HARBANS LAL - cbspd.co.in

HARBANS LAL PhD, FIAO, FACBI, FSOBSI

Former Senior Professor & Head, Department of Biochemistry,Maharaja Agrasen Medical College, Agroha (Hisar), Haryana, India

Former Sr. Professor, PGIMS, Rohtak, Haryana, IndiaEx WHO Fellow

CBS Publishers & Distributors Pvt Ltd• New Delhi • Bengaluru • Chennai • Kochi • Kolkata • Lucknow • Mumbai • Hyderabad • Nagpur • Patna • Pune • Vijayawada

Second Edition

It gives me pleasure to present the second edition of the book “Essentials of Biochemistry for BSc Nursing Students”. Contents of the syllabus have been divided into 18 chapters. In addition, chapter 19 though not in the syllabus, has been included so that the students of nursing become well aware about the details of sample collection and normal biochemical values of the common parameters. A major goal continues to provide the book to the students of BSc Nursing, that describes and illustrates the basics of biochemistry in a concise but interesting manner. All the chapters have been thoroughly revised and updated. A large number of new figures and tables, exhibiting the significance of biochemistry in nursing, have been added in each chapter. This edition has further been thoroughly revised and updated by adding many relevant clinical correlations, which have been provided in the boxes, at several places. Other important information from the point-of-view of the students has also been highlighted on different pages. All possible efforts have been made to make it error-free, however suggestions and feedback from all the readers are welcome for further improvement of the book and shall be taken care in the subsequent edition of the book. I am highly thankful to the faculty and the students of various Nursing Colleges for their feedback and helpful suggestions. I want to thank Mr Satish Kumar Jain (Chairman) and Mr Varun Jain (Managing Director) and his entire team from CBS Publishers & Distributors Pvt. Ltd., New Delhi, especially the members of the Nursing Knowledge Tree including Mr Bhupesh Aarora [Sr. Vice President – Health Science Division (Publishing and Marketing)] and Ms Nitasha Arora (Publishing Head & Content Strategist) for the help rendered in bringing out this edition of the book in a short time.

HARBANS [email protected]

Preface to the Second Edition

I am extremely delighted to present the Essentials of Biochemistry for BSc Nursing Students. This book has been written with a major goal to provide a book to the students of nursing that describes and illustrates the basics of biochemistry in a concise and interesting manner. All the chapters have been written keeping in mind the recommended INC syllabus and needs of the students. A large number of figures and tables exhibiting the significance of biochemistry in nursing have been added in each chapter. Many relevant clinical correlation boxes at various places have been added to help the students correlate the basics of the subject with a clinical point of view. The important information from student point-of-view has also been highlighted in boxes. I am highly thankful to the faculty and the students of nursing for their feedback, suggestions and help for my previously written book “Biochemistry for BSc Nursing Students”. Mr SK Jain and his team from CBS Publishers & Distributors Pvt. Ltd., New Delhi, deserve special mention for their helpful suggestions and bringing out this book in a very short time.

HARBANS [email protected]

Preface to the First Edition

Placement: First Year Time: Theory-30 Hours

Course Descriptions: The Course is designed to assist the students to acquire knowledge of the normal biochemical composition and functioning of human body and understand the alterations in biochemistry in diseases for practice of nursing.

Unit Time (Hrs)

Objective Content Teaching Learning Activities

Assessment methods

I 3 • Describe the structure Composition and functions of cell

• Differentiate between Prokaryote and Eukaryote cell

• Identify techniques of Microscopy

Introduction • Definition and

significance in nursing • Review of structure,

Composition and functions of cell

• Prokaryote and Eukaryote cell organization

• Microscopy

• Lecture discussion using charts, slides

• Demonstrate use of microscope

• Short answer questions • Objective type

II 6 • Describe the Structure and function of Cell

Structure and functions of cell membrane

• Fluid mosaic model tight junction, Cytoskeleton

• Transport mechanism: diffusion, osmosis, filtration, active channel, sodium pump

• Acid base balance-maintenance & diagnostic tests

• PH buffers

• Lecture discussion


Syllabus for BSc Nursing

Essentials of Biochemistry for BSc Nursing Studentsxii

Unit Time (Hrs)


Assessment methods

III 6 • Explain the metabolism of carbohydrates

Composition and metabolism of carbohydrates

• Types, structure, composition and uses

� Monosaccharides, Disaccharides, Polysaccharides, Oligosaccharides

• Metabolism � Pathways of glucose:

� Glycolysis � Gluconeogenesis: Cori’s cycle, Tricarboxylic acid (TCA) cycle

� Pentose phosphate pathways (Hexose mono phosphate)

� Regulation of blood glucose level

Investigations and their interpretations


• Demonstration of blood glucose monitoring


IV 4 • Explain the metabolism of Lipids

Composition and metabolism of Lipids

• Types, structure, composition and uses of fatty acids

� Nomenclature, Roles and Prostaglandins

• Metabolism of fatty acid � Breakdown � Synthesis

• Metabolism of triacylglycerols

• Cholesterol metabolism � Biosynthesis and its

Regulation � Bile salts and bilirubin

� Vitamin D � Steroid hormones

• Lipoproteins and their functions:

� VLDLs-IDLs, LDs and HDSs

� Transport of lipids � Athrosclerosis,


• Lecture Discussion using charts

• Demonstration of laboratory tests


Syllabus for BSc Nursingxiii

Unit Time (Hrs)


Assessment methods

V 6 • Explain the metabolism of Amino acids and Proteins

Composition and metabolism of Amino acids and Proteins

• Types, structure, composition and uses of Amino acids and Proteins

• Metabolism of Amino acids and Proteins

� Protein synthesis, targeting and glycosylation

� Chromatography � Electrophoresis � Sequencing

• Metabolism of Nitrogen � Fixation and

Assimilation � Urea Cycle � Hemes and

chlorophylls • Enzymes and co-

enzymes � Classification � Properties � Kinetics and

inhibition � Control



• Demonstration of laboratory test


VI 2 • Describe types, composition and utilization of Vitamins & minerals

Composition of Vitamins and minerals

• Vitamins and minerals: � Structure � Classification � Properties � Absorption � Storage &

transportation � Normal concentration



• Demonstration of laboratory tests


Essentials of Biochemistry for BSc Nursing Studentsxiv

Unit Time (Hrs)


Assessment methods

VII 3 • Describe Immu-nochemistry

Immunochemistry • Immune response, • Structure and

classification of immunoglobins

• Mechanism of antibody production

• Antigens: HLA typing. • Free radical and

Antioxidants • Specialised Protein:

Collagen, Elastin, Keratin, Myosin, Lens Protein.

• Electrophoretic and Quantitative determination of immunoglobins– ELISA etc.



• Demonstrate laboratory tests


Preface to the Second Edition ................................................................................................................................................................... iiiPreface to the First Edition ......................................................................................................................................................................... vSyllabus for BSc Nursing ............................................................................................................................................................................ xi

Section 1 Introduction

Chapter 1 Introduction to Biochemistry and its Significance ....................................................................... 3

Section 2 Structure and Functions of Cell

Chapter 2 The Cell ......................................................................................................................................................... 7

Chapter 3 Structure and Functions of Cell Membrane .................................................................................... 18

Chapter 4 Transport Mechanisms ........................................................................................................................... 25

Chapter 5 Cytoskeleton .............................................................................................................................................. 36

Chapter 6 pH, Buffers and Acid Base Balance ..................................................................................................... 40

Chapter 7 Enzymes and Coenzymes ...................................................................................................................... 50

Section 3 Composition and Metabolism of Carbohydrates

Chapter 8 Chemistry and Metabolism of Carbohydrates ............................................................................... 69

Section 4 Composition and Metabolism of Lipids

Chapter 9 Chemistry and Metabolism of Lipids ................................................................................................ 111

Section 5 Composition and Metabolism of Proteins

Chapter 10 Chemistry and Metabolism of Amino Acids and Proteins ......................................................... 151

Chapter 11 Protein Synthesis ...................................................................................................................................... 185

Chapter 12 Metabolism of Heme ............................................................................................................................... 209

Contents

Essentials of Biochemistry for BSc Nursing Studentsxvi

Section 6 Vitamins, Minerals, Electrolytes and Water

Chapter 13 Vitamins ....................................................................................................................................................... 221

Chapter 14 Minerals........................................................................................................................................................ 250

Chapter 15 Water and Electrolytes ............................................................................................................................ 262

Section 7 Immuno chemistry and Specialized Proteins

Chapter 16 Immunochemistry ................................................................................................................................... 273

Chapter 17 Free Radicals and Antioxidants ........................................................................................................... 293

Chapter 18 Specialized Proteins ................................................................................................................................. 296

Section 8 Clinical Chemistry

Chapter 19 Sample Collection and Reference Values......................................................................................... 307

Index ............................................................................................................................................................................................................... 317

Hemoglobin is a globular protein, which is present in high concentration in red blood cells. It binds oxygen in the lungs and transports it to different cells in the body. A molecule of hemo globin consists of four heme groups along with the four polypeptide chains, which are synthesized separately and subsequently, bind to four heme groups.

SYNTHESIS OF HEMEHeme consists of one atom of ferrous iron (Fe2+) and a tetrapyrrole ring, called proto porphyrin IX. It is synthesized from eight residues of glycine and succinyl CoA (Fig. 12.1). In the biosynthesis of heme, some of the reactions occur in mitochondria while others in the cytosol.

• In the first step, succinyl CoA condenses with glycine and forms δ-aminolevulinic acid (ALA), in the mitochondria.

This reaction is catalyzed by the enzyme δ-aminolevulinic acid synthase (ALA synthase), which requires pyridoxal phosphate (PLP) as a coenzyme. This is the rate limiting step of heme synthesis.

Increased levels of ALA synthase, along with the reduced levels of some enzymes of the heme biosynthetic pathway, result in a group of disorders referred to as porphyrias.

• In the next step, two molecules of δ-amino levulinic acid condenses, asymmetrically and form porphobilinogen.

This reaction is catalyzed by the enzyme aminolevulinic acid dehydratase (ALA dehydratase).

Fig. 12.1. Synthesis of heme.

Metabolism of Heme

Chapter

12

Essentials of Biochemistry for BSc Nursing Students210

ALA dehydratase is a zinc-containing enzyme, which occurs in the cytosol. It consists of eight subunits, four of which inter act with the substrate.

ALA dehydratase is sensitive to heavy metals parti-cularly, lead. ALA levels increase in lead poisoning.

• Porphobilinogen undergoes deamination, by the enzyme porphobilinogen deaminase (hydroxymethylbilane synthase or uro porphy-rinogen I synthase) and is converted to a linear tetrapyrrole, called hydroxy methyl bilane.

Decreased activity of porphobilinogen deaminase along with the increased activity of ALA synthase results in a condition called acute intermittent porphyria.

• Spontaneously, with ring closure, hydroxy-methylbilane is converted to uroporphy rinogen I.

Alternatively, uroporphyrinogen III synthase converts hydroxymethylbilane to uroporphy-rinogen III (Fig. 12.2).

Only, type I and type III isomers are found in nature. Porphyrins having symmetric arrange-ment of the substituent groups on four pyrrol rings are designated as type I while those having asymmetric substitutions are referred to as type III porphrinogens (Fig. 12.3).

Under normal conditions, uro porphyrinogen formed is, almost exclusively, type III.

Heme is also a type III porphyrin (Fig. 12.4). Abnormality of the reticulocyte uro porphyrinogen

III synthase causes an inherited disease called erythropoietic porphyria. It is associated with marked cutaneous light sensitization and increased synthesis of uroporphyrinogen I and copro-porphyrinogen I in the bone marrow.

Fig. 12.2. Conversion of porphobilinogen to uroporphyrinogens during heme synthesis.

Fig. 12.3. Type I and type III uroporphyrinogens.

Fig. 12.4. Heme – A type III porphyrin.

Chapter 12 Metabolism of Heme211

• Uroporphyrinogen I and III are converted to the respective copro porphyrinogens by the enzyme uro porphyrinogen decarboxy lase.

Iron salts inhibit uroporphyrinogen decarboxy lase. Genetic deficiency of uroporphyrinogen decarboxylase leads to a disease, known as porphyria

cutanea tarda, which shows cutaneous manifestations, primarily, sensitivity to light. The manifestation is expressed in patients who take drugs that cause an increase in porphyrin synthesis or in individuals who consume large amount of alcohol. This, in turn, leads to accumulation of iron, which further inhibits uroporphy rinogen decarboxylase.

• In the next reaction, copro porphyrinogen III enters the mitochondria and is converted to protoporphyrinogen IX. This reaction is catalyzed by the enzyme copro porphy rinogen oxidase, which requires molecular oxygen. This enzyme does not act on coproporphyrinogen I.

(These porphyrins are identified as IX since they were designated ninth in a series of the postulated isomers.)

Inherited deficiency of the enzyme coproporphyrinogen oxidase leads to a form of the hepatic porphyria, known as hereditary coproporphyria.

• Protoporphyrinogen oxidase acts on protoporphyrinogen IX and converts it to protoporphyrin IX, in the mitochondria.

Protoporphyrin IX is water insoluble. Its excessive amounts are excreted by the biliary system into the intestinal tract. Deficiency of the enzyme, protoporphyrinogen oxidase, leads to a condition called variegate porphyria.

• In the final step of heme synthesis, ferrous iron (Fe2+) is incorporated into proto porphyrin IX. This reaction is catalyzed by the enzyme ferrochelatase, which requires some reducing substances.

This enzyme is sensitive to heavy metals, especially lead. It is also sensitive to iron deprivation. Inherited deficiency of the enzyme ferro chelatase results in a disease, referred to as hereditary protoporphyria.

Regulation of Heme Biosynthesis

ALA synthase occurs in two forms. These are called hepatic (ALA-S1) and erythrocytic (ALA-S2) enzymes. ALA-S1 controls the rate-limiting step of heme synthesis. Further, heme acts both, as a repressor of synthesis of the enzyme as well as its inhibitor.

Clinical Correlation

Porphyrias

Porphyria is due to abnormality in the pathway of heme biosynthesis. It may be genetic or acquired. Six major types of porphyrias have been described, five of which are inherited as autosomal dominant (Table 12.1).


TABLE 12.1. Derangement in porphyrin metabolism in different types of porphyrias

Porphyria Enzyme defect Major symptoms Laboratory findings

Acute intermittent porphyria

Increased ALA synthase, decreased porphobilinogen deaminase

Abdominal pain, neuropsychiatric symptoms

Urinary porphobilinogen (+)

Erythropoietic porphyria Decreased uropor-phyrinogen III synthase

No photosensitivity Porphobilinogen (-), uroporphyrin (+)

Porphyria cutanea tarda Decreased uropor-phyrinogen decarboxylase

Photosensitivity Porphobilinogen (-), uroporphyrin (+)

Hereditary coproporphyria Increased ALA synthase, decreased coprophyrinogen oxidase

Photosensitivity, abdominal pain, neuropsychiatric symptoms

Urinary porphobilinogen (+), urinary uroporphyrin (+), fecal protoporphyrin (+)

Variegate porphyria Increased ALA synthase, decreased coproporphyrinogen oxidase

Photosensitivity, abdominal pain, neuropsychiatric symptoms

Urinary porphobilinogen (+), fecal protoporphyrin (–)

Hereditary protoporphyria Decreased ferrochelatase Photosensitivity Fecal protoporphyrin (–), red cell protoporphyrin (+)


Hemoglobinopathies

Patients with unstable hemoglobin develop hemoglobinopathies with characteristic features, such as anemia, reticulocytosis, splenomegaly and urobilinuria. Hemoglobinopathies are a hetero geneous group of single gene disorders.

A mutant gene may result in the substitution of one amino acid, in one type of the polypeptide chain, by another amino acid, or loss of one or more amino acid residues of a polypeptide chain. This, in turn, results in the formation of structurally abnormal hemoglobin. In some cases, the change may be clinically insignificant while in others it may cause a serious disease. The most common hemo globinopathy is sickle cell disease.

Hemoglobin C: Hemoglobin C is another variant of HbA1 where glutamic acid, normally present at the sixth position of the β-chain of HbA1, gets replaced by lysine. This, in turn, results, in the formation of aggregates and reduces survival time for red blood cells. This form of hemo globino pathy exhibits more limited pathological effects and is commonly found among certain black African population.

Sickle Cell Anemia

Sickle cell anemia or sickle cell disease is a hereditary blood disorder, characterized by red blood cells that assume an abnormal, rigid, sickle shape (Fig. 12.5).

This is a consequence of point mutation. Red blood cells of such individuals have hemoglobin S (HbS), which differs from that of the normal adult hemoglobin (HbA1) with respect to only one amino acid in their β-chains, i.e. glutamic acid normally present at the sixth position of the β chain of HbA1 gets replaced with valine in HbS. This is due to a change in a single nucleotide within the codon (from GAA or GAG, which code for glutamic acid, to GUA or GUG, which code for valine). Fig. 12.5. Altered shape of RBCs in sickle cell anemia.


HEME BREAKDOWNRed blood cells have limited life span of approximately 100-120 days. These senescent cells are recognized by their membrane changes, removed and engulfed by the reticuloendothelial system, at the extravascular site. Degradation of red blood cell occurs in spleen, bone marrow, liver and lymph glands. Degradation of heme occurs mainly, in the liver. If degradation of red blood cells occurs in the tissues other than the liver, hemoglobin is trans ported to the liver by means of hapto globulin. After the aged red blood cells are recognized by macrophages, they are rapidly engulfed by the phagocytes and form phagosomes. They fuse with the primary lysosomes and form secondary lysosomes. Lysosomal cathepsin results in complete degradation of the cellular proteins, including globin of hemoglobin, to the constituent amino acids, which are utilized for general metabolic needs. Heme is degraded in the reticulo endo thelial cells, to a linear tetrapyrrole (biliverdin IXa), by the microsomal enzyme system, which is designated as heme oxygenase. This enzyme requires molecular oxygen and NADPH, and is induced by heme. Heme oxygenase catalyzes the cleavage of α-methenyl bridge which is quantitatively converted to carbon monoxide (CO) that is trapped by the hemoglobin and eventually exhaled. Biliverdin is reduced to bilirubin by the enzyme biliverdin reductase (Fig. 12.6). One gram of hemoglobin yields about 35 mg of bilirubin.

Bilirubin

Bilirubin is an orange-yellow pigment, derived from the breakdown of red blood cells in the liver, spleen and bone marrow. Its daily production, in men, averages from 250-300 mg. Approximately, 85% of this is derived from the heme moiety of hemoglobin, which is released from the erythrocytes that are destroyed in the reticuloendothelial cells while rest of it is formed from catabolism of other heme containing proteins, such as myoglobin, cytochromes and other heme containing enzymes. Bilirubin, normally present in the blood, is bound to albumin and is transported to the liver. Hepatocytes trap bilirubin by means of a specific binding protein, called ligandin. In the hepatocytes, bilirubin gets conjugated with UDP-glucuronate, which is derived from the oxidation of UDP-glucose. This reaction is catalyzed by UDP-glucuronyltransferase (Fig. 12.7). Fig. 12.7: Conjugation of bilirubin.

Fig. 12.6. Breakdown of hemoglobin.

Clinical Correlation contd...

This missense mutation results in a mutant gene, which is present in homo zygous state and results in sickle cell disease. Such a mutation is mostly seen in some Blacks, (in some parts of the world), particularly where malaria is widespread. Hemoglobin S though can bind and release oxygen but abnormally. Heterozygous individuals do not exhibit symptoms of sickle cell anemia except under extreme conditions of hypoxia, due to the reason that such individuals have 50% of HbA1 and 50% of HbS in their red blood cells.


In the normal bile, bilirubin diglucuronide is the major form of excreted bilirubin with only a small amount of the bilirubin monoglucuronide. As bilirubin diglucuronide is much more water soluble than free bilirubin, transferase thus facilitates the excretion of bilirubin, via bile duct, into the intestine. As bilirubin diglucuronide is poorly absorbed by the intestinal mucosa, glucuronide residues are released in the terminal ileum and large intestine, by intestinal β-glucuronidases and by the enzymes produced by anaerobic bacteria. It is reduced to colorless linear tetra pyrroles, called stercobilinogen, mesobilinogen and urobilinogen. These compounds are collectively referred to as urobilinogens. A large portion of urobilinogens are excreted in the feces. Majority of these re-circulating pigments are taken up by the liver and re-excreted in the bile. Some of the urobilinogens (only up to 2%) are also reabsorbed passively from the colon and return to the liver via the portal venous blood. This is referred to as entero hepatic circulation (Fig. 12.8). Most of the reabsorbed urobilinogen is taken up by the liver and is re-excreted in the bile. A small portion of urobilinogen (2–5%) however, escapes hepatic extraction, reaches the peripheral circulation and is excreted in the urine. Serum thus contains two different forms of bilirubin, which are referred to as:

• Unconjugated (lipid soluble) form that is bound to albumin and is transported from the reticuloendothelial system to the liver, and

• Conjugated (water soluble) form which is regurgitated from the liver into the plasma. Normal value, for the sum of the unconju gated and conjugated forms, is 0.1–1.0 mg/100 ml of serum or plasma. Normally, almost all the bilirubin in plasma is unconjugated. Disorders of bilirubin metabolism lead to hyperbilirubinemia where serial measurement of bilirubin is helpful in knowing the severity of a liver disease. Bilirubin fractionation is also helpful in differential diagnosis of jaundice.


Thalassemias

Thalassemia is a family of related genetic disorders that arise due to the deletion of one or more globin-like genes in either the globin gene cluster or a defect in trans cription, and/or processing of mRNA of the globin gene. If there is reduced synthesis or total lack of synthesis of α-globin mRNA, the disease is classified as α-thalassemia. On the other hand, if β-globin mRNA level is affected, it is called β-thalas-semia.

One to four α-globin genes may be missing in the patients with α-Thalassemia. If one α-globin gene is missing, the condition is called α-Thalassemia 1 (α-thal 1). When two α-globin genes are missing, it is called α-thal 2. Both the conditions are associated with mild to moderate anemia. On the other hand, if three α-globin genes are missing it results in the synthesis of more β-globin molecules, forming a tetramer containing four β-globin sub-units. This condition is called HbH disease. When all the four α-globin genes are absent, it results in a fatal condition called hydrops fetalis.

β-Thalassemias also exhibits different degree of severity and can be caused by a variety of defects or deletions.


Fig. 12.8. Metabolism of bilirubin.


Jaundice

Jaundice is a physical sign characterized by yellow appearance of the patient and is a most characteristic clinical manifestation of hyper bili rubinemia. It results from the deposition of bilirubin (bile pigment) in the skin, mucous membrane and sclera of the patient (Fig. 12.9).

Jaundice is apparent clinically, when serum bilirubin level is more than 2 mg/dL. If serum bilirubin is below 2 mg/dL, it is called latent jaundice (subclinical jaundice) since it is not detect able at this stage, clinically.

There are three types of jaundice, referred to as pre-hepatic, hepatic and post-hepatic jaundice. Fig. 12.9. Sclera of the patient in

jaundice



Biochemical differentiation of the three types of jaundice is given in Table 12.2

TABLE 12.2. Differential diagnosis of different types of jaundice based on various biochemical tests

Biochemical parameter

Type of Jaundice

Pre-hepatic Hepatic Post-hepatic Serum bilirubin ↑↑ ↑↑ ↑↑

Type of bilirubin Unconjugated Both Conjugated

Urine urobilinogen ↑↑ − / ↑ ↓ / −

Urine bile pigments – – ↑

Stercobilinogen ↑ ↓ ↓ / −

SGPT/SGOT (mainly SGPT) N ↑↑↑ ↑

Serum alkaline phosphatase

N ↑ ↑↑↑

Serum 5′-nucleotidase N ↑ ↑↑↑

Prothrombin time (PT) N ↑ ↑

Prehepatic Jaundice

Pre-hepatic jaundice is also called hemolytic jaundice. It is characterized by the excessive presence of unconjugated bilirubin. It may be a result of increased production of unconjugated bilirubin such as in hemolysis, decreased uptake of unconjugated bilirubin across the hepatocyte membrane as in Gilbert’s syndrome, or decreased biotransformation such as in neonatal jaundice, Criggler-Najjar syndrome, etc.Hemolysis: In disorders associated with hemolysis (hemolytic anemia), rate of bilirubin production is increased, which may exceed the amount that cannot be removed by the liver.Gilbert’s syndrome: This is a heterogeneous group of disorders inherited as autosomal recessive trait. Several defects include the deficiency of bilirubin glucuronyltransferase, a defect in hepatic uptake of bilirubin, or a decrease in red cell survival.Neonatal jaundice: Neonatal jaundice is also called physiological jaundice of the newborn. Every infant exhibits some transient unconjugated hyperbilirubinemia (about 5 mg/dL) between the second and the fifth day of life, as at this stage hepatic glucuronyltransferase activity is not fully developed. Activity of the enzyme increases within 2 weeks after birth when serum bilirubin returns to normal.Neonatal jaundice is more pronounced in a premature infant.Unconjugated bilirubin levels above 18 mg/dL lead to deposition of bilirubin in the lipid-rich basal ganglia. This is referred to as kernicterus.Criggler-Najjar syndrome: This disorder is known to exist in two forms:Type I: It is clinically more severe form of the disease. It is due to complete absence of glucuronyl transferase.

Type II: It has moderate clinical findings and is due to partial deficiency of the enzyme. In both the conditions unconjugated bilirubin is significantly raised.

Hepatic Jaundice

Hepatic jaundice is due to a primary disease. Plasma, usually, shows elevated levels of both conjugated as well as unconjugated bilirubin, e.g. in viral hepatitis, liver cirrhosis, etc. There is also an increase in SGOT and SGPT levels.Elevated levels of conjugated as well as unconjugated bilirubin along with the dark-brown pigmentation, in the liver cells, is also observed in a benign, autosomal recessive condition known as Dubin-Johnson syndrome.



Inhalation, ingestion or parenteral administrations of several pharmacological and chemical agents, such as carbon tetrachloride, acetaminophen, isoniazid or chlorpromazine, which result in liver injury, also lead to hepatic jaundice.

Posthepatic Jaundice

Post-hepatic jaundice is also referred to as obstructive jaundice or post-hepatic cholestasis. It is caused by obstruction of the bile duct, may be due to gallstones, carcinoma of the head of pancreas or carcinoma of the bile duct. Serum of such a patient shows excessive amount of conjugated bilirubin. It is also characterized by the presence of the excessive amount of bilirubin (bile pigment) in the urine.

Assess Yourself

Long and Short Answer Questions 1. Describe the process of heme synthesis. How it is

regulated? 2. What is porphyria? Describe various types of

porphyrias. 3. Describe the process of heme degradation.

4. Write notes on: a. Hemoglobin S b. Sickle cell anemia c. Hemoglobinopathies d. Thalassemias e. Jaundice

1. Heme is which porphyrin a. Type I b. Type II c. Type III d. Type IV 2. Bilirubin glucuronide in the urine in the absence

of Urobilinogen suggests a. Hemolytic jaundice b. Hepatocellular jaundice c. Obstructive jaundice d. None of the above 3. Rate limiting enzyme in heme synthesis a. ALA synthase b. ALA dehydratase c. Heme synthase d. Coproporphyrinogen oxidase

4. Which of the following amino acid is required for synthesis of hemoglobin?

a. Alanine b. Glycine c. Arginine d. Histidine 5. Amino acid associated with first step in

formation of Heme is a. Histidine b. Glycine c. Alanine d. Lysine 6. Which of the following is correct about

breakdown of hemoglobin (Hb)? a. Hb-Heme-bilirubin-urobilinogen b. Heme-Hb-biliverdin-bilirubin-urobilinogen c. Hb-Heme-biliverdin-bilirubin-urobilinogen d. Hb-Heme-bilirubin-urobilinogen-biliverdin

Multiple Choice Questions

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