BIOCHEMISTRY

Finals Conference Topics

1st Semester
HMP SHUNT
G-6-PD DEFICIENCY
Case Report:
Patient Information:
 Name: R.D.
 Age: 26 yrs. old
 Gender: Male (African Descent)

History of Present Illness:

1 week PTA: R.D. developed signs of respiratory infection, low-grade fever,
and self-medicated with over-the-counter cold preparation

1 day PTA:
 Chills
 Hacking Cough
 Temperature: 40.6oC
 Dyspneic ROLE OF G-6-PD IN HMP SHUNT:
 The pentose phosphate pathway is regulated primarily at the G6PD
Physical Examination: reaction
 Slight icterus  Glucose 6-phosphate dehydrogenase (G6PD) catalyzes an irreversible
 Bronchial breathing over the left lower lung fields with scattered oxidation of glucose 6-phosphate to 6-phosphogluconolactone
rales
FIVE CLASSES OF MUTATIONS INVOLVING G-6-PD:
Vital Signs:
 Temperature: 40oC LEVEL OF
CLASS ENZYME ACTIVITY PREVALENCE
DEFICIENCY
 Pulse: 120 bpm
Severely deficient that they Uncommon;
 Moderate degree of dyspnea
I Severe produce hemolysis even in the occurs across
absence of stress populations
G-6-PD Deficiency
Varies; more
 Heritable, X-chromosome linked abnormality
Severely deficient but in common in
 Xq28 II Severe which a stress is required to Asian and
 Disease characterized by hemolytic anemia caused by the inability precipitate hemolysis Mediterranean
to detoxify oxidizing agents population
 Affects more than 400m individuals worldwide Mildly deficient with
intermittent hemolysis 10 % of black
III Moderate
Symptoms: usually associated with males in the U.S
 Hemolytic anemia infection or drugs
 Jaundice IV Mild to none
Not deficient but may be
Rare
 Dark Urine considered as genetic markers
 Fatigue Increased activity compared
V None Rare
to normal
 Pale Skin Color
 Rapid Heart Rate
ROLE OF GLUTATHIONE IN HEMOLYTIC ANEMIA IN PATIENTS WITH G6PD
 Shortness of Breath
DEFICIENY:

HEXOSE MONOPHOSPHATE SHUNT

(Pentose Phosphate Pathway)
 Also called Warburg-Dickens pathway
 An alternative route for the metabolism of glucose
 Does not lead to the production of ATP
 Occurs in the cytosol
 Two major functions:
1. The formation of NADPH
2. The synthesis of Ribose
 Consist of an irreversible Oxidative phase and a reversible Non-
oxidative phase
 No G-6-PD  no HMP shunt  no NADPH  no reduced glutathione
 increase H2O2 in RBC  decreased lifespan of RBC  increased
hemolysis  Hemolytic anemia

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DRUGS THAT PARTICIPATE IN G-6-PD DEFICIENCY: BIOCHEMICAL REACTIONS UNDERGONE BY GALACTOSE:
Antimalaria Antipyretic Antibiotics A. Conversion to Glucose
Primaquine Acetanilid Furazolidone
Nalidixic acid Niridazole
Nitrofurantoin
Sulfacetamide
Thiozolesulfone
Sulfamethoxazole
Phenylhydrazine

MALARIA
 Caused by Plasmodium parasites
 Grow and replicate in the red blood cell
 G6PD deficiency causes hemolytic anemia thus malaria cannot thrive

Diagnostic Tests
B. Becomes parts of Lactose and other Galactolipids
 Newborn screening for glucose-6-phosphate dehydrogenase
deficiency can be done
 Rapid fluorescent spot test detecting the generation of NADPH from
NADP
(+) : blood spot fails to fluoresce under ultraviolet light

Case Report Continuation:

Laboratory Findings:
Laboratory Test Result Normal Value
Hgb 8.4 g/dL >14 g/dL C. Oxidized as source of Energy
WBC 18,000/uL 5,000-10,000/uL
Bilirubin 3.2 mg/dL 0.1-0.5 mg/dL
Reticulocyte 1.2% <1%

 Diagnosis: Pneumococcus Pneumonia

 Medication: Penicillin

Laboratory Findings after Treatment:

Laboratory Test Result
Hgb 7.2 g/dL
Reticulocyte 12%

 Sputum and Blood Test: (+) Pneumococci

 PE: Afebrile and Less Pronounced Dyspnea
 Health Professionals advised the patient never to take aspirin again
and avoid certain chemicals and drugs. Thus, the patient never
experienced further hemolytic episode

GALACTOSEMIA
GALACTOSE
 Epimer of glucose at Carbon 4 GALACTOSEMIA:
 It is classified as a monosaccharide, and aldose, a hexose, and is a  It is a disorder that affects how the body processes a simple sugar
reducing sugar called galactose
 It is more commonly found in the disaccharide, lactose or milk sugar  An inborn error of metabolism which is associated with impairment
in the metabolism of galactose (autosomal recessive)
 Recognized and diagnosed in newborns. Most common biochemical
defects are a deficiency:
o Galactokinase (Galactosemia II)
o Galactose 1-phosphate uridyl-transferase
(Galactosemia I)
 Accumulation of primary substrates which are then converted to
toxic metabolites (e.g. galactitol, galactonic acid – manifest clinically
in newborn and infants as cataracts)

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TYPES OF GALACTOSEMIA DIAGNOSIS OF GALACTOSEMIA
Type of Galactosemia Deficient Enzyme Clinical Manifestation 1. Prenatal Testing – not done routinely; invasive methods
Cirrhosis Mental  Chronic Villus Sampling
GALT
I
(Galactose-1-PO4-
Retardation  Amniocentesis – ultrasound guided; with family methods
(Classical) Hypoglycemia
uridyl transferase)
Renal dysfunction 2. Newborn Screening – detects low levels of GALT enzyme; if positive do
GALK confirmatory test which are highly specific
II Cataract Formation
(Galactokinase)
GALE
Severe neurologic 3. Galactose-1-phosphate uridyl-transferase (GALT) test:
III (UDP-galactose-4’-
problems (Seizures)  Fluorimetric detection
epimerase)
 Abnormal –reduced or no fluorescence
GALACTOSEMIA TYPE I (GALT)  No enzymatic activity
 Accumulation of galactose and galactose-1-phosphate in tissues  Sensitive to heat  FALSE POSITIVE
 Cirrhosis and mental retardation  Prior blood transfusion  FALSE NEGATIVE
 ↑ blood galactose = ↓ hepatic output of glucose (hypoglycemia)
4. Total Galactose Test:
 Inhibition of amino acid transport
 Total galactose levels are determined using either fluorometric or
GALACTOSEMIA TYPE II (GALK) colorimetric metabolite assays to detect accumulation of blood
galactose
 Galactokinase deficiency
 These test methods are dependent upon lactose consumption
 Galactose accumulates in the blood and tissues
 In the lens, galactose is converted by aldose reductase to galactitol,
TREATMENT:
a sugar to which the lens is impermeable
 Diet- eliminate galactose
 As a consequence, excessive hydration occurs, together with
 Special diet – lower the blood galactose levels
decrease in glutathione in lead, leads to cataract formation
 No medications available that lower galactose levels
 For young babies – changing from breast milk or milk-based infant
formula that contains little or no galactose
 Supplements: Calcium and Vitamin D – milk is a source of calcium
and needed for the absorption of Vitamin D

Tolerance of Galactose-containing products:

 Adults tend to lessen intake of milk as they grow old and there is
increase in indigenous galactose production which is the only source
of galactose – production in small amounts leads to tolerance

GLYCOGEN STORAGE DISEASES

GLYCOGENESIS
 Intracellular synthesis of glycogen occurring chiefly in the liver and
the muscles
 Glucose-6-phosphate is converted to glucose-1-phosphate, which is
then converted to uridine diphosphoglucose and then to glycogen
by glycogen synthase
 Glucokinase: phosphorylation – addition of a PO4 group to glucose
 Phosphoglucomutase: epimerization – transfers the PO4 group
carbon 6 to carbon 1
 Glycogenin: a self-glucosylating protein which has a catalytic activity;
reactive site is the OH group of tyrosine residues – forms an O
glycosidic linkage. STIMULUS: depletion of glycogen
 Glycogen synthase: catalyze the incorporation of glucose molecule
from UDPGlc
 α-1,4 glycosidic bond: non-reducing end = Carbon 4
 Repeating disaccharide molecule in glycogen: maltose at α-1,4
 Disaccharide molecule at α-1,6 – ISOMALTASE
 Branching Enzyme: elongation of the chain which involves the
incorporation of glucose molecules at the non-reducing end

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GLYCOGENESIS Explanation: Taglish
In glycogenolysis, magbabawas ka naman ng glucose.
Removing at α-1,4, using the enzyme phosphorylase
Kapag 4 nalang natitira, pwede magtanggal ng 3 at one time. An enzyme that
can transfer a trisaccharide is glucan transferase, that will expose the
branching points. And then you remove glucose at the branching points by
the debranching enzyme.
You will remove glucose as Glucose 1-phosphate

HORMONAL REGULATION OF GLYCOGENOLYSIS AND GLYCOGENESIS

Insulin:
Explanation: Taglish  Anabolic hormone
Glycogenesis starts with a glycogen primer  Promotes the storage of glucose into glycogen
Glycogen is a highly branched molecule. Merong part na nagbr-branch,
 Also promotes converting glucose intro triacylglycerides and the
merong part na straight. There are 2 linkages in glycogen. Sa straight chain
α-1,4 …. Sa branching points α-1,6 storage of triacylglycerides in the adipose tissue
 Also promotes the protein synthesis in skeletal muscle
In glycogenesis, pinapahaba mo yung branch. Dadagdagan mo muna sa α-  Activates glycogen synthase which promotes glycogenesis
1,4 add at least 11 units. Kapag mahaba na, pwede na gumawa ng bagong
branch. Enzyme that will add glucose to α-1,4 is glycogen synthase. Pag Glucagon:
gagawa ka ng bagong branch, you can transfer a minimum of 6. The enzyme  Acts to maintain glycose availability in the absence of dietary glucose
that will do that is the branching enzyme. So sa glycogenesis, alternate lang. by stimulating the release of glucose from the liver
Add glucose to α-1,4 tapos add branches sa branching points, then ulit.  Stimulates glycogenolysis and gluconeogenesis
 Also activates the mobilization of fatty acids from the adipose tissue
You don’t add glucose directly. You have to activate it first before adding it to
the glycogen primer. Activated form of glucose is UDP-glucose
Epinephrine:
GLYCOGENOLYSIS  Is another hormone that is released in response of the central
nervous system once it is under stress
 Intracellular degradation of glycogen
 Stimulates glycogenolysis and release of fatty acids from adipose
 It is not the reverse of glycogenesis. It is a separate pathway – uses a
tissue
different set of enzymes (irreversible)
 Glycogen Phosphorylase – starts to remove glucose molecules at α-
MECHANISM OF HORMONE ACTION:
1,4 non-reducing end
1. If the substrate concentration is rate limiting, then hormones may
o Glucose residues are liberated one by one from the non-
alter the concentration of the substrate to increase or decrease the
reducing end, with the subsequent addition of a
rate of flux
phosphate group forming Glucose-1-PO4 : this process is
2. Hormones may promote the reversible phosphorylation of the flux
called Phosphorolysis (cleaving at α-1,4 and adding a
controlling enzymes to change the conformation of the enzyme’s
catalytically active PO4 group)
active site either activating or deactivating the enzyme
o Required Pyridoxal Phosphate as coenzyme
3. Hormones may promote the dephosphorylation of the flux
 The terminal glucosyl residues from the outermost chains of the
controlling enzymes
glycogen molecule are removed sequentially until approximately four
4. Hormones can affect the concentrations of allosteric effectors
glucose residues remain on either side of α16 branch
5. Hormones can induce or repress genes to change the amount of
 The debranching enzyme has two catalytic sites in a single
enzyme present in the cell
polypeptide chain
 One is a glucan transferase that transfers a trisaccharide unit from
INSULIN GLUCAGON EPINEPHRINE
one branch to the other, exposing the 16 branch point
Effect on cAMP Inhibits Stimulates Stimulates
 The other is a 1,6-glycosidase that catalyzes hydrolysis of the 16
Blood sugar Decreases Increases Increases
glycosidic bond to liberate free glucose Glycogenolysis Inhibits Stimulates Stimulates
Glycogenesis Stimulates Inhibits Inhibits
GLYCOGENOLYSIS Glycogen
Stimulates Inhibits Inhibits
synthase

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Glycogenesis (in green boxes) & Glycogenolysis (in blue boxes) Accumulation of
glycogen in
lysosomes

Infantile:
hypotonia, muscle
weakness, cardiac
enlargement and
Type II
Lysosomal acid failure, fatal early
Pompe’s Generalized
maltase
Disease
Juvenile and
adult: progressive
skeletal muscle
and atrophy,
proximal muscle
and respiratory
muscle are
seriously affected
Treatment: Nocturnal ventilator support in late-onset patients improves the
quality of life and is beneficial during a period of respiratory decompensation
Aglucosidase alfa (Myozyme)
Childhood:
Hepatomegaly,
growth
retardation,
muscle weakness,
hypoglycemia,
GLYCOGEN STORAGE DISEASES OVERVIEW hyperlipidemia,
elevated liver
transaminases,
Type III Debranching Liver, Heart,
liver symptoms
Cori’s Disease Enzyme Muscles
improve with age

Adulthood:
Muscle atrophy
and weakness.
Onset: third to
fourth decades;
variable
cardiomyopathy
Treatment: Frequent high carbohydrate meals with cornstarch supplements
or nocturnal gastric drop feedings. High protein diet during daytime plus
overnight protein enteral infusion
ENZYME ORGANS CLINICAL
TYPES Failure to thrive,
DEFICIENT INVOLVED MANIFESTATIONS
progressive liver
Inability to Muscle pain and
cirrhosis, portal
forma a weakness or
Type 0 hypertension,
complex sugar episodes of
ascites,
called glycogen fainting
Type IV esophageal
Hypoglycemia, Branching Liver and other
Andersen’s varices, liver
lactic acidosis, Enzyme organs
Disease failure; Death due
Type I hepatomegaly, to cardiac or liver
Glucose 6 Liver, Kidney,
Von Gierke’s hyperuricemia failure usually
Phosphatase Intestines
Disease with gouty before fifth year;
arthritis, some without
hyperlipidemia progression
Treatment: Continuous nasogastric infusion of glucose or uncooked starch, Treatment: No specific treatment
restricted dietary intake of fructose and galactose, dietary supplements of
Painful muscle
multivitamins and Calcium Type V Muscle
Skeletal cramps, exercise
McArdle’s Glycogen
muscles intolerance,
Disease Phosphorylase
increased CK
Treatment: Oral administration of glucose or fructose or injection of
glucagon. High protein diet; avoidance of strenuous exercise

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Hepatomegaly, ACQUIRED IMMUNODEFICIENCY SYNDROME
growth
Type VI retardation, high
Liver Glycogen AIDS
Her’s Liver glycogen content
Phosphorylase  Most extreme case of immune suppression
Disease in liver, tendency
towards  When a person’s immune system is too weak to fight off many
hypoglycemia infections
Fatigue and pain  Human Immunodeficiency Virus (HIV) is the virus that causes AIDS
with exercise,  Loss of immune competence
maybe  Infection of organism that are not usually pathogenic
Type VII associated with  Results of the progression of HIV (last stage)
Tarui’s Phosphofructokinase Muscle nausea and
Disease vomiting;
Human Immunodeficiency Virus
compensated
hemolysis;  Genus: Lentivirus (lenti = lengthy)
hyperuricemia  Family: Retrovirus; contains RNA as its nucleic acid
Treatment: No specific treatment. Avoidance of strenuous exercise prevents  Unique enzyme, reverse transcriptase (viral RNA  DNA)
acute attacks of muscle cramps and myoglobinuria  Species: HIV-1 and HIV-2
Hepatomegaly,  Spherical
Liver Phosphorylase
accumulation of  100 to 200 nm
Type VIII Liver glycogen in the  Inner core with two copies of ssRNA
Kinase
liver, mild
hypoglycemia

EASY TO REMEMBER TABLE 

ENVELOPE MATRIX CORE

Gp120: bind to CD4 in Capsid protein, p24: Two single-strand RNA
human cells HIV’s RNA genome is (ssRNA)
kept
Gp41: helps initiate Three polymerase
membrane fusion Matrix protein, p17: (Reverse transcriptase,
GLYCOGEN STORAGE DISEASE DIAGNOSIS:
between the virus and structural function Integrase and
 Glycogen storage disease is usually diagnosed in infancy or childhood the cell Polymerase)
as a result of the above symptoms. If your child’s doctor suspects a
glycogen storage disease, he or she will ask about your child’s
symptoms and medical history, then perform a physical exam. The
doctor will perform tests to rule out or confirm the diagnosis. These
tests may include:
o Biopsy of the affected organs
o Blood and urine sample
o MRI scan

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HIV GENES: Steps in HIV Life Cycle:
 Binding/Attachment: cell affected are T-helper cells/CD4+ cells
 Fusion
 Reverse Transcription
 Integration
 Replication
 Assembly
 Budding

gp120 – binding protein

gp40 – fusion protein
Integrase – enzyme used to integrate and insert ssRNA to the nucleus
CXCR4 – coreceptor

ROUTES OF INFECTION:

Three Main Genes:

 Gag – forms the building block of viral core
 Pol – main retroviral genes
 Env – encodes a single protein gp160

Accessory Genes:
 Tat: p14 – activates transcription of HIV proviral genes
 Reve: p19 – transport viral RNA out of the nucleus
 Nef: p27 – modification of host cell to enhance viral replication and
make it less likely to be destroyed
 Vif: p23 – for “virion infectivity factor”
 Vpr: p15 – helps integrate synthesized DNA into the nucleus
 Vpu: p16 – helps in assembly of new virus particles; helps them to
bud from the host cell

HIV LIFE CYCLE:

Note: Memorize the CD4 Cell count for each stage

DIAGNOSTIC TESTS
 Antibody Tests: ELISA
 Antigen Tests
o P24 antigen Test
 Nucleic acid based tests

INFECTION MONITORING TESTS

 CD4 Count: indicates –
o Strength of the immune system
o Stage of HIV infection
o Treatment guide
 Viral Load Test
o Number of HIV virus particles in the body (“copies”)
o Indicates –
 Show how well your HIV treatment is
controlling the virus, and
 Provide health information on your health
status

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ANTI-RETROVIRAL THERAPY
JAUNDICE
 HIV regimen
 Does not kill the virus, can’t cure HIC
 Slow or prevent progression from one stage to the next HEME CATABOLISM
 Can dramatically reduce the chance of transmitting HIV to someone  Heme is broken down by
else Heme Oxygenase
 CO, Fe, & Biliverdin
NUCLEOSIDE AND NUCLEOTIDE REVERSE TRANSCIPTASE INHIBITORS  Biliverdin is reduced by
(NRTIs) – competitive inhibition of reverse transcriptase Biliverdin Reductase
 Unconjugated bilirubin 
NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) – direct binds Albumin
binding to reverse transcriptase; impair polymerization activity  Liver  Conjugated bilirubin
 Excreted into Bile Duct 
PROTEASE INHIBITORS – selective binding to viral proteases; blocks cleavage enters intestine and
of protein precursors converted into Urobilinogen
 Stercobilin in stool & Urobilin
ENTRY INHIBITORS (FUSION INHIBITORS) – interferes with the binding, in urine
fusion, and entry of an HIV virion to a human cell  Heme: Principally derived
from Hgb, but also from
INTEGRASE INHIBITORS – blocks the action of integrase ineffective Erythropoeisis and
from catabolism
COMBINATION HIV MEDICINE – combination of at least three (3)  Conversion of one mole of
Antiretroviral Drugs from different classes heme-Fe3+ to biliverdin,
WHO Recommendation: CD4 count less than 500/uL carbon monoxide and Fe3+
consumes three moles of O2,
Pre-exposure Prophylaxis (PrEP) plus seven electrons provided
 Daily dose of TRUVADA (TENOFOVIR + EMCITRABINE) – drug by NADH and NADPH-
approved by the DFA for PrEP cytochrome P450 reductase
 Maximum concentration is reached after 20 days of daily dosing  Biliverdin Reductase: in
 Physicians may require assessment of HIV negative status after 1 human, reduces central
month of initial treatment methylene bridge of biliverdin
to methyl group
 Follow-up is usually after 3 months
 Bilirubin Reductase: NADPH –
 Follow-up after 12 months to evaluate need to continue PrEP
dependent enzyme

Post-exposure Prophylaxis (PEP)

BILIRUBIN CATABOLISM
 Initiated within 72 hours 1. Hepatic Uptake
 Less or not effective after 72 hours  Bilirubin is removed from
 Use of Zidovudine album
 Current combinations that may reduce the risk further:  Facilitated transport
o Lopinavir/Ritonavir  Ligandin (Glutathione-S-
o Lamivudine/Zidovudine transferase) – prevents
o Emtricitabine/Tenofovir bilirubin from re-entering
o Treatment duration: 4 weeks the bloodstream
o Follow up after 3 months and 6 months 2. Conjugation
 Conversion of bilirubin to
bilirubin diglucoronide
 Non-polar to polar
 UDP glucoronyl transferase
3. Secretion
 Active transport
 2 Transporters:
 MOAT (Multispecific
Organic Anion Transporter)
 MRP2 (Multidrug Resistance
Protein 2)

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Unconjugated Bilirubin Conjugated Bilirubin  Viral hepatitis group of infections – Hepa A, Hepa B, Hepa C
Present normally in plasma Present normally in bile  Alcoholic liver disease
Attached non-covalently to bile Conjugated to glucuronic acid  Leptospirosis – a bacterial infection that’s spread animals particularly
High Molecular Weight and cannot Small Molecular Weight and if rats
be filtered through the kidney present in plasma can be filtered  Glandular fever – a viral infection caused by the Epstein-Barr virus
through the kidney  Drug misuse
Non-Polar Polar  Primary biliary cirrhosis – a rare condition that causes progressive liver
Insoluble in plasma and can cross Soluble in plasma and cannot cross damage
BBB in neonates causing brain BBB  Crigler-Najjar Syndrome – a genetic syndrome where an enzyme
damage (glucoronyl transferase (UDPGT)) needed to help move bilirubin out of
the blood and into the liver is missing
JAUNDICE o Type I – Total absence; total absence of B2 production;
 Jaundice came from the French word, “Jaune” meaning Yellow or presence of kernictus; colorless bile
“Jaunice” meaning Yellowness o Type II – partial absence’ small
 Jaundice is the yellowing discoloration od the skin, mucous  Gilbert’s syndrome – a common genetic syndrome where the liver has
problems breaking down bilirubin at a normal rate
membranes, nailbeds and sclera
o Bilirubin transport deficit
 But for the sclera (which is the white part of the eye), it has a different
o Characterized by impaired cellular uptake of bilirubin
term known as “Icterus” (Greek term) o Mostly on young adults (20-30 yrs. old)
 Which is also considered as the earliest sign in increased Bilirubin in o Affected individuals may have no symptoms but may have
the blood because the scleral tissue is high in elastin giving bilirubin mild icterus
its high affinity for it o Lab result: Elevated B1 (< 3 mg/dL)
 Jaundice is not a disease but a symptom of an underlying disorder  Liver cancer
 So, if you experience such, this signifies that you have a primary  Exposure to substances known to be harmful to the liver – example is
problem within your body that is causing Jaundice phenol (used to manufacture plastic) or carbon tetrachloride (widely
 Jaundice is experienced if there is an increased bilirubin levels in the used in the past in processes such as refrigeration, although now its use
blood, either Unconjugated or Conjugated is strictly controlled)
 Autoimmune Hepatitis – a rare condition where the immune system
 Jaundice will not usually manifest until they reach a certain level of
starts to attack the liver
increased bilirubin in the blood. In this case, the levels should be
 Primary Sclerosing Cholangitis – a rare type of liver disease that causes
above or greater than 2 mg/dL and in some books I’ve read it should
long-lasting (chronic_ inflammation of the liver
be above 3 mg/dL  Dublin-Johnson syndrome – a rare genetic syndrome where the liver is
unable to move bilirubin out of the liver
CAUSES OF JAUNDICE:
o Bilirubin excretion deficit
- Dysfunction of the normal metabolism or excretion of bilirubin. This disruption
o Blockage of the excretion of bilirubin into the canaliculi;
in the metabolism or excretion of bilirubin can occur at various stages: caused by hepatocyte membrane defect and hereditary
A. Pre-hepatic – the problem arises before secretion to the liver disorders
B. Hepatic – the problem arises within the liver o Intense dark pigmentation of the liver due to the
C. Post-hepatic – the problem arises after bilirubin is excreted from the accumulation of lipofuscin pigment
liver o Lab result: Elevated B2 and total bilirubin

A. Pre-hepatic: Disorders of Metabolism and Diseases resulting in Hepatocellular

 It is a jaundice cause by anything which causes an increased rate of Transporter injury or destruction
hemolysis (breakdown of RBC). Unconjugated bilirubin comes from - Criggler-Najjar Syndrome - Hepatitis
the breakdown of the Heme pigment found in RBC’s hemoglobin. The - Dublin-Johnson Syndrome - Liver Cirrhosis
increased breakdown of RBC leads to an increase in the amount of - Gilbert’s Syndrome - Liver Cancer
unconjugated bilirubin present in the blood and deposition of this - Physiologic Jaundice of NB
Increased Unconjugated Bilirubin Increase Conjugated Bilirubin
unconjugated bilirubin into various tissues can lead to a jaundiced
- Physiologic Jaundice of the NB - Dublin-Johnson Syndrome
appearance
- Criggler-Najjar Syndrome - Rotor Syndrome
- Gilbert’s Syndrome
 Excess production of bilirubin: Hemolysis
 Ineffective erythropoiesis C. Post-Hepatic
 Spherocytosis: RBC Membrane defect
 Post-hepatic jaundice, also called obstructive jaundice, is caused by
 Sepsis: Oxidative stress
an interruption to the drainage of bile containing conjugated
 G6PD Deficiency: Erythrocyte enzyme defect
bilirubin in the biliary system
 In complete obstruction of the bile duct, no urobilinogen is found in
B. Hepatic:
the urine, since bilirubin has no access to the intestine and it is in the
 Intra-hepatic jaundice happens when there is a problem in the liver
intestine that bilirubin gets converted to urobilinogen to be later
– example, damage due to infection or alcohol, disrupts the liver’s
released into the general circulation. In this case, presence of
ability to process bilirubin
bilirubin (conjugated) in the urine without urine – urobilinogen –
suggest obstructive jaundice, either intra-hepatic or post-hepatic

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 Gallstones
 Pancreatic Cancer
 Gallbladder stones or Bile duct Cancer
 Pancreatitis

HYPERBILIRUBINEMIA
 Normal Plasma Bilirubin ranges from: 0.2-1.0 mg/dL
 Unconjugated Bilirubin ranges from: 0.2-0.7 mg/dL
 Conjugated Bilirubin ranged only from: 0.1-0.4 mg/dL
 If the Bilirubin levels exceeds 1 mg/dL, it is a condition called
Hyperbilirubinemia
 Levels between 1-2 mg/dL are indicative of Latent Jaundice –
Concealed, no manifestation yet
 If the Bilirubin levels exceeds 2 mg/dL, Jaundice is now evident since
it now diffuses into the tissues, producing yellowing discoloration of
the sclera, conjunctiva, skin and mucous membranes

Intra-
Pre-Hepatic Post-Hepatic
Function Test Hepatic
Jaundice Jaundice
Jaundice
Total Bilirubin Normal/Increased Increased
Conjugated
Normal Increased Increased
Bilirubin
Unconjugated
Normal/Increased Increased Normal
Bilirubin
Urobilinogen Normal/Increased Decreased Decreased/Negative
Urine Color Dark
(urobilinogen Dark (conjugated
Normal
+ conjugated bilirubin)
bilirubin)
Stool Color Normal Normal/Pale Pale
Conjugated
Bilirubin in Not Present Present
Urine

#GrindNation
“Strength In Knowledge” BESHYWAP 10