52. Types of Bilirubin
Free bilirubin Conjugated bilirubin
1 In H₂ O insoluble soluble
2 In alcohol soluble soluble
3 Normal plasma levels 0.2 mg /dl 0.2 -0.8 mg /dl
4 In bile Absent present
5 In urine Always absent Normally absent ( present in
hemolytic & Obstructive jaundice )
6 Absorption from GIT Absorbed Not Absorbed
7 Diffusion in tissue Diffuses to cause yellow Dose not diffuse
8 Van der Bergh Test Indirect positive direct positive
63. Erythroblastosis Fetalis
• Serum Bilirubin à > 20 mg/dl à no more bound to Albumin
• Bilirubin Brain (Kernicterus-deposition of bilirubin in brain )
• Basal ganglia à mental retardation
• ↓ ATPase mitochondria à fits ,spasticity ,toxic encephalitis
• Treatment : (1) phototherapy before age < 1 year à
isomerization ZZ à ZE
(2 ) Blood transfusion
64.
65.
66.
67.
68.
69.
70.
71.
72. Hepatocellular Jaundice
1. Viral Hepatitis (viruses A ,B,C,D or G )à pure hepatocellular
diseases
2. ↓ conjugated bilirubin therefore ↑free Bilirubin
3. Inflammatory odema of cells à intracellular canalculi compressed
à obstruction ( at site of bile formation )
4. Increase obstruction à ↑ obstructionà ↑conjugated Bilirubin
therefore Biphasic
5. Bilirubinuria
6. UrobilinogenàNORMAL or decreased in hepatocellular Jaundice
73. Obstructive Jaundice à conjugated Hyperbilirubinemia
1. ↑ conjugated bilirubin
2. Bilirubin in urine
3. ↓ urobilinogen ( nil if obstructive is complete )
4. Faeces clay color (↓ stercobilinogen )
5. Absence of bile salts à Stetorrhoea may result
6. Causes I Intrahepatic Cholestasis
a) Active hepatitis
b) Biliary cirrhosis
c) Lymphomas
d) Hepatoma
e) Viral hepatitis
95. Congenital Hyperbilirubinemia
vDubin Johnson’s syndrome
a) Autosomal recessive trait
b) ↑ conjugated bilirubin in blood
c) Defect in excretion of conjugated Bilirubin( ATP ase dependent
organic anion Transporter protein-MOAT mutation
d) Defect ATP dependent organic anion transport in bile canalculi
e) Bilirubin gets deposited in liver therefore Bilirubin gets deposited in
liver ( Black Liver Jaundice )
f) Diagnostic Test : Bromosulphthalein Test
129. Effect of drugs on ALA synthase activity
1. *Phenobarbital
2. * Insecticides ↑ activity of ALA synthase
3. * Carcinogen
* Metabolized by HEME containing protein cytochrome 450
↓
Increased in corporation of Heme in cytochrome 450
↓
↓ cellular level of Heme
↓
↑ ALA synthase ( de repression ) to meet cellular demands
149. 1. Acute intermittent Porphyria
• Age : after puberty (Artist –Vincet , King George III –MAD )
• Deficient enzyme : Uroporphyrinogen synthase I ( ↑ ALA –no feed back
mechanism )
• No porphyria ,no photosensitivity
• Excretion in urine : δ aminolevilinate (ALA ) & porphobilinogen ( PBG )
• Exposure of porphobilinogen ( PBG ) to air darkens ( formation of
Porphobilin )
• Diagnosis : urinary conc of PBG (darkens on exposure to air )
• Symptoms : Abdominal pain ,Vomiting ,cardiovascular abnormalities
,neuropsychiatric disturbances ( therefore ↓ Trp pyrrolase , ↑ Trp,
5 ʹOH Tyramine
• Treatment : Hematin à↓ ALA , ↓ PBG
• Adverse effects : Barbiturate ( ppt of attack )à ↑ ALA synthase (as
cytochrome 450 )àPBG↑, increase with carbohydrate diet & menopause
150.
151. 2. Congenital erythropoietin Porphyria
vCongenital
vDeficient enzyme : ↓ Uroporphyrinogen co synthtase III
• Excretion in urine : Uroporphyrinogen I & Coporphyrinogen Ià
↓ oxidation ↓
Uroporphyrin I & CoporphyrinI
Symptoms :
1.↑ Hemolysis
2. Erythrodontia ( teeth ) ,port wine color urine
3. Exposure OF SKIN à UV sensitization of porphyrin à absorbed & emit red
fluorescent light
4. Dermatitis ,scarring burning & itching of skin- ear & nose ( Leprosy like ),(as ROS ↑
à accumulation of Porphyrin )
5. port wine color urine (Uroporphyrin I & CoporphyrinI )
167. Anemia
• 75 % Indian population suffer from anemia
• Hb concentration decreases in anemia <10gm%
( normal concentration of blood Hb – 14-16 mg% -male ,13-15 mg% -female )
vI Iron Deficiency anemia –most common
a) Nutritional
b) Lack of absorption of Iron ( Gastrectomy & Achlorhydria)
c) Hookworm infection ( 0.3ml/ day / hookworm )
d) Repeated pregnancy ( ↓hemoglobin -1gm per delivery )
e) Nephrosisà Glomerular filtration →proteinuria
f) Loss of Haptoglobin /Hemopexin / Transferrin
g) Heavy metal poisoning
h) Loss of blood ( menustrual cycle , piles , peptic ulcers, Uterine hemorrhages )
170. Hemin crystals
• Fe²⁺ ↔ Fe³⁺ à Fe³⁺ + Cl⁻ à Hematin chloride or HEMIN
vMedical legal cases
• Blood + Blood stains + Nippe ’s fluid
( 1% KCL + KBr + KI + Glacial acetic acid à dark brown RHOMBIC crystal
à microscopic inspection
Heme part of Blood à Test positive
174. Sulph Hemoglobinemia
• Oxy –Hb + H₂ S à Sulph –Hb ( absorption peak at 620nm)
vFormation of Sulph –Hb by sulphonamide ,Phenacetin , Dapsone ,Acetone
vBasophilic striping of RBC
←Irreversible
175.
176. Abnormal Hb or Hb variants
1.Sickle syndrome
a) 1. sickle cell trait ( AS )
b) 2. sickle cell disease with SS ,SC,SD ,SO ,Sβ Thalassemia
2.Unstable Haemoglobins
Congenital Heinz body anemia –Hb Zurich
3. Hb with abnormal oxygen affinity
A. High affinity à Polycythemia (familial ) à Hb Chesapeake ,Olympia
B.Low affinity à Cyanosis (familial ) à Hb M, Hb –Kansas, Hb- Hoppe
4. Structural variation leading to Thalassemia's phenotype
A. Alpha Thalassemia à Hb Constant spring ,Delta beta Thalassemia, Hb –
Lepore
B. Beta Thalassemia: Hb Quong
C. 5.Hemoglobin that donot produce any clinical symptoms: HbP HbQ ,HbJ
177.
178. SICKLE CELL DISEASE
vCharacteristics of Sickle cell disease
a) Glutamic acid à Valine (6th position on beta chain)
b) Hydrophilic à Hydrophobic ( stickiness on surface of molecule )
c) Polymerization of Hb in RBC àdistortion of RBC into sickle shaped
d) Deoxy HbS has protrusion on one side & cavity on other sideà
many molecules adhere together
203. Abnormal Hb or Hb variants
III Hemolytic anaemias due to intra -corpuscular defect
a) Hemoglobinopathies : HbS ,Hbc , HbM
b) Thalessemias : major & minor
c) Abnormal shape spherocytosis & elliptocytosis
d) Enzyme deficiency à Glucose 6 Phospho dehydrogenase
IV Hemolytic anemia due extra corpuscular cause /defects
a) Infection –malarial parasites ,streptococcus
b) Autoimmune Hemolysis –RBC membrane component ,Syphilis,
Lympholenticular neoplasia
c) Isoimmune hemolysis à Rh incompatibility in Newborn
d) Hemolysis due to drug sensitization –Dopa quinone ( fixed on RBC )à
Abnormal antibodies against altered membrane