BIOCHEMISTRY 113 | WEEK

CARBOHYDRATE METABOLISM
Metabolic pathways in which molecular oxygen is not a GLYCOLYSIS MAP FROM BOOK
participant are called anaerobic pathways.

Pathways that require molecular oxygen are called aerobic

pathways.

Glycolysis is an anaerobic pathway.

GLYCOLYSIS

• An ancient pathway found in almost all organisms

a small amount of energy is captured as a glucose
molecule is converted to two molecules of
pyruvate.

• Also referred to as the Embden-Meyerhof

pathway, each glucose molecule is split and
converted to two three-carbon units (pyruvate).

• The small amount of energy captured during

glycolytic reactions is stored temporarily in two
molecules each of ATP and NADH

• Is the metabolic pathway by which glucose (a C6

molecule) is converted into two molecules of
pyruvate (a C3 molecule), chemical energy in the
form of ATP is produced, and NADH-reduced
coenzymes are produced.

Six-Carbon Stage of Glycolysis (Steps 1–3)

1. Phosphorylation:
Formation of Glucose 6-Phosphate.
2. Isomerization:
Formation of Fructose 6-Phosphate.
3. Phosphorylation:
Formation of Fructose 1,6-Bisphosphate.

Three-Carbon Stage of Glycolysis (Steps 4–10)

4. Cleavage: Formation of Two Triose Phosphates.
5. Isomerization:
Formation of Glyceraldehyde 3-Phosphate.
6. Oxidation and Phosphorylation:
Formation of 1,3-Bisphosphoglycerate
7. Phosphorylation of ADP:
Formation of 3-Phosphoglycerate.
8. Isomerization: Formation of 2-Phosphoglycerate
9. Dehydration: Formation of Phosphoenolpyruvate
10. Phosphorylation of ADP: Formation of Pyruvate

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Step 1: Phosphorylation: Formation of Glucose 6- Step 5: Isomerization: Formation of

Phosphate. Glyceraldehyde 3-Phosphate

• Begins with the phosphorylation of glucose to yield • Only one of the two trioses produced in Step 4,
glucose 6-phosphate glyceraldehyde 3-phosphate, is a glycolysis
intermediate. Dihydroxyacetone phosphate, the
• Hexokinase, an enzyme that requires Mg2 ion for other triose, can, however, be readily converted
its activity, catalyzes the reaction. into glyceraldehyde 3-phosphate.
Dihydroxyacetone phosphate (a ketose) and
• This reaction requires energy, which is provided by glyceraldehyde 3-phosphate (an aldose) are
the breakdown of an ATP molecule. isomers, and the isomerization process from
ketose to aldose is catalyzed by the enzyme
STEP 2: Isomerization: Formation of Fructose 6- triosephosphate isomerase
Phosphate
Step 6: Oxidation and Phosphorylation: Formation
• Glucose 6-phosphate is isomerized to fructose 6-
of 1,3-Bisphosphoglycerate
phosphate by phosphoglucoisomerase.

• The net result of this change is that carbon 1 of • In a reaction catalyzed by glyceraldehyde 3-
glucose is no longer part of the ring structure. phosphate dehydrogenase, a phosphate group is
added to glyceraldehyde 3-phosphate to produce
STEP 3: Phosphorylation: Formation of Fructose 1,3-bisphosphoglycerate. The hydrogen of the
1,6-Bisphosphate aldehyde group becomes part of NADH.

• The enzyme involved, phosphofructokinase, is • Step 6 is the first of two glycolysis steps in which a
another enzyme that requires Mg2 ion for its high-energy phosphate compound, that is an
activity. The fructose molecule now contains two “energyrich” compound, is formed.
phosphate group
Step 7: Phosphorylation of ADP: Formation of 3-
• Step 3 of glycolysis commits the original glucose Phosphoglycerate.
molecule to the glycolysis pathway. Glucose 6-
phosphate (Step 1) and fructose 6-phosphate • In this step, the diphosphate species just formed is
(Step 2) can enter other metabolic pathways, but converted back to a monophosphate species. This
fructose 1,6-bisphosphate can enter only glycolysis is an ATP-producing step in which the C-1
phosphate group of 1,3-bisphosphoglycerate (the
STEP 4: Cleavage: Formation of Two Triose high-energy phosphate) is transferred to an ADP
Phosphates molecule to form the ATP. The enzyme involved is
phosphoglycerokinase
• In this step, the reacting C6 species is split into two
C3 (triose) species. Because fructose 1,6- Step 8: Isomerization: Formation of 2-
bisphosphate, the molecule being split, is Phosphoglycerate
unsymmetrical, the two trioses produced are not
identical. One product is dihydroxyacetone • In this isomerization step, the phosphate group of
phosphate, and the other is glyceraldehyde 3- 3-phosphoglycerate is moved from carbon 3 to
phosphate. Aldolase is the enzyme that catalyzes carbon 2. The enzyme phosphoglyceromutase
this reaction catalyzes the exchange of the phosphate group
between the two carbons.
• GLyceraldehyde-3-phosphate

• Dihydroxyacetone phosphate

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Step 9: Dehydration: Formation of FATES OF PYRUVATE

Phosphoenolpyruvate

• This is an alcohol dehydration reaction that

proceeds with the enzyme enolase, another Mg2-
requiring enzyme. The result is another compound
containing a high-energy phosphate group; the
phosphate group is attached to a carbon atom that
is involved in a carbon–carbon double bond.

• Step 9 is the second of two glycolytic steps in which

a high-energy phosphate compound, that is,
“energy-rich” compound, is formed; the other step
was Step 6.

Step 10: Phosphorylation of ADP: Formation of

Pyruvate. OXIDATION TO ACETYL-COA

• In this step, substrate-level phosphorylation again This reaction, which involves both oxidation and
occurs. Phosphoenolpyruvate transfers its high- decarboxylation (because c02 is produced)
energy phosphate group to an ADP molecule to
produce ATP and pyruvate. The overall reaction process involves four separate
steps and requires NAD, CoA—SH, FAD, and two
• The enzyme involved, pyruvate kinase, requires other coenzymes (lipoic acid and thiamine
both Mg2 and K ions for its activity. Again, because pyrophosphate, the latter derived from the B vitamin
two C3 molecules are reacting, two ATP molecules thiamine)
are produced.
Most acetyl CoA molecules produced from pyruvate
• Step 10 is the second of two steps in which ATP is
enter the citric acid cycle
formed from ADP. This same process also
occurred in Step 7

• NADH produced during Step 6 of Glycolysis cannot

ATP Production and Consumption During directly participate in the electron transport chain
Glycolysis because mitochondria are impermeable to NADH
and NAD+

• Glycerol 3-phosphate-dihydroxyacetone
phosphate transport system shuttles electrons
from NADH, but not NADH itself, across the
membrane:

o Dihydroxyacetone phosphate and glycerol

phosphate freely cross the mitochondrial
membrane

o The interconversion shuttles the electrons

from NADH to FADH2

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GLYCOGENESIS (AND SYNTHESIS OF A phosphorylase is an enzyme that catalyzes the

DEGRADATION) cleavage of a bond by Pi (in contrast to hydrolysis,
which refers to bond cleavage by water), such as
Glycogenesis is the metabolic pathway by which removal of a glucose unit from glycogen to give
glycogen is synthesized from glucose 6-phosphate. glucose 1-phosphate.
Glycogenesis involves three reactions:
A phosphatase is an enzyme that effects the removal
Step 1: Formation of Glucose 1-phosphate. of a phosphate group (Pi ) from a molecule, such as
converting glucose 6-phosphate to glucose, with H2O
• The starting material for this step is not glucose as the attacking species
itself but rather glucose 6-phosphate (available
from the first step of glycolysis). The enzyme
phosphoglucomutase effects the change from a 6- GLUCONEOGENESIS
phosphate to a 1-phosphate.
• Gluconeogenesis is the metabolic pathway by
Step 2: Formation of UDP-glucose.
which glucose is synthesized from
noncarbohydrate materials.
• Glucose 1-phosphate from Step 1 must be
activated before it can be added to a growing o The processes of gluconeogenesis (pyruvate
glycogen chain. The activator is the high- energy to glucose) and glycolysis (glucose to pyruvate)
compound UTP (uridine triphosphate). A UMP is are not exact opposites. The most obvious
transferred to glucose 1-phosphate and the difference between these two processes is that
resulting PPi is hydrolyzed to 2Pi . 12 compounds are involved in
gluconeogenesis.
Step 3: Glucose Transfer to a Glycogen Chain.
o The last step of glycolysis is the conversion of
• The glucose unit of UDP-glucose is then attached the high-energy compound
to the end of a glycogen chain. In a subsequent phosphoenolpyruvate to pyruvate.
reaction, the UDP produced in Step 3 is converted
back to UTP, which can then react with another o The noncarbohydrate starting materials for
glucose 1-phosphate (Step 2). The conversion gluconeogenesis are lactate (from hardworking
reaction requires ATP muscles and from red blood cells), glycerol
(from triacylglycerol hydrolysis), and certain
GLYCOGENOLYSIS amino acids (from dietary protein hydrolysis or
from muscle protein during starvation). About
Glycogenolysis is the metabolic pathway by which 90% of gluconeogenesis takes place in the
glucose 6-phosphate is produced from glycogen. This liver. Hence gluconeogenesis helps to maintain
process is not simply the reverse of glycogen synthesis normal blood-glucose levels in times of
(glycogenesis), because it does not require UTP or inadequate dietary carbohydrate intake
UDP molecules. Glycogenolysis is a two-step process
rather than a three-step process. PENTOSE PHOSPHATE PATHWAY

o Phosphorylation of a Glucose Residue. The MAJOR FUNCTION:

enzyme glycogen phosphorylase effects the
removal of an end glucose unit from a glycogen 1. Synthesis of the coenzyme NADPH needed in
molecule as glucose 1-phosphate. lipid biosynthesis

o Glucose 1-phosphate Isomerization. The 2. Production of ribose 5-phosphate, a pentose

enzyme phosphoglucomutase catalyzes the derivative needed for the synthesis of nucleic
isomerization process whereby the phosphate acids and many coenzymes.
group of glucose 1-phosphate is moved to the
carbon 6 position

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 BIOCHEMISTRY 113 | WEEK 15

• The pentose phosphate pathway is the metabolic

pathway by which glucose is used to produce
NADPH, ribose 5-phosphate (a pentose
phosphate), and numerous other sugar
phosphates

• NADPH, the coenzyme produced in the pentose

phosphate pathway, is the reduced form of NADP
(nicotinamide adenine dinucleotide phosphate).
Structurally, NADP/ NADPH is a phosphorylated
version of NAD/NADH.

• There are two stages within the pentose phosphate

pathway—an oxidative stage and a nonoxidative
stage. The oxidative stage, which occurs first,
involves three steps through which glucose 6-
phosphate is converted to ribulose 5-phosphate
and CO2.

SUMMARY

Glycolysis, a series of ten reactions that occur in the

cytosol, is a process in which one glucose molecule is
converted into two molecules of pyruvate. A net gain of
two molecules of ATP and two molecules of NADH
results from the metabolizing of glucose to pyruvate

Fates of pyruvate. With respect to energy-yielding

metabolism, the pyruvate produced by glycolysis can
be converted to acetyl CoA under aerobic conditions or
to lactate under anaerobic conditions. Some
microorganisms convert pyruvate to ethanol, an
anaerobic process.

Glycogenesis is the process whereby excess glucose

6-phosphate is converted into glycogen. The glycogen
is stored in the liver and in muscle tissue

Glycogenolysis is the breakdown of glycogen into

glucose 6-phosphate. This process occurs when
muscles need energy and when the liver is restoring a
low blood-sugar level to normal

Gluconeogenesis is the formation of glucose from

pyruvate, lactate, and certain other substances. This
process takes place in the liver when glycogen
supplies are being depleted and when carbohydrate
intake is low

The pentose phosphate pathway metabolizes

glucose to produce ribose (a pentose), NADPH, and
other sugars needed for biosynthesis
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CHEMICAL COMMUNICATION bloodstream, the adrenaline will begin to flow.

Also called adrenaline rush in an emergency
Allows the activity of the cells in one part of the situation.
body to be coordinate of the other activity of the
cell. Adrenaline – a specific hormones that binds into
specific receptors in our muscles and the liver
The Body’s Three Communication System
cells.
A. Nervous System – the nerve cell
communicates through release of Once it bound it triggers the production of the
neurotransmitters. second messenger which is the Cyclic AMP
B. Endocrine Gland – communicate by Adenosine Monophosphate.
hormones
C. Immune System – communicate by Cyclic AMP Adenosine Monophosphate
cytokines second messenger which then leads to a several
modifications of enzymes that are involve in the
Neurotransmitter: a chemical messenger carbohydrate metabolism.
between a neuron and another target cell:
neuron, muscle cell or cell of a gland. • It’s important in many biological
processes. A derivative of Adenosine
Hormone: a chemical messenger released by an Triphosphate and used in intracellular
endocrine gland into the bloodstream and transaction in many different organisms
transported there to reach its target cell. conveying the CAMP dependent
pathway.
How does the communication between
neurotransmitter and hormone works?

1. External signals present (the light the smoke

the heat) which is alarmed by specific receptor
which are the eyes, nose, and skin.

2. The signals are transmuted by specific

compounds to nerve cells or neurons,
nerve cells are present through the body and
together with the brain it constitutes our
nervous system.

3. In the neurons the signals travels as electric

impulses along with the axons (part of the
nerve).

4. When the signals reach the endocrine neuron,

the signals are then transmitted to specific
compound which is the neurotransmitter.
Which carries the necessary messages from
the neuron to the muscle cells and endocrine
glands.

5. The endocrine glands are stimulated and

then hormones are designated into the

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Dendrites – where neuron receives the input from

another cells.

Both equally important, they work together. Axon

helps to move messages through the system,
dendrites receive and process those messages
form axon.

B. Endocrine System

Uses hormones to control and coordinate body’s

internal metabolism, it releases hormones that are
responsible regulating normal function of our
body, not only internal may also includes energy
levels, reproduction, growth and development.

And also in response into injuries, stress and other

environmental factors.

Hypothalamus – regulates hunger, thirst, sleep,

and wakefulness and most of the involuntary
mechanism, includes the body temperature.

Pituitary Gland – Controls all other endocrine

glands, influences growth, metabolism and
regeneration.

Thyroid Gland – regulates energy and

metabolism.

Pancreas – pancreatic islets, aids in the

digestions of fats, protein, and carbohydrates
produces insulin which controls the blood sugar
level.

Ovaries – for female, influences how blood

A. Nerve Cell circulates and determines mental labor and sex
drive.
Axon – thinner than human hair, thin nerve fibers.
Testes – for male
The electrical impulse from the neuron would
travel away to be received by another neuron, Adrenal Glands – Secretes hundreds of
which allows the nerve cell to send electrical compounds including cortisone and adrenaline.
signals and chemical messages to other nerves, It helps to react in emergency. Regulates
glands and muscle cells using the internal metabolic processes in the cell, water balance
communication processes. and blood pressure.

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Characteristic Hormones Neurotransmitter

Organ Endocrine System Nervous System
Mode of Transmission Through blood stream Across Synaptic Cleft
Transmission Speed May take a few minutes or a few Usually within millisecond
days
Transmission Distance Act on distant site from when it Reacts in direct proximity to
is produced their target cell
Functions Affect physiological processes They facilitate transmission
such as growth and between neurons by passing
development, metabolism, action potential from the axon
mood, sexual function of one neuron to the dendrite
reproduction. of the next neuron
Capability Regulation of the target organs Only capable of stimulating
and tissue postsynaptic neuron

*Synaptic Cleft – synaptic gap, this is the space after the axon terminal of a neuron between the next
target cell.

HORMONES ARE CLASSIFIED BY:

4 classes of hormones based on chemical
Hormones are diverse compound which is
structure:
secreted by specific tissue of endocrine glands
released in the blood stream and absorb into Peptides or Protein hormones:
specific receptor sites which is relative from their They are synthesized as peptides or large
sources. polypeptides precursors that
undergo processing before secretion;
• Proximity of their site of synthesis to their site
of action, Examples:
• Their chemical structure, • Thyrotropin Releasing Hormone (TRH),
• Their degree of solubility in aqueous medium made up of three amino acid residues;
• Insulin, made up of 51 amino acid
3 classes of hormones based on proximity of residues;
site of Synthesis to Site of Action • Pituitary Gonadotrophins, made up of
large Glycoproteins with subunits
• Autocrine Hormones: those that act on the
same cells that synthesize them; Amino acid derivatives:
• Paracrine Hormones: those that are Examples: Adrenaline, Catecholamines,
synthesized very close to their site of action; Thyroid Hormones;

• Endocrine Hormones: those that are Fatty acid derivatives:

synthesized by endocrine glands and
Examples: Eicosanoids (Prostaglandins);
transported in the blood to target cells that
contain the appropriate receptors; Steroid hormones:
These are derivatives of Cholesterol;
Example: Estradiol, Testosterone,
Cortisol, Aldosterone;

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Classified according to solubility in aqueous FEED BACK MECHANISM OF HORMONE

medium in cells
A feedback mechanism is a loop in which
Hydrophilic Hormones (Lipophobic a product feeds back to control its own
Hormones); production.
• Hormones that are soluble in aqueous
Most hormone feedback mechanisms
medium;
involve negative feedback loops. Negative
• They cannot cross the cell membrane,
feedback keeps the concentration of a hormone
• Thus, they bind to receptor molecules on the
outer surface of target cells, initiating reactions within a narrow range.
within the cell that ultimately modifies the
functions of the cells; 2 KINDS

Examples: Insulin, Glucagon, • Negative Feedback

Epinephrine, • Positive Feedback

A. Negative Feedback Mechanism

Lipophilic Hormones (Hydrophobic
Hormones); Negative feedback mechanism normalizes
the function when they start becoming too
• Hormones that are not soluble in aqueous extreme. MOST HORMONES ARE
medium, but soluble in lipid; CONTROLLED HERE.
• They can easily cross the cell membrane,
• Thus, they can enter target cells and bind to Negative feedback occurs when a product
intracellular receptors to carryout their action; feeds back to decrease its own production.
This type of feedback brings things back to normal
Examples: Thyroid hormones, Steroid hormones;
whenever they start to become too extreme.
Main function of Hormones
Example: Signal back to pancreas to stop
• Growth, metabolism, and maturation of many producing insulin
tissues and organs
B. Positive Feedback Mechanism
• Ionic Regulation – regulates ion
concentrations in the blood (blood chemistry) It occurs when the original effect of the
stimulus is enhanced by the output.
• Water Balance – regulates water balance by
controlling solute concentrations Positive feedback occurs when a product
feeds back to increase its own production. This
• Heart rate & Blood Pressure Regulation causes conditions to become increasingly
extreme
• Blood Glucose Regulation
Example: Pancreas – insulin
• Immune System Regulation

• Reproductive Function Control Milk production – pituitary gland – secretes

prolactin – simulates to produce milk
• Uterine Contractions & Milk Release
11. What will happen if milk production was
controlled by negative feedback mechanism?

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ORGAN HORMONE FUNCTION

Adrenal glands Aldosterone Regulates salt, water balance, and blood pressure

Corticosteroid Controls key functions in the body; acts as an anti-

inflammatory; maintains blood sugar levels, blood
pressure, and muscle strength; regulates salt and water
balance

Pituitary gland Antidiuretic Affects water retention in kidneys; controls blood

hormone pressure
(vasopressin)

Adrenocorticotropic Controls production of sex hormones (estrogen in

hormone (ACTH) women and testosterone in men) and the production of
eggs in women and sperm in men.

Growth hormone Affects growth and development; stimulates protein

(GH) production; affects fat distribution

Luteinizing Controls production of sex hormones (estrogen in

hormone (LH) and women and testosterone in men) and the production of
follicle-stimulating eggs in women and sperm in men
hormone (FSH)

Oxytocin Stimulates contraction of uterus and milk ducts in the

breast

Prolactin Initiates and maintains milk production in breasts;

impacts sex hormone levels

Thyroid-stimulating Stimulates the production and secretion of thyroid

hormone (TSH) hormones

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ORGAN HORMONE FUNCTION

Kidneys Renin and Controls blood pressure, both directly and also by
angiotensin regulating aldosterone production from the adrenal
glands

Erythropoietin Affects red blood cell (RBC) production

Pancreas Glucagon Raises blood sugar levels

Insulin Lowers blood sugar levels; stimulates metabolism of

glucose, protein, and fat

Ovaries Estrogen Affects development of female sexual characteristics

and reproductive development, important for functioning
of uterus and breasts; also protects bone health

Progesterone Stimulates the lining of the uterus for fertilization;

prepares the breasts for milk production

Parathyroid glands Parathyroid Most important regulator of blood calcium levels

hormone (PTH)

Thyroid gland Thyroid hormone Controls metabolism; also affects growth, maturation,
(Triiodothyronine nervous system activity, and metabolism
and Thyroxine)

Adrenal glands Epinephrine Increases heart rate, oxygen intake, and blood flow

Norepinephrine Maintains blood pressure

Testes (testicles) Testosterone Develop and maintain male sexual characteristics and
maturation

Pineal gland Melatonin Releases melatonin during night hours to help with sleep

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ORGAN HORMONE FUNCTION

Hypothalamus Growth hormone Regulates growth hormone release in the pituitary gland
releasing hormone
(GHRH)

Thyrotropin Regulates thyroid stimulating hormone release in the

releasing hormone pituitary gland
(TRH)

Gonadotropin Regulates LH/FSH production in the pituitary gland

releasing hormone
(GnRH)

Corticotropin Regulates adrenocorticotropin release in the pituitary

releasing hormone gland
(CRH)

Thymus Humoral factors Helps develop the lymphoid system

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PART I

Chemical Communications:
Neurotransmitters and Hormones

What Molecules Are Involved in Chemical Communications?

• Cell-to-cell communications are carried out by three kinds of molecules.

• Receptors are protein molecule

embedded in the membranes of cells.

• Chemical messengers, or ligands, interact with receptors.

• Secondary messengers carry and amplify the signals from the receptor to inside
the cell.

How Are Chemical Messengers Classified as Neurotransmitters and Hormones?

• Neurotransmitters send chemical messengers across a short distance—the

synapse between two neurons or between a neuron and a muscle or endocrine
gland cell. This communication occurs in milliseconds.

• Hormones transmit their signals more slowly and over a longer distance, from
the source of their secretion (endocrine gland), through the bloodstream, into
target cells.

• Antagonists block receptors; agonists stimulate receptors.

• Five kinds of chemical messengers exist: cholinergic, amino acid, adrenergic,

peptidergic, and steroid. Neurotransmitters may belong to all five classes,
hormones to the last three classes. Acetylcholine is cholinergic, glutamic acid is an
amino acid, epinephrine (adrenaline) and norepinephrine are adrenergic,
enkephalins are peptidergic, and progesterone is a steroid.
How Does Acetylcholine Act as a Messenger?

Nerve transmission starts with the neurotransmitters, such as acetylcholine

packaged in vesicles in the presynaptic end of neurons.
• When neurotransmitters are released, they cross the membrane and the
synapse and are adsorbed onto receptor sites on the postsynaptic membranes.
This adsorption triggers an electrical response.
• Some neurotransmitters act directly, whereas others act through a secondary
messenger, cyclic AMP

• After the electrical signal is triggered, the neurotransmitter molecules must be

removed from the postsynaptic end. In the case of acetylcholine, this removal is
done by an enzyme called acetylcholinesterase.

What Amino Acids Act as Neurotransmitters?

• Amino acids, many of which differ from the amino acids found in proteins, bind
to their receptors, which are ligand-gated ion channels. • Removal of amino acid
messengers takes place by reuptake through the presynaptic membrane, rather
than by hydrolysis.

What Are Adrenergic Messengers?

• The mode of action of monoamines such as epinephrine, serotonin, dopamine,

and histamine is similar to that of acetylcholine, in the sense they start with
binding to a receptor. • Cyclic AMP is an important secondary messenger.
• The mode of removal of monoamines differs from the hydrolysis of
acetylcholine. In the case of monoamines, enzymes (MAOs) oxidize them to
aldehydes.

What Is the Role of Peptides in Chemical Communication?

• Peptides and proteins bind to receptors on the target cell membrane and use
secondary messengers to exert their influence.
• Signal transduction is the process that occurs after a ligand binds to its receptor.
In this process, the signal is carried inside the cell and is amplified.
 How Do Steroid Hormones Act as Messengers? • Steroids penetrate the cell
membrane, and their receptors are found in the cytoplasm. Together with their
receptors, they penetrate the cell nucleus.
• Steroid hormones can act in three ways: (1) They activate enzymes
(2) they affect the gene transcription of an enzyme or protein, and
(3) they change membrane permeability.
• The same steroids can also act as neurotransmitters, when synthesized in
neurons.

Main Functions

A. Growth, metabolism, and maturation of many tissues and organs

B. Ionic Regulation – regulates ion concentrations in the blood (blood chemistry)
C. Water Balance – regulates water balance by controlling solute concentrations
D. Heart rate & Blood Pressure Regulation E. Blood Glucose Regulation
F. Immune System Regulation G. Reproductive Function Control H. Uterine
Contractions & Milk Release

Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine

monophosphate) is a second messenger important in many biological processes.
cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular
signal transduction in many different organisms, conveying the cAMP-dependent
pathway
PART II
INTRODUCTION AND NATURAL IMMUNITY
HUMORAL VS CELL MEDIATED IMMUNITY

Immunology can be defined as the study of a host’s reaction when foreign body
substance is introduced into the body. A foreign substance that induces such an
immune response is called antigen.
In the late 1800’s scientist turned to identifying the actual mechanism that
produce immunity in the host. Elie Metchnikoff a Russian scientist observed that
foreign object introduced into transparent starfish larvae became surrounded by
motile cell that attempt to destroy these invaders. He called this process
phagocytosis, meaning cells that eat cells. He hypothesizes that immunity to
disease was based on the action of these scavenger cell. Other researcher
contended that non cellular elements in the blood were responsible for
protection from microorganism. The theory of humoral immunity was thus born,
and this set off a long-lasting dispute over the relative importance of cellular
versus humoral immunity

HUMORAL DEFENSE MECHANISM

Natural or innate Immunity is the ability of an individual to resist infection by

means of normally present body functions. These are considered as nonspecific
and are the same for all pathogens or foreign substances. No prior exposure is
required, and the response does not change with the subsequent exposure.

Specific or Acquired Immunity in contrast is a type of resistance that is

characterized by specificity for each individual pathogen, or microbial agent, and
the ability to remember a prior exposure which result in an increase response
upon repeated exposure.

The natural defense system is composed of two parts:

A. External defense system

B. Internal defense system
EXTERNAL DEFENSE SYSTEM

Is composed of structural barriers that prevents most infectious agent from

entering the body. First and foremost, the unbroken skin and the mucosal
membrane surfaces. Lactic acid in sweat for instance and fatty acid from
sebaceous gland maintain the skin at pH of approximately 5.6 this acid pH keeps
the most microorganism from growing.

INTERNAL DEFENSE SYSTEM

Both cell and soluble factor play essential part. White blood cell seek out and
destroy foreign cells by participating in phagocytosis which is the engulfment of
cells or particulate matter by leukocyte, macrophages, and other cell. This process
destroys most of the foreign invaders that enters the body, and it is the most
important function of the internal defense system. Phagocytosis is enhanced by
soluble factor called acute phase reactants.

ACUTE PHASE REACTANTS

Are normal serum constituents that increase rapidly by at least 25 percent due to
infection, injury or trauma to the tissue. They are produced primarily by
hepatocyte within 12-24 hours in response to an increase in certain intercellular
signaling polypeptide called cytokines. These cell messengers are mainly
produced by monocyte and macrophages at the site of inflammation.

C-Reactive Protein

Is a trace constituent of serum originally thought to be an antibody to the c-

polysaccharide of pneumococci. It increases rapidly within 4 to 8 hours following
infections, surgery, or other trauma to the body.
CRP has a plasma half-life of about 19 hours. Elevated levels are found in
conditions such as bacterial infection rheumatic fever, viral infection, malignant
disease, tuberculosis, and after a heart attack.
CRP molecular weight of 118 Daltons.
CRP binds to specific receptor found on monocytes, macrophages, and
neutrophils which promotes phagocytosis. Thus, CRP can be thought of as a
primitive nonspecific form of antibody molecule that is able to act as a defense
against microorganism or foreign cells until specific antibodies can be produce.
CRP is the most widely used indicator of acute inflammation.
Recent research indicates that an increase level of CRP is a significant risk factor
for myocardial infarction and ischemic stroke in men and women who have no
previous history of cardio vascular disease.
A concentration of more than 2mg/L has been defined as the threshold for high
cardiovascular risk.
Normal levels in adult range from approximately 1.5 mg/dLfor men and 2.5
mg/dL for women. Thus monitoring CRP may be an important preventative
measure in determining the potential risk of heart attack or stroke.

SERUM AMYLOID-A

It is an apolipoprotein that is synthesized in the liver and has molecular weight of

11,685 daltons. It has been found to increase significantly more in bacterial
infections than in viral infections.

COMPLEMENT

Refers to series of serum protein that are normally present and whose overall
function is mediations of inflammation. There nine such protein that are activated
by bound antibodies in a sequence known as the classical cascade; an additional
number are involved in the alternate pathway that is triggered by microorganism.
The major function of complement are opsonization, chemotaxis and lysis of cell.

HAPTOGLOBIN

Its primary function is to bind irreversibly to free hemoglobin released by

intravascular hemolysis. Once bound, the complex is cleared rapidly by Kupffer
cell and parenchymal cell in the liver, thus preventing loss of free hemoglobin. A
two-fold to tenfold increase in haptoglobin can be seen following inflammation,
stress or tissue necrosis.
Normal plasma concentration range from 40 to 290 mg/dL
Haptoglobin plays important role in protection kidney from damage and in
preventing the loss of iron by urinary excretion.
FIBRONOGEN

The most abundant of coagulation factors in plasma, and it forms the fibrin clot.
The molecule is a dimer with molecular weight of 340,000 Daltons. Normal levels
ranger from 100-400 md/dL
Fibrinogen also serves to promote aggregation of the red blood cell and increase
levels contribute to an increase risk for developing coronary artery disease,
especially in women

CERULOPLASMIN

Consist of single polypeptide chain with a molecular weight of 132,000 Daltons. It

is the principal copper-transporting protein in human plasma, binding 90-95
percent of the copper found in plasma by attaching six cupric ions per molecule.
Additionally, ceruloplasmin acts as ferroxidase oxidizing iron from FE2+ to FE3+.
This may serve as a mean of releasing iron from ferritin for binding to
transferring.

A depletion of ceruloplasmin is found in Wilson disease, an autosomal recessive

genetic disorder characterized by a massive increase of copper in the tissue.
Normally, circulating copper is absorbed out by the liver and either combined
with ceruloplasmin and return to the plasma or excreted into the bile duct. In
Wilson disease, copper accumulates in the liver and subsequently in other tissue
such as the brain, cornea kidneys and bones

CELLULAR DEFENSE MECHANISM

There are five principal types of leukocytes or white blood cell in peripheral
blood: neutrophils, eosinophils, basophils, monocytes, and lymphocyte. Some of
these white blood cell participates in the process of phagocytosis; these are
known as the myeloid line and arise from a common precursor in the marrow.
These can be further subdivided into granulocyte and monocyte or mononuclear
cells. Neutrophils, eosinophils, and basophils are considered granulocyte.
Neutrophils

The neutrophils or the polymorphonuclear neutrophilic leukocyte, represent

approximately 50 to 70 percent of the total white blood cells. These are around
10-15um in diameter; with nucleus that has between two and five lobes. They
contain large number of neutral staining granules which are classified as primary
granules, secondary granules, and tertiary granules.

Primary granules also known as azurophilic granules, contains enzymes such as

myeloperoxidase, elastase, proteinase-3, lysozyme, cathepsin-G, and defensin,
small proteins that have antibacterial activity. Secondary granules are
characterized by the presence of collagenase, lactoferrin, lysozyme, reduced
nicotinamide adenine dinucleotide phosphate oxidase and other membrane.
Tertiary granules contain gelatinase and plasminogen activator. Acid hydrolases
are found in separate compartments called lysosomes.

• Diapedesis: Marginating occurs to allows neutrophils to move from

circulating blood to the tissue through a process known as diapedesis –
movement through blood vessel wall. Receptors known as selectin help
make neutrophils sticky and enhance adherence to endothelial cell that
make up the vessel wall.
• Chemotaxis are chemical messenger that cause cells to migrate in a
particular direction. Factors that affect chemotactic for neutrophils
include complement components; protein from coagulation, products
from bacteria and viruses, platelet activating factor, and secretion from
mast cells.
• In case of acute infections, an increase of neutrophils in the circulation
blood can occur almost immediately.
Eosinophil

Eosinophil are approximately 12 to 15 um in diameter, and they normally make

up between 1 to 3 percent of the circulating white blood cell in a non-allergenic
person. Their number increase in allergenic reaction or response to many
parasitic infections. The nucleus is usually bilobed or ellipsoidal and is often
eccentrically located. Eosinophil takes up the acid eosin dye, and the cytoplasm is
filled with large orange to reddish orange granules. Their most important role is
neutralizing basophil and mast cell products killing certain parasite.

Basophils

Basophils are found in very small number representing less than 1 percent of all
circulating white blood cell. The smallest of the granulocyte, they are between 10
to 15 um in diameter and contain coarse densely staining deep bluish purple
granules that often obscure the nucleus.
Constituent of these granules are histamine a small amount of heparin and
eosinophil chemotactic factor A, all of which have an important function in
inducing and maintaining immediate hypersensitive reactions. Histamine is
vasoactive amine that contracts smooth muscle, and heparin is an anticoagulant.
Basophils exist only for few hours in the blood stream

Mast Cell

Tissue mast cell resembles basophils, but they are connective tissue cells of
mesenchymal origin. They are widely distributed throughout the body and are a
larger than basophils. Unlike basophils they have long life span of between 9 to 18
months. The enzyme content of the granules helps to distinguish them from
basophils as they contain acid phosphatase, alkaline phosphatase and protease
The mast cell like the basophil plays a role in hypersensitive reaction by binding
IgE.

Monocyte

Monocyte or mononuclear cell are the largest cell in the peripheral blood, with a
diameter that can vary from 12 to 22 um they have an average size of 18 um. One
distinguishing feature is an irregularly folded or horseshoe-shaped nucleus that
occupies almost one-half of the entire cells volume. They stay in the peripheral
blood for up to 70 hours and then they migrate to the tissue and become known
as macrophages.

Tissue Macrophages

All tissue macrophages arise from monocyte. Which can be thought of as

macrophage precursor because additional differentiation and cell division takes
place in the tissue.
The transition from monocyte to macrophage is characterized by progressive
cellular enlargement to between 25 and 80 um. As the monocyte matures into a
macrophage there is an increase in endoplasmic reticulum, lysosomes and
mitochondria, unlike monocytes, macrophages contain no peroxidase.

Macrophages have specific names according to their location.

• Liver- Kupffer cell

• Lungs – Alveolar macrophages
• Brain- Microglial cells
• Connective tissue – histiocyte

Macrophages may not be as efficient as neutrophils in phagocytosis because their

motility is slow compared to that of neutrophils. However, their life span appears
to be in range of months rather than days.
Their function includes microbial killing, tumoricidal activity, intracellular parasite
eradication, phagocytosis, secretion of cell mediator, and antigen presentation.
Killing activity is enhanced when macrophages become activated by contact with
microorganism or with chemical messenger called cytokines which are release by
T lymphocyte during immune response.

4 main steps of phagocytosis

1. Physical contact between the white cell and the foreign particle
2. Formation of phagosome
3. Fusion with cytoplasmic granules to form a phagolysosome
4. Digestion and release of debris to the outside.
INFLAMMATION

The overall reaction of the body injury or invasion by an infectious agent is known
as inflammation. both cellular and humoral mechanism are involved in this
complex. highly orchestrated process. each individual reactant plays a role in
initiating amplifying or sustaining the reaction and delicate balance must be
maintained for the process to be speedily resolved.

4 cardinal signs of inflammation

• Redness
• Swelling
• Heat
• Pain

IMMUNODEFICIENCY

Immunodeficiency disorders result in a full or partial impairment of the immune

system. Primary immunodeficiencies are the result of genetic defects, and
secondary immunodeficiencies are caused by environmental factors, such as
HIV/AIDS or malnutrition.

KEY POINTS
• Immunodeficiency disorders result in partial or full impairment of the
immune system, leaving the patient unable to effectively resolve infections
or disease.
• Immunodeficiency disorders can either be primary or secondary in nature.
There are over 300 forms of primary immunodeficiency and, although rare,
the condition can be life threatening.
• Secondary immunodeficiencies are the result of disease or other
environmental factors weakening the immune system.
• Although affecting fewer patients than other classes of immune illness,
immunodeficiency patients may require expensive definitive therapy (e.g.
bone marrow transplant), or may remain lifelong patients with complex
care needs, and the cost-burden on the NHS is significant.
 • Immunological research provides hope of improved curative therapies
through the development of new technologies. Continued and increased
investment is critical to ensure these potential advances are realized.

In healthy individuals the immune response comprises two phases.

The first line of defense is the innate system, made up of specialized cells that
provide a rapid response that is not tailored to the specific microbe that has
infiltrated the body. Sometimes this can clear the infection alone but usually the
innate response will contain the infection long enough for the adaptive immune
system to activate. The adaptive response is the second line of defense and takes
several days to assemble. The response is specific to the microbe and leaves a
lasting immune memory, which makes the response to future reinfection more
efficient (see here for more information). In a person with an immunodeficiency
disorder, one or more components of either the adaptive or innate immune
response is impaired, resulting in the body being unable to effectively resolve
infections or disease. This leaves immunodeficient individuals at high risk of
recurrent infection, and vulnerable to conditions that would not usually be of
concern to otherwise healthy individuals

There are two types of immunodeficiency disorder:

1. Primary immunodeficiency (PID) – inherited immune disorders resulting from

genetic mutations, usually present at birth and diagnosed in childhood.

2. Secondary immunodeficiency (SID) – acquired immunodeficiency as a result of

disease or environmental factors, such as HIV, malnutrition, or medical treatment
(e.g. chemotherapy).

Primary immunodeficiency (PID)

PID disorders are inherited conditions sometimes caused by single-gene

mutations, or more often by an unknown genetic susceptibility combined with
environmental factors. Although some PIDs are diagnosed during infancy or
childhood, many are diagnosed later in life. PIDs are categorized based on the
part of the immune system that is disrupted.
EXAMPLE OF PRIMARY IMMUNODEFICIENCY

B cell immunodeficiencies (adaptive) – B cells are one of two key cell types of the
adaptive immune system. Their main role is to produce antibodies, which are
proteins that attach to microbes, making it easier for other immune cells to
detect and kill them. Mutations in the genes that control B cells can result in the
loss of antibody production. These patients are at risk of severe recurrent
bacterial infections.

T cell immunodeficiencies (adaptive) – T cells are the second of two key cell types
of the adaptive immune system. One role of the T cell is to activate the B cell and
pass on details of the microbe’s identity, so that the B cell can produce the correct
antibodies. Some T cells are also directly involved in microbe killing. T cells also
provide signals that activate other cells of the immune system. Mutations in the
genes that control T cells can result in fewer T cells or ones that do not function
properly. This can lead to their killing ability being disrupted and can often cause
problems with B cell function too. Therefore, T cell immunodeficiencies can often
lead to combined immunodeficiencies (CIDs), where both T and B cell function is
defective. Some forms of CIDs are more severe than others.

Severe combined immune deficiencies (SCID) (adaptive) – SCID disorders are very
rare but extremely serious. In SCID patients there is often a complete lack of T
cells and variable numbers of B cells, resulting in little-to-no immune function, so
even a minor infection can be deadly. SCID patients are usually diagnosed in the
first year of life with symptoms such as recurrent infections and failure to thrive.

Phagocyte disorders (innate) - phagocytes include many white blood cells of the
innate immune system, and these cells patrol the body eating any pathogens they
come across. Mutations typically affect the ability of certain phagocytes to eat
and destroy pathogens effectively. These patients have largely functional immune
systems, but certain bacterial and fungal infections can cause very serious harm
or death.

Complement defects (innate) – complement defects are some of the rarest of all
the PIDs, and account for less than 1% of diagnosed cases. Complement is the
name given to specific proteins in the blood that help immune cells clear
infection. Some deficiencies in the complement system can result in the
development of autoimmune conditions such as systemic lupus erythematosus
and rheumatoid arthritis (please see our autoimmune briefing for more
information). Patients who lack certain complement proteins are highly
susceptible to meningitis.

Secondary immunodeficiency (SID)

SIDs are more common than PIDs and are the result of a primary illness, such as
HIV, or other external factor such as malnutrition or some drug regimens. Most
SIDs can be resolved by treating the primary condition.

EXAMPLE OF SECONDARY IMMUNODEFICIENCY

Malnutrition – Protein-calorie malnutrition is the biggest global cause of SIDs

which can affect up to 50% of the population in some communities in the
developing world. T cell numbers and function decrease in proportion to levels of
protein deficiency, which leaves the patient particularly susceptible to diarrhea
and respiratory tract infections. This form of immunodeficiency will usually
resolve if the malnutrition is treated.

Drug regimens – There are several types of medication that can result in
secondary immunodeficiencies, but these drugs also perform critical roles in
certain areas of healthcare. Immunosuppression is a common side-effect of most
chemotherapies used in cancer treatment. The immune system usually recovers
once the chemotherapy treatment has finished. Another common use for
immunosuppressive drugs is the prevention of transplant rejection, where
medication is required to suppress the transplant recipient’s immune system and
prevent it from targeting the transplanted tissue. These drugs can have significant
side-effects and often suppress more areas of the immune system than are
required, leading to susceptibility to opportunistic infections. Use of a new
generation of medicines called biologics are becoming more widespread in
treating transplant rejection. These drugs are derived from biological sources like
cells, rather than chemical structures. Monoclonal antibodies are one such class
of biologics and these drugs are made by farming antibodies from B cells that will
act against a specific part of the disease process. These agents are more specific
in their action than traditional drugs and have fewer side effects on non-target
immune cells.
Chronic infections – There are several chronic infections which can lead to SID
disorders, the most common of which is acquired immune deficiency syndrome
(AIDS), resulting from HIV infection. The virus attacks CD4+ T cells, a type of white
blood cell that plays a critical role in preventing infection, and gradually depletes
their numbers. Once the T cell count is less than 200 cells per ml of blood,
symptoms of AIDS begin to manifest, and the patient is at high risk of recurrent
infections that will eventually lead to death. Anti-viral therapies, such as the
HAART regimen (Highly Active Antiretroviral Therapy), allow the T cell population
a chance to recover and resume normal function. These drugs have had a huge
impact on increasing the life expectancy for HIV/AIDS patients and improving
their quality of life. Prior to the introduction of HAART, patients with HIV
diagnosed at age 20 had an average of 10 years before developing AIDS.
Nowadays on average, patients diagnosed at age 20 can expect to live well into
their 60s.viii However, these drugs must be taken every day for life as they are
not curative and are only available to patients and healthcare systems that can
afford them.
 CELLULAR RESPIRATION Summary

We usually use the word respiration to mean GLYCOLYSIS:

breathing. Although respiration on the organismal a molecule of glucose is split into two
level should not be confused with cellular molecules of a compound called pyruvic acid. The
respiration, the two processes are closely related. enzymes for glycolysis are located in the
cytoplasm
Chemical process that releases energy
from organic compounds (food), gradually CITRIC ACID CYCLE:
converting it into energy that is stored in ATP (also called the Krebs cycle) completes the
molecules breakdown of glucose all the way to CO2, which is
then released as a waste product. The enzymes
for the citric acid cycle are dissolved in the fluid
within mitochondria. Glycolysis and the citric acid
cycle generate a small amount of ATP directly.
They generate much more ATP indirectly, by
reactions that transfer electrons from fuel
molecules to a molecule called NAD+
(nicotinamide adenine dinucleotide) that cells
make from niacin, a B vitamin.

ELECTRON TRASPORT:
Electrons captured from food by the NADH
formed in the first two stages are stripped of their
energy, a little bit at a time, until they are finally
combined with oxygen to form water. The proteins
and other molecules that make up electron
transport chains are embedded within the inner
membrane of the mitochondria. The transport of
electrons from NADH to oxygen releases the
energy your cells use to make most of their ATP

The main function of cellular respiration is

to generate ATP for cellular work. In fact, the
process can produce around 32 ATP molecules
for each glucose molecule consumed.

GLYCOLYSIS

The many chemical reactions that make up

cellular respiration can be grouped into three
main stages
• GLYCOLYSIS
• CITRIC ACID CYCLE
• ELECTRON CHAIN TRANSPORT

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 THE CITRIC ACID CYCLE • NADH and FADH2 transfer electrons to an
electron transport chain.
• The electron transport chain uses this energy
supply to pump H+ across the inner
mitochondrial membrane.
• Oxygen pulls electrons down the transport
chain.
• The H+ concentrated on one side of the
membrane rushes back “downhill” through an
ATP synthase.
• This action spins a component of the ATP
synthase. The rotation activates parts of the
synthase molecule that attach phosphate
groups to ADP molecules to generate ATP
• The molecules of electron transport chains are
built into the inner membranes of mitochondria
PYRUVATE – ACETYL CoA Because these membranes are highly folded,
their large surface area can accommodate
• During glycolysis, one molecule of glucose is thousands of copies of the electron transport
split into two molecules of pyruvic acid. chain— a good example of how biological
• But before pyruvic acid can be used by the structure fits function.
citric acid cycle, it must be converted to a form • Each chain acts as a chemical pump that uses
the citric acid cycle can use. the energy released by the “fall” of electrons to
• First, each pyruvic acid loses a carbon as CO2. move hydrogen ions (H+ ) across the inner
mitochondrial membrane
• This is the first of this waste product we’ve
seen so far in the breakdown of glucose.
• The remaining fuel molecules, each with only
two carbons left, are called acetic acid
• Electrons are stripped from these molecules
and transferred to another molecule of NAD+ ,
forming more NADH.
• Finally, each acetic acid is attached to a
molecule called coenzyme A (CoA), an
enzyme derived from the B vitamin pantothenic
acid, to form acetyl CoA

ELECTRON CHAIN TRANSPORT

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 CELLULAR & HUMORAL IMMUNITY HUMMORAL DEFENSE MECHANISM

Immune System has its own mechanism to be • Natural or innate Immunity

able to regulate normal body functions. *Chemical
communication (focus on how our body is the ability of an individual to resist
communicates to fight diseases and infections infection by means of normally present body
caused by certain bacteria and viruses) functions. These are considered as nonspecific
and are the same for all pathogens or foreign
Introduction to Immunology substances.

Immunology can be defined as the study of a No prior exposure is required, and the
host’s reaction when foreign body substance response does not change with the subsequent
is introduced into the body. A foreign substance exposure. (body has natural response with foreign
that induces such an immune response is called exposes)
antigen. (bacteria, germs, viruses).
• Specific or Acquired Immunity
Brief History
in contrast is a type of resistance that is
• Edward Jenner – Performed the first characterized by specificity for each individual
successful vaccination against smallpox and pathogen, or microbial agent, and the ability to
ushered in the age immunologic investigation. remember a prior exposure which result in an
increase response upon repeated exposure.
• Louis Pasteur – Discovered attenuated
vaccines. Example: fighting of common cold (since it
has prior exposure and the body has able to build
• Ellie Metchnikoff – identified phagocytic cell a antibody against these certain bacteria
as a part of cellular immunity and other
researchers postulated that a humoral or a non • i. EXTERNAL DEFENSE SYSTEM - (SKIN)
cellular immunity, factor in the blood was
involved in immunity. Is composed of structural barriers that
prevents most infectious agent from entering
• Almuth Wright – Observed that both
the body.
circulating cellular factors are necessary to
produce immunity.
First and foremost, the unbroken skin and
Levels of Immune Response the mucosal membrane surfaces. Lactic acid in
sweat for instance and fatty acid from sebaceous
1. Innate Immunity – gland maintain the skin at pH of approximately 5.6
this acid pH keeps the most microorganism from
a. External Barriers growing.
b. Phagocytic Cell • ii. NTERNAL DEFENSE SYSTEM –
(leukocytes, microphagous, cytokines)
2. Specific Immunity –
Both cell and soluble factor play essential
a. Humoral Immunity*
part. White blood cell seeks out and destroy
b. Cell Mediated* foreign cells by participating in phagocytosis which
is the engulfment of cells or particulate matter by
leukocyte, macrophages, and other cell.

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 This process destroys most of the III. COMPLEMENT
foreign invaders that enters the body, and it is
the most important function of the internal • Refers to series of serum protein that are
defense system. normally present and whose overall function is
mediations of inflammation.
Phagocytosis is enhanced by soluble factor
called acute phase reactants. • There nine such protein that are activated by
bound antibodies in a sequence known as the
*Phagocytosis – cells that eat cells, cellular classical cascade; an additional number are
process for ingesting eliminating particles which involved in the alternate pathway that is
triggered by microorganism.
are larger than 0.5 micrometers which includes
other organisms and foreign substances. • The major function of complement is
opsonization, chemotaxis and lysis of cell
ACUTE PHASE REACTANTS
IV. HAPTOGLOBIN
*Normal serum constituents that increases
rapidly by at least 25% due to injury or trauma. • Its primary function is to bind irreversibly to
These are the constituents of the cell that free hemoglobin released by intravascular
increases when the body is exposed on infections. hemolysis.

I. C-Reactive Protein (CRP) • Two-fold to tenfold increase in haptoglobin

can be seen following inflammation, stress or
• CRP is the most widely used indicator of tissue necrosis.
acute inflammation
• Normal plasma concentration ranges from 40
• CRP has a plasma half-life of about 19 to 290 mg/dL
hours. Elevated levels are found in conditions
such as bacterial infection rheumatic fever, V. FIBRONOGEN
viral infection, malignant disease, tuberculosis,
and after a heart attack • The most abundant of coagulation factors in
plasma, and it forms the fibrin clot. The
• Normal levels in adult range from molecule is a dimer with molecular weight of
approximately 1.5 mg/dL for men and 2.5 340,000 Daltons.
mg/dL for women. Thus, monitoring CRP
may be an important preventative measure in • Normal levels ranger from 100-400 md/dL
determining the potential risk of heart attack or
stroke. • Fibrinogen also serves to promote
aggregation of the red blood cell and
• A concentration of more than 2mg/L has increase levels contribute to an increase risk
been defined as the threshold for high for developing coronary artery disease,
cardiovascular risk especially in women

II. SERUM AMYLOID-A VI. CERULOPLASMIN

• It is an apolipoprotein that is synthesized in • It is the principal copper-transporting

the liver and has molecular weight of 11,685 protein in human plasma, binding 90-95% of
daltons. the copper found in plasma by attaching six
cupric ions per molecule.
• It has been found to increase significantly
more in bacterial infections than in viral • A depletion of ceruloplasmin is found in
infections. Wilson disease,
YR2 1ST TERM | 22-23 | JMAB
• an autosomal recessive genetic disorder Neutrophils
characterized by a massive increase of
copper in the tissue. • represent approximately 50 to 70% of the
total white blood cells
• Normally, circulating copper is absorbed out by
the liver and either combined with • 10-15um in diameter
ceruloplasmin and return to the plasma or
excreted into the bile duct. In Wilson disease, • Contain large number of neutral staining
copper accumulates in the liver and granules which are classified as primary
subsequently in other tissue such as the granules, secondary granules, and tertiary
brain, cornea kidneys and bones. granules

CELLULAR DEFENSE MECHANISM Eosinophil

Cellular Immunity or Cellular Mediated • approximately 12 to 15 um in diameter,

Immunity
• Nucleus is usually bilobed or ellipsoidal
Are immune responses that doesn’t and is often eccentrically located
invoked antibodies but rather invoked the
activation of phagocytes antigen cytotoxic and the • Their most important role is neutralizing
basophil and mast cell products killing
release of cytokines.
certain parasite.
These are the cells that are invoked in
Basophils
fighting the bacteria that enters our body; white
bloods cells • representing less than 1 percent of all
circulating white blood cell

• between 10 to 15 um in diameter

• Contain coarse densely staining deep

bluish-purple granules that often obscure
the nucleus

Mast Cell

• between 9 to 18 months – life span

• The enzyme content of the granules helps

to distinguish them from basophils as
they contain acid phosphatase, alkaline
phosphatase and protease

• The mast cell like the basophil plays a role

in hypersensitive reaction by binding
IgE.

*B-lymphocytes major cells invoked in the humoral

immunity

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Monocyte IMMUNODEFICIENCY

• The largest cell in the peripheral blood Immunodeficiency disorders result in a full or
partial impairment of the immune system. Primary
• 12 to 22 um they have an average size of immunodeficiencies are the result of genetic
18 um. defects, and secondary immunodeficiencies are
caused by environmental factors, such as
• horseshoe-shaped nucleus
HIV/AIDS or malnutrition.
• They stay in the peripheral blood for up
There are two types of immunodeficiency
to 70 hours
disorder:
Tissue Macrophages
1. Primary immunodeficiency (PID) – inherited
• All tissue macrophages arise from immune disorders resulting from genetic
monocyte mutations, usually present at birth and diagnosed
in childhood.
• 25 and 80 um
2. Secondary immunodeficiency (SID) –
• Macrophages have specific names acquired immunodeficiency as a result of disease
according to their location; or environmental factors, such as HIV,
malnutrition, or medical treatment (e.g.
o Liver – Kupffer cell chemotherapy).
o Lungs – Alveolar macrophages
Primary immunodeficiency (PID)
o Brain – Microglial cells
B cell immunodeficiencies (adaptive)
o Connective tissue – histiocyte
B cells are one of two key cell types of the
INFLAMMATION adaptive immune system. Their main role is to
produce antibodies, which are proteins that attach
The overall reaction of the body injury or to microbes, making it easier for other immune
invasion by an infectious agent is known as cells to detect and kill them
inflammation.
*matures in the bone marrow are
Both cellular and humoral mechanism are responsible for the humoral immunity
involved in this complex, highly orchestrated
process. Each individual reactant plays a role in *B cells deficiency causes impairment or
initiating amplifying or sustaining the reaction and damage of the humoral immunity this can be
delicate balance must be maintained for the mediated by insufficient number or functions of the
process to be speedily resolved. b cells.

4 cardinal signs of inflammation T cell immunodeficiencies (adaptive)

• Redness Mutations in the genes that control T cells

• Swelling can result in fewer T cells or ones that do not
• Heat function properly. This can lead to their killing
• Pain ability being disrupted and can often cause
problems with B cell function too. Therefore, T cell
immunodeficiencies can often lead to combined

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immunodeficiencies (CIDs), where both T and B This form of immunodeficiency will
cell function is defective. Some forms of CIDs are usually resolve if the malnutrition is treated.
more severe than others.
Drug regimens
*responsible for cell mediated immunity
There are several types of medication
* T cells deficiency caused by the decrease that can result in secondary
function of an individual t cells causes immunodeficiencies, but these drugs also
immunodeficiency of cell mediated immunity perform critical roles in certain areas of healthcare

Severe combined immune deficiencies (SCID) Chronic infections

(adaptive)
There are several chronic infections which
In SCID patients there is often a complete can lead to SID disorders, the most common of
lack of (or no production of) T cells and few which is acquired immune deficiency
variable numbers of B cells. *Therefore are syndrome (AIDS), resulting from HIV infection.
insufficient capacity to fight off foreign bodies.
The virus attacks CD4+ T cells, a type of
Phagocyte disorders (innate) white blood cell that plays a critical role in
preventing infection, and gradually depletes their
Mutations typically affect the ability of numbers.
certain phagocytes to eat and destroy pathogens
effectively. Once the T cell count is less than 200 cells
per ml of blood, symptoms of AIDS begin to
These patients have largely functional manifest, and the patient is at high risk of recurrent
immune systems, but certain bacterial and infections that will eventually lead to death
fungal infections can cause very serious harm
or death. What is blood banking?

Complement defects (innate) Blood banking is the process that takes

place in the lab to make sure that donated blood,
Some deficiencies in the complement or blood products, are safe before they are used
system can result in the development of in blood transfusions and other medical
autoimmune conditions such as systemic procedures. Blood banking includes typing the
lupus erythematosus and rheumatoid arthritis blood for transfusion and testing for infectious
(please see our autoimmune briefing for more diseases.
information).
Facts about blood banking
Patients who lack certain complement
proteins are highly susceptible to meningitis. • About 36,000 units of blood are needed
every day.
Secondary immunodeficiency (SID) • The number of blood units donated is
about 13.6 million a year.
Malnutrition • About 6.8 million volunteers are blood
donors each year.
T cell numbers and function decrease in • Each unit of blood is broken down into
proportion to levels of protein deficiency, components, such as red blood cells,
which leaves the patient particularly susceptible plasma, cryoprecipitated AHF, and
to diarrhea and respiratory tract infections. platelets.

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 • One unit of whole blood, once it's • Chagas disease
separated, may be transfused to several
patients, each with different needs. Irradiation to blood cells is performed to
• Annually, more than 21 million blood disable any T-lymphocytes present in the donated
components are transfused. blood. (T-lymphocytes can cause a reaction when
transfused, but can also cause graft-versus-
Who are the blood donors? host problems with repeated exposure to foreign
cells.)
Most blood donors are volunteers.
However, sometimes, a patient may want to Leukocyte-reduced blood has been filtered to
donate blood a couple of weeks before remove the white blood cells that contain
undergoing surgery, so that his or her blood is antibodies that can cause fevers in the recipient of
available in case of a blood transfusion. the transfusion. (These antibodies, with repeated
transfusions, may also increase a recipient's risk
Donating blood for yourself is called
of reactions to subsequent transfusions.)
an autologous donation. Volunteer blood donors
must pass certain criteria, including the following: What are the blood types?
• Rh-positive - 39%
Must be at least 16 years of age, or in
• A Rh-positive - 31%
accordance with state law
• B Rh-positive - 9%
Must be in good health, Must weigh at • Rh-negative - 9%
least 110 pounds • A Rh-negative - 6%
• AB Rh-positive - 3%
Must pass the physical and health history • B Rh-negative - 2%
exam given before donation • AB Rh-negative - 1%

Some states permit people younger than What are the components of blood?
16 or 17 years to donate blood, with parental
Red blood cells. These cells carry oxygen to the
consent.
tissues in the body and are commonly used in the
What tests are done in blood banking? treatment of anemia.

A certain set of standard tests are done in Platelets. They help the blood to clot and are
the lab once blood is donated, including, but not used in the treatment of leukemia and other forms
limited to, the following: of cancer.

• Typing: ABO group (blood type) White blood cells. These cells help to fight
• Rh typing (positive or negative antigen) infection, and aid in the immune process.
• Screening for any unexpected red blood
cell antibodies that may cause problems in Plasma. The watery, liquid part of the blood in
the recipient which the red blood cells, white blood cells, and
• Screening for current or past infections, platelets are suspended. Plasma is needed to
including: carry the many parts of the blood through the
• Hepatitis viruses B and C bloodstream. Plasma serves many functions,
• Human immunodeficiency virus (HIV) including the following:
• Human T-lymphotropic viruses (HTLV) I • Helps to maintain blood pressure
and II • Provides proteins for blood clotting
• Syphilis • Balances the levels of sodium and
• West Nile virus potassium

YR2 1ST TERM | 22-23 | JMAB

Cryoprecipitate AHF. The portion of the plasma
that contains clotting factors that help to control
bleeding.

Albumin, immune globulins, and clotting

factor concentrates may also be separated and
processed for transfusions.

YR2 1ST TERM | 22-23 | JMAB

 URINE ANALYSIS Physical examination
Urine analysis is also called Urinalysis  I. Volume

One of the oldest laboratory practices of • Normal 1-2.5L/day

medicine. It is an array of test performed in urine • Oliguria (low urine output) –
and it is one the most common laboratory o Urine output <400ml/day
procedure. o Seen in; Dehydration, shock, Acute
glomerulonephritis, Renal failure
Why performs urinalysis? • Polyuria (excessive urine output) –
• General evaluation of health o Urine output >2/5L/day
• Diagnosis of disease or disorder of the o Seen in; Increase water ingestion,
kidney or urinary tract diabetis mellitus and insipidus
• Diagnosis of other systemic disease that • Anuria (no urine output) –
affect kidney function o Urine output <100ml/dl
• Monitoring of patient with diabetes o Seen in; Renal shut down
• Screening for drug abuse
II. Color
Collection of samples
• Normal –
• Improper collection may Invalidate result o Pale yellow in color due to pigments
• Container for collection of urine should be urochrome, urobilin and
wide mouther clean and dry uroerythrin
• Analyze within 2 hours of collection else • Cloudiness –
refrigeration o may be caused by excessive
cellular material or protein,
Types of urine sample
crystallization or precipitation of
SAMPLE non-pathological salts upon
SAMPLING PURPOSE
TYPE standing at room temperature or in
Random No specific time Routine the refrigerator
specimen Most common screening • Color of urine depending upon its
Morning First urine in the Pregnancy constituent
Sample morning, most test, • Colorless –
concentrated microscopic o Diabetes, diuretics
test
• Dark yellow –
Clean catch Discard few ml, Urine culture o Concentrade, excess bile
midstream collect the rest
pigment,jaundice
24 hours All the urine Used for
passed during quantitative III. Odor
the day and night and qualitative
and next day 1st analysis of
• Normal –
sample is urine
collected substance o aromatic due to the volatile fatty
Post prandial 2 hours after Determining acid
meal glucose in • On long standing ammonical
diabetic (decomposition of urea forming ammonia
monitoring which gives a strong ammonical smeel)
Supra-pubic Needle aspiration Obtaining • Foul, offensive Pus or inflammation
aspired sterile urine • Sweet – diabetes
• Fruity – Ketonuria
Urinalysis Consist of the following
measurement: • Maple syrup – Maple syrup urine disease
a. Macroscopic • Rancid – Tyrosinaemia
b. Chemical Examination
c. Microscopic examination of sediments
YR2 1ST TERM | 22-23 | JMAB
IV. pH Chemical analysis

• Reflects ability of kidney to maintain The chemical analysis if urine is

normal hydrogen ion concentration in undertaken to evaluate the levels of the
plasma. following component
• Urine ranges from 4.5-8
• Protein
• Normally it is slightly acidic lying between
• Glucose
6-6.5
• Ketones
• Tested by litmus paper, pH paper,
Dipstick • Occult blood
• Acidic urine – • Bilirubon
o Ketosis, systemic acidosis, UTI • Urobilinogen
• Bile salts
V. Specific gravity (refractometer or reagent
strip is used to determine) o The presence of normal and abnormal
chemical elements in the urine are detected
• It is measurement of urine density which using dry reagent strip called dipstick
reflects the ability of the kidney to
concentrate or dilute the urine relative to o When the test strip is dipped in the urine the
plasma from which it is filtered, reagents are activated and a chemical
• Measure by; reaction occurs
o Urinometer, refractometer, dipstick
o The chemical reaction results in a specific
• Normal 1.001-1.040 color change
• Increase in specific gravity –
o Low water intake, Diabetes mellitus, o After specific amount of time has elapsed
Albuminuria, Acute nephritis this color change is compared against a
• Decrease in specific gravity – reference color chart provided
o Absence of ADH, renal tubular
damage Human Urinary System
• Fixed specifi gravitiy –
o Isothenuria 1.010 • Pair of beaned shaped organ - kidneys
• Kidney –
Microscopic examination o dark red, slightly flattened, 10 cm
long, 5cm wide, 2-3cm thick, 120-
• A sample of well mixed urine (usually 10- 170 grams
15 ml) is centrifuged in a test tube at • Ureters
relatively low speed (2000-3000 rpm) for 5- • Urinary Bladder
10 minute which produce a concentration • Urethra
of sediment at the bottom of the tube • Back wall of abdominal Cavity, below
diaphragm
• A drop of sediment is poured onto a
• left kidney is higher than right kidney
glass slide a thin slice of glass is placed
over it and observed under microscope • Convex-outer surface, concave-inner
surface
Elements seen un urine sediments
A. Red blood cell • Filter the waste out of blood
B. White blood cell • Regulates the quantity and compositions of
C. Mucus fluids by removing metabolic wastes
D. Various epithelial cell • Retaining proper amounts of water, salts and
E. Various Crystal nutrients in the body
F. Bacteria • Process around 200 liter of blood and 1-2 liters
G. Cast is removed as urine

YR2 1ST TERM | 22-23 | JMAB