,while the remaining amount

     reaches the kidney where it is

     converted into urobilin and excreted

     in urine.

                             |

     Remaining part of urobilinogen present

     in the intestine which is not reabsorbed,

     is converted directly to stercobilin or 

     first into Stercobilinogen and then into

     stercobilin by Intestinal bacteria.

     This stercobilin gives colour to faeces.

                         ⭐⭐⭐⭐

3) CLASSIFICATION OF JAUNDICE ON THE BASIS OF PATHOLOGY CAUSING JAUNDICE :- 

    (a) Hemolytic jaundice - 

        (I) It is caused due to increased

           hemolysis of RBCs - increased 

           bilirubin production.

        (II) Hepatocellular jaundice - 

            It occurs due to problem in liver 

            cells which affects the function of

            conjugation of bilirubin.

       (III) Cholestatic / obstructive / surgical

            jaundice - There is obstruction to

            the flow of conjugated bilirubin into

            the gut. This leads to backflow of

            bilirubin into the bloodstream .

                          ⭐⭐⭐⭐

4) HEMOLYTIC JAUNDICE :- 

    (a) It is caused due to increased

        hemolysis of RBCs. Large amounts of

        unconjugated bilirubin is produced.

        Liver is normal. Hence, it will 

        conjugate as much as possible even if

        not able to conjugate the whole 

        bilirubin.

        Therefore, as net conjugation

        increases, production of urobilinogen

        and stercobilinogen also increases.

    (b) Causes of Hemolytic jaundice :- 

        (I) Intraerythrocytic causes:- 

            # Sickle cell anemia - presence of

               abnormal sickle hemoglobin i.e 

               HbS leads to hemolysis.

               ( Mutation - glutamate is replaced

               by valine.)

            # Thalassemia - reduced or absent

               synthesis of globin chain leading

               to abnormal Hb and hemolysis.

           # Hereditary spherocytosis - 

               Mutation in red cell membrane

               protein - spherical RBCs are 

               formed which makes it difficult

               for them to pass through the

               spleen causing their hemolysis.

           # G6PD deficiency :- 

              G6PD enzyme causes production

               of NADPH in RBCs by HMP shunt.

               NADPH causes production of 

               reduced glutathione which 

               neutralizes oxygen free radicals.

               G6PD deficiency causes free 

               radical damage to RBCs.

            # Vit B12 and folate deficiency- 

               They convert homocysteine to

               methionine. Deficiency leads to

               hyperhomocysteinemia &

               increased hemolysis.

        

      (II) Extraerythrocytic causes:-

           # Antibodies - Autoimmune & 

           isoimmune hemolytic anaemia.

           # Malaria - Malarial parasite causes

           lysis of RBCs.

           # Prosthetic heart valve - Hemolysis

           due to turbulent flow through valve.

           # Drugs - Dapsone.(Hemolysis due 

           to generation of free radicals by its

           metabolite)

           Sulfasalazine.

           #Paroxysmal nocturnal 

           hemoglobinuria - there is lack of a

          protein CD55 on the surface of RBCs

           which protects them from body's

           immune response.

    (c) Clinical features of Hemolytic 

        jaundice:-

       (I) Pallor - due to hemolysis

       (II) Jaundice - due to increased

           unconjugated bilirubin in the blood.

       (III) Hepatosplenomegaly -

            Due to increased work of liver

            (Conjugation) and Splenomegaly

            due to increased workload of 

            of spleen (RE cells -                                        reticuloendothelial cells) of                            destroying the damaged RBCs

            damaged RBCs.

       (IV) STOOLS - DARK COLOURED -

            due to increased stercobilinogen 

             because of increased bilirubin

             entering the liver.

       (V) URINE - DARK YELLOW - due to

             increased urobilinogen.

      

   (d) Investigations of hemolytic

         jaundice:-

       (I) Serum bilirubin - Increased. 

         (Unconjugated hyperbilirubinemia)

       (II) Urine bilirubin - absent.

         (Unconjugated bilirubin is present in

          blood but it is not water soluble.

          Hence, it doesn't enter the kidney)

        (III) Urine  urobilinogen- increased.

         (due to increased amount of bilirubin

          reaching the liver for conjugation)

        (IV) Liver function tests.

        (V) Evidences of hemolytic anemia -

          Peripheral blood smear.

                       ⭐⭐⭐⭐

5) HEPATOCELLULAR JAUNDICE:-

   (a) It occurs due to problem in liver cells

    which affects the function of 

   conjugation.

   (b) Causes of hepatocellular jaundice:-

       (I) Viral hepatitis.

       (II) Chronic hepatitis.

       (III) Alcoholic hepatitis.

       (IV) Cirrhosis.

       (V) Drug induced hepatitis- Isoniazid,

       Rifampicin, Erythromycin.

   

   (c) In this case, both unconjugated & 

   conjugated hyperbilirubinemia is 

   present.

   Unconjugated - Ability of hepatocytes

   to conjugate bilirubin is impaired due to

   disease. Therefore, unconjugated 

   bilirubin accumulates in the blood.

   Conjugated - Some conjugation occurs

   in cells which are normal but destruction

   of hepatocytes causes spill over of 

   conjugated bilirubin into blood. Also,

   small intrahepatic bile canaliculi may be

   destroyed due to inflammation causing

   entry of conjugated bilirubin into blood.

     (d) STOOL COLOUR - NORMAL

     Not darker because net conjugated 

     bilirubin reaching the gut is decreased 

     because of damage to liver. Therefore,

     stercobilinogen production decreases.

     Not pale as in case of obstructive 

     jaundice because there is no complete 

     obstruction to the flow of conjugated

     bilirubin into the gut unlike the case of

     obstructive jaundice.

    (e) URINE COLOUR - DARKER

    because even if net urobilinogen 

    production is decreased as very less            conjugated bilirubin enters intestine

    conjugated bilirubin entering the blood        is increased due to damaged blood              vessels & it is excreted through the 

    kidney as it is water soluble & yellow

    coloured.

                         ⭐⭐⭐⭐

6) CHOLESTATIC JAUNDICE/ 

OBSTRUCTIVE JAUNDICE/ SURGICAL

JAUNDICE:-

    (a) There is obstruction to the flow of

    conjugated bilirubin into the intestine.

    It can be at the level of intrahepatic

    smalll ducts or extrahepatic ducts.

    Conjugated bilirubin doesn't enter the

    intestine. Therefore, urobilinogen & 

    stercobilinogen are not formed - PALE

    CLAY COLOURED STOOLS.

    But, URINE IS DARK because there is 

    backflow of conjugated bilirubin into

    the blood which is excreted into the

    urine. (Conjugated bilirubin is water

    soluble & yellow coloured)

   

   (b) causes of cholestatic jaundice:-

       (I) Intrahepatic duct obstruction:-

          # Drugs, Alcohol - Damage to ducts.

          # Chronic hepatitis, cirrhosis.

          # Viral hepatitis.

          # Primary Biliary Cirrhosis.

          # Severe bacterial infection.

          # Secondaries in liver.

          # Ulcerative colitis - Release of

          inflammatory agents in the colon & 

          their absorption into enterohepatic 

          circulation - sclerosing cholangitis.

          # Pregnancy - Elevated estrogen &

          progesterone may affect the proper 

         functioning of liver & gall bladder.

         # Total parentral nutrition - The 

         intestinal epithelial barrier function

         is lost because of bacterial 

        overgrowth due to deprivation of 

        enteral nutrition. These bacteria 

        in intestine release endotoxins

        which enter the liver through portal

        system & cause cholangitis & 

        cholestasis.

       # Hodgkins lymphoma - Hepatic &

       biliary infiltration by cells of lymphoma

       # Hypotension - may cause liver

       ischemia.

      # Granulomatous infections- TB, 

       Sarcoidosis - inflammation & fibrosis

       causes obstruction.

      

    (II) Extrahepatic duct obstruction:-

        # Carcinoma of bile duct, head of 

       pancreas, Ampulla of Vater.

       # Gall stones.

       # Stricture of bile duct.

       # Helminths in Common Bile Duct.

       # Sclerosing Cholangitis.

       # Choledochal cyst, Biliary atresia

       # External compression by lymph

          nodes or tumor

     (III) Inborn diseases:-

        # Benign Recurrent Intrahepatic 

        cholestasis.

        # Progressive Familial Intrahepatic

        cholestasis.

     

    (c) Symptoms of cholestatic jaundice:-

       (I) Jaundice - Conjugated bilirubin 

       enters blood.

       (II) Fever - In case of Cholangitis.

       (III) Clay coloured stools. (explained 

        above)

       (IV) Dark Urine.

       (V) Bone pain - Vitamin D3 is

        hydroxylated to 25 OH Vitamin D3 in

        liver. Loss of this function causes 

        bone pain.

       (VI) Haemorrhagic manifestation -

       Liver produces coagulation factors.

       Loss of this function causes

       Hemorrhagic manifestations.

       (VII) Abdominal pain - Stasis of bile

       causes spasm of Biliary apparatus

       leading to pain. Other cause- liver

       enlargement may stretch glisson's

       capsule rich in nerves.

       (VIII) Weight loss - due to

        malabsorption because of absence of

        bile in intestine.

       (IX) Pruritus - increased bile salts 

       cause nerve irritation. 

       Mast cells release histamine causing

       itching.

       (X) Steatorrhoea - fatty stools - bile is

       required for digestion of fats.

       Decreased bile in intestine impairs

       digestion of fats - fatty stool

       (XI) Vitamin deficiency - fat soluble 

       Vitamin K, E, D, A are not absorbed due

       to absence of bile.

    (d) Signs of cholestatic jaundice:-

        (I) Jaundice.

        (II) Scratches on skin.

        (III) Xanthoma - Cholesterol deposits

        on tendons - cholesterol is normally 

        secreted in bile. In obstructive 

        jaundice, the cholesterol doesn't 

        enter intestine due to obstruction &

        hence blood cholesterol increases.

        (IV) Xanthelasma- Yellowish deposits

        of cholesterol under skin of eyelids.

        (V) Secondary Biliary Cirrhosis.

        (Late feature)

        (VI) Signs of liver cell failure.

        (Late feature)

        (VII) Enlargement palpable Gall

        bladder due to bile accumulation -

        In case of Carcinoma of head of

        Pancreas.

   

    (e) Investigations of cholestatic 

    Jaundice:-

        (I) Urine bilirubin - Increased -

        conjugated bilirubin which enters the

        blood is excreted through kidney.

        (II) Urine urobilinogen- Absent - As 

       conjugated bilirubin doesn't enter 

       intestine.

       (III) Serum bilirubin- increased - 

       Conjugated hyperbilirubinemia.

       (IV) USG , CT.

       (V) ERCP & MRCP - obstruction,

        stricture

       (VI) PTC (Percutaneous Transhepatic

       Cholangiography)

       (VII) Liver biopsy.

       (VIII) Liver function tests.

       (IX) Prothrombin time - increased

       (X) Tumor markers- CA 19/9 - for 

         carcinoma of pancreas

       (XI) Urine test- Hays test, fouchets test

       (XII) Endoscopic ultrasound

                      ⭐⭐⭐⭐⭐

7) CLASSIFICATION OF JAUNDICE ON THE

BASIS OF FAULT IN BILIRUBIN 

METABOLISM:- 

    (a) Predominantly Unconjugated

     hyperbilirubinemia:-

        (I) Increased production of bilirubin:

           # Hemolysis.

           # Ineffective erythropoesis.

           # Reabsorption of hematoma.

        (II) Decreased bilirubin uptake by

        liver:

           # congestive heart failure - blood 

           supply to the Liver is decreased.

          # Portosystemic shunting- Liver is

          bypassed.

         # Sepsis.

         # Drugs like Flavaspidic acid - z

         protein increases net bilirubin uptake

         by binding to it. Flavaspidic acid

         inhibits z protein.

     (III) Decreased conjugation of bilirubin:

         # Gilbert syndrome- Mutation of UGT

         enzyme - UDP Glucoronosyl 

         Transferase. This enzyme helps in               glucuronidation.

         # Criggler Najjar Syndrome- Mutation

         in gene that codes for UGT.

         # Acquired dysfunction of UGT- 

         Cirrhosis & hepatitis.

    (b) Predominantly Conjugated 

     hyperbilirubinemia:-

       (I) Intrahepatic:-

          # Dubin Johnson syndrome-

          Mutation in gene coding for protein

          which causes transport of 

          conjugated bilirubin from 

          hepatocytes into biliary canaliculi.

          # Rotor's syndrome- Mutation in

          genes that code for proteins that 

          transport bilirubin from blood into

          liver. As a result, bilirubin is less

          effectively taken by liver.

         # Benign Recurrent Intrahepatic

         cholestasis.

         #Cholestatic jaundice of pregnancy.

         # Acquired cholestasis - Cirrhosis,

         hepatitis, drug induced.

     

     (II) Extrahepatic :-

         # Bile duct stones.

         # Carcinoma of stricture of bile duct.

         # Carcinoma head of pancreas.

                    ⭐⭐⭐⭐⭐⭐⭐⭐