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1 BIOL1040 Course Summary MODULE I PRINCIPLES OF CELL FUNCTION 2 MODULE II PRINCIPLES OF BIOCHEMISTRY 16 MODULE III NERVOUS SYSTEMS 29 MODULE IV CIRCULATION AND GAS EXCHANGE 40 MODULE V SUPPORT AND MOVEMENT 53 MODULE VI ENDOCRINOLOGY 70 MODULE VII DEVELOPMENTAL BIOLOGY 80 Produced by cyrion TM . © 2015. All rights reserved.

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BIOL1040  Course  Summary

MODULE I PRINCIPLES OF CELL FUNCTION 2

MODULE II PRINCIPLES OF BIOCHEMISTRY 16

MODULE III NERVOUS SYSTEMS 29

MODULE IV CIRCULATION AND GAS EXCHANGE 40

MODULE V SUPPORT AND MOVEMENT 53

MODULE VI ENDOCRINOLOGY 70

MODULE VII DEVELOPMENTAL BIOLOGY 80

Produced by cyrionTM. © 2015. All rights reserved.

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SELECTIVE PERMEABILITY

The plasma membrane is selectively permeable – it lets some substances through, and not others. The hydrophobic interior of the bilayer is one reason why cell membranes are selectively permeable.

o Hydrophobic, non-polar molecules such as hydrocarbons, carbon dioxide and oxygen, can easily pass through the membrane.

o Hydrophilic, polar molecules such as water and glucose can only pass slowly, as the hydrophobic interior of the membrane repels the passage of polar molecules. Ions, which are hydrophilic, cannot pass at all; they must pass through specific membrane transport proteins. These transport proteins have a hydrophilic channel that certain molecules or ions travel through.

OSMOSIS

The plasma membrane is permeable to water molecules, and the movement of water into and out of cells is critical to life. Diffusion of water molecules across a selectively permeable membrane is a special kind of passive transport called osmosis.

If there is an unequal concentration of solute on either side of the membrane, and the solute cannot pass the membrane, then the solvent (water) diffuses through to equalise the concentrations.

Tonicity is the ability of a surrounding solution to cause a cell to gain or lose water. When a solute cannot pass through the membrane, there are three possibilities:

o HYPOTONIC – If the solute molecules are in the cytoplasm, the cell is in a hypotonic solution. The solute molecules attract water molecules so that fewer water molecules are free to diffuse across the membrane. Thus, the concentration of free water molecules is higher on the outside of the cell than the inside. Osmosis occurs as water molecules move down their concentration gradient, entering the cell. As a result, the cell swells.

� Animal cells lack rigid cell walls. When they are exposed to hypotonic environments, water rushes into the cell, and the cell swells. Eventually, if water is not removed from the cell, the pressure will exceed the tensile strength of the cell, and it will burst open, or lyse.

� Plant cells are surrounded by rigid cell walls. When plant cells are exposed to hypotonic environments, water rushes into the cell, but is kept from breaking by the rigid wall layer. The pressure of the cell pushing against the wall makes the cell turgid, and is the desired state for most plant tissues.

Permeable Impermeable Water (slowly) Ions (𝐾 , 𝑁𝑎 , 𝐶𝑎 , 𝐶𝑙 , 𝐻𝐶𝑂 ) Oxygen Hydrophilic molecules (glucose) Carbon dioxide Macromolecules (proteins, RNA)

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o HYPERTONIC – If the solute molecules are in the extracellular fluid, the cell is in a hypertonic solution. The solute molecules attract water molecules so that fewer water molecules are free to diffuse across the membrane. Thus, the concentration of free water molecules is higher on the inside of the cell than the outside. Osmosis occurs as water molecules move down their concentration gradient, leaving the cell. As a result, the cell shrinks.

� Animal cells lack rigid cell walls. When they are exposed to hypertonic environments, water rushes out of the cell, and the cell shrinks.

� Plant cells are surrounded by rigid cell walls. When they are exposed to hypertonic environments, water rushes out of the cell, and the cell shrinks away from the rigid wall.

� The resulting cells are dehydrated and lose most or all physiological functions while in the shrivelled state. If the cells are returned to isotonic or hypotonic environments, water re-enters the cell and normal functioning may be restored.

o ISOTONIC – If there are equal numbers of solute molecules in the cytoplasm and the extracellular fluid, the cell is in an isotonic solution. Since the concentration of solute molecules is equal on both sides of the membrane, the concentration of free water molecules is also the same on both sides. Water flows back and forth through the membrane in equal amounts, and so the cell neither shrinks nor swells.

Osmolarity, or osmotic concentration, is a measure of the total concentration of all dissolved substances, in osmoles per litre (Osm/L). Whereas molarity measures the number of moles of solute per unit volume of solution, osmolarity measures the number of osmoles of solute particles per unit volume of solution.

Note that a milliosmole (mOsm) is 1/1,000 of an osmole. The distinction between molarity and osmolarity arises only when compounds can dissociate in solution.

o Non-ionic compounds do not dissociate, so the relationship between molarity and osmolarity is one-to-one.

� EXAMPLE: Calculate the osmolarity of 0.1  M glucose. Glucose  does  not  dissociate  in  solution ∴ 0.1  M  glucose ⇒ 0.1  Osm/L  glucose

o Ionic compounds such as salts, can dissociate in solution to their constituent ions, so the relationship between molarity and osmolarity is not one-to-one; the molarity must be multiplied by the number of ions which dissociated.

� EXAMPLE: Calculate the osmolarity of 1  mol/L sodium chloride 𝑁𝑎𝐶𝑙. 𝑁𝑎𝐶𝑙 ⇌ 𝑁𝑎 + 𝐶𝑙 The  solute  particles  are  one  𝑁𝑎  ion,  and  one  𝐶𝑙  ion

Hence  for  every  1  mol  𝑁𝑎𝐶𝑙  in  solution,  there  are  2  osmol  of  solute  particles ∴ 1  mol/L  𝑁𝑎𝐶𝑙 ⇒ 1 × 2  Osm/L  𝑁𝑎𝐶𝑙

⇒ 2  Osm/L  𝑁𝑎𝐶𝑙 � EXAMPLE: Calculate the osmolarity of 0.5  mM/L calcium chloride 𝐶𝑎𝐶𝑙 .

𝐶𝑎𝐶𝑙 ⇌ 𝐶𝑎 + 2𝐶𝑙 The  solute  particles  are  one  𝐶𝑎  ion,  and  two  𝐶𝑙  ions

Hence  for  every  1  mol  𝐶𝑎𝐶𝑙  in  solution,  there  are  3  osmol  of  solute  particles ∴ 0.5  mM/L  𝐶𝑎𝐶𝑙 ⇒ 0.5 × 3  mOsm/L  𝐶𝑎𝐶𝑙

⇒ 1.5  mOsm/L  𝐶𝑎𝐶𝑙

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COLLAGEN

Collagen is the most abundant protein in vertebrates. It makes up about 30% of the total body protein. Collagen provides mechanical strength to connective tissues, including skin, bone, tendon, cartilage and blood vessels. Collagen is fibrous and not soluble in water.

There are 28 different collagens – their amino acid sequences are similar but distinctly different from each other.

o 90% of collagen in the body is collagen I. This is found in the skin, tendon, organs, bone etc. o The main component of cartilage is collagen II. o The connective tissue around the liver is collagen III.

The structure of collagen can be broken down as follows: o Collagen is a rod-shaped molecule, approximately 300

nM long and only 1.5 nM thick. Each chain contains around 1,000 amino acids. Collagen fibrils are composed of these collagen molecules, aligned in a staggered fashion – they are cross-linked for strength, but the specific alignment and degree of cross-linking varies with the type of collagen.

o Collagen is frequently found in a triple helix – this is a three-stranded polypeptide chain, with each chain intertwining. From a birds-eye view, the interior of the triple helix is very crowded with atoms. Only glycine side-chains (containing only a hydrogen atom) can point inside the triple helix; other side chains are too big.

o The collagen polypeptide has repeated amino acids (typical of fibrous proteins). Note that one of the amino acids (Hyp = hydroxyproline) is not one of the twenty standard amino acids. Hydroxyproline is formed by a chemical modification to the existing structure of an amino acid.

Collagen biosynthesis involves the following steps: 1. Single strands of polypeptide procollagen are made from translation of RNA. 2. The lysine and proline side chains of the procollagen become hydroxylated. 4-hydroxyproline

forces the proline ring into a more favourable conformation, stabilising the triple helix. It also offers more hydrogen-bonding potential between the three strands of collagen. This process is catalysed by an enzyme called prolyl-4-hydroxylase in the presence of ascorbate (vitamin C).

� A vitamin is an organic compound required as a vital nutrient by an organism (it cannot be synthesised by the organism, and therefore must be obtained from the diet). Scurvy is a disease caused by the lack of vitamin C (and as such the weakening of collagen).

3. Prolyl-4-hydroxylase is a metalloenzyme and needs Fe2+ to be fully active. Vitamin C adds an electron to Fe3+, reducing it to Fe2+. This activates prolyl-4-hydroxylase, which hydroxylates the proline side chains. As such, without vitamin C, proline in collagen will have less of a tendency to become hydroxylated. This would weaken the collagen.

4. The triple helix becomes fully formed. 5. Procollagen (inactive form of collagen) is converted to tropocollagen (active form) by an

enzyme called procollagen peptidase, which breaks specific peptide bonds at the ends. 6. Bundles of collagen fibrils form. 7. Cross links form – these are covalent bonds formed between the side chains of amino acids in

two different triple helices, or within a triple helix. For example, two lysine side-chains are replaced by a CH=N covalent bond. This cross-linking makes collagen stronger and less soluble.

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Nervous and hormonal stimuli can affect the contraction of smooth muscle in arterioles. The processes of vasoconstriction and vasodilation allow for regional blood flow:

o Vasoconstriction occurs when the smooth muscle contracts, narrowing the arterioles and increasing the upstream blood pressure.

o Vasodilation occurs when smooth muscle relaxes, increasing the diameter of the arterioles and decreasing blood pressure.

Vasoconstriction and vasodilation are often coupled to changes in cardiac output, which in turn affect blood pressure. For example, during heavy exercise, arterioles in the muscles dilate, allowing greater flow of oxygen-rich blood to the muscles. By itself, this increased flow would cause a drop in blood pressure; however the cardiac output increases at the same time, maintaining the blood pressure and supporting the increase in blood flow.

Vertebrate blood is composed of several kinds of cells suspended in a liquid matrix called plasma. o The plasma occupies 55% of the blood volume. It contains:

� WATER – Water constitutes 90% of plasma, and acts as an important solvent for carrying other substances.

� IONS – Ions or blood electrolytes are mainly inorganic salts such as sodium, potassium etc. They buffer the blood against pH changes, maintain osmotic balance between blood and interstitial fluid, and regulate the membrane permeability.

� PROTEINS – Plasma proteins include albumin (for osmotic balance and pH buffering), fibrinogen (for clotting) and immunoglobulins/antibodies (for defense).

� OTHER SUBSTANCES – Other substances transported by blood include nutrients (glucose, fatty acids, vitamins), waste products of metabolism, respiratory gases (O2 and CO2,), and hormones.

o The cellular elements occupy about 45% of the volume of the blood. It contains: � ERYTHROCYTES – Erythrocytes or red blood cells are the most numerous blood cells,

totalling around 5 – 6 million per microlitre of blood. As their main function is to transport oxygen, they are shaped as biconcave discs to increase surface area, enhancing the rate of diffusion. Erythrocytes also lack nuclei, leaving more space for haemoglobin, an iron-containing protein that transports O2.

� LEUKOCYTES – Leukocytes or white blood cells are less in number than erythrocytes, with only 5,000 – 10,000 per litre of microlitre of blood. There are five major types of leukocytes: basophils, eosinophils, neutrophils, lymphocytes and monocytes. They are important in defense and immunity.

� PLATELETS – Platelets are pinched-off cytoplasmic fragments of specialised bone marrow cells – they number between 250,000 – 400,000 per microlitre of blood, and are primarily responsible for blood clotting.

As erythrocytes only have a lifespan of 3 – 4 months, the cellular elements of blood are constantly replaced throughout a person’s  life. Erythrocytes, leukocytes and platelets all develop from multipotent stem cells that are dedicated to replenishing the  body’s  blood  cell  population:

o Some multipotent stem cells differentiate into lymphoid stem cells, which then develop into B and T cells, two types of lymphocytes that function in immunity.

o Other multipotent stem cells differentiate into myeloid stem cells¸ which give rise to all other blood cells and platelets.

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� SHOCK ABSORPTION – The fluid cushions joints that are subjected to compression from shocks (elastic property).

� NUTRIENT DISTRIBUTION – The fluid continually circulates to supply oxygen nutrients to, and removing carbon dioxide and metabolic wastes from, the chondrocytes within the articulating cartilage.

Cartilage by itself is avascular (no individual blood supply); rather it contains phagocytes to remove microbes and debris that results from wear and tear of the joint.

� If a synovial joint is immobile, the fluid is more viscous (gel-like). � As movement increases, the fluid becomes less viscous and more fluid. Warming up

before exercise stimulates the production and secretion of synovial fluid, so there is less stress on joints during exercise.

There are also many accessory structures in a synovial joint, including fat pads, ligaments and menisci. o Many joints include also include accumulations of adipose tissue called articular fat pads, lying

between the opposing articular surfaces. They act as packing material for the joint. o Accessory ligaments can support, strengthen, and reinforce synovial joints. There are two types:

� Extra capsular ligaments lie outside the capsule. � Intra capsular ligaments lie inside the capsule, but are excluded from the synovial

cavity by folds in the synovial membrane. o Occasionally in synovial joints, articular discs (or menisci) may be present – these are pads of

fibrocartilage which lie between the articular surfaces of bone, and are attached to the fibrous capsule. The discs usually subdivide the synovial cavity into two spaces, allowing separate movements to occur in each space.

� By modifying the shape of the joint surfaces of the articulating bones, articular discs allow two bones of differing shapes to fit together more tightly.

� A disc will help maintain stability of the joint, and direct the flow of synovial fluid to areas of greatest friction.

A variety of factors affect the contraction and range of motion at synovial joints: o Structure and shape of articulating bones o Strength and tautness of ligaments o Arrangement and tension of muscles o Contact of soft parts o Hormones o Disuse

Joints permit a wide range of motions: o Gliding – Two opposing surfaces slide past one another, but the amount of movement is slight. o Angular – These include flexion, extension, abduction and adduction.

� Flexion is movement in the anterior-posterior plane that decreases the angle between articulating bones, whereas extension increases this angle. Extension past anatomical position is called hyperextension. Lateral flexion refers to flexion laterally (away from the body).

� Abduction is movement away from the longitudinal axis of the body in the frontal plane (e.g. swinging the upper limb to the side). Adduction refers to movement back to the anatomical position e.g. (bringing fingers back together).

� Circumduction is movement in a circle (e.g. moving the arm in a loop). o Rotation – Rotations are described with reference to a figure in the anatomical position.

Movements include left and right rotation, medial and lateral rotation, etc.

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� Contraction of smooth muscle restricts the lumen of blood vessels, moves food along the gastrointestinal tract, moves fluids through the body, and eliminates wastes. The cells shorten and broaden on contraction. Some smooth muscle tissue can produce powerful contractions as many of the muscle fibres contract in unison. However in other locations (e.g. iris of the eye), smooth muscle fibres may contract individually.

o Both cardiac and smooth muscle tissue are regulated by neurons that are part of the autonomic (involuntary) division of the nervous system, and by hormones released by the endocrine system.

3. SKELETAL MUSCLE – This is usually attached to the bones of the skeleton. � Skeletal muscle heavily features striations – alternating light and dark bands that are

visible under light microscopy. � Skeletal muscle fibres may vary from just a few centimetres to up to 30 – 40 cm in the

longest muscles. The fibres are extremely elongated, roughly cylindrical and containing many nuclei at the periphery. Within a whole muscle, individual fibres may be aligned parallel to one another. Generally, it is thought that muscle fibres extend from one end of the muscle to the other.

� Contraction is voluntary as it can be made to contract or relax by conscious control. These are via neurons that are part of the somatic (voluntary) division of the nervous system.

� Skeletal muscles generally span joints and have at least two points of attachment. x The  attachment  of  a  muscle’s  tendon  to  the  stationary  bone  (or  the  least  

moveable bone) is called the origin. The origin is usually to the proximal. x The  attachment  of  a  muscle’s  other  tendon  to  the  moveable  bone  is  called  the  

insertion. The insertion is usually to the distal. x The insertion is pulled towards the origin when the muscle contracts.

The fleshy portion of a muscle between the tendons (which connects muscles to bones) is called the belly or the body. These bellies are often divided into compartments.

The action of a muscle is the work that is accomplished when the muscle fibres contract, or the main movements that occur when the muscle contracts.

Sometimes muscles work together as a functional unit. For example, the quadriceps consists of four muscles which share a common insertion point at the kneecap, that contract together to straighten the leg. Muscles can be grouped into opposing pairs:

o The agonist (or prime mover) is the muscle required to contract during movement. o The antagonist is the opposing muscle which relaxes during movement.

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Act  on  α-adrenoceptors  and  β-adrenoceptors in target tissues

o TROPIC – Tropic hormones are hormones that when secreted bind to another endocrine gland. It then stimulates this endocrine gland to produce another hormone, which leads to a biological effect. Most of the hormones secreted by the anterior pituitary are tropic hormones.

� LH (luteinising hormone) and FSH (follicle-stimulating hormone) are tropic hormones called gonadotropins (GnRH) – they stimulate the activities of the male and female gonads (ovaries and testes).

� TSH (thyroid-stimulating hormone) is a tropic hormone that stimulates the thyroid gland to release thyroid hormones such as T3 and T4.

� ACTH (adrenocorticotropic hormone) is a tropic hormone that stimulates adrenal cortex to produce and secrete steroid hormones/glucocorticoids.

o NON-TROPIC – Non-tropic hormones are hormones that unlike tropic hormones, do not have to bind to another endocrine gland first – they can directly stimulate non-endocrine tissues to produce a biological effect.

� PRL (prolactin) is a non-tropic hormone directly responsible for stimulating mammary gland growth and milk synthesis in mammals. Note that oxytocin is simply responsible for the ejection, rather than synthesis of milk. In different species however, it has a completely different function – for example, it regulates salt and water balance in fishes.

� MSH (melanocyte-stimulating hormone) is a non-tropic hormone that acts on neurons in the brain to inhibit hunger in mammals. In fishes and reptiles however, it regulates skin colour by controlling pigment distribution in skin cells (melanocytes).

o TROPIC & NON-TROPIC – A hormone that exhibits both tropic and non-tropic effects is a growth hormone. They can bind directly to tissues in the body (non-tropic effect), or can bind to another endocrine gland for the production of more hormones (tropic effect). They exert diverse metabolic effects to raise glucose levels in the blood.

� The liver responds to growth hormones by releasing IGF (insulin-like growth factors), which circulate in the blood and directly stimulate bone and cartilage growth.

STRESS AND ADRENALINE

The endocrine gland associated with the renal organs is the adrenal gland, which sits at the top of each kidney – as such they are also known as supra-renal glands. The adrenal gland is actually made up of two glands with different cell types, not unlike the anterior and posterior divisions of the pituitary gland:

o The outer adrenal cortex contains true endocrine cells. Hormones released from here are steroid hormones called corticosteroids. The two main types are:

� Mineralocorticoids (e.g. aldosterone, which is important for mineral metabolism, and reabsorption of Na+ from the renal tubules, allowing the retention of water).

� Glucocorticoids (e.g. cortisol, which maintains the metabolism of glucose). o The inner adrenal medulla consists mainly of cells derived from neural tissue. Hormones

released here are tyrosine-synthesised amines called catecholamines, which include: � Epinephrine (adrenaline) � Norepinephrine (noradrenaline)

The hypothalamus  coordinates  the  body’s response to stress, responding in two ways: o SHORT-TERM RESPONSE – The hypothalamus sends a very quick, synaptic/neural signal to the

adrenal medulla via nerve impulses, which acutely secretes catecheloamines (epinephrine and norepinephrine) from neurosecretory cells.

o LONG-TERM RESPONSE – The hypothalamus signals the anterior pituitary to secrete ACTH. This slow, neuroendocrine signal is sent to the adrenal cortex via the bloodstream, which is stimulated to chronically secrete corticosteroids (mineralocorticoids and glucocorticoids).

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The general approach to treating cancer nowadays is with high dose chemotherapy and stem cell transplantation:

o Mutant cells and cancer cells are stopped via high-dose chemotherapy (HDC). However, as the chemotherapy kills everything, it destroys the stem cells living in the bone marrow as well. As such, stem cells must be transplanted from a donor – this is called bone marrow or blood stem cell transplantation (SCT). This type of SCT is allogenic – where the stem cells come from a donor. Note that the stem cells need to be purified before being transplanted.

o Alternatively, if the stem cells in the body are healthy enough, they are extracted first before chemotherapy wipes out the cancerous cells. Then the stem cells are injected back into the body. This type of SCT is autologous – where stem cells come from the individual themselves.

Stem cell therapies are not limited to therapies for cancer. o The cornea of the eye overlies the iris and allows light to enter the eye. It consists of an outer

epithelium and inner endothelium layer, with a fibrous collagen matrix sandwiched in between, containing keratocytes (fibroblasts unique to the cornea). Problems to the cornea may include scarring of epithelium and water retention, giving the cornea a cloudy appearance. There are two approaches to corneal transplant:

� A cornea from a donor or a cadaver may be transplanted into the eye. � Stem cells may be taken from the limbus –

the outer border of the cornea. These limbal cells differentiate and send cells into the cornea, repopulating the corneal cells continuously – i.e. they are the multipotent cells of the cornea. Limbic stem cell transplantation involves extracting these limbal cells and growing them in a tissue culture ex vivo, before surgically removing the damaged cornea and replacing it with the cultured limbal cells.

o The skin can also be repaired using stem cells. An artificial product called Dermagraft TC is used for severe burns as a temporary covering for wounds – this is made from the cells of the foreskins of newborns. These cells (dermal fibroblasts) are grown a mesh that serves as a three-dimensional scaffold. As they grow on the scaffold, they secrete human skin collagen, growth factors and structural proteins. Finally, a synthetic outer skin layer is added. One foreskin can grow 250,000 square feet of skin. Note that limb defects cannot be repaired by stem cell therapy.

ANIMAL CLONING

In 1996, Roslin Institute and PP Therapeutics collaborated to create Dolly the Sheep, the first animal cloned from a cell taken from the udder of an adult sheep. Success rates of cloning have remained low since, with published data showing that only about 1% of reconstructed embryos lead to live births.

In late 2004, British scientists were given permission to perform therapeutic cloning using human embryos for the first time – producing embryonic stem cells to treat disease.

In  2002,  the  Australian  parliament  passed  the  “Research  Involving  Embryos  and  Prohibition  of  Human  Cloning  Bill’,  which  banned all human cloning whether for reproduction or research.

In 2006, the Federal Parliament passed a private members bill that allowed therapeutic cloning. Since then, many State governments have introduced laws that mirror this.

In  2007,  the  world’s  first  primate embryonic stem cells were cloned. This was done by removing the nuclear material from an unfertilised oocyte, replacing it with nuclear material from the skin cells of an adult monkey. Eventually, the oocyte developed into a blastocyst, where the embryonic (pluripotent) stem cells were extracted from the inner cell mass and allowed to differentiate into all monkey cells.