Biol10002 Notes PDF

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BIOL10002 Notes - pdf
Biomolecules And Cells (University of Melbourne)
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• Bacteria cells
1. Cell Structure o Cells typically have a wall (peptidoglycan)
o One surrounding membrane (Gram +ve)
o Two surrounding membranes (Gram -ve)
1.1 Foundations of Biology
• 1st foundation: Evolution via natural selection

o all life evolved from pre-existing life
o homology
o fossils
• 2nd foundation: Unity of Biochemical Processes
o all organisms share main biochemical
reactions
o 1. All organisms have genetic material, the
DNA, that contains the instructions on how
that organism will develop.
o 2. Organisms also have hardware to carry out • Ribosomes
the instructions - the proteins. o All cells have ribosomes
• 3rd foundation: Cell Theory o Two sub-units (small and large) consisting of
o All known living things are made up of one or ribosomal proteins and rRNA.
more cells. o Site of translation – translates mRNA sequence to
o All living cells arise from pre-existing cells by a protein sequence. Small unit reads mRNA, large
division. unit forms polypeptide chain.
o The cell is the fundamental unit of structure o Prokaryotic ribosomes are small 70s (17-23nm)
and function in all living organisms. o Bacterial ribosomes are sensitive to drugs like
o Cells contain hereditary information (DNA) chloramphenicol, erythromycin and tetracycline –
which is passed from cell to cell during cell antibiotics. (Different from eukaryotic ribosomes)
division. • Prokaryotic flagellum
o Motility appendage - long thin filament
1.2 Evolution o Corkscrew action
o Composed of flagellin protein
• Darwin’s 3 observations: o Extracellular
o Variation in population → Fitness o Base is integrated into membrane and can
o Traits passed on to offspring → Heredity change the length and direction of rotation.
o Never enough resources → Competition for • Prokaryotes divide via binary fission. Constricting
survival and reproduction ring pinches parent cell into two.
• Evolution is a 2-step process: • All prokaryotes have no nucleus. Prokaryotes
1. Variability consist of Bacteria and Archaea.
2. Ordering variability by natural selection
1.4 Eukaryotes
1.3 Prokaryotes
• Eukaryotic features not in prokaryotes:
• Characteristics: o Division of labour in the cytoplasm.
o Usually microscopic (1-10µm) o Nucleus and histones (Archaea have histones)
o DNA is single, circular chromosome (‘nucleoid’) o Endomembrane system
o No proteins attached to DNA (Bacteria) o Endoplasmic Reticulum and Golgi complex
o DNA of archaea have proteins(histones) attached o Cytoskeleton, microtubules, microfilaments and
o Peptidoglycan wall similar in bacteria and archaea intermediate filaments.
o Motor proteins and movement
• Eukaryotic nucleus features:
o Double membrane/nuclear envelope
o Presence of nuclear (annular) pores(75nm)
o Linear DNA with histones (chromatin
o Nucleolus – site of ribosome synthesis
o RNA transcribed from DNA leaves nucleus via
pores and goes out into the cell to be translated.

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• Nuclear pores:
o Pores are lined with proteins
o Attached to lamina (nuclear skeleton)
o Traffic of proteins and RNAs into/out of nucleus
o Located at site where inner membrane curls
around to become outer membrane
o Outer nuclear membrane/nuclear envelope is
continuous with the RER and SER.
o The cis face of a Golgi stack is the end where

substances enter from the endoplasmic reticulum
for processing, while the trans face is where they
exit in the form of smaller detached vesicles (near
the plasma membrane).
• Endoplasmic reticulum: • Cytoskeleton:
o Consists of membrane cisternae that ramify o Not composed of membrane, acts as a form of
through the cytoplasm. The result is internal scaffolding/structure within the cytoplasm of
compartments and channels. cells. Cytoplasm is NOT part of the cytoskeleton.
o The ER is a dynamic structure, ever changing in o Cytoskeletal components help maintain cell shape
structure and function. and are involved in certain cell movements.
o There is RER (with ribosomes) and SER. o Major components of cytoskeleton:
o Actin filaments 7nm (actin protein) - gelsolin
controls filament assembly
o Microtubules (tubulin protein), 13 protofilaments
form cylinder (25nm diameter)
o Intermediate filaments (vimentin protein) 10nm
filament diameter
• Functions of intracellular membranes:

1. Provide a surface for biochemical reactions.
2. To establish compartments to prevent mixing.
3. To provide transport of materials within the cell,
from the cell to its exterior, or from the cell to an
adjacent cell.
• Golgi Complex: o Motor elements of the cytoskeleton:
o Consists of flattened stacks of membrane or - actin filaments interact with myosin motors
cisternae called Golgi bodies. Collectively, all the - microtubules interact with kinesin+dynein motors
Golgi bodies in a cell are the Golgi complex. - intermediate filaments are predominantly static
o Golgi bodies are functional extensions of the ER. o Actin filaments:
o The Golgi complex collects, packages, and - Interact with myosin motors
distributes molecules synthesised in the cell. - Responsible for muscle contractions, cytoplasmic
o Almost all the polysaccharides in cells is streaming and microvilli movement
manufactured within the Golgi bodies. o Microtubules:
o Polysaccharides may be attached to either protein - They assemble and disassemble.
or lipid molecules in the Golgi bodies. - Tubulin protein forms protofilament. 13
protofilaments form cylinder/microtubule.

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- Eukaryotic flagella beat (prokaryotic flagella • Triglycerides form by the condensation of 3 fatty
rotate), made of microtubules and dynein motors. acid chains and a glycerol molecule, forming an
- E.g. ciliates(unicellular eukaryotes) covered in cilia ester bond.
- Dynein can slide one microtubule against another, • Phospholipid bilayer: it is selectively permeable
allow it to curve and move. and acts as a barrier to most water-soluble
substances.
o The more unsaturated the tails, the more fluid the
membrane as unsaturated fatty acid tails are bent
and therefore fit together more loosely.
o The longer the tail, the less fluid the membrane.
• Phospholipid: The hydrophilic head contains a
phosphate group and glycerol while the
hydrophobic tail contains 2 fatty acid chains. This
is due to the partial negative charge on the
phosphate group that gets attracted to the partial
positive charge on the hydrogen atom of the
- Kinesin help move vesicles along microtubules water molecule.
o Intermediate filaments: • Individual phospholipids and protein molecules
- They help with intra and inter-cellular stabilisation move around within their own monolayer.
• Molecules enter a membrane in several ways:
2. Lipids and Membranes o Diffusion
o Facilitated diffusion
2.2 Lipids o Active Transport
o Pinocytosis
• Lipids consist of: o Phagocytosis
o sterols
o fats, oils & waxes 2.4 Membrane Transport
o phospholipids
• Uses of lipids: • Osmosis is the movement of water through a
o Fats and oils for energy storage and insulation differentially permeable membrane from a region
o Waxes for protective coatings of high-water concentration/low solute
o Chemical messengers (e.g. sterols) concentration to a region of low water
o Structural components of membranes concentration/high solute concentration.
o Osmotic potential/pressure is the pressure
2.3 Membranes required to prevent the movement of water into a
solution if the solution is separated from that
• All membranes composed of phospholipid bilayer water by a selectively permeable membrane.
contain other components such as proteins, o The ability of an extracellular solution to make
glycoproteins, and sterols. Different membranes water move into or out of a cell by osmosis is
have different ancillary components known as its tonicity.
o RBCs are crenated in a hypertonic solution, and
haemolysed in a hypotonic solution.

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o Exocytosis: This is the movement of substances

out of the cell. A secretory vesicle from Golgi body
moves towards the plasma membrane with the
help of cytoskeleton, using energy from ATP. The
vesicles fuse with the cell surface membrane
releasing the contents outside.
o Endocytosis: is the engulfing of material by fusing
with the plasma membrane to form an endocytic
vacuole in the form of phagocytosis (bulk uptake
of solids e.g. ciliates eating algae) or pinocytosis
(bulk uptake of liquids) using ATP.
• Role of Membrane Proteins and Glycoproteins:

o Some are enzymatically active.
3. Proteins and Enzymes
o Some have a structural role - they can restrict to a
limited space a set of interdependent reactions. 3.1 Proteins
o Determinants of individuality
o Surface receptors for stimuli. • Protein functions:
o Transport mechanisms. o hardware (interpret software code)
o Role as a selective barrier o enzymes (direct reactions)
• Facilitated diffusion is passive diffusion, however, o structure and movement (cytoskeleton and
molecules go through transport proteins instead connective tissues)
of passing through phospholipids. o regulation (hormones) and defence
o Channel proteins: water-filled pores that allow • Amino acids (20 in total) are the building blocks of
charged substances, usually ions, to diffuse protein. Each amino acid has four groups bonded
through the membrane. They have a fixed shape to a central atom called the alpha (α) - carbon.
and can be gated to control ion exchange. This • Amino acids R - groups (total of 20):
does not use ATP and is in facilitated diffusion. o Some are polar but uncharged (hydrophilic)
o Some are charged (hydrophilic)
o Some are non-polar (hydrophobic)
o Some form rings
o Some have special properties (e.g. cysteine links
two amino acids by forming disulphide bonds) S-S
• Protein formation:
o condensation of amino acids
o Peptide bonds - polypeptide
o Linear chain of amino acids
o Variable length and order of amino acids gives
o Carrier proteins: can flip between two shapes and
almost infinite possibilities
is mainly in active transport where it uses ATP to
change shape and carry ions/molecules up the
concentration gradient. It is also involved in
passive transport (facilitated diffusion) down the
concentration gradient without the use of energy.
• Active transport: Movement of substances from a
region of low concentration to a region of high
concentration against a concentration gradient.
This occurs via specific carrier proteins that use
energy from ATP e.g. Na+/K+ pump.

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• Denaturation disrupts the tertiary and secondary

structure of a protein and destroys the protein’s
biological functions.
• Renaturation is sometimes possible, but usually
denaturation is irreversible.
3.3 Enzymes
• Enzymes act as catalysts and are typically proteins

(some RNA molecules have enzyme activity):
o Increases reaction rate
o Do not alter final equilibrium
o Do not alter Δ G
o Recyclable
o Decreases Ea
o Regulated
• Cell chemistry largely achieved by coupling
3.2 Levels of Protein Structure endergonic reactions with exergonic reactions
o Endothermic and exothermic refer to transfer of
1. PRIMARY STRUCTURE - the amino acid sequence. heat or changes in enthalpy.
o Endergonic and exergonic refer to changes in free
2. SECONDARY STRUCTURE - the conformation
changes in primary structures due to the energy (usually the Gibbs Free Energy).
formation of electrostatic and hydrogen bonds o An endergonic reaction (also called a heat absorb
between nearby amino acids. nonspontaneous/unfavourable reaction) has a
positive change in free energy, and an additional
driving force is needed to perform this reaction.
o An exergonic reaction(spontaneous/favourable)
has a negative change in free energy and can
occur without the addition of energy.
• There is an enzyme for almost every cellular
reaction. All enzymes have their own specificity
and there are multiple copies of each enzyme.
3. TERTIARY STRUCTURE - the ultimate • Active site - the shape of the active site is
configuration that a polypeptide chain takes in precise and substrates that are not
reaching the configuration of minimal free energy. complementary to the shape of the active site
4. QUATERNARY STRUCTURE - association of the cannot bind. The E-S complexes formed enable
individual polypeptide chains in proteins the reaction to take place more easily.
made of multiple polypeptides e.g. haemoglobin • Induced fit theory: the enzyme’s active site is not
initially an exact fit to the substrate molecule.
However, the enzyme molecules are more flexible
and can change shape slightly as the substrate
enters the enzyme. This means that the enzyme
molecule will undergo conformational changes as
the substrate combines with enzyme’s active site,
forming the enzyme-substrate complex.
3.4 Regulation
• Competitive Inhibitors (reversible):

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• Non-competitive Inhibitors (usually reversible): • Enzyme partners include:

o Vitamins (e.g. vitamin C is an essential partner for
enzyme that makes collagen for connective
tissues. Lack of vitamin C leads to scurvy)
o Metal ions (e.g. Mg2+)
o Temporary electron holders (e.g. NAD/NADH)
o ATP
• Allosteric inhibitors (negative modulators):

o Negative allosteric modulation occurs when the
binding of one ligand decreases the affinity for
substrate at other active sites.
• Allosteric cooperativity (positive modulators)
o Positive allosteric modulation occurs when
binding of the effector enhances the enzyme's
affinity for other ligands.
4. Energy
4.1 ATP
• ATP is a molecular battery & coenzyme
• Feedback loops such as negative feedback e.g.

end product inhibition, or positive inhibition also
play a part in regulation.
3.5 Enzyme Partners
• Enzymes for particular pathways are often

physically linked - substrate channelling.
• Energy released from an exergonic reaction is
used to phosphorylate ADP, which is then
dephosphorylated to drive an endergonic reaction

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• Respiration pathways:
o Net gain for each glucose molecule is:

o 2 Pyruvate, 2 ATP, 2NADH + 2𝐻 +
• Link Reaction/Pyruvate Oxidation:

• Cells use either light energy or chemical energy to
o In the matrix of mitochondrion which needs
set up proton gradients
pyruvate to actively be transported into matrix
• Enzyme partners such as NAD+ and FAD+ often
o Decarboxylation occurs - the removal of CO2
receives the electron – reduction is gain of
o Dehydrogenation also occurs - removal of H2
electrons; oxidation is loss of electrons.
o Coenzyme A acts as a carrier for acetyl groups to
the Krebs cycle
4.2 Aerobic Respiration

o Net gain for each pyruvate molecule(x2):
• Respiration is the process in which organic o 1 Reduced NAD, 1 𝐶𝑂2
molecules act as a fuel: (2 pyruvates formed in glycolysis so net gain is x2)
1. Glycolysis
2. Link reaction • Citric acid/Krebs’s cycle
3. Krebs cycle o Closed pathway also occurs in the matrix
4. Oxidative phosphorylation o No oxygen used in this or previous pathways as it
is only used in oxidative phosphorylation.
• Glycolysis o Net gain for each acetyl CoA molecule(x2):
o Is the splitting, or lysis, of glucose to form 2 o 2 𝐶𝑂2 , 1 Reduced FAD, 3 Reduced NAD, 1 ATP
molecules of pyruvate (3C) which occurs in the (Note: Remember there is 2 acetyl CoA molecules so
cytoplasm of the cell. net gain is 2 times)
o First stage is phosphorylating glucose using 2 ATP
o Hexokinase transfers 2 phosphates onto hexose (Phosphatase protein removes phosphate group,
which forms fructose biphosphate(6C) and then kinase protein adds phosphate groups to molecules)
splits into two molecules of triose phosphate(3C).

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• ATPase is only second known rotational shaft

design in biology:
o F0 = 7 fold symmetry
o F1 = 3 fold symmetry
• Aerobic respiration
requires oxygen and
pyruvate from glycolysis is
sent to the mitochondrion
and completely oxidised to
CO2 and H2O therein
4.3 Anaerobic Respiration
• When no oxygen is present hydrogen cannot be

disposed in the ETC therefore chain stops, and
reduced NAD not oxidised hence soon Krebs cycle
• At the end of glycolysis: also stops. An alternative H acceptor (pyruvate) is
o All carbons from glucose now released as CO2 required, and hence fermentation takes place.
o Extra 2 ATP molecules generated • In plants:
o Large numbers of reduced NAD and FAD carriers o Glycolysis takes place normally then pyruvate is
• Overall net gain of each glucose molecule: decarboxylated to ethanal, and then reduced to
o 6 𝐶𝑂2 , 10 NADH + 𝐻 + , 2 𝐹𝐴𝐷𝐻2 , 4 ATP ethanol by the enzyme alcohol dehydrogenase
o Reaction cannot be reversed
• Oxidative Phosphorylation and ETC: o This conversion is called alcoholic fermentation
o At this stage chemiosmosis takes place in the
inner mitochondrial membrane (Cristae)
o Reduced NAD and FAD are passed to ETC and
release hydrogen which splits up into 𝐻 + and 2𝑒 −
o Electrons flow down ETC release energy to pump
𝐻 + ions from the matrix to the intermembrane
space producing a proton gradient
o 𝐻 + then move down proton conc. gradient
through ATP synthase and form 𝐻2 𝑂 by
combining with oxygen and the 2 electrons
o ADP + Pi → ATP occurs while the hydrogen passes
through the ATP synthase and uses hydrogens
electrical potential energy for chemiosmosis
• In animals:
o Pyruvate is reduced to lactate/lactic acid by the
enzyme lactate dehydrogenase
o Reaction can be reversed by the same enzyme:
- By transporting the lactate to the liver via blood
plasma which is then converted back to pyruvate
- About 20% is oxidized directly to form CO2 and
o Net gain of around 28 molecules of ATP in ETC H2O in the liver when oxygen is available
(Overall 32 ATP produced in aerobic respiration) - Remainder is converted by the liver to glycogen

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o Arrangement of respiration machinery in

α-proteobacterium (Gram negative) is same as the
arrangement in mitochondrion
• Plastids are double-membrane organelle which
are found in the cells of plants and algae. They
manufacture and store food:
o Plastids and mitochondria contain small, bacterial-
sized ribosomes (70S).
o Translates own proteins from their genome (DNA)
o Plastids have circular DNA
o Considered to be endosymbiotic Cyanobacteria
• Theory of Endosymbiosis
o Complex organelles believed to have been derived
from relict symbionts:
o Mitochondria: thought to have originated as
o Process can be toxic and inefficient overtime, so symbiotic aerobic bacteria (alpha-purple)
aerobic respiration is preferred. o Chloroplasts: believed to be derived from
symbiotic photosynthetic bacteria (cyanobacteria)
5. Endosymbiosis 5.2 Chloroplasts
5.1 Mitochondria • Chloroplasts are energy catchers of plant cells:

o Cells may contain one or many chloroplasts
• Mitochondria is the powerhouse of the cell: o Surrounded by two membranes, an outer
o Cells may contain several of these organelles or membrane plus an inner membrane that forms a
have a single, large mitochondrion. complex internal network of lamellae/thylakoids.
o Surrounded by two membranes, an outer o Photosynthetic pigments are located at thylakoids
membrane and a highly convoluted inner o Chloroplasts are responsible for photosynthesis,
membrane, with inward projections called cristae or the conversion of light to chemical energy
o Mitochondria carry out the aerobic respiration of o Believed to have derived from cyanobacteria
all eukaryotic cells. o Fossils known as stromatolites tell us that
cyanobacteria existed 3.5 billion years ago.
• Evidence mitochondria evolved from prokaryotes:

o ETC and turbine ATPase of inner membrane are • Structure:
same as the plasma membrane of bacteria o Thylakoid membrane: where light-dependent
o Circular DNA chromosome (genome) occurs. Associated with chlorophyll, accessory
o Ribosomes (small, sensitive to chloramphenicol) pigments, electron transport chain.
o Divide by binary fission (presence of FtsZ protein) o Grana: stacks of thylakoid membranes which
o Bacteria have membrane folds like mitochondria enclose hydrogen reservoir used in chemiosmosis
o Lamella: extensions form network between grana

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o Stroma is where rubisco catalyses light 3. The Electrons then recombine with a proton to
independent reaction form a hydrogen atom, which is taken up by the
o Starch granule → insoluble storage carbohydrate hydrogen carrier NADP forming Reduced NADP.
product of photosynthesis 4. The combination of the water splitting, and the
pumping caused protons to build up inside the
5.3 Light Dependent Reactions thylakoid lumen, generating a proton gradient
across the thylakoid membrane. ATP is therefore
• Takes place in the thylakoid membranes photophosphorylated using the ATP synthase
• Photosystems are required to trap wavelengths of enzyme in exactly the same way as respiration.
light (photons) to energize the electron found in
the primary pigment • Cyclic Phosphorylation:
• Accessory pigment arranged in light harvesting o Only involves Photosystem I
clusters that pass on absorbed energy to the o Electron photoactivated and instead of falling
primary pigment (chlorophyll α) at reaction centre back into the photosystem and loosing energy as
• Photosystem I absorb wavelengths of 700nm thermal energy, the excited electron is captured
• Photosystem II absorbs wavelengths of 680nm by electron acceptor
o It is then passed on via a chain of electron
carriers, during which, enough energy is released
to synthesize ATP by chemiosmosis
o Electron then returns back to Photosystem I
• Non-Cyclic Phosphorylation:
(Light energy is captured to make ATP and reduce
1. Accessory pigments in PSII absorb photons of NADP, which are then used to fix CO2 into sugars)
light, and the energy is passed onto primary
pigment (chlorophyll α) exciting primary pigments
electrons (photoactivation) to a higher energy
level causing them to escape and also causes the
splitting (or photolysis) of water molecules:
2H2O → O2 + 4H+ + 4e−
o Oxygen diffuses out of the chloroplast into the air
o The protons build up in the thylakoid lumen
causing a gradient to be formed
o The electrons in water replace the electrons that
have left the primary pigment (Photosynthesis is like aerobic respiration, but
2. The energized electrons are taken up by electron electron is released by light energy instead of glucose
acceptor, and are passed down electron carrier oxidation)
chain. They are passed from PSII to carrier
proteins, where the energy is used to pump
protons from stroma to lumen. The electrons are
then passed to PSI, where more light energy is
absorbed by the chlorophyll molecules and the
electrons is reenergised.

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5. Their metabolism is like existing prokaryotic

5.4 Light Independent Reaction organisms (cyanobacteria for chloroplast and a
purple bacterium for mitochondrion).
• Occurs in the stroma of chloroplast and is called 6. Some chloroplasts still have the bacterial
the Calvin Cycle. peptidoglycan wall between the inner and outer
• ATP and Reduced NADP is taken from the light membranes.
dependent stage • Photosynthesis and respiration make the
biosphere work. Bacteria invented both processes
before eukaryotes even existed and eukaryotes
co-opted both processes by endosymbiosis.
• Cryptic chloroplasts/relict plastids exist in malaria
parasites and are ideal targets for new drugs.
Antibacterial kill malaria parasites by interfering
with the plastid or mitochondrion.
6. Cell Division
6.1 Bacterial Division
• Divides by binary fission

• FtsZ protein (filament temperature sensitive)
o FtsZ is a homologue of eukaryotic cytoskeletal
protein tubulin (flagella, mitosis)
1. Carbon dioxide binds to the 5-carbon sugar o It is involved in division of chloroplasts and
ribulose bisphosphate (RuBP) to form an unstable mitochondria (endosymbiotic bacteria)
intermediate, this is catalysed by the enzyme
rubisco. The intermediate is then broken down to
form 2 molecules of (3C) glycerate phosphate.
2. GP is reduced and activated to form triose
phosphate (TP). The ATP and NADPH from the
LDRs provide the energy for this step. ADP/NADP
return to the thylakoid membrane for recycling.
3. Most of the triose phosphate continues through a
series of reactions to regenerate the RuBP using
ATP and complete the cycle.
o Some of the triose phosphate molecules combine
to form glucose, starch for storage, cellulose for
cell walls and sucrose for translocation
o Others converted to glycerol and fatty acids to
produce lipids for cell membranes or acetyl
coenzyme A (CoA).
6.2 Cell Cycle
5.5 Evidence for the Endosymbiotic Origin of
• The cell cycle has 3 phases - interphase, nuclear
Mitochondria and Chloroplasts
division and cell division (cytokinesis).
o Interphase (G1, S, G2) is where the cell grows to
1. These organelles appear morphologically similar
normal size after cell division and synthesises
to bacteria.
important substances e.g. proteins etc.
2. They are surrounded by an outer membrane
1. Growth 1 phase (G1) is the gap after cell division
similar to a cell membrane while their inner
and before S phase.
membrane invaginates to form lamellae or
o Cell prepares for growth and DNA synthesis (S
cristae. Derives from Gram negative Bacteria.
phase) by producing RNA, proteins and enzymes.
3. Mitochondria and chloroplasts are semi-
o If there are insufficient growth factors, or cell has
autonomous, retaining their own genome (DNA,
reached its maximum size, cell will not divide.
RNA, proteins).
4. They also retain their own machinery for
synthesizing proteins, including ribosomes.

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2. S phase: synthesis of DNA (in euchromatin form) 6.3 Meiosis

or DNA replication so each chromosome consists
of two identical chromatids (short phase). • Meiosis is reductive cell division to produce cells
3. Growth 2 phase: gap after S phase and before (gametes) with half genetic material - diploid(2n)
nuclear division (prepares for mitosis) cells to haploid(n).
o New DNA checked, and errors are repaired. o Meiosis is essential for sex so that two gametes
o Increase in the production of tubulin to make can fuse to restore the full amount of DNA to the
microtubules for the formation of mitotic spindle. offspring and so DNA doesn’t double every time
o Nuclear envelope envelopes nucleus. o Also causes genetic variation for gametes which is
the raw material for natural selection in species
o Mitosis is nuclear division producing two
genetically identical daughter nuclei, each
containing the same no. of chromosomes as the
parent, due sister chromatids with identical DNA
• Variation is caused by:

o During late prophase I, crossing over takes place
where two chromosomes (bivalents) attach to
each other forming chiasma and switching genetic
information
• During metaphase I, independent assortment
(Note: nuclear envelope breaks down into vesicles
occurs which is the random lining up of
during prophase and reassembles when the vesicles
homologous chromosomes across the equator
fuse to form the envelope back at telophase)
and so maternal and paternal genes can mix
• A nucleosome is DNA wrapped around 8 histones
molecules(proteins).
• Chromatin is a combination of DNA (acidic)
wound around histones proteins (basic).
o Heterochromatin is tightly coiled (condensed)
chromatin, most condensed at metaphase and
also densely stained under microscopy.
o Euchromatin is loosely coiled at interphase
(between divisions) and not as densely stained.
• Two kinetochores at centromere on each
chromatid during metaphase:
o Made of proteins that bind to DNA in centromere 7. Carbohydrates & nucleic acids
and also to microtubules.
o Microtubules extend from kinetochore to the • Major macromolecules:
poles of spindle. o Lipids
• Centrosome: poles of spindle and act as MTOC o Proteins
with a pair of centrioles that are surrounded by o Carbohydrates
proteins which make microtubules. o Nucleic Acids (DNA and RNA)
• Humans have 46 chromosomes:
o 22 pairs of autosomes and 1 pair of sex 7.1 Carbohydrates (polysaccharides or sugars):
chromosomes (XX or XY)
• If the chromosomes aren’t captured by both • Source of energy and form structural components
kinetochores, one cell ends with three copies of a • Most abundant organic compounds in nature
chromosome and one cell with none – • General formula (𝐶𝐻2 𝑂)𝑛 (where n is number of
aneuploidy. This causes Down’s Syndrome. carbon atoms, usually between 3-8)

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o Hydrogen bonds are also formed between parallel

cellulose molecules. 60 and 70 cellulose molecules
become tightly cross-linked to form bundles called
microfibrils. Microfibrils are in turn held together
in bundles called fibres by hydrogen bonding.
o Fibres increase tensile strength to withstand
osmotic pressure, making the plant rigid and
determine cell shape. Also, freely permeable.
• Three main groups of carbohydrates are

monosaccharide, disaccharides & polysaccharides
• Starch is a macromolecule that is found in plant
cells and is made up of two components known as
amylose and amylopectin. These components are
polysaccharides that are made from glucose
molecules and contains 1,4 glycosidic bonds:
• Cellulose is the most abundant organic,

macromolecule on earth. Plant cell walls are
mainly composed of cellulose. Arthropod
exoskeleton/fungi cell wall are composed of chitin
7.2 Nucleic Acids
• DNA and RNA are linear, unbranched chains made

up of four types of nitrogenous bases.
• In DNA the 4 bases are:
o Adenine - (A)
o Cytosine - (C)
o Guanine - (G)
o Thymine - (T)
• In RNA Thymine – (T) is replaced by the closely
o Amylopectin is branched in structure and related base Uracil - (U).
therefore also contains α 1,6 glycosidic bonds. • DNA is made up of two antiparallel
o Amylose is helical in shape and more compact polynucleotides strands lying side by side, held
while amylopectin in branched. Starch is highly together by hydrogen bonds. The H bonds ensure
compact and stores energy. stability, 3d structure and makes DNA replication
• Glycogen is a macromolecule that is used for the easier. These strands are arranged into a ladder-
storage of energy is animal cells and is also made like structure called a double helix. The phosphate
from α glucose molecules. The structure of and the sugar form the back bone of the DNA
glycogen is very similar to that of amylopectin; molecule while the base pairs form the rings.
however, it is more branched and therefore o Complementary base pairing:
contains more α 1,6 glycosidic bonds. - between adenine and thymine
• Cellulose is found in the cell wall of plant cells and (or adenine and uracil in RNA)
is made from β-glucose units that form β-1,4 - between guanine and cytosine.
glycosidic bonds.
o Alternate β- glucose molecules are rotated 180
degrees in order to form these bonds.

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7.3 Protein Synthesis
• Genetic language
o DNA language has 4 letters and 64 three letter
words (triplets/codons). Gene for each protein.
o Protein language has 20 letters (amino acids) and
infinite number of words of any length
o Order of amino acids is prescribed by the
nucleotide sequence of the gene
o Order of amino acids determines shape of protein
and shape of the protein determines the function
• Transcription occurs in the nucleus:
o DNA unwinds to form two strands and the
antisense strand acts as a template.
o Free activated RNA nucleotides line up with their
complimentary base.
o Phosphodiester bonds formed between sugar
phosphate groups with help of RNA polymerase
o Starts at Promoter (initiates transcription)
o Ends at terminator (the enzyme stops adding
• RNA is a single stranded polynucleotide chain nucleotides to the growing mRNA)
present in the nucleus, cytoplasm, and ribosome. o Hydrogen bonds between the DNA and mRNA
o It contains a pentose sugar (ribose) and has 4 strand are then broken
nitrogenous bases: o DNA is reformed and mRNA strand then leaves
- Adenine, uracil, guanine, and cytosine the nucleus through the nuclear pores
- There are different types of RNA which include: • Translation:
1. mRNA (messenger RNA): carries the genetic o Small ribosomal subunit attaches to mRNA
information in the form of a template from the o tRNA enters the ribosome and attaches to mRNA
nucleus to the ribosome for translation. o A codon on the mRNA attaches to a specific
2. tRNA (transfer RNA): has a specific amino acid at anticodon on the tRNA
one end and an anticodon at the other end. It fits o AUG is start codon - complementary anticodon is
onto the mRNA at ribosomes at complementary UAC that brings amino acid methionine
mRNA codon for protein synthesis. o Only 2 tRNA molecules can fit in the ribosome at
the same time
o Each tRNA carries a specific amino acid
o A peptide bond is formed between the amino
acids of 2 adjacent tRNA molecules with the help
of peptidyl transferase
o Ribosome moves along the mRNA, reading the
next codon. A third tRNA molecule brings a third
amino acid, which joins to the second one. The
first tRNA leaves and is reused.
o The polypeptide chain continues to grow until a
‘stop’ codon: UAA, UAC or UGA.

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7.4 New Genetic Technology 8. Tissues and Homeostasis

• Some diseases potentially able to be treated with
8.1 Types of Cells
gene therapy:
o Severe combined immunodeficiency (SCID or
• Fat cells, neurons, macrophage, smooth muscle
“bubble boy” syndrome)
cells, glial cells etc.
o Haemophilia A & B
o Hypercholesterolemia • We are made up of 1000s of cells and over 200
o Thalassemia different types of cells, arranged into organs
o Sickle cell anaemia • Organs are composed of tissues
o Duchenne muscular dystrophy • There are four tissue types:
o Cancers 1. Epithelial Tissues
o Cystic fibrosis CF o Epithelial tissues are densely packed and cells are
• SCID is the inability to produce the enzyme tightly connected cells, which creates boundaries
adenosine deaminase (ADA) hence causes between the internal and external environment
immune system to be crippled, and sufferers and between compartments.
usually die in infancy from common infections o Line blood vessels, various tubules, and ducts
• CRISPR is derived from a bacterial ‘immune’ o Functions
system where bacteria can ‘remember’ the DNA - Create barriers and regulate transport across
sequence of a previous virus infection and use it those barriers
to destroy the virus’ DNA whenever it ties to - May be involved in secretion and absorption.
reinfect the bacterium (or its offspring). Genetic - May be involved in smell and taste
engineers have now adapted CRISPR to change a o Three Types:
gene sequence with absolute precision. - Columnar
- Cuboidal
• Cystic fibrosis is a recessive allele that codes for a
- Squamous(flattened)
transport protein called CFTR, causing the
production of abnormal thick mucus that is
difficult to be removed. Other body parts such as
pancreatic duct can become blocked as well as
reproductive ducts causing infertility.
o Gene therapy can be applied by altering the
genotype and inserting the normal allele into
appropriate cells, but there can be side effects
• Sickle cell anaemia
o single mutation in haemoglobin
o altered tertiary structure of protein
o deformed red blood cells
o poor blood flow
o Confers resistance to malaria so gene maintained
despite reduced fitness. People who have
heterozygous sickle cell (HbA HbS) are partially
immune to malaria. o Columnar Epithelial Cells are polarised. Basal side
• Stem cell research: growing new parts or attached to organ; apical side faces the lumen.
regenerating tissues and organs
• Synthetic Biology:
o Chemically synthesise artificial bacterial
chromosome that has desired genome
- Remove genome from recipient bacterium
- Insert new genome in recipient
- grow and set to work
• Other genetic technology: Cloning, Lazarus project 2. Muscle Tissues
o Most abundant tissue in body.
o Muscle cells contain long filaments of myosin and
actin – allow muscles to contract and exert force.
o 3 types of muscle tissue
- Skeletal muscle (attached to bone)

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- Cardiac muscle (heart) 4. Nervous Tissues

- Smooth muscle (in outer walls of hollow internal
organs e.g. stomach, bladder, blood vessels) o Nervous Tissue includes neurons and glial cells
o Two basic cell types
- Neurons: many shapes and sizes, encode
information as electrical signals and communicate
with other cells via secretion of neurotransmitters
- Glial cells (Glia): do not conduct electrical signals
but provides support and protection to neurons.
E.g. creates a barrier that protects brain from
chemicals in blood.
3. Connective Tissue
o Connective Tissue includes blood, bone, and fat
o Consists of loose cells (fibroblast or stromal cell)
embedded in an extracellular matrix
• Organs are composed of more than one tissue
o Extracellular Matrix (ECM) can be considered a
types e.g. small intestine
‘scaffold’ or ‘meshwork’ that provides a structure
for the connective tissue cells (cells sit on matrix)
o Called ‘Extracellular’ because the proteins in the
matrix are secreted by cells (cells make matrix)
o Composition and properties of the ECM is
different in different connective tissues
o Extracellular Matrix (ECM) proteins:
- Collagen: Most common, long fibres that are
strong and resistant to stretch, provide structural
strength to organ e.g. bone, skin.
- Elastin: long fibres that can be stretched then
recoil, abundant in tissues that can be regularly
stretched e.g. lung, arteries.
8.2 Body Fluids
• Amoeba - a unicellular organism - living in pond

water – can fulfil its needs by exchange across its
cellular membrane and its external environment.
• Complex multicellular must have a stable internal
environment of interstitial fluid (the fluid inside
organs/tissues) to function.
• Intracellular fluid exchanges with interstitial fluid
o Blood is considered a connective tissue, blood

matrix not a meshwork but a fluid.

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• Extracellular fluid is the fluid found in interstitial - Evaporation (helps to release heat from the body)
fluid, plasma, and lymph: - Convection
- Conduction
o Evaporation of water from body surfaces or
breathing passages cools the body
o Blood flow to skin is another way to reduce body
heat as heat from body via blood to skin is lost to
the environment.
o Metabolism - energy reactions in the body are
inefficient and produce heat as a by-product.
8.3 Homeostasis 8.5 Hypothalamus as Temperature Regulator
• Homeostasis is the maintenance of stable • The basal metabolic rate (BMR) of an endotherm
conditions in the internal environment and is an is the lowest metabolic rate/daily energy
essential feature of multicellular complex animals. necessary for biochemical and physiological
processes of a resting animal.
• Maintaining homeostasis requires control and
• The hypothalamus is the control centre in brain
regulation in response to changes in both the
that regulates mammalian body temperature:
external and internal environments.
o Negative feedback: tells the regulatory system to
• Regulatory systems controlling the organ systems reduce or reverse a process
are the nervous system and the endocrine system. o Positive feedback: tells the regulatory system to
amplify or increase a response beyond set-point
o In an experiment:
- If hypothalamus temperature is raised, metabolic
rate decreases to favour heat loss and body
temperature decreases.
- If hypothalamus temperature is cooled, metabolic
rate increases to produce heat and body
temperature increases.
• Vitamins, hormones, proteins, potassium, sodium,
TSH, Cholesterol etc. all have to be regulated
• Temperature must be regulated in the body over
a narrow range, otherwise hyperthermia occurs
leading to improper function of proteins and cell
membranes, and can ultimately lead to cell death
o Heat stress and injuries occurs when the body’s
ability to dissipate heat is inadequate.
o Heat cramps -> Heat Exhaustion -> Heat Stroke
8.4 Endotherms and Ectotherms • Changes in body temperature can lead to fever,
hypothermia, and hibernation. Hibernation is
• Endotherms regulate body temperature by Regulated drop in hypothermia/body temp in
producing heat or active mechanisms of heat loss animals to scarce food or periods of cold.
e.g. mouse have a constant body temperature • Heterotherm: an animal that regulates its body
• Ectotherms are animals whose body temperature at a constant level sometimes but
temperatures are determined mainly by external not at other times, such as a hibernator.
sources of heat e.g. lizard body temperature
equilibrates to temperature of the environment
• Endotherms regulate their body temperature by
altering rates of heat gain and heat loss
o All gains and losses of thermal (heat) energy that
an animal experiences occur via:
- Metabolism (generates heat in the body)
- Radiation

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9. Cell Communication/Signalling 9.3 Signalling Molecules
• Signalling molecules/ligands can act at a distance,

9.1 Signalling
in which it is known as hormone action.
o Signalling molecules/ligands secreted travels via
• Proliferation (cell division), apoptosis
the blood to the cells or tissues
(programmed cell death) and morphogenesis (cell
shape change) etc. all require signalling pathway
• Example of signals that lead to specialisation and
proliferation of different blood cell types:
• Signalling molecules/ligands can act locally which

can be paracrine or autocrine action.
o Paracrine signalling is when signalling molecule
binds to receptors on nearby cell
• A cell can process information (signal) from its o Autocrine signalling is signalling molecule binding
environment which can be a molecule, light etc. to receptors located on the cell that secreted it.
• The presence of a signal does not mean the cell - Signalling molecules/Ligand do NOT enter the
will respond. In order to respond, a cell must have blood. They travel only in the interstitial fluid.
a specific receptor that can detect it.
o A receptor is a molecule on the cell’s surface or
within a cell that recognises and binds with a
specific signalling molecule. They are proteins.
o that may lead to a cellular response.
o Signalling molecule -> Receptor binding causes
the receptor to change shape, triggering cellular
response directly or via one or more other steps
9.2 Signalling Transduction Pathway
• Basic steps to signal transduction pathway:

1. A signalling molecule or ligand binds to a receptor
2. Transduction (conveying message to cell)
3. Response (effects) • Juxtracrine signalling involves contact between
• The signal transduction pathway is a sequence of cells, in which a ligand/signalling molecule on one
molecular events that lead to a cell’s response cell surface binds to a receptor on the other.
• Cells are exposed to many signals and may have o Requires physical contact between 2 cells.
different responses to different signals - Between plant cells: plasmodesmata
- Between animal cells: gap junctions/connexons

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9.4 Receptors
• Receptors can be classified by location:
2. G-protein linked receptor

o Intracellular receptors can be cytoplasmic or
o The exchange of GDP for GTP is a way to activate
nuclear depending on their location.
a protein – receptor protein or cellular protein
o The G-protein has 3 molecules/polypeptide

subunits which:
1. Can bind to a membrane bound receptor
2. Has a GDP/GTP
3. Can bind to an effector protein
• Membrane bound receptors usually have: o When a signalling molecule binds to the receptor,
o An extracellular domain(binds signalling molecule) there is a conformational change in the receptor,
o Transmembrane region (anchors receptor to the which makes it possible for the G-protein to
plasma membrane)
interact with the receptor. The intracellular
o An intracellular region (which plays an important
domain of the receptor exchanges GDP for GTP
role in the response to signal)
and activates the G protein.
o The subunit of the G-protein containing the GTP,
is now able to move through the membrane and
bind to an effector molecule (e.g. Adenylyl
cyclase). After activating the effector molecule,
GTP is hydrolysed back to GDP.
o The diagram above shows the final step, after the
G-protein subunit activates the Effector Protein,
9.5 Types of Membrane Bound Receptors energy (in phosphate bond) is used up activating
the effector protein – so GTP is hydrolysed back to
• Ligand-Gated Ion Channel, G-protein linked GDP and the G-protein is now inactivated.
receptor and Protein Kinase Receptor.
1. Ligand-Gated Ion Channel Receptor: Direct

Transduction

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o A cascade of steps/reactions lead to cellular o In cancer cells, mutation in Ras causes constant
response e.g. altered level of enzyme activity in activation – signal not switched off and this leads
liver cells: to tumour formation.
10. Vertebrate Heart Structure and

- Cyclic AMP is a secondary messenger molecule
- Protein kinase A is important because it not only Function
activates PPK but also inhibits glycogen
synthetase so that there are two mechanisms that 10.1 Circulatory System
help release a lot of stored glucose quickly from
the liver when needed. • Animals need a circulatory system because:
o O2, nutrients must be transported around the
3. A Protein Kinase Receptor: Indirect transduction body to tissues and organs
via second messenger o Waste products must be removed
o Communication via hormones
o Temperature regulation and reproduction, etc.
o Circulatory systems evolved along with increased
metabolic demands in complex, larger animals
• Open circulatory systems:
o Blood (haemolymph) flows freely within body
cavities making direct contact with tissues/organs
o Hearts pump the fluid to different regions of the
body via blood vessels
o Vessels are open-ended so haemolymph flows out
and bathes tissues
o All components of haemolymph leave the vessels
o Fluid drains back to heart. Enters the heart when
relaxed via ostia (openings), which act as valves to
ensure one-way flow of fluid.
o Secondary messenger lead to activation of Ras
proteins, family of proteins called small GTPases
o After a normal cell has responded the signal is
regulated/switched off under normal conditions:
• Closed circulatory systems:

o Circulating fluid (blood) contained in a continuous
series of vessels
o Hearts pump fluid to different regions of the body
through blood vessels
o Specific components of the fluid filter out of the
vessels (in capillaries) to penetrate tissues

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- Small solutes and water leave - Left receives oxygenated blood from lungs
- Larger molecules blood cells remain - Right receives deoxygenated blood from body
o Transport fluid (blood) is kept separate from fluid o Gill specialisations: low-resistance by-pass to lung
that surrounds cells (interstitial fluid) and direct link to aorta
o Fluid returns to the heart via veins, with valves to o Oxygenated blood is separated from
ensure one-way flow of fluid deoxygenated blood
o Blood can be oxygenated in air or water.
• Advantages of a closed circulation:

o Faster transport and more efficient delivery of
fluid to tissues • Amphibians:
o Ability to control distribution of blood to specific o 3-chambered hearts
tissues (by changing vessel resistance) - Left atrium: oxygenated blood from lungs
o Assists in the delivery of larger molecules (i.e. - Right atrium: deoxygenated blood from body
nutrients and hormones) to specific tissues - Single ventricle: potential for some mixing of
o Enabled the evolution of circulatory systems blood, BUT a septum directs blood movement and
which keep oxygenated blood separated from maintains separation (≥90%)
deoxygenated blood
- Partial separation of pulmonary and systemic
10.2 Evolution of vertebrate heart chambers circuits allows different pressures
• Fish:
o One atrium and one ventricle, one circulation
o Specialisation of vessels (arteries & veins)
o Blood pumped over gills to become oxygenated
but leaves under very low pressure
o Very low pressure in capillary beds and limits
efficiency of delivery of nutrient and O2 to tissues
• Reptiles:
o 3 (or 4) chambered hearts
o Have 2 aortae:
- Left: oxygenated blood from left ventricle to body
- Right: receives blood from both ventricles – mixed
o Reptiles do not always breathe. Blood by-passes
o Sinus venosus – preliminary collecting chamber. lungs and flows directly to the systemic circuit via
- In teleost it is filled primarily from the hepatic the right aorta – shunt
veins. No muscular wall. o Direction of blood flow is controlled by resistance
o Bulbus arteriosus – in teleost (conus arteriosus in in the pulmonary circuit (lower when animal is
elasmobranchs). Elastic and work to reduce breathing)
extreme pulsing of blood leaving the ventricle,
giving a more constant, even flow.
• Air breathing Fish:
o 2 circulations: pulmonary & systemic
o Partially divided atrium and ventricle:

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o Shortness of breath, fainting, irregular heart

rhythm & fatigue after mild activity
o Treatment – hole can vary in size and may close
on its own or require surgery.
• Birds and Mammals:

o 4-chambered hearts
o Separate pulmonary and systemic circuits with
these advantages:
- Pulmonary and systemic circuits can operate at
10.2 Mammalian Heart Structure
different pressures
- Systemic circuit always receives blood with higher
• Mammalian Heart Structure:
O2 content
- Gas exchange is maximised
• Blood flow(double circulation) in human heart:
• The foetus does not use its own lungs until birth,
so its circulatory system is different from that of
a newborn baby. Before birth, the fetal heart does
not have to pump blood to the lungs to pick up
oxygen, so the fetal heart does not need a
separate pulmonary artery and aorta.
o Veins bring blood to heart

o Arteries take blood away
o 4 separate chambers
o Valves prevent backflow
o Blood flows: high → low pressure
• Atrial septal defect (ASD): • Atrioventricular (AV) valves:
o Hole in the septum (muscle wall) between atria. o Left: mitral/bicuspid valve
Congenital = present at birth o Right: tricuspid valve
o Both between the atria and ventricles and prevent
o Deoxygenated and oxygenated blood mix, and the
backflow into atria when ventricles contract
heart does not work efficiently

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• The pulmonary semilunar valve and aortic • Pressure changes during cardiac cycle:
semilunar valves lie between the ventricles and
the major arteries and prevent backflow into
ventricles when ventricles relax
• Cardiac muscle
o Cardiomyocytes(cardiac muscle cell) are branched
with cross striations formed by myosin and actin
o Intercalated discs provide mechanical adhesion
and contain gap junctions
o Gap junctions allow rapid transmission of
electrical signal (syncytium)
- The cardiac syncytium is a network of
cardiomyocytes connected by intercalated discs
that enable the rapid transmission of electrical
impulses through the network,
o The thickness of the myocardium affects the
pressure generated (muscular middle layer of the
wall of the heart)
10.3 Cardiac Cycle and Heart Sounds in Humans

• Heart murmurs:
• Blood flows: high → low pressure o Narrowing or leaking of valves (e.g. mitral
• Two normal heart sounds: regurgitation) can cause murmurs
o The sounds reflect the turbulence created when o Congenital, age-related changes, infections, etc.
the heart valves snap shut. o Increases heart work and decreases efficiency,
o ‘Lub’ - first heart sound (S1) produced by the may decrease O2 levels in the blood
closing of the atrioventricular valves. o Heart murmurs: e.g. whooshing, swishing,
o ‘Dub’ – second heart sound (S2) produced by the galloping sounds
closing of the semilunar valves. o Asymptomatic, shortness of breath, pain, etc.
o Valve repair surgery is the only treatment option
if condition is serious
10.4 Cardiomyopathy
• Cardiomyopathy is a chronic disease of the heart

muscle that makes it harder to pump blood:
o Estimated that 1 in 500 people are affected
o Dilated cardiomyopathy: heart is weak and
enlarged and cannot pump blood effectively.
Caused by various medical problems. It is the
most common type of cardiomyopathy

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o Hypertrophic cardiomyopathy (HCM): heart • Only turbulent sounds can be heard through a
muscle is thickened, reducing the space for blood stethoscope and this is achieved via a
leading to reduced output. Often genetic. sphygmomanometer:
o Restrictive cardiomyopathy: ventricle(s) do not o First sound of flow (tapping) = systolic pressure
properly fill because heart muscle is stiff. Rare. o Continuous “whoosh” sound = diastolic pressure
o As heart beats, pulses are transmitted smoothly
via laminar (non-turbulent) blood flow throughout
the arteries, and no sound is produced.
o If cuff of a sphygmomanometer is placed around a
patient's upper arm and inflated to a pressure
above the patient's systolic blood pressure, there
will be no sound audible – occluded blood flow.
o The systolic blood pressure is the pressure when
the 1st Korotkoff sound is heard. When the
pressure in the cuff is the same as the pressure
produced by the heart, some blood will be able to
pass through the upper arm when the pressure in
the artery rises during systole. This blood flows in
spurts as pressure in artery rises above pressure
in the cuff and then drops back down beyond the
cuffed region, resulting in turbulence that
• Structural differences in hypertrophic produces an audible sound.
cardiomyopathy (HCM) o When the sound becomes muted and almost
disappears, the pressure at which this occurs is
the diastolic pressure – 4th Korotkoff sound.
• Hypertrophic Cardiomyopathy causes and effects: 11. Circulation of Blood

o Genetic (mutations e.g. myosin)
o Infections: damaged cardiac muscle (myocarditis) 11.1 Blood Vessels
o Excess, long-term alcohol consumption (toxic to
cardiomyocytes) • Blood vessels help perform the function of the
o Nutritional deficiencies (e.g. vitamin B, K+) and circulatory system and transport materials.
hormone imbalances damage the myocardium • Arteries, veins, and capillaries:
o Extreme physical activity e.g. athletes
o Shortness of breath, chest pain, palpitations,
dizziness, fatigue, fainting, sudden cardiac death
o Leading cause of sudden death in athletes
10.4 Measuring Blood Pressure
Sphygmomanometer – inflatable cuff attached to arm

Stethoscope – placed against heart to listen to pulse
(Used together to listen to pulse) 11.2 Arteries
• Laminar blood flow is silent (pulse present)
• Occluded blood flow is silent (no pulse) • Arteries carry blood away from heart so they must
• Turbulent flow is noisy withstand high pressure

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• Aorta expands during contraction phase of cardiac

cycle and contracts elastically (elastic recoil)
between contractions (Windkessel effect)
o Reduces pressure fluctuations between beats
o Helps propel blood in aorta and prevent back-flow
• Arteries and arterioles adjust their diameter (and
therefore resistance to flow) and so change the
amount of blood flowing through them.
o This is an important characteristic of arterioles
called resistance vessels because they control
blood flow to specific tissues
• Structure of arteries:
o High pressure – many collagen and elastin fibres • Deep vein thrombosis(DVT):
in the tunica adventitia strengthen the vessel wall o Deep vein thrombosis is the formation of blood
o Elastin fibres help aorta expand and recoil clot ("thrombus") in a deep vein
between contractions o In a person sitting upright, gravity causes blood to
o Smooth muscle in tunica media contracts to cause accumulate in the veins of the lower body, which
vasoconstriction, adjusting diameter of artery can cause swelling and inflammation below the
(and therefore resistance to flow) blockage site (DVT).
o Endothelial cells in tunica intima produce factors o Decreased flow rate of blood due to immobility
that cause vasodilation or vasoconstriction can lead to venous thrombosis
(widening or narrowing of artery diameter) o Aerodynamic anti-gravity suit prevents blood
pooling in the lower part of the body during
acceleration which deprives the brain of blood.
• Differences between veins and arteries:
o Arteries have more elastin, more smooth muscle,
and more fibrous collagen in tunica adventitia
o Veins have valves, less collagen and elastin, and
less smooth muscle than arteries.
11.4 Capillaries
• Function:
o Receive high pressure blood from arterioles and
11.3 Veins allow exchange of materials between blood and
interstitial fluid.
• Function: • Structure:
o Drain blood from capillary beds under very low o Capillaries are very narrow (diameter 5-10µm)
pressure (not sufficient to propel blood to heart) - RBCs are ≈ 7 microns
o Venules and veins are called capacitance vessels o Single layer of endothelial cells(endothelium)
because of their ability to stretch and store blood improves diffusion and osmosis
• Structure: o Have tiny holes - “fenestrations”
o Vein walls are expandable because have little - Allows water, some ions, solutes like glucose, and
muscle or less collagen in the adventitia very small proteins to leak out.
o Smooth muscle contracts to help return blood to
the heart under low pressure.
- Thin smooth muscle layer BUT large blood volume
in veins → small contraction pushes lots of blood
towards the heart
- One-way valves in veins prevent back-flow
• Venous return to heart:
o Gravity affects venous return
o Larger veins have some smooth muscle which
contracts to assist venous return
o Skeletal muscles contract in surrounding muscles
o Valves in veins prevent back-flow

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• Pressure, area, and velocity in system: • Atherosclerosis:

o Healthy arteries have a smooth endothelial lining
o Atherosclerosis begins with damage to endothelial
cells and usually occurs over decades
o Inflammatory response -> deposits (plaques) form
o Smooth muscle cells migrate towards lumen and
attract lipid (cholesterol) so plaque becomes fatty
o SMC also produce fibrous connective tissue which
causes “hardening” of the artery
o Artery narrowed which can cause CHD and other
diseases, plaque can burst, blood may clot etc.
• Blood supply to the heart:
o Arterioles branch into extensive networks of o There are 2 main coronary arteries which both
branch off base of the aorta
capillaries which hugely increases the overall
o They are the only blood supply to heart muscles
cross-sectional area (CSA)
o If they become blocked, heart muscle can become
- Extensive branching reduces pressure and flow
damaged or stop beating – this is a heart attack
- Enough pressure remains for water and small
• Treatment of chronic heart diseases:
solutes to be squeezed through capillaries and
o Aspirin to help prevent blood clots from forming
into interstitial spaces
in arteries and reduce risk of having heart attack
• Starling’s forces are two opposing forces that
o Calcium channel blockers to relax arteries, lower
maintain water balance and hence blood volume
blood pressure, and reduce strain on the heart
in the capillaries:
o Nitrates (such as nitro-glycerine) to stop chest
o Blood pressure (hydrostatic) — tends to force
pain and improve blood supply to the heart
water and small solutes out
o Statins to lower cholesterol:
o Osmotic pressure — tends to draw water back
- Apolipoprotein E-deficient (ApoE- deficient) mice
into capillaries. Osmotic pressure is due to large
are a widely used mouse model of human
protein molecules (e.g. albumin) that cannot leave
atherosclerosis. Effects of the statin rosuvastatin
the capillaries – stays constant through capillary.
treatment showed a significant reduction in
plaque progression in treated mice.
12. Regulation of Circulation

12.1 Basics of nerve function
• Circulation regulation occurs via nerves/hormones

• Membranes of cells have a charge gradient:
o Also called membrane potential. Membrane
potential in resting state is more negative inside
than outside. (Around -70mV for a neuron)
o At rest, there are relatively more sodium ions
outside the neuron and more potassium ions
inside that neuron i.e. 3 Na+ ions are transported
11.5 Diseases out and 2K+ ions into the cell via Na+/K+ pump.
• Activation of cells caused by depolarisation:
• Lymphatics & oedema o Charge difference switches to being more positive
o Tissue fluid drains into the lymphatic system and inside due to ion movement
is returned to the CVS • Inhibition of cells caused by hyperpolarisation
o An imbalance between blood pressure, osmotic o Charge difference becomes more negative than
pressure and lymphatic draining can lead to resting potential. Therefore, harder to depolarise.
oedema (fluid retention in tissues)
• Coronary heart disease (CHD) is narrowing of the
small blood vessels that supply blood/oxygen to
heart. This can lead to heart attacks and strokes.

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12.2 Muscle Contraction important as the ventricles must push blood

upwards into the Aorta and the pulmonary artery.
• Muscle contraction is caused by Ca2+ movement
inside muscle cell
o Occurs when muscle cell membrane is depolarised
o Depolarisation triggers calcium ions to be
released from the sarcoplasmic reticulum
o Muscle contraction inhibited by hyperpolarisation
• Cardiac muscle is controlled by changes in • Atrial syncytium is the network of cardiac

electrical charge across the membrane muscle cells connected by gap junctions that
• A moving wave of change in electrical charge is allows coordinate contraction of the atria.
called an action potential • Ventricular syncytium is the network of cardiac
muscle cells connected by gap junctions that
12.3 Control of Rhythmic Heart Contractions allows coordinate contraction of the ventricles
• Rhythmic heart contractions are controlled by: 12.4 Cardiac Arrest

o Autorhythmicity
- Contractions of the heart originate within muscle • Cardiac arrest is the sudden loss of cardiac
cells - myogenic. Hence, the heart has its function when the heart abruptly stops beating.
own autorhythmicity. This autorhythmicity is due
• Most common loss of function is ventricular
to a small number of muscle cells that are
fibrillation caused by irregular electrical activity in
specialized to generate and conduct action
the heart (arrhythmia). When this happens, the
potentials without external stimulus.
heart pumps little or no blood to the body
o Gap junctions
• Treatment of cardiac arrest:
o Two groups of pacemaker cells:
o Defibrillation - using electricity to “shock” the
- Sinoatrial node(SAN)
heart to try and restore its regular rhythm
- Atrioventricular node (AVN)
o Implantable cardiac defibrillator (ICD) delivers an
• Control of the heart beat
electrical "shock" to the heart to return the heart
o The cardiac cycle begins in the right atrium. There
rhythm to normal when abnormality is detected
is a specialised patch of muscles in the wall of the
right atrium known as the Sino-Atrial node. Cells
12.5 Arterial Pressure
at the SAN set the rhythm for all of the cardiac
muscle cells to beat as they send out electrical
• Both the heart and blood vessels control blood
impulses to the rest of the atria - spontaneous,
arterial pressure which is maintained within a
rhythmic depolarisation. This causes atrial
certain range via negative feedback:
contraction. The electrical impulses do not pass
down to the ventricles. Instead, a second node
(Atrioventricular node) picks up the electrical
impulses from the atria.
o The AV node causes the impulse to be delayed by
0.1 seconds, so the atria contract before the
ventricles, giving the ventricles time to fill up with
blood. APs sent to ventricles via the bundle of His
and run to ventricular apex via right and left
bundle branches, down the septum. APs spread
through ventricles via Purkinje tissue/fibres. Once
the impulse arrives at the base of the ventricles, it
moves outwards and upwards through ventricular o Both epinephrine and norepinephrine increase
walls. This causes the ventricle to contract. This is blood sugar levels, heart rate and contractility and
affect blood vessels. However, norepinephrine

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can also make your blood vessels become 12.8 Vasoconstriction

narrower, increasing blood pressure.
• Calculating mean arterial pressure: • Contraction (tone) is controlled by [Ca2+] which is
regulated by noradrenaline:
(𝑆𝑦𝑠𝑡𝑜𝑙𝑖𝑐)+(2 𝑋 𝐷𝑖𝑎𝑠𝑡𝑜𝑙𝑖𝑐)
o MAP =
3
- Diastolic part of cycle is twice as long as systolic,

therefore we calculate weighted average
- A minimum MAP of 60 is required to perfuse
important tissues: brain, coronary arteries, kidney
12.6 Demands on Body
• There are demands on the body for arterial

pressure and also oxygen.
o Change in blood pressure – rapid response • MLCK regulates the latch state of prolonged
(signalled by baroreceptors -> baroreceptor crossbridge formation (energy efficient tone):
reflex, uses the autonomic nervous system – o Phosphorylates MLC to enable myosin crossbridge
parasympathetic and sympathetic) to bind to the actin filament and allow contraction
o Increased demand for oxygen – rapid response
(chemoreceptors, uses autonomic nervous system
and hormones, but autonomic is immediate one)
12.7 Regulation of Blood Vessels
• Arterioles can vasoconstrict and vasodilate and

change blood flow and vascular resistance.
o Extrinsic (nervous and endocrine systems) factors
alter arteriole and vein diameters by acting on the
smooth muscle
• Factors which affect vessel diameter:
o Noradrenalin from sympathetic neurons causes
vasoconstriction 12.9 Vasodilation
o Release of paracrine factors from endothelial cells
cause vasoconstriction e.g. endothelin 1 or • Many different pathways through which
vasodilation e.g. nitric oxide vasodilation can take place:
o Hormones also affect vascular smooth muscle
- e.g. angiotensin II from the kidney causes
vasoconstriction
• Noradrenalin increase Ca2+ concentration in
vascular smooth muscle cells:
• Local vasodilation can create positive and

negative feedback loops:

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12.11 Changes in Blood Pressure
• BP varies in the body i.e. standing or prone

• Body responds to changes in mean arterial
12.10 Autonomic Nervous System pressure (MAP)
• Baroreceptor reflex: initiates response to bring
• Extrinsic (nervous and endocrine systems) factors MAP back to normal
alter heart rate by acting on the pacemaker cells • Orthostatic hypotension - known as postural
(intrinsic) in the SAN hypotension or a dizzy spell:
• SAN innervated (supplied) by both sympathetic o Stand up causes pooling of blood in lower body
and parasympathetic autonomic neurons which causes decrease in venous return and
• Autonomic Innervation of the heart: hence decrease in mean arterial pressure (MAP)
o Occurs when a person's blood pressure suddenly
falls as they stand up:
- Typically, greater than 20/10 mm Hg fall and may
be most pronounced after resting.
- Incidence increases with age!!!
o Gravity-induced blood pooling in lower
extremities affects:
- Venous return
- Decreased cardiac output and subsequently
lowering of arterial pressure
o Overall effect is a transitory insufficient blood
perfusion in the upper part of the body,
particularly the brain
• Baroreceptors (stretch receptors in the walls of
o Sympathetic nerves innervate all of heart tissue. the large arteries going to the brain, carotid
They affect (increase) heart rate and contractility. arteries, and aorta)
- NA o In the aorta are baroreceptors which send
- β1 adrenoceptors information to the brain stem about the pressure,
o Parasympathetic (2) vagus nerves innervate the then a coordinated response is enacted. Can go
nodes, affecting (decrease) heart rate. down parasympathetic nerve to slow heart rate,
- Acetylcholine (ACh) or sympathetic nerve to increase contractility and
- Muscarinic (M2) receptors rate. There is no parasympathetic innervation to
• Increasing Heart Rate: most blood vessels.
o NA and adrenalin → increase HR and contractility
o NA and adrenalin bind to β1 adrenoceptors
o SAN cells increased rate of depolarisation
o Myocytes – increased [Ca2+] from binding
- Beats faster and harder
• Decreasing Heart Rate:
o ACh binds to muscarinic (M2) receptors
o SAN cells hyperpolarised
o Time for depolarisation takes longer

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• Baroreflex: 12.13 Increased Demand for O2 During Exercise

o Baroreflex occurs via rapid negative feedback loop
o When mean arterial pressure decreases, • Exercise requires increased delivery of oxygen,
baroreceptor firing reduces so reduced signalling metabolic substrates to muscles and brain,
to CNS. Mean arterial pressure increases, as it removal of waste products
increases sympathetic activity to heart and blood • Rapid response (central command,
vessels and decreases parasympathetic activity on chemoreceptors, autonomic nervous system,
heart. Sympathetic activity increases in 2 ways: hormones e.g. adrenalin)
1. Increased cardiac output(CO) means more blood • Redistribution of blood flow – decreased flow to
coming out of heart due to increased heart rate. visceral beds (internal organs/structures except
2. Total peripheral resistance is also increased by muscle) and increased flow to skeletal muscle
constricting blood vessels, so mean arterial • Increased cardiac output – elevated heart rate
pressure increases. • Increased breathing rate
12.14 Preeclampsia
• A pregnancy-specific cardiovascular disease that is

characterized by hypertension, usually begins >20
weeks into gestation and there is excess of serum
protein levels in the urine ≥ 300 mg (proteinuria)
• Generalised oedema (accumulation of body fluids)
• Signs and symptoms become apparent relatively
late in the course of the disease, usually during
the third trimester of pregnancy
• May progress to eclampsia (seizures, coma)
• Serious consequences for health of mother+baby
12.12 Different Receptors of the ANS
• The brain regulates the ANS. 13. Endocrine System

• Baroreceptors detects changes in blood pressure
• Arterial chemoreceptors – primarily detect 13.1 Hormones
changes in blood chemical composition
o E.g. ↑CO2 ↓O2 (carotid arteries & aorta) • Hormones are molecular signals released by
• Medullary chemoreceptors – detect changes in specific cell types and influence other cells
increases in CO2 levels (brainstem) • Endocrine system – includes a variety of
cells/tissues/organs that produce hormonal
molecular signals
• Cells communicate with each other to maintain a
stable internal environment:
o Target cell: Cells which have a specific receptor
site for a specific hormone
o Receptor: A molecule that the hormone binds to
and initiates a response
• Hormones can act at a distance (hormone action):
o Secreted into the interstitial fluid, pass into the
blood then travel to target cell.
• Hormones can act locally:
o Paracrine and autocrine activity where hormones
are released into the interstitial fluid.
- Carotid baroreceptors are responsive to both o Autocrine action when hormones bind to
increases or decreases in arterial pressure, while receptors located on the cell that secreted them.
aortic baroreceptors are only responsive to o Paracrine action when hormone binds to
increases in arterial pressure receptors on nearby cell.
- Aortic chemoreceptors detect changes in blood • Hormones can be divided into 3 chemical groups:
oxygen and carbon dioxide, but not pH, o Peptides of proteins
while carotid chemoreceptors detect all three. - Major group
- Water soluble so easily transported in blood

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- Packaged within vesicles in cells and secreted by 13.3 Adrenal Gland

exocytosis, e.g. insulin
o Steroid hormones (Lipid hormone): • The adrenal gland has two parts:
- Synthesised from steroid cholesterol o Outer cortex, which produces cortisol and
- Lipid soluble so can pass through cell-membranes. aldosterone hormones
Hence, they are not stored in vesicles – secretion o Inner Medulla which produces epinephrine and
is regulated by regulating synthesis. norepinephrine, stimulated by the brain
- Act by altering gene expression in the target cell
o Amines
- Mostly synthesised from tyrosine (amino acid)
- Can be water-soluble or lipid soluble so mode of
action differs e.g. epinephrine, thyroxine
• Hormone receptors can be membrane bound or
cytoplasmic or nuclear.
13.2 Glands
• The pancreas functions as both an exocrine gland

and an endocrine gland – mixed functions • Fight and Flight response:
• Endocrine glands: o Brain detects danger - Signals sent to adrenal
o Aggregation of cells that secrete hormones gland to release E and NE.
o e.g. endocrine pancreas secretes insulin, glucagon o The release is very rapid as adrenal medulla is
directly into blood. They are ductless. regulated by nervous system.
• Exocrine glands: o Epinephrine (E) and Norepinephrine (NE) are
o Have ducts carrying molecules to specific location released in response to stressful situations
o e.g. exocrine pancreas secretes enzymes and o Actions:
Bicarbonate via duct to duodenum - Heart beats faster,
• Endocrine glands in the human body: - Blood Pressure increases
- Divert blood flow to skeletal and cardiac muscles
- Liver cells break down glycogen and secrete
glucose - energy
- Fat cells release fatty acids – energy
o Target cells:
- Circulatory system, muscles, liver and fat cells
o The steroid cortisol is also released when you are
suddenly alarmed – effects takes minutes to
appear but lasts hours unlike E and NE.
13.4 Pituitary Gland
• Below hypothalamus and made of the anterior

and posterior pituitary(sits in the sella turcica):
o Hypothalamus is made of neural tissue
• Target cells of hormones released from pituitary: o Posterior pituitary is made neural tissue and
continuous with the hypothalamus, while anterior
pituitary is cellular(made of epithelial tissue).

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• Trans-sphenoidal surgery is the type of surgery • The anterior pituitary works via a negative
commonly used to remove a pituitary tumour. feedback loop:
• The posterior pituitary releases neurohormones:
1. Hypothalamic neurons produce ADH and Oxytocin
and transport them to the posterior pituitary
2. Neurohormones released into posterior pituitary
travel into capillaries
(Neurohormones is any hormone produced and
released by neuroendocrine cells into the blood)
13.5 Thyroid Gland
• Thyroid gland is located in the neck

• Histology of thyroid gland:
• The anterior and posterior pituitary have different

capillary networks:
• Synthesis and secretion of Thyroxine in one cell in

the circle of a follicle:
o Posterior pituitary have long neurones, anterior

have short neurones. Hormones get to anterior
pituitary via portal vessels because short
neurones end on portal vessels. For the posterior
pituitary, neurotransmitters are directly released
from the axons into the capillaries.
• The Anterior Pituitary is regulated by the
hypothalamus:
1. The terminals of hypothalamic neurons release
neurohormone into the hypothalamic capillaries –
these neurohormones are releasing factors, and
travel to anterior pituitary via portal vessels.
2. Neurohormones travel to anterior pituitary
capillaries, are released into the anterior pituitary, - T3 has 3 iodine molecules, while T4 has 4.
then stimulate or inhibit production and release - The normal thyroid gland produces about 80% T4
of hormones from anterior pituitary cells and about 20% T3, however, T3 is more potent
3. Anterior pituitary hormones released by anterior than T4, about 4 times as strong.
pituitary cells make their way into bloodstream • Thyroxine:
o Anterior pituitary makes its own hormones but o Lipid soluble hormone – binds to nuclear receptor
posterior pituitary does not. o Regulates metabolic rate of most cells in the body
- i.e. targets nuclear receptors in almost all cells

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o Action of Thyroxine: o Treatment:

- Thyroxine and Receptor activate transcription of - Levothyroxine: daily, pure synthetic form of T4
enzymes involved in energy metabolic pathway - Increased daily iodine intake
- Thus it elevates metabolic rates (MR) of most cells o Symptoms:
- E.g. exposure to cold -> thyroxine increases MR o Weakness, Lethargy, Weight gain, Blurry eyesight,
o Function of Thyroxine: Dry skin, Irritability, Memory loss.
- Regulates metabolic rate.
- Crucial for normal development and growth
- Too little impedes fetal/child growth leading to a
condition called cretinism
• TSH is regulated via a negative feedback loop:
• Both hyperthyroidism and hypothyroidism lead to

ineffective or no negative feedback. Regulation of
TSH release is involved in both diseases.
(Look at arrow thickness in each diagram)
• Hyperthyroidism and hypothyroidism both cause
Goiter - an enlarged thyroid.
13.6 Diseases of the Thyroid Gland
14. Digestion
• Hyperthyroidism (Graves’ Disease):
o Problem 14.1 Carbon Skeleton
- Autoimmune disease where an antibody binds to
the TSH receptor, causing enlarged thyroid. This • Plants can synthesize organic compounds – and
antibody-receptor binding mimics the binding of are autotrophs. Animals (us) are heterotrophs
TSH to the TSH receptor on the thyroid gland and cannot synthesize organic compounds and so
leading to high levels thyroxine and low levels must eat plants and other animals.
TSH. Negative feedback is ineffectual as o E.g. animals do not have their own carbon
antibodies are stuck on receptors. skeletons such as the acetyl group and must eat
o Anti-thyroxine medication treatment: other animals to obtain it.
- Propylthiouracil, Methimazole, Neomercazol -
inhibits the enzyme thyroperoxidase, preventing 14.2 Essential Nutrients
iodination of thyroglobulin.
o Symptoms: • Carbohydrates
- Weakness, lethargy, weight loss, blurry eyesight, o Provide energy via ATP (adenosine triphosphate)
moist skin, insomnia, palpitations bulging eyes Stored as Glycogen
and nervousness. • Fats
• Hypothyroidism: o Provide more energy via ATP
o Causes: • Amino acids:
- Main cause is low dietary iodine (Follicle cells fail o building blocks for proteins
to make Thyroxine) causing enlarged thyroid. • Mineral elements in different amounts:
- Autoimmune disease (Hashimoto’s disease), o Macronutrients (Ca, Mg, P, K, Na, S) and
pituitary disease and thyroiditis can also cause micronutrients (Cr, Co, F, I, Fe, Mn, Mo, Se, Zn)
o Problem:
• Vitamins:
- Low thyroxine levels cause no negative feedback
o Organic molecules that must be obtained from
of TSH so thyroid gland continues to make
food. Function as co-enzymes.
Thyroglobulin but there is a lack of iodine to make
thyroxine. Low iodine, low thyroxine but high TSH

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14.3 Vitamin Deficiency 14.6 Energy
• Vitamin B1 (thiamin) deficiency • The energy in chemical bonds is measured in

o Causes Beriberi(muscle weakness), lost of calories (kcal or joules) – 1cal = 4.18kJ
appetite, fatigue, weight loss etc. o 1 calorie is the amount of energy required to raise
o Present in liver, legumes, whole grains, yeast the temperature of 1gram of water by 1°C
o Coenzyme in cellular respiration o Fats yield 9.5 kcal/g, carbohydrates 4.18kcal/g,
• Vitamin C (absorbic acid) deficiency proteins 4.1 kcal/g.
o Causes scurvy – softening/bleeding of the gums. • Insufficient caloric intake causes
Excessive bruising, foul breath, diarrhoea, undernourishment and animals must metabolize
lung/kidney problems, weakness, depression. its stored glycogen, fat, and lastly protein.
o Present in citrus fruits, tomato, potato Overnutrition can cause obesity.
o Aids formation of connective tissue prevents o Carbohydrates stored as glycogen, which has a
oxidation of cellular components. high water content and so is heavy. Hence the
• Vitamin B1 and vitamin C are both water soluble rapid initial weight loss when you fast.
• Vitamin D(calciferol) is fat soluble(stored in the • A prolonged increase in fat/carbohydrate intake
liver), and unlike water soluble vitamins, can be or reduced physical activity can lead to obesity
become toxic at high concentrations. • Obesity = mutation in leptin:
o Reduction in Vitamin D levels induces depression o Wildtype “ob” allele codes for a protein called
and causes Rickets – skeletal disorder causing LEPTIN, which is produced by fat cells and
weak bones, stunted growth. regulates body weight. Circulates in blood
o Vitamin D helps absorbs calcium and phosphorous o Mice with mutations on both ob genes (ob/ob
o Present in milk, fish oil, sunshine mice) cannot produce leptin so they are unaware
of when they have sufficient amounts of fat
14.4 Essential Amino Acids and Fatty Acids stored. Hence, they overeat and become obese.
o Receptors for leptin found in the ventromedial
• There are 8 essential amino acids in which hypothalamus responsible for control of hunger
deficiency impairs protein synthesis. All are o Most obese people actually have higher levels of
available in meat, milk or eggs, but not all are leptin than normal. However, leptin receptors
available in vegetables. Vegans risk malnutrition. have reduced sensitivity to excess leptin and
o Tryptophan therefore leptin cannot have its normal “appetite
o Methionine suppressing” effects. Hence long term leptin
o Valine treatment is not effective in obese people.
o Threonine • The classic food pyramid does NOT work, where
o Phenylalanine fats are limited. Fat does NOT make you fat, sugar
o Leucine does. Limit sugar/salt intake and eat healthy fats.
o Isoleucine
o Lysine 15. Regulation of Digestion
• Linoleic acid is an essential fatty acid needed to
synthesise other fatty acids and prostaglandins
15.1 Digestive Process
14.5 Types of Feeding
• Physical Digestion - the physical breakdown of
food into small particles by grinding or chewing to
• Saprobes obtain carbon and energy directly from
increase surface area:
dead organic matter e.g. bacteria or fungi
o Requires strong jaw muscles, and evolution of
• Detritovores obtain energy from the waste teeth of different types:
products of other organisms - Incisors for cutting, chopping or gnawing
• Filter Feeders trap tiny particles or organisms - Canines for stabbing, ripping and shredding
suspended in water e.g. baleen whales, molluscs - Molars and premolars for grinding/crushing
• Predators catch and kill another organism for
food: carnivores, omnivores, herbivores

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• Enzymatic Digestion - the breakdown of complex • Gastric Pits

molecules by hydrolytic enzymes usually secreted o Gastric pits have 3 types of secretory cells:
into the gut lumen: - Chief cells, secrete pepsinogen
o Enzymatic digestion breakdown of complex food - Parietal cells, produce hydrochloric acid
molecules into monomers that can be absorbed - Epithelial cells, secrete mucus, which protects the
and utilized by cells. tissues from the acids and enzymes.
o In most animals, digestion is extracellular,
occurring in a tubular gut with regions specialized
for different digestive functions.
15.2 Compartments of the Digestive Tract
o Chief cells secrete pepsinogen, the inactive form

• Oral Cavity or zymogen of the protease pepsin.
o Physical breakdown/mastication of ingested food. o Low pH converts it to the active form.
Necessary for efficient chemical digestion o Pepsin activates other pepsinogen molecules—a
(increases surface area) process called autocatalysis.
o Mixing with saliva & amylase from salivary glands o Acid secretion by parietal cell:
- Enzyme: Salivary Amylase - CO2 and H2O form bicarbonate ion and H+
- Substrate: Starch/glycogen catalysed by carbonic anhydrase.
- End Product: Maltose(disaccharide) - Bicarbonate is transported out of the basolateral
membrane in exchange for chloride. Bicarbonate
maintains blood pH and neutralises pH of chyme
from the stomach to prevent duodenum damage
- Cl- and K+ ions are transported into the lumen by
conductance channels, to help secrete acid.
- H+ ions are pumped out of the cell, into the
lumen, in exchange for K+ via proton pump.
- Potassium is recycled.
- Accumulation of H+ ions in the lumen generates
gradient across membrane resulting in diffusion of
water out of lumen, leaving us with gastric acid
• Oesophagus
o Muscular tube which transports food through the
thorax and diaphragm to the stomach.
Peristalsis is a series of
wave-like muscle
contractions that moves
food to different
processing stations in the
digestive trac

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• Stomach
o Thick muscular walls churn food.
o Secretes protective mucus from secretory cells
o Gastric glands secrete gastric juice (including HCl
and pepsin, HCL activates pepsinogen -> pepsin):
- Enzyme: pepsin
- Substrate: polypeptide bonds
- End Product: large peptides
o Pyloric sphincter controls food entry into the
small intestine
• Small Intestine
o Long muscular tube/large surface area
o Different regions: duodenum, jejunum & ileum
o Moves chyme forwards from stomach
o Continues enzymatic digestion with secretions
from cells in wall and accessory digestive glands
• Large Intestine(colon):
o Absorbs products of digestion through villi.
o Absorption of water and inorganic ions
o Pepsin is inactive in small intestine as pH is
o Formation and storage of faeces from indigestible
neutralised by pancreas secretions so no HCl.
material. Excretion via rectum.
• Liver
o The liver synthesizes bile salts from cholesterol
and secretes them as bile.
o Bile also contains phospholipids and bilirubin
(breakdown product of haemoglobin/RBC)
o Bile flows through the hepatic duct to the
duodenum and through the cystic duct to the
gallbladder where bile is stored.
o Bile salts emulsify fats in the chyme. One end of
molecule is lipophilic and other end is hydrophilic
o Lipophilic ends merge with fat droplets and keep
them from sticking together, forming micelles.
o This enlarges the surface area exposed to lipases
that digest fat.
o Two layers of smooth muscle outside submucosa:

- Circular muscle layer—innermost cells oriented
around the gut; constrict gut
- Longitudinal muscle layer—outermost cells
oriented along the gut; shorten gut
- Controlled by the Enteric Nervous System
15.3 Enzymes in the Digestive Tract
• Small intestine and pancreas secrete digestive

enzymes into the duodenum

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• Lactase break down lactose -> galactose + glucose 15.7 Summary of Digestion
• Sucrase break down sucrose -> fructose + glucose
• Digestion converts large organic molecules
15.4 Endosymbiotic Bacteria present in food into small molecules that can pass
through cell membranes.
• Endosymbiotic bacteria colonize the intestines.
They obtain nutrition from the food passing
through and contribute to the host’s digestion.
• Microorganisms in the human gut are the
“forgotten organ.” They aid digestion, prevent
harmful microbes from establishing, and produce
vitamins K and biotin.
15.5 Absorption of Products in Small Intestine

16. Nervous System
• Carbohydrates are absorbed as monosaccharides
into capillaries of villi. Glucose is taken up by 16.1 Nerve Cells
active transport. Blood vessels drain into hepatic
portal vein which carries blood to liver. The liver • Neurons are excitable cells — they generate and
converts carbohydrates into glycogen(stored). transmit electrical signals, called action potentials.
• Proteins are absorbed into capillaries as amino o Neurons have 4 regions:
acids. Taken up directly by cells which are
synthesising proteins. Excess de-aminated by liver
which uses nitrogen to form urea for excretion.
• Water, salts and alcohol absorbed directly into
underlying blood vessels irrespective of need.
Excess excreted by kidneys. Alcohol is also
absorbed directly through stomach - intoxication.
• Fats absorbed as glycerol and neutralised fatty
acids into lacteals and then via lymphatics back to
major veins near the heart. Excess stored in
adipose tissue(fat storage).
o Neurons vary greatly:
15.6 Control of Digestive Secretion
• Enzyme release is under hormonal and nervous

control. Salivation is under nervous control:
o Food entering the stomach stimulates release of
the hormone gastrin from the stomach mucosa
into the blood - this causes release of HCl and • Glial cells provide support, nourish and can
pepsin from the stomach mucosa. insulate neurons
o Acid in duodenum causes release of the hormone o Gilia outnumber neurons in the human brain
secretin from intestinal mucosa into the blood - o Glia do not transmit electrical signals but can
this causes the pancreas to release HCO3 and the release transmitters – glia transmitters.
gall bladder to release bile. o Glia also give support during development, supply
nutrients, and maintain interstitial environment.
o Others insulate axons, consume debris, and
provide immune functions.
o Can assist in neuronal repair

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16.2 Central and Peripheral Nervous System 16.4 Action Potentials
• Central nervous system (CNS) consists of the • When the neuron is not active the membrane
brain and the spinal cord. potential is at resting potential (-70mV)
• Peripheral nervous system (PNS) consists of: • An action potential is a rapid change in charge
o Autonomic nervous system (Involuntary), which is difference across the nerve cell membrane due to
divided into the sympathetic, parasympathetic opening or close of ion channels in membrane.
and enteric nervous system. • Membrane potential is the electrical potential
across membrane due to K+, Na+ and Cl- ions.
o In axons at resting, due to leaky K+ ion channel
more positive charge outside leading to net
negative charge inside.
Depolarisation results
in a less negative
charge inside the cell.
o Sensory-Somatic Nervous System (Voluntary).
16.3 Gilia/Neurons
• Types of Glia that insulate neurons:

o Oligodendrocytes (CNS) and Schwann cells (PNS)
wrap their branch-like extensions around axons
creating a myelin sheath.
o Composition varies by cell-type but mostly lipids
fatty white substance – white matter of brain
o Function is to insulate and increase speed of • An action potential is an all-or-none event – it
communication between neurons either goes or it does not i.e. must hit threshold
• An action potential is self-regenerating because it
spreads to adjacent membrane regions in axon.
16.5 Synapse
• Neurons pass information at synapses:

o Presynaptic neuron sends the message
o Postsynaptic cell receives the message
• 3 Types of Neurons:
o Afferent neurons (sensory) carry sensory
information to the CNS. Their dendrites are found
in e.g. skin, muscle, organs. Their terminals end in
spinal cord connecting to interneurons.
- Sensory receptor cells transduce (convert)
physical/chemical stimuli into action potentials by
opening or closing ion channels in cell membrane
o Efferent neurons (motor) carry information from
the CNS to muscles and organs. Dendrites in
spinal cord. Terminals in muscles or organs.
o Interneurons (relay) enable communication
between sensory, motor neurons and the CNS

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o Neuromuscular junction is neuron-muscle • The ‘association cortex’ is the ‘not so easy to

synapse. How AP travels to muscle cells: define’ cerebral cortex regions.
1. When action potential arrives at neuron terminal, o Integrate/associate higher order, complex,
Na+ ion channels open, causing depolarization sensory information or memory.
which causes Ca2+ channels to open. o We will use language areas to illustrate the term
2. Ca2+ ions enter the cell terminal and trigger ‘association cortex’:
fusion of neurotransmitter (Ach) vesicles with the 1. Broca’s area is essential for speech:
presynaptic membrane. - Damage causes loss of ability to produce language
3. Acetylcholine molecules diffuse across the and broken speech. Patient is aware and can
synaptic cleft and bind to receptors on the understand language but cannot speak.
postsynaptic membrane. 2. Wernicke’s area is involved with sensory more
4. When receptors on muscle cells bind to Ach, they than motor aspects of language
open and allow Na+ ions to enter which - Damage causes inability to understand – unable
depolarises postsynaptic membrane. This leads to to choose correct words to express thoughts.
an action potential in the post synaptic cell. Patient speaks clearly but does not make sense.
o Acetylcholinesterase is an enzyme which breaks o Language abilities are localised to left hemisphere
down Ach and thus switches off the Ach signal. and damage to left hemisphere can lead to
Some medications blocking the function of this Aphasia – inability to use/understand words.
enzyme so that the stimulus is prolonged:
16.6 Purpose of Nervous System
• Interoception - sensitivity to stimuli originating

inside of the body. This helps maintain a stable
internal environment (homeostasis)
• Exteroception - sensitivity to stimuli originating
outside the body so we can plan, react etc.
• Communication takes place via neurons exciting o Normal language depends on the flow of
or inhibiting other neurons information among various areas of the brain:
16.7 Cerebral Cortex and Association Cortex
• The cerebral cortex is the outermost layer of the

cerebrum, made of grey matter and convoluted.
This allows for greater area of cortex for given
brain volume. Gyri are ridges, Sulci are valleys.
o Plays a major role in sensory perception, learning,
memory and conscious behaviour.
• Cerebrum has left and right cerebral hemispheres.
Each cerebral hemisphere has 4 lobes:
o Frontal: cognitive skills, emotions, memory
o Parietal: touch and pressure via thalamus
o Temporal: recognising and identifying objects
o Occipital: processes visual information
16.8 Sleep
• Sleep is a period of reduced activity and

decreased responsiveness to external stimuli.
• Sleep is a state that is relatively easy to reverse
compared to hibernation or coma.
• Sleep state characterized by changes in brain
wave activity, breathing, heart rate, temperature
and other physiological functions.

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• REM(rapid eye movement) has similar EEG to • Blood immune cell production:
awake stages. Dreaming is rare in NREM sleep.
• Melatonin is the hormone that regulates the

sleep-wake cycle, released by pineal gland.
o Different immune cells associated with innate or
• Sleep is a highly active process where the day’s
adaptive system e.g. killer T cells are part of both
events are processed and energy is restored.
• Interaction between innate and adaptive system:
• Sleep helps memory in 2 ways:
o Helps you focus well during waking hours
o Forms neural connections (memory) to store
newly acquired information while you sleep
17. The Immune System

17.1 Innate and Adaptive Immune System
• Pathogens – harmful organisms and viruses

• Immunity – ability to resist invading pathogen
17.2 Human Lymphatic System
• Innate immunity
o Non-specific and very rapid response
o Involves recognising components that are
common to many pathogens
• Adaptive immunity
o Able to distinguish between your healthy self-cells
and abnormal non-self-cells i.e. pathogens, etc.
o Typically slow to develop but long-lasting effect
o Involves recognising components that are specific
to each particular pathogen
• The innate and adaptive immune systems interact
to remove pathogens:
• Plasma is fluid remaining when white blood cells,

red blood cells, platelets are removed.
• Plasma considered the connective tissue of blood
• Composition of Plasma:
o 90% water
o 10% other components:
- Proteins, hormones, nutrients, gases, nitrogenous
waste, electrolytes
• Blood contains both white and red blood cell but
lymph contains no red blood cells, only WBCs.
o When centrifuging, RBCs are densest and lies on
bottom, then WBCs + Platelets, and finally plasma.

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17.3 Immune Response Basics • 1st and 2nd lines of innate defence:
• Lymph nodes are small, round structures at many

sites along the lymph vessels and contain white
blood cells. As lymph passes through the nodes, it
is filtered for non-self pathogens. Immune cells
travel via the blood and lymphatic system.
• The innate immune response is the first line of
defence. It consists of soluble factors, such as
complement proteins, and granulocytes,
basophils, eosinophils and neutrophils, mast cells,
macrophages, dendritic and natural killer cells.
• The adaptive immune response is slower to
develop but manifests as increased antigenic
specificity and memory. It consists of antibodies, B
• Inflammation:
cells, and CD4+ and CD8+ T lymphocytes. Natural
1. Injury causes histamine release from mast cells
killer T cells and T cells are cytotoxic lymphocytes
and are part of innate and adaptive immunity. which are attracted to the area of injury
• Macrophages: 2. Histamine causes vessels to become more leaky
o Part of innate and adaptive immune systems (more permeable to proteins):
o Engulfs and digests pathogens, cellular debris, and - Complement proteins move from blood into
infected cells (containing pathogens). infected area attracting (chemotaxis of)
o Can move through leaky blood vessels phagocytes to engulf pathogens.
o Phagocytes use defensins, nitric oxide and other - Complement proteins binds to pathogen to help
factors to kill pathogens after engulfing them. phagocytes recognise and kill pathogens
• Mast Cells - Blood plasma also moves into infected area
o Found surrounding blood vessels and nerves in causing swelling (edema/oedema), leading to
the connective tissue of most organs and in the inflammation in injured area
boundary between internal/external environment
3. Platelets release growth factors – stimulates
o Releases histamine which increases capillary
dermis cells to divide to heal the wound:
permeability to WBCs to kill pathogens.
o Also secretes prostaglandins and tumour necrosis - Increased pressure of swelling and prostaglandins
factor involved with inflammation, clot etc. released from mast cells increase the sensitivity of
pain receptors, hence inflammation is painful.
17.4 Innate Immunity - Aspirin(painkiller) blocks prostaglandin synthesis
• The complement system is specialised proteins of

the immune system that enhances the ability of
other defences to clear pathogen:
o >20 different proteins
o Most are made in the liver
o Activated by innate and adaptive immune systems
o Functions:
1. Chemotaxis (attracting phagocytes to injury area)
2. Attach to antigens on pathogen surface or to an
antibody bound to a pathogen - helps phagocytes
to recognise and kill pathogens.
o Lead to lysis(break down) of cells • Allergic reactions:
o The C1 complex is a protein complex of x1 C1q, o Non-self-molecule that is normally harmless binds
x2 C1r and x2 molecules of C1s. It is involved to mast cells, causing release of histamines then
with initiation of complement cascade. inflammation and itchy, watery eyes and rashes
o Non-self-molecule can come from food or
environment (e.g. pollen, dust).
• Autoimmune diseases:
o Immune system fails to distinguish between self
and non-self-cells and attacks tissues in the body

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o Inflammation can be more general and found o An antigenic determinant (epitope):

throughout the body like in rheumatoid arthritis. - Specific region on an antigen that is recognised by
• Sepsis a specific antibody or T-cell receptor.
o A bacterial infection caused by damage to the - Antigen can have many antigenic determinants.
body does not stay localised to one area and
spreads throughout the body and dilation of
blood vessels spreads throughout body.
o Inflammation spread throughout body, resulting
in drop in blood pressure. Can damage multiple
organs and is a life threatening.
• Lymph vessels are found in almost all tissues: o Immunogens are those substances that trigger a
o Lymph is not pumped - it moves through vessels response from the immune system, whereas
by body movements e.g. muscle contraction of antigens can be defined as molecules that bind to
muscle. This shows the importance of exercise. specific B-cell or T-cell receptors.
o Lymph also transports dietary fats and lipid- - Not all antigens produce an immunogenic
soluble vitamins. response, but ALL immunogens are antigens
17.6 Four Key Features of Adaptive Immune System
1. Specificity
• The humoral immune response uses antibodies
secreted by plasma cells to target antigens in
body fluids. Involves antibodies and B cells.
o Antibodies are proteins called immunoglobulins:
- Composed of 4 polypeptide chains (2 light, 2
heavy) The light chain has a variable region and a
constant region. The heavy chain has a variable
• Oedema is caused by abnormal fluid balance of region and a constant region.
plasma, interstitial fluid and lymph flow: - Disulphide bonds hold the two peptides (light and
o Increased blood flow due to dilation of blood heavy chains) together.
vessels (arterioles) supplying the region of injury - Variable region of light chain and variable region
1. Increased capillary permeability due to histamine of heavy chain form the antigen binding site
increasing endothelial gaps - Each variable region is specific for ONE antigen —
2. Increased capillary permeability to proteins making up specificity of antibody.
3. Decreased plasma protein (oncotic) pressure o Each antibody is bivalent – has two identical
4. Oedema occurs binding sites for antigens that are the same.
o Antigens bind in the antigen binding region via
17.5 Adaptive Immunity their antigenic determinants - each antibody is
specific for a single antigenic determinant
• Adaptive immune system proteins: o The constant region of the heavy chain
o Antibodies (B-cells) determines class of antibody molecule. There are
o T-cell Receptors (T-cells) 5 classes of antibodies: IgA, IgG, IgM, IgD, IgE
o MHC (Major Histocompatibility Complex)
o Cytokines
- Can be peptides, proteins or glycoproteins
- Secreted by TH cells via specific receptors, and
activate or inhibit B-cells, macrophages, T-cells.
• Antigens and Antigenic determinants
o An antigen is a molecule that interacts with
specific receptors on T-cells and B-cells.
- For B-cells, receptor is membrane bound antibody
- An antigen is a molecule from the environment
e.g. pollen or molecules on surface of bacteria etc.
- It is a non-self molecule.
- An antigen may also be formed within the body,
such as bacterial toxins.

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• The cellular immune response uses T cells to 2. Breaks down antigen into fragments
attack cells altered by viral infections or mutation 3. A Class II MHC molecule binds antigen
or to target antigens that have invaded the body’s fragment and carries it to the membrane.
cells. Involves T cells and T cell receptors 4. Allowing MHC to ‘present’ antigen to TH cell
o Each T cell and each antibody is specific for a
single antigenic determinant.
• 2 types of B-cells (humoral):
1. Plasma cells that secrete antibodies (short
acting cells and die quickly)
2. Memory cells have membrane bound
antibodies (long acting)
o B-memory cells have membrane bound antibodies
that bind to pathogens then the complex is
endocytosed. This causes memory cells to
differentiate into plasma cells which then produce o MHC molecules are membrane bound
and secrete more antibodies to kill pathogen. glycoproteins that helps distinguish between self
• 2 types of T cells (cellular): from non-self-molecules in the body
1. T Helper cells (TH cells, CD4) assist both o MHC Class I proteins – on all nucleated cells:
humoral (B-cells) and cellular (T-cells) - When a normal cell becomes infected or
- TH cells produce cytokines that enhance abnormal, it displays pathogen or antigens on
action of other cells (B cells, Tc, macrophages) MHC I that are recognised by TC cells as non-self.
2. T Cytotoxic cells (TC cells, CD8, T-killer cells)
respond by releasing perforins that lyse the
infected and abnormal cells e.g. cancer cells
o T-cell receptors are glycoproteins (proteins that
have carbohydrate side-chains):
- Membrane bound receptor
- Made up of 2 polypeptide chains (α and β)
- Variable region of the 2 peptide chains directs o MHC Class II proteins – found on Macrophages, B-
specificity of the antigen binding site cells and Dendritic cells:
- Present pathogen antigens to TH cells
3. Diversity—response to wide variety of pathogens

• Millions of specific antibodies and T-cell receptors
from the many possible DNA recombinations
• B and T cells can ‘make’ new gene combinations
to create millions of different variable regions in
antibodies and T-cell receptors:
2. Ability to distinguish self from non-self

• The immune system must recognize the body’s
own antigenic determinants and not attack them
4. Immunological Memory
• MHC molecules:
• The adaptive immune system “remembers” and
o Major histocompatibility complex(MHC) is cluster
can respond more quickly and powerfully if some
of genes that encodes many membrane proteins
pathogen invades again for the second time:
o MHC molecules are found on all cells. Most cells
o Clonal selection:
have MHC class I. Macrophages, B cells and
- Antigens presented to the immune system trigger
dendritic cells have MHC class II.
the proliferation of lymphocytes (T cells and B
o MHC molecules in macrophages, B cells etc. bind
cells) specific for that antigen
processed antigen and present it to T cells
- The lymphocytes proliferate and generate a clone
o Antigen presenting cell:
of genetically identical cells.
1. Macrophage takes up antigen

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o Clonal deletion: Summary of Adaptive Immune System:

- During early differentiation, any immature B or T
cell that shows potential to mount an immune
response against self-antigens, undergoes
programmed cell death (apoptosis)
o Clonal selection and memory cell production for T
cells is similar to B cells:
- Antigen binding and TH cells signalling selects a B-
cell for proliferation (cell division) to form
effector cells/clone and memory cells
18. Stem Cells

18.1 Stem Cells
• Stem cells are unspecialised cells capable of self-

renewal and can become specialised cell types.
o Self-renewal is where stem cells divide to form
more stem cells, that are undifferentiated.
• Immunization is when exposure to pathogen

provides natural immunity in the form of memory
B and T cells i.e. refers to getting a vaccine +
becoming immune after vaccination
• Vaccination (artificial) is introducing an
attenuated pathogen that does not cause disease
and the immune system remembers in the form
of memory B and memory T cells)
• Potency and types of stem cells:
• Autoimmunity may occur due to:

o Failure of clonal deletion
o Molecular mimicry — self antigens have
components that resemble non-self and are
recognised by T cells, triggering immune response
o Examples of autoimmune diseases:
- Type I diabetes, hyperthyroidism, rheumatoid
arthritis(severe joint inflammation)

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• Cell culture(in vitro) conditions: • Differences between Somatic/MSC stem cells and
o Cells grown in nutrient rich solution (media) ES/iPS cells:
o House in incubator at 37°C with 2-20% oxygen o Potency:
o Cells will grow, divide, and can be induced to - Somatic/MSC Stem cells are multipotent
become specialised cells - ES/iPS cells are pluripotent
o Quantity and in vitro expansion:
18.2 Stem Cell Development - Somatic tissue stem cells for most tissues occur in
low numbers, cannot be cultured very long.
• Zygote divides into many cells which then - ES/iPS cells can be kept in culture long term so
undergo compaction to form a blastocyst. can be expanded into large numbers needed for
o ICM of the blastocyst later becomes the embryo stem cell therapies
o Trophoblast develops into the placenta later • Immunocompatible Designer Cells:
• Embryonic stem cells can be collected by isolating

inner cell mass and culture in vitro. They are
immortal, self-renew and pluripotent. • Somatic cell nuclei are not permanently
specialised and can be induced to change
18.3 Mesenchymal stem cells (MSC) and ES/iPS Cells specialisation - given correct signals.
o Generating any cell type from a pluripotent cell
• MSC (somatic) are cells isolated from the bone (ES or iPS) is a matter of finding correct signals.
marrow and shown to be capable of making bone, • ES or iPS cells can become any specialised somatic
cartilage and fat cell. Grown from other tissue too cell spontaneously (a mixture of cell types) OR by
o Somatic are cells other than the reproductive cells adding combinations of specific signals can make
and are multipotent - can differentiate only into a particular cell type
different cell types present in the tissue of their • Applications of ES or iPS cell technologies:
origin. Embryonic stem cells are pluripotent.
• iPS cells are somatic cells that have been

reprogrammed back into ES-like cells:
18.4 Stem Cell Therapy
• Stem cells have been used to treat blood

disorders (e.g some Leukaemias) and at the early
stages of treating disorders involving damaged
nerves such as spinal cord injuries:
o A traumatic spinal cord injury is due to sudden
blow to your spine that fractures, dislocates, or
compresses one or more of your vertebrae.

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o A non-traumatic spinal cord injury may be caused • Partial pressure is component of total pressure
by arthritis, cancer, inflammation, infections or contributed by a single free gas within a mixture
disk degeneration of the spine. • Rate of diffusion of O2 between air and body
• Oligodendrocytes and myelin are lost after a fluids depends on difference of partial pressures
traumatic spinal injury. Oligodendrocyte produces • Air is a better respiratory medium than water.
the myelin sheath insulating neuronal axon. Oxygen diffuses 8000 times more rapidly in air
o Rat embryonic stem cell-derived oligodendrocyte than in water, and air requires less energy to
progenitors are used to treat spinal cord injury: move as a medium than water.
19.3 Respiration vs Size
• Small animals can take up O2 directly from the

environment through the body surface:
o Simple diffusion distributes O2 throughout the
body, into cells, and throughout their cytoplasm
o No specialised respiratory structures required for
O2 uptake or CO2 loss, usually all through skin.
• Diffusion is the result of random thermal motion
of molecules. If there is a concentration or partial
pressure gradient there will be a net movement of
19. Respiration the gas down the gradient.
o Diffusional transport of O2 is only efficient if
19.1 Respiration distance < 1mm.
• Larger, more complex animals have higher cellular
• Animals rely on aerobic metabolism to sustain metabolic rate and reduction in total surface area
their resting energy requirements. 20x more ATP for gas exchange. Diffusion is not enough.
is synthesised via aerobic than anaerobic. o Aquatic and terrestrial animals have evolved
• Respiration is oxidation of the end-products of respiratory systems with large SA for adequate
glycolysis (by O2 in eukaryotes) respiratory supply of oxygen to their tissues
o Breathing or physiological respiration
• Ventilation is the movement of the medium (air, 19.4 Components of Respiratory System
water) over a gas exchange surface
• The gas exchange surface is evolved to increase
rate of exchange, described by Fick’s Law:
(𝑃2 −𝑃1 )
o 𝑟𝑎𝑡𝑒 𝑜𝑓 𝑑𝑖𝑓𝑓𝑢𝑠𝑖𝑜𝑛 = k X A X
𝐷
- k = diffusion coefficient which depends on gas

solubility and temperature.
- A = surface area
- 𝑃2 − 𝑃1 = difference in partial pressure which
represents concentration gradient
- 𝐷 = diffusion distance
• Oxygen cascade from air to mitochondria:
19.2 Oxygen in the Environment
• 21% oxygen in the atmosphere.

• Atmospheric pressure decreases with altitude –
decreased O2 concentration as altitude increases.
• Still water and water not in contact with the
atmosphere has lower O2 concentration.
• Oxygen conditions:
o Hypoxia = low O2 (in blood or environment)
o Anoxia = complete absence of O2 in environment
o Hypercapnia = excessively high CO2 level in blood

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• An exchange site such as lungs or gills has: • Transport of oxygen in the blood:
o A large surface area
o Small diffusion distance (thin endothelium) between
respiratory medium and blood or blood and tissues
o Highly vascularised respiratory surface
o Respiratory gases DIFFUSE across the exchange site
(respiratory epithelium and capillary endothelium)
• A ventilation system keeps a constant supply of
medium moving across respiratory exchange site:
o Improves rate of gas exchange
o Ensures fresh supplies of O2-rich medium are
supplied to the exchange surface
• Internal transport (circulatory) system: o Positive co-operativity: binding of 1st O2 molecule
o Moves the dissolved O2 from the exchange site to increases binding affinity of subsequent O2
the respiring tissues and also transports CO2 away
• Affinity of respiratory pigments for O2 depends on:
from the metabolising tissues.
o Type of respiratory pigment
o Essential because diffusion is exceedingly slow over
o pH – if blood has lower pH, H+ ions bind to the
even moderate distances
haemoglobin molecule in place of O2 – lowers the
• Circulatory system:
o The heart acts as a pump to increase the movement affinity for O2 (the Bohr effect)
of blood around the body o 2,3-bisphosphoglyceric acid (BPG) – metabolite
found in RBCs, lowers Hb affinity for O2:
19.4 Respiratory Pigments - Level of BPG in RBCs increases at high altitude or
with increased exercise and helps Hb deliver more
• Body fluids (including blood plasma) can only hold O2 to tissues where it is most needed
0.3% of dissolved 𝑂2. Oxygen-carrying capacity of - 2,3 BPG lost during blood storage
blood is increased by respiratory(blood) pigments:
o Complexes of proteins and metal ions
o Characteristic colour that changes when it binds 𝑂2
- Haemoglobin dark to bright red when oxygenated
- Haemocyanin colourless→blue when oxygenated
• Haemoglobin - main vertebrate respiratory pigment:
o 𝑂2 binds reversibly to a metal ion associated with
the protein chain of the respiratory pigment
o Each haem group combines with 1 𝑂2 molecule.
Haemoglobin can combine with 4 𝑂2 molecules.
o CO has a stronger haem group binding affinity than
𝑂2 and can cause rapid poisoning if in blood.
• Respiratory pigments in muscle cells:
o Muscle cells have their own 𝑂2 binding molecule
called myoglobin (monomeric – 1 subunit):
o Myoglobin has a higher affinity than Hb for 𝑂2
and binds to 𝑂2 at 𝑃𝑂2 values much lower than Hb
o Myoglobin provides an 𝑂2 reserve in muscles
• Sickle cell anaemia occurs when an abnormal form • Llamas live at high altitudes. Llama Hb must bind
of haemoglobin (HbS) is produced: O2 in an environment that has a low pO2:
o HbS molecules clump together, making red blood o Llama Hb has an O2 binding curve to the left most
cells sticky and into a curved, sickle shape other mammals i.e. Llama Hb stays saturated with
o Sickle cells can clog blood vessels and deprive the O2 at lower PO2 levels than in other mammals
body's tissues and organs of oxygen
o Anaemia – when the body's number of red blood
cells (or amount of haemoglobin) falls below normal
o Anaemic people often feel weak and tired
o Carriers have more resistance to malaria

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19.5 Transport of Carbon Dioxide in the Blood • Lamellae (helps transfer of O2 from water):
o Increases surface area for gas exchange
• CO2 is transported in 3 forms in the blood: o Reduces diffusion distance between water&blood
1. 10% dissolved in plasma
2. 30% reversibly bound to Hb - when Hb is bound to
CO2 it is known as carbaminohaemoglobin
3. 60% as bicarbonate
• Blood buffer eqn catalysed by carbonic anhydrase:
• 𝐻 + is buffered by haemoglobin when CO2 diffuses

from respiring muscle to RBC. 𝐻 + binds to
haemoglobin which also causes release of O2.
o This prevents decrease of blood pH and also
decreases O2 affinity of haemoglobin.
• Chloride/bicarbonate exchange (‘chloride shift’)
also takes place. In respiring tissues, bicarbonate • Mechanism of ventilation in fish:
diffuses out while chloride diffuses in. o Uni-directional flow of water through the gills in
most fish is achieved by:
- sequential opening/closing of mouth + operculum
- a small pressure differential between the buccal
(mouth) and opercular cavities
• Counter current flow increases gas exchange as
there is always a diffusion gradient:
• In the lungs, the reverse reactions occur (also

catalysed by carbonic anhydrase):
o Bicarbonate ions diffuse back in RBCs to form
𝐻2 𝐶𝑂3 and consequently 𝐶𝑂2 . 𝐶𝑂2 is then
exhaled out of the body via the lungs.
• Bohr Effect shows that an increase in 𝐶𝑂2 partial
pressure of blood or decreases in blood pH result
in a lower affinity of haemoglobin for oxygen.
o Oxygen dissociation curve shifts to the right
• Air breathing fish have specialised accessory
20. Regulation of Reproduction breathing organs (ABOs) that they use in addition
to or instead of gills when breathing air.
20.1 Respiratory Organ - Gills
20.2 Respiratory Organ – Lungs
• Properties of gills:
o Invaginated extension of the body surface • Properties of lungs:
o Highly folded to increase surface area o Invaginated internalised extension of body surface
o Protected by a specialised cover (operculum) o Highly folded to increase surface area
o Pumping mechanism moves water over gills o Protected by ribs and thorax
o Internal circulatory system distributes blood o Ventilation mechanism moves air in and out lungs
throughout the gill and body o Internal circulatory system distributes blood
throughout the lungs and body
• Air Conduction:
o Trachea conducts air into the body – protected
o Bronchi are the major air passageways of the lung
- Bronchi branch into bronchioles
- At end of the bronchioles are the alveoli
o Conduction: trachea -> bronchi -> bronchiole

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o Trachea has C-shaped cartilage. Bronchus has 20.4 Mammalian Ventilation System
both C-shaped and irregular plate cartilage.
o Bronchioles has a layer of smooth muscle, to • Diaphragm:
adjust diameter. No cartilage present. o Inhalation is when diaphragm contracts and pulls
- Exercise -> bronchioles dilate down on the thoracic cavity and pleural
- Asthma -> bronchioles constrict (bronchospasm) membranes, and the lungs, air enters through the
o Alveoli: trachea, and lungs expand – negative pressure
- Volume of thoracic cavity increases and pressure
decreases, causing air to rush/be pulled in lungs
o Exhalation is when diaphragm relaxes and elastic
lung tissues pull the diaphragm back up and push
air out of the airways – positive pressure
- Volume of thoracic cavity decreases and pressure
increases, airflow forced out of lungs.
o Pleural membrane has two layers – outer parietal
layer covers the inside of the rib cage and the
diaphragm while the inner visceral layer covers
the lungs. The space between the two layers is the
pleural cavity which contains fluid secretions.
20.3 Respiratory Problems
• Respiratory Tract Secretions:

o Many epithelial cells lining the airways produce a
sticky mucus that captures dirt + microorganisms
- Goblet cells and mucous glands secrete mucus
o Other cells lining the airways have cilia whose
beating continually sweeps the mucus, with its • Intercostal muscles:
trapped debris, up toward the pharynx o Inhalation is aided by contraction of external
• Smoking immobilises the cilia of the airways for intercostal muscles, which pushes out ribs and
hours. Smoker’s cough = malfunctioning mucus increases thoracic volume
escalator – cannot clear mucus from airways o Exhalation is aided by contraction of internal
• Cystic fibrosis when: intercostal muscles, which pulls in ribs and
o Unusually thick and dry respiratory mucus decreases thoracic volume
o Obstructs the airway and also cilia function
o Single gene mutation results in non-functional
chloride channel protein so chloride ions cannot
leave the cell – a very thick mucus forms, which
becomes clogged with debris and bacteria
20.5 Regulation of Ventilation
• Normally involuntary but can be voluntary:

o Sensory inputs are sent to the central nervous
system. Respiratory centre in the brainstem
(medulla and pons) determines depth, amplitude
• Respiratory Distress Syndrome (RDS) – and frequency of breathing
Premature baby issue: difficulty breathing due to o Phrenic nerve controls contraction and lowering
surfactant deficiency at birth of diaphragm and efferent nerves (spinal motor
o Lung surfactant is a phospholipoprotein secreted neurons) activate intercostal muscles
by alveolar cells and reduces surface tension of a
liquid. Results in less force needed to inflate lungs

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• How we alter breathing rate: 21. Excretion of Waste Products

21.1 Kidney
• Kidney structure：
o Breathing rate is more sensitive to increased CO2

than to decreased O2
o Increase in blood PCO2 causes an increase in
breathing rate to match metabolic demand
• Loop of Henle:
o Loop of Henle produces a concentration gradient
in the surrounding medullary tissue
o Causes the urine to become more concentrated,
hyperosmotic to the blood
o Loop of Henle is found in birds and mammals.
Important adaptation for water conservation.
• Filtrate concentration change along renal tubule:
• Hypoxia - short-term:
o When O2 is reduced at high altitude, an animal
hyperventilates, due to activation of
chemoreceptors in aortic and carotid bodies to
maintain sufficient O2 delivery
o In aquatic hypoxia – causes an increase in gill
ventilation in fish due to stimulation of
chemoreceptors in the gills
o Animals reduce energy expenditure and use
anaerobic metabolic pathways to survive periods
of reduced O2 availability
o Increased BPG, H+ causes more O2 dissociation
o Thick ascending limb actively pumps out NaCl and
• Long term high altitude exposure(low PO2):
is impermeable to water so water does not follow
o Reset the thresholds of the chemoreceptors for
- NaCl raises the solute concentration in the
O2 so that they are more sensitive to low PO2
surrounding interstitial fluid of the renal medulla
o Increase the number of red blood cells and blood
o Thin descending limb is highly permeable to
Hb content (increases O2 capacity of the blood)
water BUT not to 𝑁𝑎+ or 𝐶𝑙 − . Since surrounding
o Reduction in blood O2 stimulates production of
interstitial fluid tissue is more concentrated,
erythropoietin in the kidney and liver. This acts on
water exits the descending loop by osmosis
bone marrow to produce more red blood cells
- Renal fluid in descending limb: more concentrated
• Hyperventilation:
o Distal convoluted tubule: the renal fluid is LESS
o Can be involuntary or voluntary. Voluntary
concentrated than the interstitial fluid
hyperventilation before diving can cause shallow
- Reabsorption of salts, amino acids, etc occurs and
water blackout due to hypocapnia(low CO2 levels)
some water moves out by osmosis. Renal fluid
o CO2 dilates blood vessels and triggers breathing.
becomes isosmotic with interstitial fluid.
Low CO2 levels cause failure in urge to breathe.
o As the renal fluid moves down the collecting duct,
it becomes highly concentrated as water is drawn

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out due to the high solute concentration in the 21.3 Regulation of Blood Pressure
interstitial fluid of the medulla.
o Urea is major solute in the renal fluid of collecting • Massive blood loss (haemorrhage):
duct. Some urea leaks from collecting duct into o Decreased blood volume ⇒ decreased pressure
the interstitial fluid of medulla, further increasing o Detected by kidneys, which function to restore
osmotic concentration in renal medulla blood pressure by increasing blood volume
- Urea diffuses back into thin ascending limb and is o Also triggered by dehydration
returned to the collecting duct • Renin-Angiotensin-Aldosterone System (RAAS):
o PCT is a major site for reabsorption of ions and o An important autoregulatory mechanism is renin
salts and also some secretion. release by the kidney when blood pressure falls
o Renin cleaves angiotensinogen into angiotensin I
21.2 Regulation of Water Absorption (AngI). AngI is converted to AngII by Angiotensin
converting enzyme (ACE). AngII causes:
• Changes in kidney osmolarity influence release of - Constriction of peripheral blood vessels which
antidiuretic hormone or vasopressin, which increases blood pressure.
controls permeability of collecting duct to water, - Release of aldosterone (which enhances Na+
thus amount of water reabsorbed from urine reabsorption and hence water reabsorption in
o ADH stimulates expression of aquaporin 2 - a distal convoluted tubule and collecting duct)
water channel in collecting duct cell membranes - Stimulation of thirst and drinking
• Two mechanisms regulate ADH control of water o Juxtaglomerular cells make, store, secrete Renin:
reabsorption:
22. Reproduction
• AQPs are found in the renal tubule epithelium:
22.1 Asexual and Sexual Reproduction
• Asexual Reproduction:
o Budding:
- Involves similar process to regeneration
- Occurs without damage
- May give rise to individuals or colonies
- In Hydra - new individual arises from outgrowth of
body wall of parent, asexual reproduction.
o AQP2 regulates movement of water molecules in o Regeneration:
the collecting duct: - Repair of damage to body
- Nephrogenic diabetes insipidus (NDI) is a disease - A form of reproduction in some species
characterised by excessive urination and thirst - Involves mitosis and differentiation
due to a mutation in the Aqp2 gene o Parthenogenesis:
- Symptoms mimicked in Brattleboro rats - Development of egg without fertilization
• Hangover: - New individual may be haploid or diploid
o High blood alcohol blocks production of - Invertebrates and few vertebrates
vasopressin in the pituitary gland and kidneys do o Asexual reproduction does not generate genetic
not return water to blood -> frequent urination diversity – bad for evolution or adaption.
o Frequent urination leads to dehydration and loss
of electrolytes, causing headaches, nausea etc.

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• Sexual reproduction: - Spermiogenesis is the final stage of

o Gametogenesis (making sex cells) spermatogenesis, where spermatids mature into
- Germ cells need to proliferate (finite time for spermatozoa. Spermatids are circular cells.
females, indefinite time for males)
- Germ cells need to undergo meiosis in order to 22.3 Oocytes
exchange genetic material and to half their
chromosome complement/karyotype • Oogonia proliferate through mitosis but when
o Spawning or Mating (getting sex cells together) they enter into primary oocytes they immediately
o Fertilization (getting sex cells to fuse) enter prophase of meiosis I and in humans stay in
o Meiosis vs Mitosis: this state for years - Germinal Vesicle (GV) Stage.
- In meiosis, nucleus divides twice but the DNA is • Oogenesis takes place in the ovaries
replicated only once, resulting in 4 haploid cells. o Germinal epithelial cells divide by mitosis to
produce diploid oogonia
o Meiosis is started but stops at prophase I - at this
stage it is primary oocyte (still diploid)
- All this occurs before a baby girl is born and at
birth has around 400 000 primary oocytes
o At puberty meiosis continues to end of first
meiotic division and becomes secondary oocyte
o However, division is uneven - the other half (Polar
body) does not have enough cytoplasm and so is
of no more use (i.e. only one haploid cell made)
o Each month one secondary oocyte is released to
get fertilised; it continues to divide to form an
22.2 Sperm ovum. If ovum is fertilised, then a diploid cell is
formed called a zygote -> embryo -> fetus
• Spermatozoa:
• Gametogenesis in male mammals:

o Each spermatogonium gives rise to FOUR haploid
• Spermatogenesis:
sperm. Mitosis ceases in the embryo and meiosis
begins at puberty through to end of life.
• Gametogenesis in female mammals:
o In females, each oogonium gives rise to ONE
haploid egg and 2 polar bodies. Meiosis begins in
the embryo and Meiosis I arrested around birth.
o A cohort of primary oocytes arrested at Meiosis I
resume meiosis at puberty, and at each cycle, but
ends at menopause.
• Types of follicles:
o Primordial follicle - present in the ovary from
o Seminiferous tubules - site of spermatogenesis birth, located in the stroma of the ovary cortex
beneath the tunica albuginea. The primordial
follicle is oocyte + surrounding follicular cells.
o Primordial germ cell - oocyte present in the
primordial follicle ovary from birth
o Primary Follicle – single layer of follicle cells,
presence of zona pellucida

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o Secondary Follicle – two or more layers layers of • Summary of fertilisation in mouse:

follicle cells surrounding the ovum o Sperm swim through cumulus cells
o Antral (Graafian) Follicle – early or late - presence o Sperm bind to zona pellucida with and activate
of cavity and multiple layers of cells acrosome reaction – enzymes released that digest
a path through zona pellucida, lysis of zona.
o Sperm membrane fuses with egg membrane and
triggers egg activation through PLC-z (PLC-zeta):
- Centriole and sperm nucleus enter egg cytoplasm
(sperm nucleus now known as pronucleus)
- Cortical granule reaction releases proteases to
block polyspermy – prevents multiple sperm cells
fusing with one egg (slow block to polyspermy)
- Fast block to polyspermy is when Na+ enters the
egg via opening of Na+ ion channels in membrane
- Egg completes meiosis and begins development
22.4 Fertilisation
• In most mammals, the oocyte does not complete

meiosis until after fertilisation.
• External fertilization requires an aquatic habitat.

Many, many gametes and timing very important • Sperm provides the activation factor but it does
• Internal fertilization requires copulation. Two not provide the calcium. Calcium increases during
types of internal fertilisation: egg activation and causes an increase in cellular
o Oviparous (egg bearing), development occurs respiration in the egg cell during activation
outside mother’s body.
o Viviparous (live bearing), development occurs 23. Regulation of Reproduction
inside the mother’s body.
• Fertilisation in sea urchin:
23.1 Male Reproduction System
• Testes:
o Located outside the body to maintain optimal
temperature for sperm production
• Sperm:
o Produced in seminiferous tubules of testes
o Matured and stored in the epididymis
o Delivered to the urethra via the vas deferens
o Sperm is just 5% of the volume of the ejaculate
• Semen:
o Consists of sperm suspended in a fluid that
nourishes them and facilitates fertilization
o Components of seminal fluid produced in seminal
vesicles, prostate gland and bulbourethral glands
o All components of semen join in the urethra and
ejaculated through penis by muscle contractions
o 60% of volume from seminal vesicles – seminal
fluid is thick, containing mucus and fibrinogen
o 30% of the fluid is from the prostate gland, which
is alkaline to neutralise the acid environment of

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the vagina and contains a clotting enzyme to act 23.3 Hormonal Control of Male Reproduction
on fibrinogen from seminal vessel to convert
semen into a coagulum, a gelatinous mass. • Hormones controlling reproduction released by
the anterior pituitary gland:
o Anterior pituitary is regulated by the
hypothalamus via GnRH.
o Anterior pituitary releases tropic hormones i.e.
controls activities of other endocrine glands e.g.
- LH = luteinizing hormone
- FSH = follicle stimulating hormone
23.2 Female Reproductive System

• Reproductive hormone control:
• Female reproductive tract:
• Sperm to oocyte:
• In males, Leydig cells produce testosterone in the

presence of LH and Sertoli cells helps promote
spermatogenesis in the presence of FSH:

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• Spermatogenesis and male secondary sexual o FSH and LH are in relatively high concentrations
characteristics depend on testosterone produced during menstruation and cause follicle to mature
by the Leydig cells: o FSH and LH stimulates oestrogen to be produced
o At puberty sensitivity of the hypothalamus to –ve by the cells surrounding the follicle. Oestrogen,
feedback by T declines and so T increases. however, has a negative feedback on FSH and LH
o At puberty - increase in GnRH release and hence so their concentrations decrease.
an increase in LH and FSH and hence T. o When oestrogen reaches 2 to 4 times initial value,
it stimulates a surge of LH and FSH causing the
graafian follicle to burst and ovulation occurs
o Corpus luteum is formed and oestrogen and
progesterone is released – both inhibit secretion
of FSH and LH so that no more follicles develop.
o Corpus luteum then begins to degenerate and so
decrease in progesterone causing menstruation
23.4 Hormonal Control of Female Reproduction
• Menstruation cycle:
- The corpus luteum (follicle after releasing gamete)

secretes both oestrogen (stimulates endometrium
to thicken and develop) and progesterone (to
• Hormonal control in female reproduction maintain the uterus lining/endometrium)
23.5 Methods of Contraception
• Natural methods:
o Rhythm method – avoid high fertility period
o Pull-out method
• Barrier methods:
o Condom
o Spermicide jelly in vagina
o Diaphragms
• FSH and LH are the main gonadotropins released • Hormone based contraception:
from the anterior pituitary: o ‘The pill’ – contains oestrogen and progesterone
and prevents ovulation by supressing FSH and LH
o Progesterone only pill (Plan B) – does not prevent
ovulation but reduce ability of sperm to reach egg
cell by increasing mucus levels in the cervix
• Implantation blocking contraception:
o IUD - prevents implantation of fertilised egg
o Mifepristone (‘Morning after pill’) – used to abort
an already pregnancy by blocking progesterone
receptors so endometrium not maintained.

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• Sterilization contraception: o Cadherin mediates adhesion between blastomere

o Vasectomy – vas deferens cut so sperm can’t pass o The cell outlines coalesce/merge to form a morula
into the urethra, semen still ejaculated. o Blastomere become polarised(inside and outside)
o Tubal Ligation – oviducts are tied so eggs can’t and an epithelium(trophoblast) is formed
reach uterus and sperm can’t meet eggs.
23.6 Assisted Conception
• IVF Process
o Stage 1 - Follicles are stimulated using • Blastulation:
gonadotropins (FSH and then LH or hCG) o Formation of blastocyst/blastula from morula
o Stage 2 - Mature eggs are removed from ovaries o Cleavage of blastomeres results in some cells
o Stage 3 - Eggs are fertilized with sperm enclosed within inner compartment of morula
o Stage 4 - Fertilized embryos are grown in lab and o Fluid accumulates between blastomeres called
subsequently replaced into the uterus cavitation. Results in formation of a blastocoel or
• Intracytoplasmic Sperm Injection (ICSI) is performed blastocoelic cavity -> fluid filled cavity
as extra part of an IVF treatment cycle where a single - Na+/K+ ATPase activity(3 Na+ in, 2 K+ out) on the
sperm is injected into each egg to assist fertilisation basolateral membrane of the trophectoderm
using very fine micro-manipulation equipment. forms an ionic gradient and water flows into the
• Decline in fertility of a woman at around 30 years old. embryo through aquaporins
Trisomy risk also increases with maternal age. o Outer layer of cells become trophoblast
• Embryo biopsy for genetic analysis to test for - Trophectoderm/trophoblast becomes placenta
trisomy disorders e.g. Down syndrome etc. o Inner cells become the Inner Cell Mass (Pluriblast)
- ICM becomes the embryonic stem cells
24. Mammalian Development
24.1 Cleavage, Compaction and Blastocyst
• Cleavage is the initial divisions to form the

multicellular embryo – slow process
o Cleavage stage cells are called blastomeres.
o Mitotic cell cycle without G1 and G2 phases:
- Restricted mitosis – cells split but become smaller
with each division -> restoration of nuclear to
cytoplasm ratio, no growth in mass of cell/embryo
o Holoblastic, rotational cleavage - complete
cleavage(as little/no yolk in egg) to produce equal • Zona hatching:
and separate blastomeres. o Zona prevents cell to cell contact of embryo and
oviduct wall to prevent tubal implantation
o If there is premature hatching -> tubal pregnancy
o Hatching occurs in uterus just before implantation
o Blastocyst and uterus secretes proteases that
weaken the zona. Failure to hatch cause infertility.
• Embryonic Genome Activation:

o Between 4- and 8-cell stage a large number of
embryonic genes begin to be transcribed.
o With activation of embryo genome, there is:
- Destruction of pre-stored maternal mRNA
- Pre-stored proteins may still continue to function
and regulate development for some time.
• Compaction: • Zygote:
o 8-cell embryo undergoes compaction via cadherin o Low QO2 (consumption rate) - relatively
in membrane. Cadherin is a Ca++ dependent cell quiescent
adhesion molecule. o Limited capacity to utilize glucose

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o Generates energy from low levels of oxidation of 25. Development

pyruvate and/or lactate with aspartate
• Blastocyst:
25.1 Cytoplasmic Segregation
o High QO2 (metabolically very active)
o High capacity to utilize glucose
• As well as providing the DNA, the sperm passes on
o Generates energy from both aerobic glycolysis
its centriole, in the neck of the spermatozoa.
and the oxidation of glucose.
• Cytoplasmic segregation:
o Polarity in the oocyte (not seen in mammals).
Vegetal pole is the more yolky pole.
o Cytoplasmic factors in the oocyte set up the
signalling cascades that regulate major events
24.2 Implantation
• Endometrium most receptive when thickest

• Three phases of implantation are apposition(line
up with endometrium), attachment and invasion:
• Gray crescent in amphibians and reptiles:

o Sperm binding sites are found in the Animal
hemisphere. The sperm centriole initiates the
• Attachment phase to endometrium:
reorganisation of microtubules in the vegetal
o Loss of zona and glycocalyx
hemisphere which rotates the egg.
o Trophoblast directly contacts uterine epithelium
o Cortical cytoplasm rotates towards the site of
o Decidual reaction in stroma
sperm entry and forms the Gray Crescent
o Vascular changes
o The gray crescent is a cortical region that forms
o Trophoblast cells start to penetrate epithelium
opposite the point where the sperm entered.
• Embryo implantation in humans is interstitial and

very invasive - initiated by adhesive interaction • How fertilization activates development:
o After adhesion trophoblast cells penetrate uterine o The centriole from sperm causes microtubules in
epithelium, decidua and 1/3 of the myometrium vegetal hemisphere to form a parallel array to
o Target maternal blood vessels and degrade them guide cytoplasm. As cytoplasm moves,
to provide adequate blood supply to growing developmental signals are distributed.
foetus and placenta o β-catenin, a transcription factor important for
development is produced from maternal mRNA
and distributed throughout cytoplasm.
o GSK-3 phosphorylates and degrades b-catenin. It
is distributed throughout the cytoplasm.
o A GSK-3 inhibitor is found only in the vegetal
cortex. After fertilization, the GSK-3 inhibitor

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moves along microtubules to the gray crescent o In the second division the blastomeres divide at
and prevents degradation of b-catenin. right angles to each other—one is parallel to the
o Results in higher concentration of β-catenin in the axis and the other is perpendicular to it.
dorsal region (opp. side of where sperm enters)
25.3 Gastrulation
• In mosaic development each blastomere

contributes certain aspects to the adult animal. If
one blastomere is removed, a particular portion of
the embryo will not form.
• Blastulation in frog:
o A Blastula is NOT the same as a Blastocyst.

The blastocyst differs from blastula in that it is
composed of two already differentiated cell types.
• Salamander Blastulation:
25.2 Patterns of Cleavage
• Complete cleavage occurs in eggs with little yolk;

the blastomeres are similar in size.
o In frogs vegetal pole has more yolk; division
unequal so daughter cell in animal pole smaller
• Incomplete cleavage occurs in eggs with a lot of
yolk when cleavage furrows do not penetrate.
o In discoidal cleavage(incomplete) the embryo
forms as a blastodisc that sits on top of the yolk.
• Superficial cleavage is a variation of incomplete
cleavage in insects:
o i.e. mitosis occurs without cell division, forming a
syncytium - cell with many nuclei
• In mammals cleavage is rotational:
o First cell division is parallel to the animal – vegetal
axis and yields two blastomeres.

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• In regulative development other cells

compensate for any lost cells (many vertebrates).
o In humans, one blastomere can be removed for
genetic analysis without harming the embryo
• Gastrulation is the transformation of the blastula
into an embryo with multiple tissue layers and
body axis – cells MOVE to achieve this.
o 3 germ layers:
- Endoderm – innermost layer which gives rise to
digestive and respiratory tracts
- Ectoderm – outer layer which forms nervous
systems and epidermal layer of the skin
- Mesoderm – middle layer which develops from
cells that migrate between the endoderm and
ectoderm, and which makes many organs, e.g.
heart, muscle, bones
• Gastrulation in sea urchins:
• Outcomes of gastrulation:
o Formation of the body plan – head to tail, back and
front, left and right.
o Formation of 3 germ layers
- Mesenchyme forms a part of the mesoderm
o Formation of new cavity – Archenteron
o Radial symmetry converted to Bilateral symmetry

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BIOL10002 Notes - pdf

Biomolecules And Cells (University of Melbourne)

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• 1st foundation: Evolution via natural selection

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o The cis face of a Golgi stack is the end where

• Functions of intracellular membranes:

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o Exocytosis: This is the movement of substances

• Role of Membrane Proteins and Glycoproteins:

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• Denaturation disrupts the tertiary and secondary

• Enzymes act as catalysts and are typically proteins

• Competitive Inhibitors (reversible):

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• Non-competitive Inhibitors (usually reversible): • Enzyme partners include:

• Allosteric inhibitors (negative modulators):

• ATP is a molecular battery & coenzyme

• Feedback loops such as negative feedback e.g.

3.5 Enzyme Partners

• Enzymes for particular pathways are often

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o Net gain for each glucose molecule is:

• Link Reaction/Pyruvate Oxidation:

4.2 Aerobic Respiration

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• ATPase is only second known rotational shaft

4.3 Anaerobic Respiration

• When no oxygen is present hydrogen cannot be

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o Arrangement of respiration machinery in

5.1 Mitochondria • Chloroplasts are energy catchers of plant cells:

• Evidence mitochondria evolved from prokaryotes:

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5. Their metabolism is like existing prokaryotic

• Divides by binary fission

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2. S phase: synthesis of DNA (in euchromatin form) 6.3 Meiosis

• Variation is caused by:

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o Hydrogen bonds are also formed between parallel

• Three main groups of carbohydrates are

• Cellulose is the most abundant organic,

7.2 Nucleic Acids

• DNA and RNA are linear, unbranched chains made

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7.3 Protein Synthesis

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7.4 New Genetic Technology 8. Tissues and Homeostasis

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- Cardiac muscle (heart) 4. Nervous Tissues

8.2 Body Fluids

• Amoeba - a unicellular organism - living in pond

o Blood is considered a connective tissue, blood

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8.3 Homeostasis 8.5 Hypothalamus as Temperature Regulator

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9. Cell Communication/Signalling 9.3 Signalling Molecules

• Signalling molecules/ligands can act at a distance,