Biomedical Science - Semester 2

Epicardium - Outer layer also known as visceral pericardium (mesothelial cells = serous connective tisue)
Myocardium - Muscular wall of the heart, containing cardiac muscle tissue, vasculature and nerves
Endocardium - Inner lining of the heart, made up of simple squamous epithelial cell

We are multicellular organisms and our cells require oxygen and nutrients from the environment. Thus it is the role of the CV system to transport nutrients and oxygen via haemoglobin on our RBC’s to tissue and cells in our body. Additionally, our cells produce carbon dioxide and other metabolic wastes that require removal This is done through cellular transport processes, such as diffusion requiring a concentration gradient, between cells and the capillaries.

Pulmonary Circulation
Systemic Circulation

Pulmonary Circulation begins as deoxygenated blood from the body enters the right atrium of the heart (via vena cava) then passes through to the right ventricle. The right ventricle then pumps the blood to the lungs via the pulmonary artery (the only artery not carrying oxygenated blood). In the lungs, blood releases carbon dioxide and picks up oxygen which then returns to the heart’s left atrium via the pulmonary vein (the only vein carrying oxygenated blood)

Systemic Circulation begins as oxygenated blood from the left atrium enters the left ventricle and is pumped via the aorta (body’s largest artery) to the body via arteries, arterioles (small branch of an artery, leading into capillaries) and capillaries. In tissues, blood delivers oxygen and nutrients required for homeostasis whilst the blood simultaneously picks up CO2 and other waste. This deoxygenated blood then returns to the heart to begin pulmonary circulation again

Our heart has two atriums and two chambers.

Right atrium: thin-walled and recieves its blood from sup / inf vena cava and coronary sinus. Blood is sent to the right ventricle

Right ventricle: thicker-walled, recieving its blood from the right atrium and sending it to the lungs via the pulmonary artery

Left atrium: Thin-walled upper left chamber, it recieves its blood from the lungs via the pulmonary vein and passes it through to the left ventricle

Left ventricle: Thickest-wall due to high blood pressure, recieving its blood from the left atrium and sending it to the aorta for systemic circulation

The heart features four valves, each with a shared function of ensuring 'one-way' flow of blood to prevent backflow. The heart has two atrioventricular valves and two semilunar valves.

Atrioventricular Valves:
- Tricuspid Valve: Between the right atrium and right ventricle
- Bicuspid (mitral) Valve: Between the left atrium and left ventricle

Semilunar Valves:
- Pulmonary Valve: Between the right ventricle and pulmonary artery
- Aortic Valve: Between the left ventricle and the aorta

Body ➡️Inferior / superior vena cava ➡️ Right atrium ➡️ Tricuspid valve ➡️ Right ventricle ➡️pulmonary valve ➡️ Pulmonary artery ➡️ Lungs ➡️ pulmonary vein ➡️ Left atrium ➡️ Bicuspid valve ➡️ left ventricle ➡️ aortic valve ➡️ Aorta ➡️ BACK TO THE BODY

Coronary arteries feed working cardiac tissue with the right and left coronary arteries feeding from the base of ascending aorta. This blood flow is crucial for the heart's function as a pump and is regulated by various factors to meet the heart's oxygen demands.

- Involuntary and self-exciting (pacemaker cells)
- Striated and involves sarcomeres (functional unit of myosin and actin)
- Electrically coupled via intercalated discs which involve gap junctions and desmosomes

Begins at Sinoatrial (SA) node and progresses through the atrium towards the Atrioventricular (AV) node. This atrioventricular node slows the impulse, allowing the atria to fully contract before ventricle contraction. The AP continues down to the Bundle of His which conducts the impulse from the AV node to the ventricles (left and right bundle branches). Finally, the bundle branches branch into the Purkinje fibers, which spread the electrical impulse rapidly throughout the ventricular muscle, causing the ventricles to contract

1. SA Node
2. AV Node
3. Bundle of His
4. Left and right bundle branches
5. Purkinje fibres

Autorhythmic Cells (eg; SA node)
- These have no resting membrane potential but rather a pacemaker potential which is characterized by continuous depolarisaton
- Pacemaker potential and its rate of depolarization varies in different key parts of the hearts conduction pathway. EG; SA node is 100x per minute whilst the AV node is 40-60 times per minute
- Thus, slower depolarization compared to a neuron. Slow Na+ inflow --> Threshold --> Ca++ influx (depolarisation) --> K+ Outflow (Repolarisation)

Contractile cells/fibres
- These have a resting membrane potential around -90mv
- Depolarisation is initiated by neighbouring cells (AV node, bundle of his, purkinje fibres) via gap junctions
- Process is as follows:
1. Rapid Na+ influx (depolarisation) due to voltage-gated Na+ channels.
2. K outflow as Na channels close to return TMP to 0
3. A plateau phase where depolarisation is maintained by slow Ca++ channels, balancing K+ outflow.
4. Repolarisation as K leaves the cell restoring the membrane potential and Ca channels close (contraction)
5. The RMP is restored via the Na / K pump

1. The heart is self-exciting via pacemaker cells which allow a slow influx of Na until it reaches a threshold known as the pacemaker potential
2. Once reached, the pacemaker potential opens calcium channels causing quick depolarisation
3. This depolarisation of the intrinsic conduction system means this electrical impulse spreads to neighbouring cells via gap junctions (intercalated discs)
4. First the AP travels through the AV node, bundle of His and the purkinje fibres reaching cardiac muscle cells
5. Voltage-gated Na channels open causing rapid depolarisation of cardiac muscle cells which initiates the process of excitation-contraction coupling
6. Ca channels open causing an influx and slight repolarisation --> muscle contracts and pumps blood

This refers to how the electrical activity of the heart can be detected at the skin surface. The recording of this electrical activity is known as an electrocardiogram. A ECG involves 10 electrodes, with one on each limb (limb leads) and the remaining 6 in an arc around the heart (chest leads).

P Wave = Atrial depolarisation as they contract to pump blood into the ventricles.
PR Interval = Time for impulse to travel from SA --> AV node
QRS Complex = Ventricular depolarisation as they contract to pump blood out to the body (and atrial repolarisation --> occurs simultaneously)
ST Segment = Plateau phase in ventricles
T Wave = Ventricular repolarisation as they relax and prepare for the next contraction

The sympathetic nervous system increases heart rate and force of contraction through the release of Norepinephrine on adrenergic receptors. This increases Na+ and Ca++ influx in pacemaker cells causing faster depolarisation.

The parasympathetic nervous system works to decrease heart rate. This is achieved as the Vagus nerve releases acetylcholine (ACh) on muscarinic receptors, opening K+ Channels in the SA node --> Hyperpolarisation, thus slowing the speed of depolarisation.
- The parasympathetic maintains resting heart rate

Haemodynamics is concerned with the factors affecting the flow of blood throughout these vessels in the blood.

Tunica Intima - Innermost layer containing endothelial cells (specialised epithelium). It is very smooth to minimise friction. Arteries have elastic fibres to help with distension (ability to increase in size or girth)

Tunica Media - Middle layer of elastic and smooth muscle fibres. Much thicker in arteries and is the layer of blood vessels responsible for vasoconstriction and vasodilation

Tunica Externa - Outermost layer constructed from connective tissue. This layer fuses with adjacent tissue to anchor the vessel.

Elastic arteries are the largest arteries in the body (include aorta and pulmonary trunk), these contain a high proportion of elastic fibres in turnica media known as elastic lamellae. These arteries help move blood away from the heart

Muscular arteries are distributing arteries in the body. The tunica media contains more smooth muscle fibres and fewer elastic fibres compared to elastic arteries. These arteries have a greater ability of vasoconstriction and vasodilation. These arteries also have a continuous partial muscle contraction known as vascular tone to help maintain pressure and blood flow.

Arterioles are small arteries. Our body has around 400 million of these small arteries, comprised of only 1-2 layers of smooth muscle cells. These regulate bloodflow across capillary networks. Arterioles have structures call precapillary sphincters which can contract and reduce blood flow to capillaries

Pressure difference refers to blood flows from an area of higher pressure to an area of lower pressure. The higher the pressure difference the greater the blood flow

Vascular resistance refers to the friction caused between the blood and vascular wall. Its dependant on three factors
- Lumen size of blood vessel (eg; smaller size = increased resistance)
- Viscosity of blood (thickness – higher viscosity = higher resistance)
- Length of blood vessel (longer blood vessel = greater resistance - further to flow)

Systolic pressure is the maximum blood pressure during contraction of the ventricles

Diastolic pressure is the minimum pressure recorded just prior to the next contraction

MAP is the averaging out of systolic and diastolic pressure, providing a good indication of perfusion (delivery of blood to tissues)

Vasodilators are those that widen blood vessels to decrease resistance. These include:
- Nitric Oxide (local): Released by endothelium, relaxes smooth muscle
- CO₂, H⁺, adenosine, lactate: Indicate tissue needs triggering local dilation
- Decreased sympathetic system stimulation: Causes Epinephrine and norepinephrine to act on B-2 receptors, allowing passive dilation

Vasoconstrictors are those that narrow to increase resistance. These include
- Norepinephrine (NE), Epinephrine (high dose): Increase vascular tone
- Increased Sympathetic system output: Causes A-1 receptor-mediated vasoconstriction

Capillaries are the smallest blood vessels (approximately 5-10 micrometeres) which provide a huge surface area to aid the diffusion of gases, nutrients and wastes with surrounding tissue. A layer of endothelial cells with a basement membrane.

- Continuous capillaries: the most numerous type found in the CNS, lungs, muscle and skin

- Fenestrated capillaries: Found in kidneys, small intestine villi, choroid plexus in brain, ciliary process of the eye and endocrine glands. These endothelial cells have small holes called fenestrations

- Sinusoid capillaries: Found in the liver, red bone marrow, the spleen, anterior pituitary, adrenal glands. These have a large diameter compared to other capillaries and can have very large fenestrations. These have no basement membrane and permit the passage of large proteins and blood cells

Hydrostatic pressure and osmotic pressure are two opposing forces that regulate fluid movement across capillary walls.

Hydrosatic Pressure is the pressure exerted by a fluid against the walls of a capillary, primarily generated by the pumping action of the heart. This pressure tends to push fluid / blood out of capillaries

Osmotic pressure is the pressure required to prevent the flow of water across a semi-permeable membrane (like a capillary wall) from a solution with low solute concentration to a solution with high solute concentration. This is primarily determined by the concentration of proteins (especially albumin) in the blood plasma which will draw fluid into the capillaries.

- Diffusion
- Transcytosis
- Bulk flow

- Most common method where substances move from a high concentration to a low concentration (osmotic pressure)
- 02 and Nutrients are higher in blood and thus diffuse down the concentration gradient into the interstitial fluid and cells whereas CO2 and wastes are in higher concentrations in cells and interstitial fluid thus will diffuse down their concentration gradient into blood

- Whereby large molecules like proteins (eg; insulin) are enclosed inside a vesicle and enter the capillary / endothelial cell via endocytosis. The pinocytic vesicle then travels across the cell and exits the capillary via exocytosis into interstitial fluid.

Blood Hydrostatic Pressure (BHP) – Blood pressure in vessels which pushes out fluid from the capillaries into interstitial space (OUT OF CELL)

Osmotic pressure (BCOP & IFOP) – which is reliant on the ratio of solutes to solvent, particularly plasma proteins.
- Blood Colloid Osmotic Pressure (BCOP) attracts water from interstitial space into blood (INTO CELL)
- Interstitial Fluid Osmotic Pressure (IFOP) draws water from the blood into interstitial space (OUT OF CELL)

Filtration occurs at the arterial end of a capillary and is when fluid is pushed out of the capillary (IFOP & BHP). Reabsorption occurs at the venous end of capillary and is when fluid is drawn back into the capillary (driven by BCOP + IFHP)

- The movement of large amount of material in the membrane structure. It is faster than simple diffusion of but still relies on a concentration gradient
- Involves filtration and reabsorption: Filtration is driven by Blood hydrostatic pressure (BHP – blood pressure in vessel) and interstitial fluid osmotic pressure (IFOP). Reabsorption is driven by Blood colloid osmotic pressure (BCOP) which is created by the presence of albumin in blood.
- The balance between these two processes is known as Net filtration pressure (NFP) which dictates the movement of fluids and solutes.
NFP = (BHP + IFOP) - (BCOP + IFHP)

Venous return is the flow of blood back to the heart. It must match CO to maintain stable circulation. Since venous pressure is low, return is assisted by:
- Skeletal muscle pump: Venoconstriction and valves
- Respiratory pump: During inhalation, pressure in thoracic cavity drops, drawing blood
- Venous valves: ensure unidirectional flow of blood towards the heart
- Sympathetic Nervous stimulation: Causes venoconstriction

Reperfusion injury occurs after restoring blood flow (reperfusion) to tissues that were previously ischemic (deprived of oxygen). It is essentially tissue damage that follows returning blood to areas that experienced ischemia (lack of blood flow) or hypoxia (lack of oxygen in body tissue).

Neural regulation is for short-term control and rapid adjustments via the ANS to maintain homeostasis. Neural regulation is performed through baroreceptors and chemoreceptors.

- These detect changes of pressure within blood vessels and are found in the aorta, internal carotid arteries and large arteries of the neck and chest

- If blood pressure rises, these baroreceptors stretch more and information is sent to the CV centre (medulla oblongata), if blood pressure falls less stretch is detected by baroreceptors and the signal is sent to the CV centre.

- Depending on the stimulus, the CV centre decreases/increases parasympathetic stimulation of the heart via Vagus nerves (for decreased heart rate) or cardiac accelerator nerves (for increased heart rate)

- In summary, Low BP or decreased strech = Increased sympathetic activity / decreased parasympathetic activity to activate cardiac accelerator nerves for increased heart rate. High BP or increased stretch = increased parasympathetic activity to decrease heart rate via vagus nerve

- These measure the chemical composition of blood (02, CO2 and H) and are found close to baroreceptors

- After detecting concentration of 02, C02 and H they send this information to the CV centre.

- If hypoxia is detected (eg increased CO2 or low O2), increased sympathetic stimulation occurs to increase HR to increase blood pressure alongside with respiratory system stimulation for oxygen uptake (Rate and depth of breathing)

Hormones play a major role in regulating blood pressure, they can achieve this is three ways by modulating; cardiac output, systemic vascular resistance and total blood volume. The main systems or hormones involved include:
- Renin-angiotensin-aldosterone system (RAAS)
- Catecholamines (epinephrine and norepinephrine)
- Antidiuretic hormone (ADH)
- Atrial natriuretic peptide (ANP)

Activated when there is a reduction blood pressure to increase vasoconstriction and Na+/water retention. First the kidneys release renin in response to low BP, this onsets:
- aldosterone released from the adrenal cortex will increases Na+ and water reabsorption from the kidneys which in turn raises water blood volume for increased blood pressure
- Angiotensin is a potent vasoconstrictor (narrowing of blood vessels) that increases blood pressure and stimulates the release of aldosterone.

Secreted from the adrenal medulla by the sympathetic nervous system to increase blood pressure by raising the heart rate and force of contraction.

ADH is produced in the hypothalamus and secreted from the posterior pituitary in response to low blood volume or dehydration. ADH acts as a vasoconstrictor increasing blood pressure and also increases reabsorption of water from kidney tubules increasing water volume and BP

Hormone secreted by cells in the atria which reduces blood pressure by promoting vasodilation and inhibits the reabsorption of sodium and water in the renal tubules, increasing their excretion in urine – causing a loss of water which will in turn reduce blood volume and pressure

Systole and diastole are the two main phases of the cardiac cycle, referring to the contraction and relaxation of the heart, respectively, as it pumps blood. Systole is when the heart muscle contracts to pump blood out, while diastole is when the heart muscle relaxes and refills with blood.

- End-diastolic volume – Volume of blood in the ventricles once the ventricles have fully relaxed (diastole) and are filled with blood. Typically, around 120ml

- End-systolic volume – Volume of blood that remains in the ventricles after ventricular contraction (systole). Typically, around 50ml or 40% (considering EF is 60%)

- Ejection fraction is the percentage of the end-diastolic volume ejected during systole (amount of blood pumped). Normally 60% and is used to clinically assess heart function.

Stroke Volume (SV) – Volume of blood pumped out of the ventricles during systole

Factors influecing SV include:
- Preload
- Contractility
- Afterload

Preload describes the degree of stretch of cardiac muscle fibres prior to contraction. The higher the preload the greater the force of muscle fibre contraction. Therefore preload is proportional to the end-diastolic volume as ventricles will fill with more blood if ventricular walls undergo greater stretch and increased volume.

Inotropes are medications that affect the force of heart muscle contractions. Positive inotropes increase the strength of these contractions, while negative inotropes decrease the force. Essentially, positive inotropes help the heart pump more strongly, while negative inotropes help the heart relax and reduce its workload.

Contractility is the strength of contraction independent of preload where higher contractility will increase the stroke volume. Influenced by Ca Inotropes which are agents that can increase or reduce contractility eg; dopamine or epinephrine are positive agents whilst Ca channel blockers are negatuve agents

Afterload is the pressure that must be achieved by the blood in the ventricles to open the semilunar valves so blood can be transported out too the body. It's the pressure the left ventricle (in the case of systemic circulation) must overcome to open the aortic valve and eject blood.

Increased afterload can make it harder for the heart to pump blood effectively as it must overcome the pressure, thus Increased afterload reduces SV and increases end-systolic volume.

Hypertension and atherosclerosis (build-up of plaque on arterial walls) will increase afterload

Our respiratory system is responsible for facilitating the exchange of gases between the air we breathe, blood and cells ▫ O2 and CO2. This is vital as we produce most of our energy aerobically and we have a high demand for energy due to our size and complexity.

Diaphragm - Contracts and flattens ncreasing the space in the chest cavity (thoracic cavity) and allowing air to rush into the lung
External Intercostal muscles - Contract elevating the rib cage

While the diaphragm and external intercostals are the main players, other accessory muscles, such as the sternocleidomastoid, scalenes, and pectoralis, can assist in quiet inspiration, especially when needed

The upper respiratory tract consists of the; Nose/nasal cavity, pharynx and Larynx

- The external nose is constructed from bone and hyaline cartilage.
- It is lined with mucus membrane and divided internally by the nasal septum
- Olfactory receptors are located in the olfactory epithelium in the roof of the nose or nasal cavity

Posterior to the nasal cavity and extends to the larynx. It is made up of three regions:
- Nasopharynx (lined with pseudostratified epithelium for mucociliary clearance)
- Oropharynx (lined with stratified squamous epithelium for food passage)
- Laryngopharynx / hypopharynx (lined with stratified squamous epithelium for food passage)
- Contains the openings of the auditory tubes (eustachian tubes) which are linked to the middle ear and function to equalise ear pressure
- It is constructed of circular and longitudinal skeletal muscle and its contraction is involved in swallowing. This is also lined with a mucus membrane containing the tonsils (palatine and lingual)
- These are (tonsils) patches of lymphatic tissue similar to lymph nodes which play a role in immunity and are subject to inflammation (tonsilitis)

- Connects the pharynx with the trachea
- Constructed from 9 sections of cartilage and contains the vocal cords for speech
- Contains the epiglottis which is a leaf-shaped elastic cartilage which closes off the glottis preventing food or fluid from entering the trachea during swallowing

The lower respiratory tract consists of the trachea, bronchial tubes and alveoli

- Tubular windpipe extending from the larynx to the two primary bronchial tubes (around T5).
- It is constructed from four layers: Mucosa, Submucosa, Hyaline cartilage, adventita
- Mucosa is the innermost layer made of pseudostratified ciliated epithelium where the mucus traps particles and is propelled by the cilia to be swallowed
- Submucosa is mostly areolar connective tissue (loose CT) and contains mucus secreting glands and their ducts
- Hyaline cartilage is 16-20 incomplete cartilage rings as the open portion faces posteriorly towards the oespohegus
- Adventitia is the outer layer made of connective tissue

- The trachea divides into two primary bronchi where each bronchus feeds air into and out of the right and left lungs
- These bronchi are lined with pseudostratified ciliated epithelia and also has those same incomplete cartilage rings for structure
- The lower internal ridge where the right and left bronchi originate and branch off is known as the carina
- The primary bronchi divide into secondary or lobar bronchi which feed a single lobe of the lungs. These further divide into tertiary or segmental bronchi and futher into smaller bronchioles. The smallest bronchioles are known as terminal bronchi

Primary, secondary and tertiary bronchi are made of pseudostratified ciliated columnar epithelium with goblet (mucus secreting cells)

Large bronchioles are made up of simple columnar ciliated with some goblet cells

Smaller bronchioles are made of simple columnar ciliated with a few goblet cells

Terminal bronchioles are simple cuboidal epithelium making the end of the conducting zone of the respiratory system

The Bronchioles also see a decrease in cartilage and an increase in smooth muscles as they descend down

- Paired organs that sit inside the thoracic cavity surrounding the heart
- The left and right lungs reside in separate double-walled structures called pleaural membranes (parietal pluera = inside and visceral pleura = outside)
- Site of gaseous exchange

- Each terminal bronchus gives rise to multiple respiratory bronchioles
- Clusters of grape shaped, hollow structures called Alveoli exist here and are made up of simple squamous epithelial cells (type I pneumocytes)

- Type II pneumocytes produce surfactant and are simple cuboidal cells

- Each alveolus is covered in pulmonary capillaries (for gas exchange) and also covered in elastic fibres to assist in stretching during inspiration and recoil in exhalation

Our respiratory system must constantly deliver oxygen-rich atmospheric air to the alveoli and expel carbon dioxide-rich air from the alveoli to the atmosphere. This is the process known as Pulmonary ventilation

- This movement of air into and out of the lungs is dependant on different air pressures. This air movement follows Boyles law.
- Boyles law is concerned with the association of the pressure and volume of gas, i.e At constant temperature, pressure and volume are inversely related (P ∝ 1/V). A simple bicycle pump uses the same principle as air only enters the tyre once the pressure is high enough in the pump cylinder.

:*\ If the volume of a gas is increased (the space for it), its pressure reduces while if the volume of a gas is reduced its pressure increases

During inhalation, lung volume increases → intrapulmonary pressure decreases (air within the lungs is enlarged) → air flows in.

During exhalation, lung volume decreases → intrapulmonary pressure increases (air within the lungs is compressed) → air flows out.

Atmospheric pressure (Patm) = external air pressure
Alveolar pressure (Palv) = pressure inside alveoli (fluctuates with breathing)
Intrapleural (PIP) = pressure in pleural cavity (space between visceral and parietal pleura)

Inhalation: Palv < Patm as air flows into the lungs (increase in volume = decreased pressure)

Exhalation: Palv > Patm as air flows out of lungs (high to low pressure)

PIP stays negative to maintains lung inflation

Alveolar surface tension
- Where water molecules are bound by hydrogen bonds.
- The stronger attraction to each other (water to water) than to the gas molecules in the air, this surface tension will pull the alveoli slightly inwards, in turn reducing their volume

Lung compliance
- Describes the ease of lung expansion during inhalation. This is caused by the difference in intrapleural and alveolar pressures.
- High compliance means its easy to expand per unit of pressure change whereas low compliance means its difficulty to expand (stiff lungs or fibrosis)

Airway resistance
- Resistance caused by walls of the bronchial tubes (airway diameter), modulated by the ANS.
- The bronchial tubes typically dilate (relax) during inhalation and constrict a little during exhalation however any narrowing or obstruction to airways will increase the resistance

- Residual volume (volume of air remaining in the lungs after forced/maximal exhalation)
- Tidal volume or TV (the amount of air inhaled or exhaled during a normal breath)
- Inspiratory reserve volume (excess volume inhaled beyond the normal tidal volume)
- Expiratory reserve volume (excess volume exhaled beyond the normal tidal volume)

Lung capacities are combinations of different lung volumes often used to determine lung function. The main types include:
- Inspiratory capacity (Inspiratory reserve volume + Tidal Volume) indicating the maximum volume of air inhaled from normal expiratory level
- Functional residual capacity (Expiratory reserve volume + residual volume) indicating the volume of air remaining in lungs after normal expiration
- Vital Capacity (Inspiratory reserve volume + TV + Expiratory volume) indicates the maximum volume of air that can be inhaled and exhaled
- Total Lung capacity (the maximum amount of air the lungs can hold after a full inhalation) = Vital capacity + Residual volume

Two clusters of neurons are responsible for breathing, collectively they are known as the respiratory centre;
- Medullary respiration centre in medulla oblongata
- Pontine respiratory group in the pons

Partial pressures of gases are important in our respiratory system as we rely on simple diffusion for the transport of gases from alveoli to blood and from blood to cells. This diffusion as we know is reliant of concentration gradients and thus we know that the partial pressure of oxygen must be higher in the alveoli compared to blood in pulmonary capillaries so that oxygen can diffuse across. Similarly the partial pressure of CO2 must be higher in pulmonary capillary blood compared to the alveoli.

Henry’s law states that when a gas is in contact with a liquid, the dissolved gas is proportional to its partial pressure and the solubility of the gas in that liquid. These principles are dependant on a gas’s solubility, eg; O2 has poor solubility in water due to its non-polar nature whereas CO2 is 24x more soluble in water despite 02 having a higher atmospheric partial pressure.

The formula is C = K x P, where C is the concentration of the dissolved gas, k is the solubility constant and P is the partial pressure of that gas

Direction of Oxygen: Atmosphere → Alveoli → Blood → Tissues
Driving Gradient of Oxygen:
160 → 105 → 100 → 40 → 1–2 mmHg

Direction: Tissues → Blood → Alveoli → Atmosphere
Driving Gradient:
45 → 45 → 40 → 0.3 mmHg

As we know Co2 is 24x more soluble than water, so the fact that CO₂ loses so little partial pressure is because it’s more soluble and requires less of a partial pressure gradient. In contrast, O2 loses much more as its less soluble (readily dissolvable in a solvent) and thus requires a larger and longer concentration gradient to move the same amount as carbon dioxide.

Oxygen has poor solubility in water however 98.5% of our oxygen binds to haemoglobin in RBCs. Each haemoglobin molecule contains four haem units --> Each one binds one O2 molecule. When Oxygen is bound to haemoglobin, it is known as oxyhaemoglobin. Haemoglobin that is fully converted to oxyhaemoglobin is said to be fully saturated. The saturation of oxyhaemoglobin is dependent on the partial pressure of oxygen.

Other factors affecting oxyhaemoglobin saturation is acidity, carbon dioxide partial pressure and temperature.
- Low blood pH (acidity) reduces saturation whereas high pH (alkalinity) increases saturation
- Increased carbon dioxide partial pressure decreases oxygen binding as carbon dioxide binds to haemoglobin instead
- Increased heat reduces oxygen binding to haemoglobin

Alveolar ventilation refers to the amount of fresh air reaching the alveoli per minute. This is influenced by tidal volume (resting volume of air inhaled and exhaled), dead space and breathing rate. In a normal adult at rest, it is expected around 4.2L/min.

Pulmonary capillary perfusion is the amount of blood reaching the pulmonary capillaries per minute. Perfusion is also greater at the base of the lungs as gravity results in more blood flowing to lower sections of the lungs. Perfusion is determined by cardiac output and pulmonary circulation. In a healthy adult at rest, it is expected around 5L/min.

The ideal V/Q is 0.8 (ventilation slightly less than perfusion) In a healthy individual the following V/Q ratios are observed:
- V/Q in middle of the lung = 1 (ventilation matches perfusion)
- V/Q in base of lung = 0.3 = Greater perfusion
- V/Q in apex (top) of lung = 2.1 = Greater ventilation

Low Alveolar oxygen content:
- Local pulmonary vasoconstriction (narrowing of blood vessels to direct blood to better ventilated areas)
- Limits blood flow to these alveoli
- Bronchioles dilate to flow more air to increase oxygen delivery

High Alveolar Carbon dioxide content:
- Local bronchioles dilate to increase ventilation, causing more air to flow in to increase carbon dioxide and oxygen diffusion.

Low Alveolar Carbon dioxide content:
- Local bronchioles constrict to direct ventilation to better-perfused (blood flowing) areas.

Obstructive — problem getting air out (↑ airway resistance).
Restrictive — problem getting air in (↓ lung compliance).
Vascular — problem with blood supply to lungs (e.g., pulmonary embolism, pulmonary hypertension or scar tissue).

Pulmonary fibrosis – Scarring of lung tissue whereby normal tissue is replaced by fibrotic tissue
- This reduces lung compliance (stiff lungs), inhibiting oxygen diffusion
- It is often caused by autoimmune disorders, tuberculosis or asbestosis

Pulmonary Oedema – Congestive heart failure
- Causes left ventricle and/or right Av valve dysfunction
- Blood backs up on the left side of the heart as it cannot be pumped effectively into the systemic circuit
- This increased pressure in pulmonary blood vessels then force fluids out into the alveoli where the fluid collects and pools

Asthma – Chronic inflammation of the bronchial tubes
- Characterized by bronchospasms, increased mucus secretion and other airway obstruction.
- Caused by genetic and environmental factors such as allergens, pollutants and drugs

Chronic Bronchitis – Inflammatory condition of the bronchioles
- Causes increased thick mucus secretion, a loss of ciliary function and increased risk of infection
- This will narrow the airways, increasing resistance.

Emphysema – Loss of alveolar walls
- Causes large air spaces that remain full of air after exhalation
- This prevents new, oxygen rich air from entering the lungs

Nervous system:
- Parasympathetic (vagus nerve) releases Ach on muscarinic receptors to cause bronchoconstriction, vasodilation and increased mucus secretion
- Sympathetic system (adrenal medulla) releases adrenaline onto adrenergic receptors causing bronchodilation

Endocrine system:
Adrenal medulla – releases adrenaline for adrenergic receptor activation for bronchodilation
Histamine – released from mast cells to cause bronchoconstriction is response to allergens or asthma
Cortisol – anti-inflammatory response reducing airway hyperreactivity

Acidosis (low pH) results in the depression of the CNS as it causes a loss of synaptic transmission. Alkalosis (high pH) on the other hand causes overexcitement of the CNS and PNS which may cause nervousness, muscle spasms or even death

Respiratory Acidosis:
- A result of inadequate removal of CO2 causing a high partial CO2 concentration – above 45mmHg.
- Common causes include: Lung disease (COPD, airway obstruction) or damage to respiratory muscles/innervations

Metabolic Acidosis:
- Too much acid is produced by working cells and there is a failure of the kidneys to remove H+ from blood
- Causes include; Kidney disease, diabetic acidosis (ketoacidosis), lactic acidosis (ineffective oxidative metabolism), poisoning (aspirin, methanol).

Respiratory Alkalosis:
- Excessive removal of Carbon Dioxide causing a decrease in CO2 Partial pressure – below 35mmHg
- Causes include hyperventilation from anxiety, pain, fever, high altitude (removal of too much Co2)

Metabolic Alkalosis:
- High systemic blood concentration of HCO3 (hydrogen carbonate) which binds more hydrogen, in turn reducing acidity OR loss of acids
- Caused by prolonged vomiting (loss of gastric acids) or high intake of alkaline drugs (antacids)

The three mechanisms used to regulate pH include; Buffering systems, removal of Carbon dioxide and excretion of H+ from the kidneys.

Buffering systems (quickest)
- The primary buffering system in the body is the carbonic acid-bicarbonate buffer system
- When pH is low (High H+ content) Bicarbonate ion accepts H+ from the strong acid to form carbonic acid which then dissipates into Co2 and Water
- When pH is high (Low H+ Content) Carbonic acid donates H+ to the strong base to neutralise it

Removal of carbon dioxide (minutes)
- Usually the increase in pulmonary ventilation rate and depth (breathing rate and depth) to remove excess CO2

Kidney Excretion (Slowest)
- The only mechanism in the body that eliminates H+ from the body. Hydrogen causes a decrease pH (more acidic) thus the removal of it raises pH

The CV and respiratory systems are closely related as they require each other to achieve their primary goals. That is, the delivery of oxygen (CV) and the removal of Co2 (Respiratory). In response to exercise a major demand is placed on the body to increase oxygen delivery to working tissue while having to remove the simultaneously produced carbon dioxide.
- Pulmonary ventilation and perfusion are increased
- Vasodilation occurs to increase bloodflow
- Po2 and PCo2 drive diffusion

- Loss of elasticity from the airways down to the alveoli (baggy alveoli). This loss of elasticity or elastic fibres means decreased recoil and increased residual volume. This also means increased lung compliance

- The chest wall also becomes more rigid as the rib joints stiffen and respiratory muscles become weaker and less compliant.

- Weakening of mucociliary clearance (loss of bronchial tube ciliary function) and a reduction in alveolar macrophages, reducing immune response and increasing susceptibility to disease/infection.

1. Catabolism (Breakdown Reactions)
o Large molecules are broken down into smaller units.
o Releases energy (exergonic reactions).
o Example: Cellular respiration (glucose → ATP).

2. Anabolism (Building Reactions)
o Small molecules combine to form complex molecules.
o Requires energy (endergonic reactions).
o Example: Protein synthesis (amino acids → proteins).

Oxidation is used in the production of ATP in mitochondria and can occur in three ways and is usually exergonic/catabolic:
- The addition of oxygen
- Removal of electrons from an atom or molecule
- Removal of hydrogen

The mnemonic OIL RIG can help you remember:
- Oxidation reactions Is the Loss of electrons

Reduction reactions are chemical reactions where a molecule or atom gains electrons, resulting in a decrease in its oxidation state. Its essentially the opposite of oxidation eg; digestion of food in our body is an example of reduction reaction. Reduction can also occur in three ways and is usually endergonic/anabolic:
- Removal of oxygen
- Additions of electrons to a molecule
- Addition of hydrogen

The mnemonic OIL RIG can help you remember:
- Reduction reactions Is a Gain of electrons

1. Glycolysis
2. Krebs Cycle or Citric Acid Cycle
3. Oxidative Phosphorylation (addition of a phosphate group)

Glycolysis is the anaerbobic process in the cytosol of the cell whereby one molecule of glucose is oxidised into two molecules of Pyruvate which then produces a net gain of two molcues of ATP and reduced NAD (NADH).
- A 6C glucose molecule is divided into two 3C intermediate molecules
- These 3C molecules are oxidised into pyruvate and NAD is reduced to NADH
- ATP is made via substrate-level phosphorlyation

The process which occurs in the mitochondrial matrix whereby acetyl-Coenzyeme A is oxidised to form CO2, NADH and FADH which will be used in the electron transport chain in the next process.

Before this cycle Pyruvate enters the mitochondria and is turned into Acetyl-CoA via pyruvate dehydrogenase which produces 3 NADH, 1 FADH and 2 CO2 (waste) per pyruvate.

The last cycle of glucose catabolism whereby the energy from NADH and FADH are used to make large amounts of ATP in the inner mitochondrial matrix.

1) NADH and FADH donate electrons to protein complexes I-IV (electron carriers). This electron flow releases energy which pumps H⁺(protons) into intermembrane space (between mitochondrial matrix and outer membrane).
2) These hydrogen Ions flow back into the matrix via ATP synthase as the energy from this flow powers the phosphorlyation of ADP to ATP

Net Yield is 28 ATP, Oxygen and NAD / FAD is regenerated for glycoslysis and Krebs Cycles

Glycogenesis is the formation of glycogen, a polysaccharide stored in skeletal muscle and the liver. Glycogenesis is driven by the hormone insulin which encourages beta cells to increase the uptake of glucose by tissue when Blood sugar is too high. When glucose is needed, we reverse this process (glycogenolysis)

Gluconeogenesis is the synthesis of new glucose molecules from the catabolism of non-carbohydrate substrates like lactate, amino acids, or glycerol in the liver.
- Cortisol a major glucocorticoid from the adrenal gland
- Glucagon from pancreatic alpha cells

1. A triglcyeride is broken down into 3 fatty acids and one glycerol (hydrolysis)
2. Glycerol is converted into glyceraldehyde 3-phosphate which is converted into glucose if cellular ATP is high or catabolised to pyruvic acid if ATP is low
3. These fatty acids are essentially long hydrocarbon chains which undergo beta oxidation in the mitochondrial matrix and then are attached to Coenzyme A to from acetyl coenzyme
- A Beta oxidation involves the removal of two carbon atoms from the fatty acid at a time.
4. This Acetyl CoA enters the Krebs cycle and oxidative phosphorylation. A palmitic acid molecule contains 16 carbon atoms, thus if fully oxidised through the two cycles it can yield 129 ATP molecules

The synthesis of lipids is known as lipogenesis which takes places in the liver and adipocytes. This anabolic process is initiated by insulin and occurs in response to a positive energy balance, that is, more energy consumed then used. Carbohydrates, proteins and fats are all converted into triglycerides and stored

Lipids are non-polar and hydrophobic so they must be encased in a hydrophilic shell before transportation in blood can occur. This occurs in two locations:
1. Intestines form chylomicrons to transport dietary triglycerides from intestine to lymph and then blood
2. Liver produces very low density and low density lipoproteins (VLDL, LDL) which deliver triglycerides from liver to tissues. LDL (bad cholesterol) delivers cholesterol to tissues whereas the liver and intestine produce fresh / new high density lipoprotein (HDL) (good cholesterol) which collects cholesterol from tissues to return them to liver for excretion

Protein catabolism is driven mainly by the glucocorticoid cortisol
- Proteins are broken down into their individual amino acids
- These amino acids can be used to construct new proteins, converted to fatty acids, ketone bodies or glucose or oxidised to make ATP (conversion to acetylCoA)

Deamination and transamination are both metabolic processes that involve the removal or transfer of amino groups from amino acids and are both crucial for amino acid catabolism and play a role in nitrogen metabolism

- Deamination involves the removal of the amino group from the amino acid in the liver or kidney to produce ammonia / urea, while the carboxyl group can be used for energy. This occurs when amino acids are being used for energy

- Transamination involves the transfer of amino group from one amino acid to keto acid, forming a new amino acid and a new keto acid. This allows conversion between different amino acids recycling nitrogen to produce non-essential amino acids

1. Ingestion – Taking in food and drink.
2. Propulsion – Moving food along the GI tract.
• Includes swallowing (voluntary) and peristalsis (involuntary waves of contraction).
3. Mechanical digestion – Physical breakdown of polymers into monomers
• Chewing, churning in stomach, segmentation in intestines.
4. Chemical digestion – Enzymatic breakdown of food molecules into building blocks.
• Proteins → amino acids, carbs → monosaccharides, fats → fatty acids + glycerol.
5. Absorption – Movement of nutrients from GI lumen → blood or lymph.
6. Defecation – Elimination of indigestible substances, waste, bacteria, dead cells or other unabsorbed products as faeces.

the GI tract is one continuous tract 5-7m long with the same four layers throughout: Mucosa, Submucosa, Muscularis externa, serosa

Mucosa (innermost layer lining the GI tract)
- Moist due to glandular secretions, mucosa can be divided into surface epithelium, lamina propria and muscularis mucosae
- Epithelium for protection, secretion and absorption
- Lamina propria is connective tissue with blood / lymph vessels
- Muscularis mucosae is thin smooth muscle layer to move mucosa

Submucosa (Vascularity, nervous supply and lymphatics)
- Dense connective tissue with blood vessels, lymphatics, glands and nerves.
- Contains the submucosal plexus (part of the enteric nervous system)

Muscularis externa (smooth muscle layer)
- Smooth muscle layer divided into two layers – a inner circular and outer longitudinal layer
- This muscle is responsible for peristalsis and contains the myenteric plexus which controls motility

Serosa (outermost layer)
- Thin connective tissue + visceral peritoneum (epithelium)
- Provides structural support and reduces friction with other organs

The stomach is a J-shaped organ between the oesophagus and small intestine divided into four sections: cardia (entry), fundus (dome), body (main part), pylorus (funnel-shaped, connects to duodenum). The stomach has two main structures: Sphincters and Rugae (folds in the mucosa).
- The lower oesophageal sphincter permits entry of food and fluid into stomach whilst the Pyloric sphincter controls the exit into the duodenum

Mucosa – simple columnar epithelium that secretes alkaline mucus

Muscularis externa – three layers (inner oblique, middle circular, outer longitudinal) for strong churning

Serosa – visceral peritoneum (epithelium)

The longest part of the GI tract around 7 m long and 2.5cm in diameter extending from pylorus to the ileocecal junction, where it meets the large intestine. The small intestine is divided into three segments and is highly folded to maximise SA:V:
- Duodenum (smallest C-shaped segment mixing chyme with digestive liver/pancreatic secretions)
- Jejunum (major absorption and chemical digestion)
- Ileum (longest segment that absorbs bile salts + vitamin B12).

Mucosa – simple columnar epithelium with enterocytes (absorptive cells with microvilli = brush border / brush border enzymes) goblet cells for mucus, circular folds and villi (finger-like projections with blood capillaries)

These brush-border enzymes complete the digestion of the chyme

The large intestine is wider than the small intestine and attached via mesocolon to the posterior abdominal wall. It is around 1.5m long with four regions:
- Cecum (with appendix)
- Colon (ascending, transverse, descending, sigmoid)
- Rectum
- Anal canal

Mucosa – Simple columnar epithelium which contains absorptive cells primarily for water absorption and goblet cells to produce mucus for lubrication

Submucosa – standard connective tissue

Muscularis externa – inner circular + outer longitudinal

Serosa – forms small fat-filled pouches called epiploic appendages

Saliva
Gastric Juice
Bile
Pancreatic juice

Saliva comes from one of the three major salivary glands; Parotid, sublingual and submandibular. Saliva is 99.5% water with
- Amylase (carbohydrate digestive enzyme)
- Lipase (Lipid digestive enzyme)
- IgA (immunoglobulin for immune function)
- Lysozyme (antibacterial enzyme)
- Ions (sodium, potassium, chloride, phosphate, bicarbonate)

Gastric juice is secreted by gastric glands in the epithelial lining and enters the stomach via gastric pits. These juices serve to enhance digestion with around 2-3 litres of gastric juice produced and secreted each day.

Gastric Juice in the stomach contains
- Hydrochloric Acid (HCL) which kills most microorganisms, denatures proteins, breaks down plant cell walls, promotes the flow of bile and production of pepsin for protein digestion
- Pepsinogen, intrinsic factor, gastric lipase and mucus

Bile is both a digestive aid and an excretory product produced by hepatocytes (in the liver), released into the duodenum, playing a crucial role in breaking down fats in food and aiding in the absorption of nutrients. Bile contains:
- Bile salts to emulsify fats to increase SA for pancreatic lipase
- Water
- Cholesterol
- Bile pigment (bilirubin) from the breakdown of haemoglobin

Released from the exocrine gland in the pancreas, it secretes Bicarbonate which neutralises acidic chyme for the optimal functioning of digestive enzymes
- These enzymes (amylase, lipase, proteases and nucleases) can then optimally do their respective functions of breakdown and absorption

Located in the stomach mucosa, these gastric glands open into gastric pits to release Parietal cells, chief cells and G cells

Parietal cells secrete HCL and intrinsic factor (required for the later absorption of B12). This is a crucial component of gastric juice in the stomach

Chief cells secrete pepsinogen (which forms pepsin) and gastric lipase which breaks down triglycerides into fatty acids and glycerol. This is another vital component of gastric Juice in the stomach

G cells produce and release gastrin which stimulates HCL secretion by parietal cells, stimulates chief cells to secrete pepsinogen, causes lower oesophageal sphincter (upper) to contract, increasing gastric motility and causing the pyloric sphincter (lower) to relax

Think G cells for 'such a G' (daddy cell)

- Pancreatic Amylase breaks down polysaccharides into disaccharides and brush border enzymes (lactase, sucrase and maltase) break down disaccharides into monosachharides (glucose, galactose and fructose)
- Na / K pump sets up pressure gradient for Na which drives...
- Glucose and Galactose --> Secondary active transport with Na+
- Fructose --> Facilitated diffusion
- All these monosaccharides will enter the capillaries, hepatic portal vein and eventually the liver

- Pepsin, pancreatic proteases and brush border peptidases breakdown proteins into free amino acids, dipeptides or tripeptides
- Na / K pump sets up pressure gradient for Na which allows..
- Amino acids are absorbed into the enterocyte via Na+ dependant active transport (secondary)
- Dipeptides/tripeptides are absorbed via H+ dependant active transport then broken down inside enterocytes
- Once in the enterocyte these amino acids cross the basal enterocyte membrane by facillitated diffusion and enter the blood

Lipids (absorbed as fatty acids + monoglycerides)
- Lipids are mechanically broken down via stomach churning and chemically broken down via gastric lipase which breaks down complex triglycerides
- Lipids then enter the small intestine where Bile salts emulsify the fats
- Pancreatic lipase catalyzes reactions to digest these lipids into free fatty acids and monoglycerides
- Bile salts, free fatty acids and monoglycerides combine to form Micelle's which encapsulate these lipid products to the enterocyte membrane
- These fatty acids pass into epithelial cells (enterocytes) where they are packaged into chylomicrons (a lipoprotein) and secreted into lacteals (lymphatic capillaries) to eventually reach the blood via the lymphatic system

The pancreas is around 12-15cm long, sitting below and behind the stomach. It has a tapering structure consisting of three regions:
- The head (largest section near the duodenum)
- The body (central section)
- The tail (tapering section)

The pancreas is connected to the duodenum via two ducts (main pancreatic duct and accessory duct).

The Exocrine Pancreas (Acinar + Duct cells) – release digestive juice into ducts → duodenum
• Acinar cells → secrete digestive enzymes (pancreatic amylase, lipase, proteases, nucleases, trypsin, chymotrypsin).
• Duct cells → secrete bicarbonate-rich fluid (neutralizes acidic chyme by raisng pH).

Mechanism: secretion controlled by hormones (CCK → enzymes, Secretin → bicarbonate) and vagal stimulation.

The Endocrine Pancreas (Islets of Langerhans) – release hormones into blood
• α (alpha) cells (17%) → Glucagon → raises blood glucose (stimulates glycogenolysis, gluconeogenesis, lipolysis).
• β (beta) cells (70%) → Insulin → lowers blood glucose (stimulates glucose uptake, glycogenesis, lipogenesis, protein synthesis).
• δ (delta) cells (7%) → Somatostatin → inhibits insulin + glucagon, slows digestion (paracrine control).
• PP (F) cells (6%) → Pancreatic polypeptide → regulates exocrine secretion + bile release, inhibits gallbladder contraction and somatostatin

Mechanism: endocrine hormones act via receptors on target tissues (insulin → tyrosine kinase receptor, glucagon → GPCR → cAMP, etc.).

The main pancreatic duct (duct of Wirsung) joins the common bile duct at the ampulla of Vater (Hepatopancreatic ampulla). The flow of pancreatic juice and bile through this duct is controlled by a sphincter muscle of the hepatopancreatic ampulla also known as the Sphincter of Oddi.

The Accessory duct or the duct of Santorini functions as a secondary drainage pathway for pancreatic secretions, particularly from the dorsal portion of the pancreas reducing pressure in the main pancreatic duct, preventing conditions such as acute pancreatitis

The liver is the largest gland in the body (seocnd largest tissue), primarily responsible for: Metabolic regulation (we will touch on this), detoxification, storage, bile production and horome + Plasma protein synthesis

Hepatocytes are the main cell of the liver (around 80%) capable of performing many different tasks – metabolic, secretory and endocrine. These hepatocytes form 3D layers called hepatic laminae while networks of ducts between these laminae are called bile canaliculi

Hepatocytes secrete bile into bile canaliculi → bile ducts → leftight hepatic ducts → common hepatic duct → + cystic duct → gallbladder (for storage) or directly to duodenum. Bile is for lipid emulsification and bilrubin excretion

Dual blood supply:
• Portal vein (≈75%): nutrient-rich, deoxygenated blood from GI tract.
• Hepatic artery (≈25%): oxygenated blood from systemic circulation.
• Both mix in sinusoids → hepatocytes extract nutrients + oxygen.
• Go to Central vein → hepatic vein → IVC (systemic circulation).

Bile flows in the oppositie direction

• Excretory function:
o Eliminates bilirubin (Haemoglobin breakdown), cholesterol, drug metabolites, heavy metals

• Digestive function:
o Bile salts = amphipathic → emulsify fats → increase surface area for pancreatic lipase.
o Form micelles with fatty acids + monoglycerides → transport across enterocyte membrane.
o Critical for absorption of fat + fat-soluble vitamins (A, D, E, K).

The absorptive state (fed state)
- Period during and shortly after a meal (approximately four hours) where nutrients are plentiful and anabolism (energy storage) is greater than catabolism
- Recently digested and absorbed nutrients are available, this includes glucose for ATP production (the primary fuel)
- Insulin secretion increases after the meal promoting anabolism of glucose to glycogen, the formation of triglycerides in adipocytes and liver, and amino acid absorption

The postabsorptive state (fasting state)
- Period between meals and overnight where nutrient levels in blood fall and catabolism (energy release) is greater than anabolism
- No nutrients are available thus metabolic needs of the cells must be met by mobilising nutrients stored in the body

• Used immediately by most cells for ATP (via glycolysis → Krebs cycle → oxidative phosphorylation). Approximately 50%

• Stored as glycogen in liver and skeletal muscle (Insulin-secreting beta cells = glycogenesis). Approximately 10%

• Excess converted to fatty acids + glycerol → triglycerides in adipose tissue (lipogenesis). Approximately 40%

• Packaged into chylomicrons → enter lymph → blood.

• Broken down by lipoprotein (HDL or VDL, VLDL) lipase into fatty acids + glycerol.

• Stored in adipose tissue as triglycerides. As mentioned lipids are delivered to adipocytes by chylomicrons and VLDL (from liver)

• Some fatty acids used directly for energy (esp. cardiac and skeletal muscle).

• Adipocytes also synthesis triglycerides from excess glucose

• Absorbed as amino acids → enter circulation.

• Used for protein/polypeptide synthesis (growth, repair, enzymes, hormones).

• Excess amino acids → deaminated in liver → keto acids → used in Krebs cycle or converted into triglycerides.

In this state, cells still require glucose for ATP production, especially the cells in the CNS as fatty acids cannot pass the blood-brain barrier

The aim is to maintain a blood glucose concentration of around ≈ 70–110 mg/dL

1. Glycogenolysis – breakdown of liver glycogen via glucagon → releasing glucose into blood.

2. Gluconeogenesis – liver (and kidney) synthesize glucose from lactate, glycerol, and amino acids. Cortisol and glucagon promote this

3. Lipolysis – triglycerides in adipose → fatty acids (used for ATP by most tissues) + glycerol (gluconeogenesis).

4. Protein catabolism – skeletal muscle proteins broken into amino acids → gluconeogenesis.

5. Fatty acid oxidation – most tissues (except brain & RBCs) use fatty acids for ATP.

6. Ketogenesis – liver converts fatty acids → ketone bodies (used by brain during prolonged fasting/starvation). The cause of the state known as Ketosis (high blood ketone volume)

As aforementioned the absorptive state involves Insulin (pancreatic β-cells) to:

• ↑ glucose uptake (GLUT-4 in muscle/adipose).

• Stimulate glycogenesis, lipogenesis, protein synthesis.

• Inhibits glycogenolysis (splitting of glycogen), gluconeogenesis (production of new glucose molecules), lipolysis (splitting of lipids which promotes insulin resistance and releases glycerol, a direct substrate for gluconeogenesis).

Glucagon (pancreatic α-cells):
• Stimulates glycogenolysis, gluconeogenesis, lipolysis all used for the increasing of blood glucose levels

Epinephrine & norepinephrine (adrenal medulla):
• Enhance glycogenolysis and lipolysis, esp. in stress/exercise.

Cortisol (adrenal cortex):
• Stimulates protein catabolism (for energy for ATP production in prolonged periods) & gluconeogenesis (long-term fasting/stress).

Growth hormone:
• Mobilizes fats (uses fats for energy), reduces glucose uptake (anti-insulin effect).

Ketone bodies are produced in the liver mitochondria (hepatocytes) during prolonged fasting, low-carb intake and low insulin concentration in a process known Ketogenesis. Our body is constantly producing small quantities however once glucose has been exhausted, production is increased.

Ketone bodies = Acetoacetate, β-hydroxybutyrate, acetone (Acetyl-CoA that has bypassed Krebs cycle and can cross the Blood-Brain Barrier)

• Many cells can use fatty acids to produce ATP however these fatty acids cannot pass the blood-brain barrier thus large quantities of these fatty acids undergo beta oxidation to produce acetyl-CoA which then skip the Krebs cycle and are used to form Ketone bodies which can pass the BBB providing the cells of the CNS with ATP after being converted to NADH and FADH (for use in the electron transport chain = Oxidative phosphorylation). THIS IS KNOWN AS KETOGENESIS

• Provide alternative fuel for brain, skeletal muscle, and heart.

• Reduce reliance on glucose during prolonged fasting.

- Excretion – removal metabolic waste products (urea, creatinine, drugs, toxins)
- Regulation – Blood volume & pressure (via water balance, RAAS system), electrolytes, Acid-base balance/pH (H+ Secretion, HCo3 (Bicarbonate) reabsorption)
- Endocrine function – Erythropoietin (RBC production), Renin (blood pressure regulation), Calcitriol
- Gluconeogenesis – In prolonged fasting, kidneys can produce glucose

Cortex:
• Outer layer containing nephrons (filtering units)
• Contains renal corpuscles (glomerulus + capsule) and parts of tubules.
• Site of filtration and reabsorption

Medulla:
• Inner region.
• Contains renal pyramids, each with parallel collecting ducts.
• Ends in a renal papilla that drains into minor calyces → major calyces → renal pelvis

Renal pyramids:
• Cone-shaped structures in the medulla.
• Contain loops of Henle and collecting ducts → concentrate urine

Nephrons are the functional units of the kidney with each kidney containing 1-1.25 million nephrons – cortical and juxtamedullary. Each nephron is divided into renal corpuscle (for filtration) and renal tubule (reabsorption and secretion).

• Cortical nephrons (85%) – mainly in cortex, short loops. Flow with efferent arterioles where reabsorbed and secreted material enter

• Juxtamedullary nephrons (15%) – long loops into medulla; key for urine concentration.

Renal corpuscle (in cortex):
• Glomerulus (capillary tuft – fenestrated capillaries) receives blood from afferent arterioles + Bowman’s capsule.
• Site of filtration.

Renal tubule (extends into medulla):
• Proximal convoluted tubule (PCT) → reabsorption of most water, ions, glucose, amino acids.
• Loop of Henle → descending limb (water reabsorption), ascending limb (Na⁺/Cl⁻ reabsorption).
• Distal convoluted tubule (DCT) → fine-tuning of electrolytes, acid–base balance.
• Collecting duct → receives input from many nephrons; regulated water reabsorption (ADH sensitive).

1. Renal artery → segmental arteries → interlobar arteries → arcuate arteries → interlobular arteries.

2. Afferent arteriole → glomerulus (capillary #1, filtration).

3. Efferent arteriole → peritubular capillaries (cortical nephrons) OR vasa recta (juxtamedullary nephrons).

4. These capillaries → interlobular veins → arcuate veins → interlobar veins → renal vein → IVC.

Glomerular (Bowman’s) capsule:
• Surrounds glomerulus (a fenestrated capillary network that receives blood from afferent arterioles)
• Inner visceral layer consists of specialised cells called podocytes which cover the fenestrated capillaries and pedicels extending to form filtration slits around the capillaries
• Outer parietal layer constructed from squamous epithelial cells
• Collects filtrate (plasma without proteins).
• Filtration driven by blood pressure (hydrostatic).

Renal tubule (three main sections):
• Filtrate begins its journey from the capsular space through the renal tubule – becoming tubular fluid
• Surrounded by peritubular (fenestrated) capillaries with three main sections ⬇️
• PCT → bulk reabsorption (65% of filtrate volume, including, ions and water). Almost 100% of glucose and amino acids reabsorbed here (also part of filtrate volume). Simple cuboidal epihtelium for diffusion
• Loop of Henle (nephron loop) → counter current mechanism for urine concentration.
• DCT → selective reabsorption (Na⁺, Cl⁻) & secretion (H⁺, K⁺, drugs). Simple cuboidal cells
• Collecting duct → final water reabsorption (ADH), urea recycling.

- Descending limb constructed from simple squamous epithelium, thin ascending limb in juxtamedullary nephrons also simple squamous epithelium and thick ascending limb constructed from cuboidal or low columnar epithelium

- Reabsorption here is 20% water via descending limb and 25% Na and Cl via ascending limb

• Structure: simple cuboidal epithelium, dense microvilli on apical surface (brush border).

• Function: bulk reabsorption (65–70% of filtrate – 100% of glucose and amino acids)

• Lots of mitochondria → active transport

Nephron Loop (Loop of Henle)
• Descending limb: thin simple squamous epithelium, permeable to water (driven by kidney intersitial high osmotic gradient – not solute), not solutes.

• Ascending limb: thicker epithelium (columnar or cuboidal), permeable to Na⁺, K⁺, Cl⁻ (ion transporters), not water

• Function: countercurrent multiplier → establishes medullary osmotic gradient (needed for concentrated urine).

• Structure: columnar/cuboidal cells, variable permeability.

• Function: final adjustment of water & solute balance. Mainly active transport of Na

• Responsive to ADH (↑ water reabsorption via aquaporins) & aldosterone (↑ Na⁺ reabsorption, K⁺ secretion).

• Structure: columnar/cuboidal cells, variable permeability.

• Function: final adjustment of water & solute balance. Mainly active transport of Na

• Responsive to ADH (↑ water reabsorption via aquaporins) & aldosterone (↑ Na⁺ reabsorption, K⁺ secretion).

- Principle cells – reabsorb Na (in response to aldosterone) and K

- Intercalated cells – secrete H and secretes or reabsorbs HCO3 (Bicarbonate ion)

The renal pelvis feeds urine into the ureter and exits the body via the urethra. Urine is stored in the bladder. The ureter is
• Paired muscular tubes that carry urine from renal pelvis → bladder.
• Peristaltic waves move urine.
• Mucosa = transitional epithelium (able to stretch and distend without damage)
• Muscularis = circular (outer) and longitudinal (inner) smooth muscle
• Adventitia = loose connective tissue, blood, lymph and nervous supply

• Hollow, muscular organ (detrusor muscle).
• Stores urine until micturition.
• Mucusoal layer = transitional eputhelium, muscularis (detrusor layer) = long, circular, longtitudinal muscle layers
• Internal urethral sphincter = involuntary (smooth muscle).
• External urethral sphincter = voluntary (skeletal muscle).

• Conducts urine outside body carrying it from bladder to outside of the body.
• Inner mucosa = epithelium differs between males and females
• Male = longer, passes through prostate + penis.
• Female = shorter, higher UTI risk.

the process in which the kidneys filter excess fluid and waste products from the blood into a fluid called filtrate, the first step in urine formation. This filtration occurs in the glomerulus, a tiny network of capillaries surrounded by Bowman's capsule. The filtration rate, known as the Glomerular Filtration Rate (GFR), is a key indicator of kidney health

1. Afferent arterioles feeds blood into renal corpuscle (glomerulus)
2. Once inside, blood encounters the filtration membrane made of fenestrated capillaries and podocytes
3. Fenestrations alone would permit all blood solutes except blood cells & platelets to exit
4. Podocytes extend to form pedicels to form a much smaller filtration slit around the capillaries
5. This limits the material able to pass through into the capsular space.

Net filtration is driven by three different pressures we have previously touched on:

Glomerular blood hydrostatic pressure (BGHP)
- Forces fluid out of the glomerular capillaries into Bowman’s capsule
- 55mmHg

Capsular hydrostatic pressure (CHP)
- Hydrostatic pressure within the glomerular capsule that resists fluid exiting the glomerular capillaries (opposes filtration)
- 15mmHg

Blood colloid osmotic pressure (BCOP)
- Osmotic pressure of blood solutes (plasma proteins like albumin) that retain water thus opposing filtration. (Solute concentration in glomerular capillaries)
- 30mmHg

GFR is maintained by three means; Renal autoregulation, Neural regulation and Hormonal regulation

Maintaining GFR is crucial: 125m/min in males & 105ml/min in females
• Too high → substances pass too quickly/solutes are lost → not reabsorbed.
• Too low → waste products not fully excreted and would result in build-up in blood.

This the process that occurs simultaneously in the nephron loop as the ascending limb is permeable to solutes and not water, meaning as solutes are actively transported out, water cannot follow, making the interstitial fluid hyperosmotic while the tubular fluid becomes progressively hypoosmotic.

This hyperosmotic gradient is what drives the diffusion of water out of the nephron tubule in the descending limb

• Triggered by ↑ plasma osmolality (concentration of a solution per 1kg of tissue) detected by osmoreceptors, triggers perception of thirst from hypothalamus in response to ↓ blood volume / pressure and production of angiotensin II.

• Drives water intake.

• Produced by hypothalamus and is released from posterior pituitary when osmolality ↑ or blood volume ↓ to act on DCT and collecting ducts

• Increases water reabsorption in collecting ducts (via aquaporins) and reduces water lost in sweat and is a vasoconstrictor – decreased production of urine opposing diuretics like alcohol and Xanthines

• Bone and teeth
• Muscle contraction (binds to troponin to move tropomyosin to exposing binding sites on actin in the cross-bridge cycle)
• Neurotransmitter release (enters axon terminal and triggers exocytosis of synaptic vesicles containing neurotransmitter)
• Blood clotting.

• Enzyme cofactor
• ATP stabilization
• Nerve & muscle function (competes with Ca facilitating muscle relaxation and subsequent contraction).
• 50-60% found in bone matrix as magnesium salts with the remaining in tissues (mainly muscle fibres)

Parathryoid hormone is release by the parathyroid glands in response to low blood calcium ion concentration to stimulate osteoclasts to increase the resorption of bone. This will release calcium ions in blood and reabsorption by the kidneys

• PTH will increase blood calcium ions and magensium ions via reabsorption in kidneys and cause a loss of some phosphate ions as it inhibits reabsorption thus increasing its excretion.

Calcitriol will↑ both calcium and phosphate intestinal absorption

o Amino acids act as amphoteric molecules (can accept or donate H⁺) in intracellular fluids and plasma

o Amino acids contain a carboxyl group and an amino group – When pH rises the carboxyl group can release H to reduce pH. When pH falls the amino group can bind to excess H to reduce the concentration of H and thus cause an increase in pH

o Example: hemoglobin buffers H⁺ in RBCs or Albumin in plasma

o H₂PO₄⁻ ⇌ H⁺ + HPO₄²⁻ Phosphates are key anions (negative ions)

o Dihydrogen phosphate functions as a weak acid, buffering hydroxide ions (Strong base or High pH) by donating a H. Monohydrogen phosphate acts as a weak base, binding too H in a solution to from dihydrogen phosphate

o Strong in the renal tubules where phosphate concentration is higher.

As proteins rely on specific 3D shapes (hydrogen bonds and ionic bonds), excess H or a low pH will cause these bonds to break and thus the proteins to denature. This will cause a loss of protein activty (eg; enzymes, transporters, receptors etc). Acidosis is known to also cause a:

- Depressed CNS causing a loss of synaptic transmission, prompting confusion, disorientation and possibly coma

- Reduced cardiac contractility → Arrhythmias (irregular heartbeats and rhythms)

- Widespread enzyme dysfunction

The kidneys provide long-term regulation of pH and are the slowest of all buffering systems yet provide the most powerful input. It has three main mechanisms

1) Secretion (removal) of H⁺from the distal tubule & collecting duct to remove excess acid from the blood and maintain blood pH (In response to low pH).

2) Reabsorption of HCO₃⁻ (Bicarbonate) which prevents bicarbonates loss in urine, increasing blood pH as bicarbonate ions are an alkalotic substance. (In response to low pH)

3) Geeration of new HCO₃⁻via metabolism of glutamine (produces NH₄⁺ + HCO₃⁻).

Acidosis (<7.35): Kidneys will increase H⁺ secretion and HCO₃⁻ reabsorption.

Alkalosis (>7.35): Kidneys will excrete more HCO₃⁻ into urine and secrete (remove) less H from DCT etc.

1. Mutation
• Random permament changes in DNA sequences.
• Source of new alleles (some beneficial, some harmful, most neutral).

2. Genetic Recombination (Crossing Over & Independent Assortment)
• During meiosis, homologous chromosomes exchange segments (crossing over).
• Independent assortment = random distribution of maternal/paternal chromosomes.

3. Gene Flow (Migration)
• Movement of alleles between populations through interbreeding.
• Increases genetic diversity and adaptability.

Advantages:
• Genetic variation: Combines genes from two parents, creating offspring with unique genotypes — increases adaptability and evolution.
• Improved disease resistance: A more diverse gene pool reduces the risk of species-wide susceptibility to pathogens.
• Natural selection efficiency: Beneficial traits spread more effectively in a sexually reproducing population.

Disadvantages:
• Energy cost: Requires finding and competing for mates.
• Slower reproduction rate: Involves meiosis, fertilisation, and gestation rather than simple cell division.
• Risk of genetic errors: Non-disjunction and chromosomal anomalies can occur during meiosis.
• Dependence on both sexes: Population growth is slower compared to asexual reproduction.

The primary organ - Testes which produce sperm and testosterone

Acessory ducts include the epididymis (sperm maturation), the vas deferenes (transports mature sperm from epididymis to the urethra)

Accessory glands include the seminal vesicles which produce fructose-rich secrement for sperm energy, the prostate gland which sercetes alkaline fluid to neutralise vaginal acidity and the bulbourethral glands which secrete mucus for lubrication.

The primary organ is the Ovaries which ovulate one egg per cycle, store eggs and produce key sex hormones (progesterone and oestrogen)

Accessory ducts include the uterine (fallopian) tubes which transport the egg from the ovaries to the uterus. Typically the place where fertilisation occurs. The uterus is the site of implantation and foetal development, the cervix regulates passage to and from the uterus

The external genitalia of the female reproductive system is the vulva - consisting of labia majora and minora, clitoris, vaginal and urethral opening

• Spermatogenesis begins in the seminiferous tubules (inside the testes) where spermatogonia (2m) divides via mitosis to form primary spermatocytes

• These primary spermotocytes undergo meoisis I to form secondary spermacytes which are haploid (n)

• Secondary spermotocytes undergo meiosis II to form spermatids (n)

• Spermatids mark the beginning of spermogenesis, the process whereby spermatids mature into spermatozoa. This is supported by sertoli cells, FSH, testosterone and is a continual process from puberty onwards

Oogenesis is the production of a female gamete or ovum / egg.
• Oogonium (2n) stem cells undergo mitosis to produce primary oocyte (2n) which is arrested in prophase until puberty
• At ovulation after puberty, Meiosis I completes to produce a secondary oocyte (n) and a first polar body that may or may not divide again
• This secondary oocyte begins Meiosis II as fertilisation triggers the oocyte to split into an ovum (n) and a second polar body. This process is discontinuous meaning it pauses at stages and it is alos controlled by FSH and LH

The secondary oocyte can only successfuly become an ovum after fertilisation has occured.

Random segregation is the seperation of allele pairs (different traits of the same gene) during Meiosis II (anaphase) so that they transfer specifically into seperate gametes

Independant assortment is where the homologous chromosomes are randomly shuffled into two daughter cells during Meoisis I (anaphase) causing genetic recombination

Sex hormones are controlled via the hypothalamus and anterior pituitary in a pathway know as the hypothalamic-pituitary gonadal axis (HPG axis)

Major gonadotropins include luteinizing hormone and follicle stimulating hormone. These are controlled by GnRH (Gonadotropin-releasing hormone) from the hypothalamus.
• GnRH → anterior pituitary → releases FSH & LH.
• Regulated via negative feedback by sex hormones (oestrogen, progesterone, testosterone).

In males, LH stimulates testosterone production via Leydig Cells

In females LH promotes follicle maturation, the maturation of the endometrium for implantation (LH from corpus luteum) and it also provides a surge mid-cycle to help trigger ovulation (onset by oestrogen levels)

In males FSH promotes the development of secondary spermatocytes from primary spermatocytes by stimulating sertoli cells (spermatogenesis)

In females FSH promotes the growth of ovarian follicles necessary for oestrogen production as they mature

The ovarian cycle is that which produces one ovulated oocyte per cycle. It can be divided into three stages:

• Follicular phase (Days 1-14) FSH promote follicle growth and oestrogen rises

• Ovulation (approximately day 14) LH surge into oocyte release in response to ooestrogen levels

• Luteal phase (Days 15-28) Corpus luteum secretes progesterone which maintains the endometrium lining while FSH and LH drop due to negative feedback

The uterine cycle is that which creates an ideal uterine environment for implantation to occur. It can alos be divided into three main stages:
• Menstrual Phase where endometrial shedding occurs as FSH and LH begin to rise

• Proliferative phase where ovarian follicles increase oestrogen which rebuilds the endometrium. LH and FSH surge in response to higher oestrogen levels. After ovulation progesterone levels rise due to the corpus luteum.

• Secretory phase where progesterone thickens lining, causes glandular secretions of glycogen and ultimately prepares the endometrium for implantation. LH and FSH drop during this phase

As we have learnt, Meoisis II in oogenesis is only completed if fertilisation occurs and so it is very important in the production of an ovum to zygote (fertilised ovum).
The process of fertilisation can be looked at like this:
• Sperm capacitation whereby the membrane chnages enabling acrosomal reaction

• Acrosomal reaction where enzymes digest zona pellucida (membrane of ovum)

• Oocyte activation which is the fusion of sperm and oocyte membranes. Its this entry of sperm allows the secondary oocyte to transistion to an ovum to complete Meiosis.

• Eventually this will form a zygote via pronuclei fusion (the joining of the haploid set of chromosomes from both parents to form a diploid zygote)

This is the rapid post-fertilisation cell division known as cleavage. The first division occurs after 24 hours to form blastomeres, the subsequent cell divisions occur more rapidly and are seen below.
1. Zygote (Day 1) → divides (cleavage).

2. Morula (Day 3–4) → solid ball of cells.

3. Blastocyst (Day 5): Hundreds of cells with two distinct regions
o Outer cell ring (Trophoblast): Becomes placenta.
o Inner cell mass (embryoblast): Becomes embryo.

4. Zona pellucida breaks down → ready for implantation.

This is when the blastocyst attaches to the uterine wall ar around 6 days with the embryoblast (inner cell mass) nearest the endometrium. At 7 days the blastocyst is firmly attached and endometrial vascularisation increases while the blastocyst secretes enzymes that allow it to enter endometrium walls.

Post implantation the endometrium is known as the decidua which wull surrond the developing embryo to eventually form the maternal placenta

Gastrulation is the third week of embryonic development whereby the bilaminar embryonic disk (which is the collection of the hypoblast and epiblast - two layers of the embryoblast) becomes a trilaminar disk of primary germ layers.

The three layers
- Endogerm: Develops into epithelial lining of GI, respiratory tracts and other organs
- Mesoderm: Develops into muscles, bones and other connective tissue
- Ectoderm: Develops into epidermis and nervous system

First trimester (CONCEPTION - 12 WEEKS)
• Embryological and early foetal development
• Rudiments of major organ systems appear (organogenesis)

Second Trimester (12-24 WEEKS)
• Nearly complete development of all organ systems

Third trimester (24-40 WEEKS)
• Rapid foetal growth
• Most organ systems become fully functional
• Deposition of adipose tissue

1. Physical and chemical barriers – skin, mucous membranes, stomach acid, tears, etc.

2. Cells – white blood cells (leukocytes) and other immune cells.

3. Tissues and organs – lymph nodes, spleen, thymus, bone marrow, tonsils, etc.

4. Molecules – antibodies, cytokines, complement proteins, interferons.

• Recognise foreign (“non-self”) substances.

• Destroy pathogens or infected cells.

• Remember previous invaders (immunological memory)

• Lymphatic vessels: Drain interstitial fluid (lymph) from tissues and return it to venous circulation.

• Lymph: A clear fluid containing white blood cells, proteins, and sometimes pathogens.

• Lymphoid organs:
o Primary lymphoid organs: Bone marrow and thymus (where immune cells mature).
o Secondary lymphoid organs: Lymph nodes, spleen, tonsils, MALT.

• Transports immune cells and antigens (pathogen) from tissues to lymphoid organs

• Filters lymph for pathogens.

• Absorbs dietary fats (via lacteals in small intestine)

• Transports dietary lipids

Granulocytes are a type of white blood cell containing granules in their cytoplasm that help the immune system fight infections and respond to allergic reactions

Neutrophils - first responders which engluf (phagocytose) bacteria and debris

Eosinophils - Attack parasites

Basophils - Release histamine and heparin for inflammation and allergy

Agranulocytes are a type of white blood cell that lack granules in their cytoplasm and include lymphocytes and monocytes

Monocytes or macrophages - engluf pathogens and dead cells (debris)

Lymphocytes (B & T cells + NK cells) - These cells coordinate adaptive and innate immune responses EG; B & T cells are adatpvie and specific while NK cells are innate (non-specific) and serve to destroy virus-infected and tumour cells

Spleen is the largest lymphoid organ which filters blood (not lymph) removing old and defective blood cells and platelets It also recyles breakdown products such as iron from RBCs.

It can be divided into two regions
• White pulp: Contains lymphocytes for immune surveillance.
• Red pulp: Removes old RBCs and platelets; stores iron.

• Includes tonsils, Peyer’s patches (intestine), and appendix

• Provides local immunity in mucosal linings — first line of defence at entry sites (mouth, gut, respiratory tract).

Innate immunity is the non-specific immune system, including the first two lines of defence (physical/chemical barriers and inflammation with phagocytes). This is inherited from birth and does not change throughout life (unless caused to by a disease).

First line of defence serves to act as a barrier to prevent pathogens from entering the body or colonising cells through non-specific physical or chemical barriers.

Examples of physical barriers include:
• Skin – the epidermis consists of cells covered by a special barrier called keratin which repair skin.
• Cilia – Are microscopic hairs lining your windpipe, respiratory tract and ears that move trapped particles away from your lungs to prevent diseases
• Mucous – protects the linings of the body (lungs, sinuses, mouth, stomach, intestines) by trapping foreign substances such as pathogens and dust. When mucus traps the bacteria and/or viruses they expel them via spitting, sneezing, coughing or swallowing (where they are destroyed in stomach acid).

Examples of chemical barriers include tears, gastric secretions and digestive enzymes
• They all contain antimicrobial substances such as the enzyme lysozyme (found in tears, mucus and saliva) that kill pathogens by creating an acidic environment.

When pathogens are successful in penetrating the barriers against entry into an organism, antigens trigger non-specific responses called the second line of defence that try to destroy invaders before they cause damage. Examples of these defences include:

• Inflammation (Vasodilation)– when damage or infection is localised (eg. bacteria infecting a cut), the release of chemicals such as histamines causes blood vessels in the area to dilate, increasing blood flow to the site of infection. These chemicals also increase the permeability of blood vessels allowing certain white blood cells to move into tissues to attack pathogens.

• Natural Killer (NK) cells – Attack infected and abnormal cells

• Phagocytosis (done by macrophages) – the process by which phagocytes change their shape to surround a foreign particle such as bacterium and completely enclose it. Once the particle is inside the cell, enzymes are released to destroy it

These are a group of 30 plasma proteins that enhance immune reactions. They are the major mechanism for destroying pathogens contributing to both innate and adaptive immune responses.

There are three major pathways which all lead to the cleavage of C3 into C3a and C3b

Fever is defined as abnormally high body temperature and is caused by the release of chemicals call pyrogens.

Cause:
• Triggered by pyrogens (from pathogens or immune cells).
• Pyrogens act on the hypothalamus, raising the set-point for body temperature.

Role:
• Inhibits bacterial and viral replication.
• Enhances immune reactions (phagocytosis, interferon action).
• Speeds tissue repair.
• Too high (> 41°C) = damaging to enzymes and tissues.

Adaptive immunity (third line of defence) occurs when the innate immune response fails to clear a pathogen from the body, triggering an immune response that is specific to the pathogen and has memory – it can remember certain antigen markers. It is acquired throughout life and is specific to the pathogen invading the body. The adaptive immune response can be split into two different responses:
- Humoral Cell response
- Cell-mediated response

The Humoral immune system uses B-cells to target pathogens outside of cells such as in tissues and fluid. When protein-containing antigens are present, helper T-cells are activated by binding to the antigen releasing molecules known as cytokines (interleukin-2).

When B-lymphocytes are exposed to cytokines, they proliferate and differentiate into two types of cells:
• B-plasma cells – produce Y-shaped proteins called antibodies that bonds to antigens creating the antibody-antigen complex, deactivating the antigen and allowing it to be eliminated by phagocytes.

• B-memory cells – remain in the body after infection and will stimulate B-plasma cells to produce antibodies if they come into contact with the antigen in the future.

The Cell-Mediated system uses T cells to target intracellular pathogens as well as tumour cells. T cells make direct contact with infected cells via special surface receptors that trigger an immune response. There are 4 types of T-cells:
• Helper T-cells – secrete cytokines activating both the humoral and cell mediated immune responses, as well as stimulating the activity of some macrophages.

• Cytotoxic (killer) T-cells – activated by helper T-cells and respond by cloning themselves. They move to the site of the infection and bind with the infected cells to release toxic cytokines that destroy the infected cell causing the lysis (breaking down the membrane) of the cell.

• Suppressor T-cells – responsible for stopping the adaptive immune response when the infection has been defeated.

• Memory T-cells – clones of original T-cells that remain in the body to respond to future exposure from same pathogen

Antigen is any molecule that the body recognises as foreign triggering an immune response. On the surface of body cells, there are marker molecules that identify the cells as ‘self’ to prevent an auto-immune attack. Pathogens contain a number of markers that the body recognises as ‘not-self’ triggering an immune response.

Antibodies are Y-shaped molecules consist of four chains of protein and are secreted by plasma cells. An antibody has two binding sites - each antigen-binding site is specific for a particular antigen. When an antigen and antibody bind, it is known as an antigen-antibody complex

When the adaptive immune system is first exposed to a pathogen the response by B and T lymphocytes is called the primary immune response. In this response, antibody producing plasma cells and cytotoxic T cells are produced and work to clear the infection. The body is then able to store memory cells which are essentially pre-made cells for the next time it encounters the same pathogen.

When the adaptive immune system is exposed to the same pathogen again, there is a faster response and the production of antibodies is much greater, as the memory cells that are specific to the pathogen already exists in the body at the time of reinfection. This is referred to as the secondary immune response

This is why vaccines are effective, as they create memory cells required for a rapid immune response so that when exposed to a live and dangerous pathogen, the body can initiate