intro to physiology and pharmacology Flashcards
what 3 fluids is the body’s internal environment made up of
blood plasma, interstitial fluid and intercellular fluid
what are the 3 vital parameters that need to be controlled in the body
oxygen in blood plasma, ATP concentration in intracellular fluid and concentration of ions in all fluids
what are the main ion in extracellular fluid
higher concentration of sodium, chloride and calcium ions than in the intercellular fluid
what are the main ions in intracellular fluid
higher concentration of potassium ions
what is homeostasis
the mechanism of keeping the internal environment of the body stable, it is an active process
what is osmolality
the concentration of particles that are free in a solution measured in millimoles (mOsm)
what is a negative feedback loop
a change that brings the system back to a steady state after it is disrupted
what is the mechanism of a negative feedback loop
- Receptors detect a change in the vital parameter (input) that disrupts the steady state.
- Receptors feed into the control centre (brain: hypothalamus or brain stem) which compares the input against a set value, if the values don’t match they change their output.
- A signal such as a hormone is sent from the control centre to effector.
- The effector (muscle: skeletal, cardiac or smooth) brings about a change that restores the stable state.
what is meant by redundancy (negative feedback loop)
in a negative feedback loop there are multiple mechanisms so if one mechanism fails there is another way to ensure the system returns to steady
how do positive and negative ions move across a cell membrane
cells have a resting voltage of -60 to -70V so positive ions will move into the cell down the electrochemical gradient but negative ions need to move down their concentration gradient
what is a pore (non-gated channel)
A protein that forms a tunnel through the membrane they are used for facilitated diffusion and are always open, they are made up of multiple subunits and require an electrochemical gradient to drive movement
what is a channel (gated pore)
Tunnel with a gate that can open and close to control movement of a solute by facilitated diffusion they are also made up of multiple subunits and require an electrochemical gradient
what is a carrier
the solute has to bind to move through
used for facilitated diffusion
driven by an electrochemical gradient
it has two gates (extracellular and intercellular)
what is a pump
Like a carrier but requires energy from ATPase to allow the solute to move through
what do all channel proteins contain
- A moveable gate consisting of amino acids that shift to open/close it
- A sensor: either voltage, ligand or mechanical
- A selectivity filter: the sequence of amino acids that determines which specific ion is selected and can move through the channel
- An open channel pore that the solute moves through
what are the differences between primary and secondary active transport
- Primary: uses pumps and energy from the hydrolysis of ATP
- Secondary: uses cotransporters and exchangers, uses energy from the electrochemical gradient of another solute
what happens in cotransporters
two solutes move in the same direction, one moves down its electrochemical gradient and the other moves against it
what happens in exchangers
two solutes move in opposite directions
how is the rate of simple diffusion affected
permeability of the membrane (permeability coefficient) and the size of the concentration gradient
the more permeable the membrane and the larger the concentration gradient the faster the rate of diffusion
straight line on a graph
how is the rate of facilitated diffusion affected
number of carriers and the speed by which the carrier can cycle through the steps
the more carriers and the faster the cycle is the quicker the rate of diffusion
curved line on a graph
what is the mechanism of protein carriers
- the carrier is open to the outside and the substrate binds at a binding site
- the outer gate closes and the substrate is concluded
- the inner gate opens and the substrate exits into the inside of the cell
- the inner gate closes and the carrier can receive another substrate
why are protein carriers slow
it takes time for the gates to open and close so they can become saturated easily
what transporters does passive transport use
pores, channels and carriers
what transporters does active transport use
only carrier proteins: pumps, cotransporters and exchangers
what is the role of the vagus nerve
when stimulated it slows heart rate
what are chemical mediators
extracellular signal molecules such as hormones, neurotransmitters or inflammatory mediators released from cells in response to a stimulus
what is contact-dependent communication
communication between two cells, it has the shortest range, it is used in immune response to identify antigens and allow cytotoxic T-cells to attach to pathogens
what is paracrine communication
communication between two cells that are next to each other, the chemical mediator only diffuses a short distance and acts locally
what is synaptic/neuronal communication
between two neurones, this uses specialised synapses and only sends signals to specific target cells, it is fast and can communicate over short or long distances, it uses neurotransmitters such as acetylcholine and noradrenaline
what is endocrine communication
hormones are secreted into and transported by the blood stream over long distances to wide-spread areas, it is slow and not specific
what is autocrine communication
similar to paracrine signalling but the mediator acts on the same cell that released it, this is useful for feedback
what is signal transduction
the process of converting an extracellular signal to an intracellular signal
how are chemical mediator synthesised
can be synthesized by specific enzymes that modify existing mediators, which mediators a cell can produce depends on which enzymes are active
how are chemical mediators that can’t diffuse easily stored
need to be synthesized and stored in vesicles so they can be released by exocytosis, inside vesicles mediators can be packed into high concentrations so communication is rapid as lots of mediator can be released at once meaning the signal is sent quickly
how are chemical mediators that easily diffuse stored
made on demand and released by constitutive secretion (continuous release)
what is convergence in cell signalling
Cells have multiple receptors so they can take in information from different places and produce one big response
what is divergence in cell signalling
Most extracellular signal molecules act on more than one type of cell because the same receptor can be expressed by more than one cell type to allow coordinated responses that involve multiple organs for example in the autonomic nervous
what are ligand-gated ion channels
ionotropic receptors
Allow ions to move into the cell, the response occurs instantly but doesn’t last very long
It produces electrical signals that trigger action potentials or exocytosis for ion movement
what are G protein-coupled receptors
metabotropic receptors
They are coupled to a G protein and influence the metabolic reactions in a cell, the response is fast but not instantaneous and lasts a few hours
what are kinase-linked receptors
They have a catalytic effect that allows enzymic activity in the cell and initiate gene transcription and protein synthesis, the response is slower but lasts for days at a time
what are nuclear receptors
found inside the cell, the response produced is slow but long-lasting
Stimulates more channels to be inserted into the cell membrane
what is a ligand
any molecules that binds to a receptor, it may be an agonist or an antagonist
what is an agonist
anything that can bind to a receptor and initiate a response in a cell
what is an antagonist
anything that can bind to a receptor and block a response in a cell
what is an endogenous agonist
natural agonists found within a cell e.g. acetylcholine and insulin
how are ligand-gated ion channels arranged
They are composed of 3-5 different subunits that are arranged to form a central aqueous pore that allows ions to move through
The channel opens when the agonist binds and closes when it is removed or becomes desensitised
how does the nicotinic acetylcholine receptor (nAchR) work
It is activated by Ach which opens the channel and allows ions to flow into the cell depolarising the membrane, the ions act as a second messenger to regulate functions such as contraction, secretion and gene transcription
how are ligand-gated ion channels inhibited
Some gated ions respond to GABA receptors that cause the channel to open allowing chloride ions to enter the cell, this hyperpolarises the membrane (ions are negative)
what is contact-dependent signalling and how does it work
CAR (chimeric antigen receptor)
T-cells are taken from cancer patients and engineered to make CAR T-cells by adding a specific antigen that identifies cancer cells, the CAR T-cells bind to cancer cells via the antigens causing the immune system to attack the cancer cells
how do opioids work
Opioid receptors are G-protein coupled receptors, there are many receptors in the spinal cord and sensory nerve endings that are useful for pain relief if targeted by opioids
However there are also receptors in an area of the brain to do with reward making opioids very addictive
what are the 3 main types of hormone
peptide (insulin), amino acid derived (adrenaline) and steroid (oestrogen)
how are the 3 types of hormone synthesised
peptide: from amino acids
amino acid-derived: derivatives of tyrosine (requires specific enzymes)
steroid: metabolites of cholesterol (requires specific enzymes)
how are the 3 main hormones released
peptide: exocytosis through secretory granules
amino acid-derived: exocytosis through vesicles
steroid: lipid soluble (simple diffusion)
what receptors do the 3 main hormones target
peptide and amino acid-derived: cell membrane surface receptors
steroid: diffuse in to cells and bind to intracellular receptors
what are the response times of the 3 main receptors
peptide and amino acid-derived: seconds to minutes
steroid: hours to days
what hormones does the thyroid gland release
The thyroid gland releases T3 and T4 which are both amino acid derived hormones, synthesis and release depends on the hypothalamic-pituitary releasing hormones and iodine
they are transported across the cell membrane by facilitated diffusion
what is parathyroid hormone (PTH)
a peptide hormone that regulates plasma calcium and phosphate
it targets bone, intestine and kidneys. Bones use and store calcium
intestines absorb calcium and phosphate into the body and kidneys excrete calcium and phosphate
what is the negative feedback loop of PTH (when Ca conc is too high)
Chief cells detect that the plasma calcium ion concentration is too high so less PTH is released
this causes more calcium to be excreted as kidney tubule reabsorption of calcium decreases
bone calcium reabsorption into the plasma decreases and less calcium is absorbed into plasma by the intestines which lowers the plasma calcium ion concentration
what hormones does the adrenal cortex release
Releases steroid hormones, it is split up into 3 layers two of which are glucocorticoid that releases cortisol (stress hormone) and mineralocorticoid that releases aldosterone (controls sodium concentration)
what hormones does the adrenal medulla release
Chromaffin cells release adrenaline and noradrenaline via exocytosis from vesicles to target the autonomic nervous system
what hormones are released from the anterior pituitary gland
troph cells within the anterior pituitary to release trophic hormones that cause growth of endocrine cells
hormones are released via the portal system: blood is taken straight from one organ to another without going back to the heart to be reoxygenated
what hormones does the posterior pituitary gland release
includes antidiuretic hormone, oxytocin and vasopressin
hormones are released into the blood that is carried from the heart to organs
what are some of the main things that happen during sympathetic stimulation
heart rate and force of contraction increase, diameter of airways increase, more glucose released into the blood, adrenaline released
what are the main things that happen during parasympathetic stimulation
rate and force of contraction of the atria decrease, more smooth muscle motility of the GI tract for digestion, bladder contracts
what is the sympathetic pathway
ACh binds to the nicotinic ACh receptor
norepinephrine is released and binds to alpha and beta adrenergic receptors activating them causing enzyme and second messenger cascades
what is the adrenal medulla sympathetic pathway
Chromaffin cells release adrenaline that binds to alpha and beta adrenergic receptors on lots of different tissues creating a widespread response across the body
what happens when G-alpha stimulatory protein (GaS) is stimulated
adenylyl cyclase activity increases which increases the concentration of 2nd messenger cAMP and increases the amount of protein kinase A (PKA) in the cell
Activates adrenergic beta1 and beta2 receptors
what happens when G-alpha inhibitory protein (GaI) is stimulated
adenylyl cyclase activity decreases which decreases the concentration of cAMP and decreases the amount of PKA
Activates adrenergic alpha2 and muscarinic M2 receptors
what happens when G-alpha Q protein (GaQ) is stimulated
activates the enzyme phospholipase C (PLC) which breaks down IP2 to form DAG and IP3 which is a 2nd messenger that causes calcium channels in the endoplasmic reticulum to open allowing calcium to move into the cell, this increases intracellular calcium concentration and PKC (a protein kinase) concentration
Activates adrenergic alpha1, muscarinic M1 or M3 receptors
what are cholinomimetic drugs
they mimic the effect of excess acetylcholine, block the enzyme acetylcholinesterase (AChE) to prevent acetylcholine break down
they are long-lasting (irreversible) and cause an excess of ACh at the synapse
Muscarinic antagonists can be used to reverse poisoning by AChE drugs as they block the muscarinic receptors
how are adrenoreceptor agonists used
agonists bind to beta 1 receptors to increase force of contraction in the ventricles
how are adrenoreceptor antagonists used
bind to beta 1 adrenergic receptors blocking them
used to treat hypertension, heart failure and anxiety
There are some side effects such as bronchoconstriction so beta blockers should not be used for patients with asthma
what are the 2 types of cholinergic receptors
nicotinic and muscarinic receptors
where are M2 receptors found and what happens when they are stimulated
found in the atria of the heart and nodal tissue and are activated by the parasympathetic system
they cause cardiac inhibition by decreasing heart rate
what is the mechanism of M2 receptors
When M2 receptors are activated by acetylcholine it activates G-alpha inhibitory proteins that open potassium ion channels so potassium ions move out of the cell depolarising it
this causes heart rate to decrease and the force of contraction in the atria decreases
what are adrenoreceptors
receptors for noradrenaline and epinephrine
where are B1 receptors found and what happens when they are stimulated
found on the surface of cardiac myocytes
they increase heart rate and force of contraction
what is the mechanism for B1 receptors
noradrenaline activates B1 receptors and G-alpha stimulatory proteins
this causes an increase in adenylyl cyclase activity and cAMP and PKA levels increase, calcium channels are phosphorylated causing them to stay open longer so more calcium ions move into myocytes increasing the force of contraction in the ventricles
what is epithelial tissue
the boundary between the controlled internal environment and the uncontrolled external environment within the body
what are the 3 layers that develop into epithelial tissue
endoderm, mesoderm and ectoderm
epithelia are so widespread that they can come from any 3 of these germ layers
what is the arrangement of epithelial cells
there is an anchored surface at the bottom called the basolateral membrane that is anchored to the basement membrane
there is a free surface called the apical membrane
cells are joined by tight junctions that decrease free diffusion between cells
what are tight junctions made up of
claudins that hold cells togetherand determine the tightness of the junctions
Between epithelial cells there can be high barrier function which means movement of ions and water is restricted
what is the mesenchyme and what is its role
layer of tissue underneath an epithelial tissue, epithelial cells are adhered to it to keep them in place and stop cells moving apart
what are gap junctions and why are they important
they have gaps between them so allow ion to diffuse between the cytoplasm of one cell to the cytoplasm of neighbouring cells which is important in neurons to propagate an action potential, these cells are called electrically coupled cells because ion movement means electrical movement
what are desmosomes and why are they important
very strong adhesion points between cells that can bear mechanical stress, they connect myosin filaments of one cell to another cell for movement
what are stratified epithelia
contain two or more layers of cells
what is the integumentary system and what is it made up of
it a system made up of the skin and accessory organs such as hair, nails and glands
it is made up of 2 layers: the dermis and the epidermis separated by a dermal-epidermal boundary
what is the structure of the dermis
Cells in the dermis called fibroblasts produce ECM proteins
There are two main zones of the dermis: the papillary layer which is involved in the movement of immune cells and the reticular layer which contains adipocyte (fat) clusters
The dermis also contains accessory organs and nerve endings
what is the structure of the dermal-epidermal boundary
a boundary with finger-like projections made up of dermal papillae and epidermal ridges
hold tissues together and withstand high mechanical stress
what is the structure of the epidermis
made up of stratified squamous epithelium contains lots of the protein keratin
has no blood vessels
what are the 5 types of glands in the skin
Eccrine (sweat) glands: temperature regulation
Apocrine (another sweat) glands: release sweat into scent ducts
Holocrine sebaceous glands: secrete oils
Ceruminous glands: secrete earwax into ear
Mammary glands: release breast milk
how does the skin act as a barrier
physical barrier: cross-linked keratin layer protects against cuts and burns
biochemical barrier: mildly acidic and secretes bactericidal agents to kill bacteria
how does the skin thermoregulate
the skin is overperfused with blood so the extra is used for thermoregulation through arteriovenous anastomoses (AVA)
sweating through the skin is used to control temperature
what are the roles of epidermal langerhans and dermal cells
act as an immunological barrier and are able to self-renew, display antigens that can cause an immune response
why is vitamin D synthesis in the skin important
vitamin D is needed for absorption of calcium, magnesium and phosphate ions
the skin is involved in the first step in the synthetic pathway of vitamin D
in muscles what is the endomysium, fascicles, perimysium and epimysium
endomysium: sheath that surrounds muscle cells
fascicles: a group of muscle fibres that work together as a unit within a muscle
perimysium: sheath surrounding fascicles
epimysium: sheath surrounding muscles
what is the sarcomere made up of
thick myosin filaments and thinner actin filaments
what are the other proteins aside from actin and myosin in the sarcomere and what do they do
nebulin: attached to actin filaments to help arrange them
titin: anchors myosin filaments to the Z disks
what happens to the sarcomere during contraction
the I band gets smaller as actin is pulled inwards, the A band stays the same and the Z lines get closer together
what happens during the latent (first) phase of muscle twitch
the action potential travels down the sarcolemma causing the release of calcium ions
what happens during the contraction period (second phase of muscle twitch)
when the muscle contraction occurs, it is slower than generating the action potential and repolarisation so the membrane can be depolarised again and contract again before the first contraction has finished
why does summation occur
occurs in skeletal muscle when the frequency of action potentials is too high and there is not enough time for the muscle to relax before it has to contract again, the next contraction is more powerful because there is more signalling and more fibres contracting
which muscles have a striated appearance
skeletal and cardiac (not smooth)
how are the myocytes in cardiac muscle different from myocytes in skeletal
shorter than those in skeletal muscle and are more branched
what are the two types of smooth muscle
multiunit and unitary
multiunit: smooth muscle cells aren’t coupled and there are no neuromuscular junctions, acetylcholine binds directly to receptors on cardio myocytes to stimulate contraction
unitary: smooth muscle cells are electrically coupled so an action potential move through cells to cause a contraction and produce a coordinated response
what are type 1 (slow-twitch) muscle fibres
they rely on oxidative phosphorylation to generate ATP so they work in aerobic conditions
they contain lots of mitochondria, myoglobin and have a rich blood supply
they fatigue much slower (endurance)
what are type 2B (fast-twitch) muscle fibres
they rely on glycogen to generate ATP so are anaerobic
they contain high reserves of glycogen and fewer mitochondria and myoglobin
they fatigue faster but contract more powerfully and faster
what are type 2A (fast-twitch) muscle fibres
can use oxidative phosphorylation and glycogen to generate ATP
lots of glycogen, lots of mitochondria and myoglobin
fatigue faster but contract faster too
how are calcium ions released in skeletal muscle
L-type calcium ion channels in the T-tubule membrane are activated when muscle cells are depolarised, this causes 2 effects:
* The L-type calcium ion channels open and calcium ions move into the sarcoplasm causing muscle contraction
* L-type calcium ion channels change shape and become tethered to ryanodine type 1 receptors in the sarcoplasmic reticulum, this causes calcium ions to be released into the sarcoplasm from the sarcoplasmic reticulum stimulating muscle contraction
what are dyad structures in cardiac muscle
a T-tubule membrane that interacts with one branch of the sarcoplasmic reticulum
how are calcium ions released in cardiac muscle
cardio myocytes are depolarised and L-type calcium ion channels are activated so calcium ions move into the sarcoplasm, there is no tethering of L-type channels to ryanodine receptors
* The movement of calcium ions into the sarcoplasm activates ryanodine type 2 receptors causing calcium ion channels in the sarcoplasmic reticulum to open and calcium to move into the sarcoplasm to amplify the cascade (calcium influenced calcium release)
what are caveolae structures in smooth muscle
shallow cavities that contain calcium ion channels
there are two layers of the sarcoplasmic reticulum: the peripheral SR that surrounds the caveolae and the central SR that runs through the cell
how are calcium ions released in smooth muscle
smooth muscle cells are depolarised so L-type calcium ion channels open which activates ryanodine receptors causing them to release calcium ions into the sarcoplasmic reticulum (calcium influenced calcium release)
G-alpha Q receptors are activated which causes IP3 production stimulating IP3 receptors in the sarcoplasmic reticulum that open calcium ion channels to release calcium ions
what is a motor unit in skeletal muscle
a motor neuron and a muscle fibre joined together by a neuromuscular junction
how is contraction initiated in skeletal muscle
Impulses are received by the motor neuron and stimulates acetylcholine to be released at the neuromuscular junction, the acetylcholine binds to ach receptors on the muscle fibres and stimulates an action potential which depolarises the sarcolemma (plasma membrane) causing muscle contraction
what is troponin
where calcium ions bind
it has 3 subunits: troponin C which is where calcium ions bind, troponin I which lies over the actin binding sites and troponin T helps position tropomyosin on actin
what is the mechanism of contraction for skeletal and cardiac muscle
calcium ions bind to troponin which is linked to tropomyosin and causes it to change shape so it moves and exposes binding sites on actin where myosin can form cross-bridges
what are the proteins calponin and caldesmon in smooth muscle
they inhibit interactions between actin and myosin
what is the mechanism of contraction in smooth muscle
caldesmon is stimulated by calcium ions and the myosin light chain kinase is activated, it phosphorylates the light chain of myosin which stops the inhibitory effects of calponin and caldesmon so cross-bridges can form and the muscle contracts
To stop contraction the light chain of myosin needs to be de-phosphorylated by myosin light chain phosphotase
how are calcium ions removed from the sarcoplasm
there are two ways:
calcium can move out of the cell via sodium-calcium exchangers and plasma membrane calcium ATPase (PMCA) pumps
Calcium ions can also be taken back up into the sarcoplasmic reticulum by sarcoplasmic reticulum calcium ATPase (serca pump) and stored there
how are neuromuscular junctions inhibited
preventing depolarisation of muscles so they dont contract or preventing repolarisation of muscles so new action potentials cant be generated
what is the pericardium
fluid-filled sac surrounding the heart
what are the 4 chambers within the heart
the right atrium which receives deoxygenated blood from systemic venous return, the right ventricle which pushes blood to pulmonary circulation to be oxygenated, the left atrium which receives oxygenated blood from pulmonary circulation and the left ventricle which pumps oxygenated blood to the head and body under high pressure
what are the 2 types of valve in the heart
the atrio-ventricular valves (mitral and tricuspid) between the atria and ventricles
the semi-lunar valves (aortic and pulmonary) between the ventricles and arteries
what are the 3 layers of the heart wall
the epicardium (a visceral outer layer that maintains the integrity of the heart), the myocardium (the main muscle) and the endocardium (the smooth inner lining)
what are the 2 types of cardio myocytes
conducting cells: allow the rapid spread of action potentials through the SAN, atrial internodal tracts, AVN, bundle of His and Purkinje system
contractile cells: contract when stimulated by an action potential, they generate the force of contraction and pressure within the heart
what is excitation-contraction coupling
electrical signals and contraction of myocytes are linked by extracellular calcium ion concentration
what is the myocardium made up of
extensively branched muscle fibre cells that are connected by intercalated disks (ID) that allow action potentials to be propagated cell to cell
ID contain lots of desmosomes to hold the cells together when they are under high mechanical stress and gap junctions that allows depolarising current to flow between cells creating a wave-like response known as syncytium
what happens during atrial systole (A on diagram)
The SAN is stimulated which causes cells in the atria to depolarise, the atria contract increasing their pressure, the ventricles are relaxed so atrioventricular valves are open and the ventricles keep filling with blood
what happens during ventricular contraction (B on diagram)
Purkinje fibres are electrically activated causing the ventricles to contract so pressure within them increases but the volume stays the same for a second, ventricular pressure is higher than atrial pressure so the atrioventricular valves close
what happens during rapid ventricular ejection (C on diagram)
Ventricular pressure is greater than aortic pressure so semi-lunar valves open and stroke volume (blood in ventricles) is ejected, ventricular pressure decreases and arterial pressure increases, meanwhile the atria begin to slowly fill increasing their pressure slightly
what happens during reduced ventricular ejection (D on diagram)
The ventricles are repolarised and the pressure decreases, semi-lunar valves are open so blood keeps moving out of the ventricles but at a slower rate decreasing the volume of the ventricles
Arterial volume decreases slightly due to elastic recoil (the walls of the aorta stretch and then return to original diameter) and blood goes from the aorta to smaller arteries (arterial tree). Atrial pressure increases as blood returns to the heart
what happens during ventricular relaxation (E on diagram)
This begins after the ventricles are fully repolarised, they are relaxed so the pressure decreases and semi-lunar valves close as arterial pressure is higher than ventricular pressure so ventricle volume stays constant
what happens during rapid ventricular filling (F on diagram)
The pressure in the ventricles is lower than the pressure in the atria so they atrioventricular valves open and blood moves into the ventricles from the atria causing the volume of the ventricles to rapidly increase but the pressure stays low because it is passive
what happens during reduced ventricular filling (G on diagram)
the ventricles continue to fill
what does the P wave represent on an ECG
depolarisation of the atria, the duration of the P wave shows the atrial conduction time (the time it takes for the action potential to move across the atria)
why cant the repolarisation of the atria be seen on an ECG
the repolarisation of the atria is masked by the QRS wave so would need to be picked up by different electrodes
what does the PR interval represent on an ECG and why is ventricular depolarisation bigger
this is the time between the atrial and ventricular depolarisation
ventricular depolarisation is much bigger because it is a bigger muscle which allows it to push blood out of the heart to the tissues
what does the QRS segment represent in an ECG
depolarisation of the ventricles
what does the ST segment represent in an ECG
region between the end of the ventricular depolarisation and the start of the ventricular repolarisation
what does the T wave represent in an ECG
repolarisation of the ventricles
what is the depolarisation sequence of the heart
an electrical signal originates in the sinoatrial node (SAN) which is known as the primary pacemaker
the signal moves right to left through internodal pathways to the atria causing them to contract
there is a delay in the AVN so the atria can fill before contracting, non-conductive tissue prevents signals reaching the ventricles so they dont contract early
the signal passes over the AVN to the His-purkinje fibre system
ventricles contract
what is the blood pressure in the arteries
high pressure (stressed volume)
arteries have lower compliance (how much the walls can stretch to accommodate blood) and capacitance (the volume of blood that can be carried)
what is the blood pressure in the arterioles
arterioles are tonically active meaning they always have some contraction, this is due to the vascular smooth muscle (VSM) in the arteriole walls
have the highest resistance to blood flow
what is the blood pressure in the capillaries
low pressure and slow flow rate for gas exchange
not all are perfused with blood
blood flow to capillaries is controlled by dilation and constriction of arterioles
what is the blood pressure in the veins and venules
lower pressure, walls contain less elastic tissue
higher capacitance so they can increase their volume lots (reservoir)
smooth muscle in walls for dilation and constriction
what is systemic and pulmonary circulation
systemic: part of the vascular system that carries blood from the left ventricles to organs and tissues
pulmonary: part of the vascular system that carries blood from the heart to the lungs and back to the heart, pressure is lower in pulmonary as there is lower resistance
what does pulse pressure represent and how is it calculated
volume of blood ejected from the left ventricle
systolic pressure - diastolic pressure
what does mean arterial pressure represent and how is it calculated
the average pressure in a complete cardiac cycle
diastolic pressure + 1/3 of pulse pressure
what are baroreceptors
receptors that detect changes in blood pressure, they are located in carotid and aortic sinuses
how do baroreceptors respond to an increase in arterial pressure
baroreceptors stretch more which increases afferent nerve firing into the central nervous system, the information is processed in the medulla and the parasympathetic nervous system is stimulated which sends signals to the SAN via the vagus nerve, this causes a decrease in heart rate and blood pressure
how do baroreceptors respond to a decrease in arterial pressure
baroreceptors stretch less which decreases afferent nerve firing into the CNS, the medulla stimulates the sympathetic nervous system and the SAN increases the heart rate, cardiac muscle contracts more which increases stroke volume (blood ejected from left ventricle), arterioles constrict which increases the total peripheral resistance, veins constrict which decreases the unstressed volume causing blood pressure to increase
how is velocity calculated
velocity = flow/cumulative cross-sectional area
if two blood vessels have identical flow, if cumulative cross-sectional area increases velocity will decreases
how is blood flow determined
the pressure difference between two points in a blood vessel and resistance to blood flow of the vessel
how is blood flow calculated
blood flow = pressure difference/resistance
what does Poiseuilles’s law suggest (resistance to blood flow)
Resistance to blood flow is directly proportional to the vessel length and blood viscosity, it is inversely proportional to the fourth power of the blood vessel’s radius
where is the largest decrease in blood pressure and where is there no decrease in blood pressure
largest decrease is between arteries to arterioles as arterioles have high resistance to flow
there is no decrease between aorta to major arteries because of elastic recoil in the aorta
why does pressure decrease with blood flow
energy is lost overcoming resistance at each level
how does the RAAS system in the kidneys respond to a decrease in blood pressure
In the kidneys a decrease in pressure causes a decrease in renal perfusion pressure which is detected by the kidney afferent arteriole mechanoreceptors, this causes prorenin to be converted into renin which is released into the blood
renin is converted to angiotensin II causes aldosterone to be released which increases sodium ion reabsorption this is detected by the hypothalamus causing ADH to be released which increases water reabsorption so ECF volume increases, so cardiac output and aterial pressure increase
arterioles vasoconstrict which increases total peripheral resistance to increase blood pressure
what is blood made up of
watery plasma with erythrocytes (red blood cells), leukocytes (white blood cells) and platelets (involved in blood clotting)
what are the main proteins in blood plasma
albumin (most abundant), fibrinogen (involved in clotting) and immunoglobulins (produced by B cells during a humoral immune response)
what is the structure and function of erythrocytes (rbc)
biconcave disk structure and no organelles for a large surface area to volume ratio and maximum haemoglobin to carry oxygen, this structure is maintained by the cytoskeleton
3 main functions: carrying oxygen to tissues, carrying carbon dioxide from tissues and acting as a buffer against acids and bases
what are the 3 types of granular leukocytes (wbc)
neutrophils which phagocytose bacteria, eosinophils which combat viruses and basophils which release histamine
what are the 2 types of non-granular leukocyte (wbc)
lymphocytes which mature into T cells and B cells and monocytes which form macrophages and dendritic cells
how are platelets synthesised
they bud off from large cells in bone marrow called megakaryocytes during thrombopoiesis which happens in response to factors called thrombopoietin (TPO) and IL-3
what is the feedback loop for synthesising platelets
they will bind to TPO via receptors on their surface removing TPO from the blood, this causes a decrease in blood TPO so megakaryocytes aren’t generated and platelet production is stopped, this means that there are no receptors to bind to TPO so TPO levels increase and stimulate megakaryocyte production which makes more platelets again
what is the intrinsic blood clotting pathway
Activated by surface damage and is initiated when factors within the blood come into contact with the negatively charged surface membrane of the activated platelet
This causes a cascade of protease reactions that activate factor Xa which generates the enzyme thrombin to produce stable fibrin
what is the extrinsic blood clotting pathway
Initiated by damage or trauma to the endothelium, it activates a receptor called tissue factor in the subendothelial cells when blood factor VII comes into contact with it, this also activates factor Xa to produce stable fibrin to form mesh within clots
how is the anti-thrombotic state (clotting not needed) maintained
Paracrine factors such as prostacyclin promotes vasodilation to inhibit platelet adhesion and aggregation
Thrombomodulin is an anti-coagulant factor that forms a complex with thrombin to stop it forming stable fibrin
how is the thrombotic state (clotting needed) maintained
Initiated during vascular damage
Hypoxia (lack of oxygen) causes an expression of procoagulants to promotes coagulation
what are the 4 mechanisms of preventing haemostasis (blood loss)
Vasoconstriction: the blood vessels contract to shut off blood flow
Increased tissue pressure: fluid released into tissue surrounding the blood vessels to increase pressure in the tissue so there is a lower pressure gradient and less blood moves out of the blood vessels
Platelet plug: transient (temporary) to prevent blood loss, they fill in small breaches in the vascular endothelium by adhesion, activation and aggregation
Clot formation: the weak platelet plug is stabilised by fibrin
what do alpha granules in platelets contain
VWF (a clotting factor), fibrinogen, clotting factors and platelet derived growth factor). Dense-core granules contain ATP, ADP and calcium ions
what happens during platelet adhesion
When the endothelium is damaged it exposes subendothelial collagen which forms clots, VWF in the plasma binds to the exposed collagen and platelet receptors so the platelets bind to each other
what happens during platelet activation
causes dense and alpha granules to be secreted, the granules contain VWF for platelet adhesion and ADP for platelet activation
Platelet derived growth factor (PDGF) is secreted causing wound healing, thromboxane is also released which causes vasoconstriction to reduce blood loss
Changes in the platelet cytoskeleton causes fibrinogen receptors to be expressed
what happens during platelet aggregation (forming clusters)
Fibrinogen receptors on platelets bind to fibrinogen in the blood plasma forming molecular bridges between the platelets to join them together into clumps
what happens during blood clot formation
involves cascades of clotting factors to form a more permanent fibrin mesh
It forms a semisolid mass containing red and white blood cells, serum and mesh (containing fibrin and platelets)
how will potassium and sodium ions move in and out of the cell
intracellular fluid has a high conc of potassium so it will move out of the cell down its concentration gradient
extracellular fluid has a high conc of sodium ions so it will move into the cell down its concentration gradient
what is the structure of the kidney
it is surrounded by a thin but tough fibrous layer called the capsule, the pelvis is a structure at the centre of the kidney that collects urine, the ureter is a tube that connects the kidney to the bladder so it is used to transport urine to be stored in the bladder
what are the two sections of the kidneys
the cortex (outer) and the medulla (inner)
what are the 6 sections of the nephron
the glomerulus, Bowman’s capsule, proximal tubule, loop of henle, distal tubule and collecting duct
what are the two types of nephron and which is more common
a superficial nephron: most common, glomerulus and Bowman’s capsule are found in the outer part of the cortex
a juxtamedullary nephron: glomerulus and Bowman’s capsule sit lower in cortex near to cortex-medulla boundary
what happens in the glomerulus
plasma is filtered and passes into the Bowman’s capsule
around 20% of plasma is removed
what is the average glomerular filtration rate (GFR) of humans
125ml/min
what is renal failure described as
a fall in GFR which leads to an increase in serum, urea and creatinine
what are the 2 types of renal failure
acute: there is no change in the haemoglobin levels or size of the kidney and there is no peripheral neuropathy (damage to nerves in the nephron)
chronic: haemoglobin levels decrease and so does the size of the kidney as renal tissue is destroyed, peripheral neuropathy causes problems with muscle contraction
what happens in the nephron when a patient has chronic renal failure
glomerular membrane thickens so can’t produce filtrate (tubular atrophy), the glomeruli and nephron break down, the glomerulus is scarred (glomerulosclerosis)
what are the symptoms of renal failure (uraemia)
less salt and water excreted leading to retention and hypertension, less potassium excreted leading to hyperkalaemia, less hydrogen ions excreted causing mild acidosis, less urea and creatinine excreted leading to nausea, vomiting and inflammation of the pericardium
how is renal failure treated
limiting salt and water in the diet, sodium bicarb to treat acidosis, diuretics to treat sodium retention
what are the functions of the cardiovascular system
distribute gases and molecules for nutrition and growth and repair, allow chemical signalling (hormones), lose heat to maintain stable body temperature, mediate inflammatory responses
which blood vessels have the largest cross-sectional area
capillaries
why does the vena cava have lower blood pressure if the same volume of blood flows through both the vena cava and aorta
larger diameter
what is the vascular wall made up of
endothelial cells, elastic fibres, collagen fibres and vascular smooth muscle cells (VSCM)
what are the 3 layers of blood vessel walls (except capillaries they only have one layer)
tunica intima(inner), tunica media (middle) and tunica externa (outer)
capillaries only have tunica intima
why do veins have valves and arteries dont
veins have a larger lumen so their cross-sectional area is larger and blood pressure is lower so valves are needed to prevent backflow of blood
what are the structure and function of large arteries
also known as elastic arteries, they have a high compliance meaning they can easily stretch without tearing in response to pressure increases and cope with peak ejection pressures in the aorta
contain lots of elastic fibres which allow them to recoil and force blood to move even when the ventricles are relaxed
what are the structure and functions of medium arteries
also known as muscular arteries, they contain lots of vascular smooth muscle cells (VSMC) which are arranged in a circle around the artery which allows them to constrict and dilate to adjust blood flow rate
have vascular tone which means they are always partially contracted to make the lumen smaller and maintain vessel pressure to direct blood flow and keep it efficient
what are the structure and functions of arterioles
contain VSMC which enables blood flow regulation to the capillary beds, this flow through capillaries is intermittent due to periodic contraction of the VSMC which is regulated by microcirculation
what are metarterioles
terminal regions on the ends of arterioles, blood can be diverted through them
what are precapillary sphincters
they monitor blood flow to the capillary, they aren’t innervated (controlled by nerves) but they are sensitive to conditions of local tissues
what are the structure and functions of veins
less muscular and elastic but they are still distensible and able to adapt to variations in blood volume and pressure, they can act as stores/reservoirs for blood because they have a large lumen
what are the structure and functions of postcapillary and muscular venules
postcapillary: have pores to exchange nutrients and waste products
muscular: have a thin layer of VSMC which allows them to contract and push blood into arterioles
what are the structure and functions of capillaries
composed of only endothelial cells
contain fenestrations (openings) that allow exchange of substances between the blood and interstitial fluid
slow blood flow for exchange
rbc flattened against walls for diffusion
what is the role of the loop of henle
regulates urine conc and reabsorbs water, sodium, chloride, calcium and magnesium ions
what are the 3 areas of the loop of henle and their roles
thin descending limb: where water is reabsorbed, cells are impermeable to sodium and chloride
thin ascending limb: reabsorbs sodium and chloride, permeable to water, sodium and chloride ions
thick ascending limb: reabsorbs sodium and chloride ions, impermeable to water
what happens across the apical membrane in the cells of the thick ascending limb (NKCC2 and ROMK)
sodium, potassium and 2 chloride ions move into the cell via the sodium-potassium-chloride cotransporter 2 (NKCC2) which is driven by the sodium ion conc gradient
potassium ions leave through renal outer medullary potassium (ROMK) channels and is recycled
what happens across the basolateral membrane in cells of the thick ascending limb (CLCK)
sodium ions leave through sodium-potassium ATPase pumps, there is a net absorption of sodium
chloride ions leave through CLCK channels which are linked to a protein called barttin
what is Bartter’s syndrome in the thick ascending limb caused by
it is a syndrome that prevents reabsorption of sodium and chloride ions
mutations in NKCC2, ROMK, CLCK, or barttin
what are the symptoms of bartter’s syndrome in the thick ascending limb
sodium and chloride ions lost to urine (salt wasting), less water reabsorbed so more urine excreted (polyuria), lower ecf volume causing hypotension, more potassium secreted causing hypokalaemia, more hydrogen ions secreted causing metabolic alkalosis
how do loop diuretics work to lower blood pressure in the thick ascending limb
inhibit NKCC2 so less sodium and chloride reabsorbed, less water reabsorbed so ecf volume decreases, cardiac output decreases so arterial pressure decreases
what happens across the apical membrane in cells of the early distal tubule (NCC)
sodium and chloride ions move into the cell via sodium-chloride cotransporters (NCC)
what happens across the basolateral membrane in cells of the early distal tubule (CLCK)
sodium leaves through sodium-potassium ATPase pumps
chloride leaves via CLCK and barttin
potassium used in pumps leaves via potassium ion channels
how does the diuretic thiazide work in the early distal tubule
inhibit NCC so less sodium and chloride ions reabsorbed, less water reabsorbed, ecf volume decreases, cardiac output decreases and arterial pressure decreases
what is Gitelman’s syndrome in the early distal tubule and how is it caused
less sodium and chloride reabsorbed
caused by a mutation in NCC preventing it from being trafficked to the membrane
what are the symptoms of Gitelman’s syndrome in the early distal tubule
sodium and chloride ions excreted in urine (salt wasting), less water reabsorbed so more urine excreted (polyuria), less water reabsorbed so lower ecf (hypotension), more potassium secreted (hypokalaemia), more hydrogen secreted (metabolic alkalosis)
what happens in alpha intercalated cells (AE1)
secrete hydrogen ions and reabsorb bicarbonate ions
in the apical membrane hydrogen ions are secreted via proton ATPase pumps
in the basolateral membrane the exchange protein AE1 absorb bicarbonate ions in exchange for chloride ions
chloride ions leave through the apical membrane via chloride channels and are recycled
what happens in beta intercalated cells (AE1)
reabsorb hydrogen ions and secrete bicarbonate ions
in the apical membrane bicarbonate ions are secreted in exchange for chloride ions via AE1 exchanger
chloride ions leave via chloride channels on the basolateral membrane
hydrogen ions are reabsorbed via proton ATPase pumps on the basolateral membrane
what is Liddle’s syndrome in principal cells and why is it caused
causes too much sodium to be reabsorbed and retained
caused by a mutation in the ENaC channel causing them to be stuck in the membrane and keep reabsorbing sodium
what are the symptoms of Liddle’s syndrome in principal cells
more water reabsorbed causing hypertension, more potassium lost in urine causing hypokalaemia, more hydrogen ions secreted and lost in urine causing metabolic alkalosis
what happens in principal cells (ENaC)
sodium ions move into the cells via epithelial sodium channels (ENaC) across the apical membrane and are removed from the cell via sodium-potassium pumps across the basolateral membrane
there is a net absorption of sodium
potassium ions are removed from the cell via Kir2.3 channels across the apical membrane to drive sodium reabsorption
aquaporins reabsorb water
how does the diuretic amiloride work in principal cells
blocks ENaC channels to prevent sodium reabsorption, less water reabsorbed, decreases ecf volume, decreases cardiac output which lowers arterial pressure
how and where is ADH released from
ADH is released from the posterior pituitary gland when neurosecretory neurones recieve signals from the hypothalamus causing them to fire action potentials into the posterior pituitary, there is an influx of calcium ions that causes vesicles containing ADH to fuse with the membrane and be released into the blood
what is the role of ADH
reabsorb or conserve water to regulate fluid osmolality
when is ADH released and what causes this
it is released in response to an increase in osmolality
this can be caused by ingesting salt, not drinking enough water, stress or drugs such as nicotine and ecstasy
what is the effects of ADH release on principal cells
ADH is released from the posterior pituitary and binds to vasopressin 2 (V2) receptors on the basolateral membrane of principal cells, this activates protein kinase A (PKA) which phosphorylates proteins within insertion vesicles, this causes vesicles containing aquaporin 2 channels to fuse with the membrane so more aquaporins are in the apical membrane to reabsorb water
what is diabetes inspidus and what are the two types
doesn’t affect blood glucose levels
affects reabsorption of water in nephron
central (type 1): no ADH is released
nephrogenic: no response to ADH because V2 receptor is non-functional
what are the roles of hormones renin and aldosterone
renin is released from the juxtaglomerular apparatus (JGA) and works with aldosterone to regulate fluid volume and sodium and potassium ion levels
what is the juxtaglomerular apparatus (JGA)
a structure in the kidney that regulates the function of each nephron by releasing renin
what is the renin-angiotensin cascade
a fall in extracellular fluid volume causes renin to be released from the JGA, renin catalyses the conversion of angiotensin to angiotensin 1 which is converted to angiotensin 2 by the enzyme ACE1
angiotensin 2 stimulates aldosterone release from the zona glomerulosa
aldosterone causes arterioles to vasoconstrict which increases blood pressure so more water is reabsorbed which increases ecf volume
where is aldosterone released from and what is it in response to
released from a layer in the cortex of the adrenal gland called the zona glomerulosa
it is released in response to an increase of 0.1mM in plasma potassium and a decrease in ecf volume via renin-angiotensin
where does aldosterone act and what are its effects
acts on the late distal tubule and the collecting duct
causes more reabsorption of water and sodium and more secretion of potassium and hydrogen into urine
what is the effects of aldosterone release on principal cells
aldosterone is released and binds to cytosolic mineralocorticoid receptors inside principal cells, it moves to the nucleus and stimulates transcription and protein synthesis by producing more ENaK, ROMK, sodium-potassium ATPase and sodium-hydrogen exchange proteins
what is the effect of aldosterone on alpha intercalated cells
increases sodium ion transport so more water is reabsorbed and ecf volume increases
this also increases potassium and hydrogen ion secretion as sodium provides a driving force for this so levels of potassium and hydrogen in plasma decrease
what are the two types of respiration
internal: occurs within the cell
external: ventilation (breathing) and the exchange of gases around the body
what is the conducting zone and the respiratory zone
conducting zone: made up of the trachea, bronchi and bronchioles, no gas exchange occurs here it is only the movement of air
respiratory zone: made up of the alveoli, alveolar ducts and sacs, the place where gas exchange happens
what is the structure and function of the bronchial walls
reinforced with cartilage rings to prevent them from collapsing and maintain an open shape, layer of smooth muscle to control airway diameter, mucous glands secrete mucous to trap large particles and move them away from the lungs
what is the structure and function of the respiratory epithelium
ciliated epithelial cells and goblet cells that secrete mucous, the cilia move mucous and trapped particles up away from the lungs, contains sensory nerve endings to detect chemicals such as smoke
what is the structure and function of the bronchioles
not supported by cartilage so prone to collapsing, lined with epithelium and have more smooth muscle
what is the structure and function of the alveoli
have a large surface area for gas exchange, very thin walls for short diffusion distance, surrounded by capillaries for exchange
what is the air-blood barrier made up of and what is its role
a “sandwich” made up of thin type 1alveolar cells (where gas exchange occurs) and type 2 alveolar cells (that produce surfactant)
what are the two types of inspiration and expiration
quiet: at rest
forced: during activity
what are the mechanisms of quiet and forced inspiration
quiet: diaphragm and external intercostal muscles contract causing thoracic and lung volume to increase lowering lung pressure to below atmospheric pressure so air moves into lungs
forced: same as quiet but secondary muscles such as scalenes and upper respiratory tract muscles pull ribs upwards expanding the chest to reduce pressure in the lungs more
what are the mechanisms of quiet and forced expiration
quiet: diaphragm and external intercostal muscles relax and the lungs recoil to original size causing lung volume to increase and increase pressure in the lungs to above atmospheric pressure so air moves out
forced: internal intercostal muscles and abdominal muscles contract to further increase pressure in the lungs
what is the pleura
a thin layer of tissue that covers the lungs and lines the inner chest cavity forming a pleural cavity that secretes fluid to prevent the lungs sticking to the chest cavity
how does the pleural cavity prevent lungs collapsing
there is a slight vaccum because pleural pressure is lower than atmospheric pressure
what is the job of the nose during respiration
condition incoming air by filtering, warming and humidifying it
filtering: hairs and mucous remove large particles
warming: as air hits the back of the throat it is warmed to make gases less soluble and prevent air bubbles forming in the blood
humidifying: when air is breathed it it becomes saturated with water to prevent airways drying out
what is compliance in the lungs and how is it measure
compliance is the measure of elasticity and it is equal to detensibility (how easy it is for the lungs to expand and relax during pressure changes)
compliance = volume/pressure
what does it mean if lung compliance is low
a larger pressure change is needed for the lungs to expand so the lungs need to work harder and fibrous tissue builds up making the lungs more rigid and harder to expand (pulmonary fibrosis)
what happens if lung compliance is high
a small pressure change is needed for lungs to expand so the lungs lose elastic tissue causing less elastic recoil so there is risk of the lungs collapsing
what is needed for elastic recoil in the lungs
lots of elastic and collagen fibres in lung tissue and surface tension in the airways
how does surface tension develop in the airways
it is due to the difference in forces of water molecules at the air-water interface
what is Laplace’s equation and what does it suggest
pressure = 2*surface tension/radius of a gas bubble
it suggests that in a gas bubble there is a balance between the pressure exerted by the gas and the surface tension at the gas-water border
why is surfactant needed in the lungs
some alveoli are smaller than others and as air moves from a small alveoli to a larger one the small one can collapse
surfactant reduces surface tension to prevent this happening this is why small alveoli have a large surfactant density
how is bronchiole smooth muscle controlled by the autonomic nervous system
the parasympathetic nervous system causes acetylcholine to be released which acts on muscarinic receptors causing airways to constrict
the sympathetic system causes norepinephrine and epinephrine to be released which causes the airways to dilate
what are the 3 factors that affect airway resistance
airway diameter: smaller diameter = more resistance
oedema: more fluid retained around lung tissue causes airways to swell and narrows the diameter increasing resistance
airway collapse: causes airways to narrow increasing resistance
what is meant by anatomical dead space
volume of conducting airways that don’t carry out gas exchange
what is tidal volume
measured using a spirometer, it is the amount of air that moves in and out of the lungs in one breath
what is vital capacity (VC)
the amount of air you expire after a normal inhalation
what is forced expiratory volume (FEV) and FEV1
FEV: maximum amount of air you can expire after inhaling as much air as possible
FEV1: the forced expiratory volume in one second
what is inspiratory air volume
the amount of air you can still inspire after exhaling
what is expiratory reserve volume
the amount of air left in the lungs after expiring
what are the two types of lung disease
obstructive: a reduction in airway flow caused by bronchoconstriction
restrictive: inability to expand the lungs
they both reduce ventilation
what can cause obstructive lung disease
excess secretions of mucous, bronchoconstriction due to smooth muscle contracting (asthma) or inflammation causing extra fluid in the lungs
what are the symptoms of obstructive lung disease
coughing, excessive mucous secretion (chronic bronchitis), chronic obstructive pulmonary disease (COPD) and loss of elastic tissue (emphysema)
what are the two factors that trigger asthma
atopic (outside the body): allergies
non-atopic (inside the body): respiratory infection, stress, cold air, exercise
why do airways constrict during asthma attacks
triggers cause inflammatory cells to move to the airways causing inflammatory mediators such as histamine to be released causing the airways to constrict
how is respiration controlled
the preBotC area generates a breathing pattern, the dorsal respiratory (DRG) neurones send signals to inspiratory muscles to control quiet inspiration and are inactive during forced inspiration and all expiration
the ventral respiratory group (VRG) neurones control forced inspiration and expiration and is inactive during quiet inspiration
the Pons centers send stimuli to the medulla to regulate breathing rate and depth
the pneumotaxic centre increases respiratory rate by shortening inspirations
the apneustic centre increases breathing depth and reduces respiration rate by prolonging inspirations
what is the mechanism of stretch receptors in the lungs (Hering-Breuer reflex)
the lungs expand stimulating stretch receptors to send signals back to the medulla via the vagus nerve to limit inspiration and prevent lung from over-inflating so they expand less, this is the Hering-Breuer reflex)
how do central chemoreceptors in the lungs work
they detect when levels of carbon dioxide are too high in the cerbo-spinal fluid and cause ventilation and respiration to increase to remove carbon dioxide
what is the mechanism of peripheral chemoreceptors in the lungs
they are stimulated when carbon dioxide levels in the carotid body and aortic arch are too high and cause ventilation and respiration to increase so more carbon dioxide is removed
what does restrictive lung disease cause
reduced chest expansion, loss of compliance in the lungs and an increase in collagen fibres in lung tissue
how does asbestos cause restrictive lung disease
causes build up of fibrous tissue in the lungs decreasing lung compliance so it is harder for them to expand
what does dalton’s law (mixtures of gases) suggest
the total pressure of a mixture of gases is the sum of their individual partial pressures
what are the differences in the compositions of dry and wet air
dry air has more nitrogen, oxygen, argon and no water
what does henry’s law (concentration of dissolved gases) suggest
the concentration of a gas dissolved in a solution = solubility coefficient (different for each gas) * the partial pressure of the gas
what is the structure of haemoglobin
tetrameric structure (4 subunits) each subunit consists of a haem unit and a globin chain
how is the structure of adult haemoglobin different to the structure of fetal haemoglobin
adult: 2 alpha globin chains and 2 beta globin chains
fetal: 2 alpha and 2 gamma globin chains
what is the structure of the haem unit in haemoglobin and what are its states
it is a porphyrin ring containing a single iron atom
for oxygen to bind the iron must be in a Fe2+ state, the enzyme methaemoglobin converts it from Fe2+ to fe3+
what 2 states does haemoglobin exist in
tense: low affinity for oxygen making it difficult for it to bind
relaxed: high affinity for oxygen making it easy for it to bind
what is meant by total carbon dioxide in the blood
carbon dioxide is carried in the blood in a group of states called total carbon dioxide
the states are: dissolved carbon dioxide, carbonic acid, bicarbonate, carbonate and carbamino compounds
what is most of the carbon dioxide in the blood carried as
bicarbonate which is dissolved in blood plasma
what happens to carbon dioxide that is produced by cells
around 10% remains in the plasma and can bind to plasma proteins, be converted to bicarbonate or stay dissolved in plasma
the other 90% enters red blood cells
how is carbon dioxide converted to bicarbonate in plasma
it combines with water to form carbonic acid and this is converted to bicarbonate using carbonic anhydrase
what are the 3 ways carbon dioxide enters red blood cells
through aquaporin 1, through associated glycoproteins or diffusing through the lipid bilayer
what happens to carbon dioxide that enters red blood cells
some carbon dioxide dissolves in the cytoplasm, some forms carbamino proteins and the rest is converted to carbonate using carbonic anhydrase
what are mesenteries in the GI tract and what do they do
membranes that hold the intestine in place in the abdominal cavity
they provide a source of inflammatory and stem cells to protect against infection
what are sphincters in the GI tract and what do they do
muscular rings that separated organs of the GI tract
they control the movement of food and prevent backflow
what are the 4 main functions of the GI tract
move food through the body (motility), secrete fluids from glands, hydrolyse food into small molecules that can be absorbed, absorb electrolytes and water in the bloodstream
what is the first layer of the GI wall and what is it made up of
the mucosal layer (inner layer)
made up of epithelial cells, lamina propria (connective tissue), enteric (GI) neurones and thin muscularis mucosae (muscle tissue)
what is the second layer of the GI wall and what is it made up of
submucosal layer
made up of collagen and elastin tissue, glands and blood vessels
what is the structure and function of the mouth in the GI tract
contains salivary glands, chews up food to increase surface area for enzymic action, lipase and amylase in salvia start to hydrolyse lipids and starch, saliva also destroys bacteria and neutralises acid from food
what is the structure and function of the oesophagus in the GI tract
the lumen is lined with stratified squamous epithelia, a wave of movement called the peristaltic wave causes contractions to move food along
what is the structure and function of the stomach in the GI tract
the upper region of the stomach called the orad relaxes to receive food, the muscular layer of the stomach contracts to mix food with gastric juice to form chyme
what is the structure and function of the small intestine in the GI tract
amino acids, water, carbohydrates and fats hydrolysed and absorbed by enzymes in the brush border membrane, plica (folds) and microvilli increase absorption
what are the 3 sections of the small intestine
duodenum, jejunum, ileum
what is the structure and function of the pancreas in the GI tract
a fluid rich in bicarbonate ions is secreted into the duodenum to neutralise stomach acid
what is the structure and function of the liver and gall bladder in the GI tract
the liver secretes bile into the gall bladder where it is stored
release of the hormone CCK stimulates bile secretion
what is bile made up of and what is its job
made up of water, amphipathic bile salts, bilirubin and electrolytes
it emulsifies lipids, hydrolyses fats and neutralises stomach acid
what is the structure and function of the large intestine in the GI tract
it absorbs water and electrolytes, makes and absorbs vitamins K and B and forms faeces
it is made up of columnar epithelial cells and contains crypts that secrete substances
what is the enteric nervous system (ENS) and how does it work
the ENS is the intrinsic section of the autonomic nervous system that controls the GI tract
it is modified by the brain
how is the GI tract controlled by neurones
postganglionic neurones relay information between the GI tract and the CNS
what are the 2 secretory sections of the stomach and what do they secrete
the proximal section: secretes hydrochloric acid, pepsinogens, intrinsic factors and mucins
the distal section: secretes gastrin, somatostatin and pepsinogens
what are the 8 types of cell in the stomach
epithelial cells
mucous neck cells
parietal cells
enterochromaffin-like cells
chief cells
enterochromaffin cells
D cells
G cells
what do epithelial cells in the stomach secrete
secretes bicarbonate ions to neutralise acid
what do mucous neck cells in the stomach secrete
secrete mucus to protect epithelia
what do parietal cells in the stomach secrete
secretes HCL to activate pepsinogens, denature proteins and destroy pathogens and intrinsic factor for absorption
what do enterochromaffin-like cells in the stomach secrete
secrete histamine to increase HCL secretion in parietal cells
what do chief cells in the stomach secrete
secrete pepsinogen to digest proteins
what do enterochromaffin cells in the stomach secrete
secrete seratonin, VIP for motility and secretions and substance P for smooth muscle contractions
what do D cells in the stomach secrete
secrete somatostatin to inhibit gastrin release
what do G cells in the stomach secrete
secrete gastrin to increase HCL secretion in parietal cells, increase motility and increase pepsinogen release
what are the two states parietal cells can be in and what happens when they are activated
resting and active state
when activated vesicles and tubes fuse to form a highly folded apical membrane, hydrogen-potassium ATPase pumps are inserted into the membrane
chloride and potassium ion channels are also inserted
what is the mechanism of HCL secretion in parietal cells
carbon dioxide produced in respiration combines with water to form carbonic acid which dissociates into bicarbonate and hydrogen ions
hydrogen ions are secreted across the apical membrane via hydrogen-potassium ATPase pumps
bicarbonate ions leave the cell across the basolateral membrane via chloride-bicarbonate exchanger
chloride ions leave across the apical membrane via chloride ion channels
potassium is recycled into the lumen through potassium ion channels
what is the mechanism of carbohydrate absorption
glucose, galactose and fructose are absorbed into epithelial cells in the small intestine
glucose and galactose move in with sodium in cotransport
fructose moves in by facilitated diffusion
sodium moves out through sodium-potassium ATPase pumps
glucose, galactose and fructose are absorbed into the blood by facilitated diffusion
what is the mechanism of protein absorption
amino acids move into epithelial cells of the small intestine in cotransport with sodium
dipeptides and tripeptides move across the apical membrane in cotransport with hydrogen
hydrogen ions move out via the sodium-hydrogen exchanger
internal peptidase in the membrane hydrolyses di and tripeptides
what is the mechanism of secretion of chloride and sodium in crypt cells in the intestines NKCC2)
sodium, potassium and chloride ions move into the cell via sodium-potassium-chloride cotransporter 2 (NKCC2) on the basolateral membrane
chloride ions move out across the apical membrane via chloride ion channels that are activated by cAMP, AcH and VIP
sodium ions follow the chloride channels and are secreted paracellularly
what is the mechanism of absorption of sodium and bicarbonate in cells in the jejunum (Na-H exchangers)
low intracellular sodium levels provides the driving force for sodium to enter the cell in sodium-hydrogen exchangers
hydrogen ions dissociate into bicarbonate ions
sodium moves out across the basolateral membrane via sodium-potassium ATPase pumps
bicarbonate ions stimulate the sodium-hydrogen exchanger
what is the mechanism of absorption of sodium and bicarbonate secretion in the ileum (cotransport with glucose)
sodium moves into the cell across the apical membrane in cotransport with glucose or amino acids
sodium moves out across the basolateral membrane via the sodium-potassium ATPase pump
bicarbonate ions move out of the cell across the apical membrane via chloride-bicarbonate exchangers
what is the mechanism of secretion of sodium and hydrogen in ductal cells of the pancreas (chloride-bicarbonate exchangers)
bicarbonate ions move out of the cell across the apical membrane in chloride-bicarbonate exchangers
hydrogen ions move out across the basolateral membrane via sodium-hydrogen exchangers
sodium ions moves out of the cell across the basolateral membrane via sodium-potassium ATPase pumps
what is the mechanism of absorption of sodium and potassium in cells of the large intestine (aldosterone)
when the cell is stimulated with aldosterone sodium channels are synthesised on the apical membrane and sodium moves into the cell
sodium leaves the cell via sodium-potassium ATPase pumps
potassium leaves the cell via potassium ion channels on basolateral and apical membranes
what is the mechanism of lipid absorption
bile salts hydrolyse lipids into cholesterol, lysophospholipids, monoglycerides and free fatty acids which are made soluble in micelles
micelles diffuse into the cell and the products are converted back to triglycerides, phospholipids and esters of cholesterol
these products associate with lipoproteins and are packages into chylomicrons that are exocytosed
chylomicrons enter the lymphatic system to the thoracic duct where the enter the circulatory system
what are the 5 types of secretory cells in the pancreas and what do the secrete
beta langerhans cells: insulin, proinsulin, C peptide and amylin
alpha langerhans cells: glucagon
delta langerhans cells: somatostatin
PP/F cells: pancreatic polypeptide
enterochromaffin cells: grehlin protein
how is insulin secretion regulated
receptors on beta islet cells detect high blood glucose and stimulate insulin synthesis and secretion
the sympathetic nervous system activates beta adrenergic receptors to stimulate insulin release
the parasympathetic nervous system stimulates the vagus nerve via acetylcholine to initiate insulin release
what is the mechanism of insulin secretion in beta islet of langerhans cells (first pathway)
glucose enters the cell by facilitated transport via the GLUT2 transport protein
the glucose is phosphorylated by glucokinase and oxidised to release ATP which inhibits ATP-dependent potassium channels
the potassium channel shuts so the cell is depolarised which opens calcium ion channels
calcium ions enter the cell causing vesicles containing insulin to move and fuse to the membrane and release insulin
what are the second and third pathways of insulin release in beta islet of langerhans cells
second pathway: acetylcholine binds to CCK receptors causing insulin to be released through the PKC pathway
third pathway: adenyl cyclase mediator causes cAMP levels to increase releasing insulin through the PKA pathway
what is the effect of insulin on heterotetrametric receptors
when insulin binds to the receptor it initiates a cascade of phosphorylation events that either inhibit or activate PKC
this activates phospholipases and G proteins causing cell growth, proliferation and gene expression
what is the effect of insulin on blood glucose
insulin decreases blood glucose levels by increasing glucose uptake into cells
it causes GLUT4 channels to be inserted into cell membranes
what is the effect of insulin on cells
increases sodium-potassium ATPase pump activity to increase potassium uptake and prevent hypokalaemia
what are the 3 effects of insulin on the liver
promotes the formation of glycogen from glucose (glycogenesis) and inhibits the breakdown of glycogen (glycogenolysis) and formation of new glucose (gluconeogenesis)
what are the 4 effects of insulin on muscles
promotes glucose uptake into cells, promotes synthesis of glycogen, promotes breakdown of glycogen (glycolysis) and promotes protein synthesis
what are the 3 effects of insulin on fat cells (adipocytes)
increases glucose uptake into cells, increases triglyceride synthesis and inhibits oxidation of fat stores
what are the 3 sections of the ovaries
medulla: where the blood and lymph vessels are
cortex: where the oocytes (immature eggs) are located
follicle: surrounds the cortex
how does the follicle develop in the ovary
its starts as a primordial follicle and develops into the primary, secondary and then tertiary follicle
before ovulation it develops from the tertiary to the graafian follicle
when the mature ova leaves the follicle it is called the corpus luteum
what are the 2 layers of follicular cells and what do they secrete
the granulosa secreted oestrogen
the theca secretes progesterone
what is the structure and function of the fallopian tubes
transport the egg from the ovary to the uterus
smooth muscle in the walls of the tubes performs peristalsis (waves of contraction) to move the ova along
what is the structure and function of the uterus
has 3 layers: perimetrium, myometrium and endometrium
the endometrium is made up of simple columnar cells with leukocytes, macrophages, lamina propria and spiral arteries
what is the structure and function of the cervix
the canal that links the uterus to the vagina
it secretes mucus to prevent microbes reaching the uterus
what is the structure and function of the vagina
the wall contains 3 layers: adventitia, muscularis and mucosa
it is made up of stratified squamous epithelia to reduce friction during birth
cells are rich in glycogen which is fermented by bacteria to produce lactic acid to kill microbes
what happens during the follicular phase of the ovarian and endometrial cycles
ovarian: the follicular phase is controlled by the hormones FSH and LH
there is an increase in proliferation of the follicle cells causing oestrogen levels to rise
endometrial (proliferative phase): this rise in oestrogen levels causes proliferation of endometrial tissue to build up the uterus lining
there is a rapid increase in oestrogen and when it reaches the critical level it upregulates LH release and the mature ova is released (ovulation)
what happens during the luteal phase of the ovarian and endometrial cycles
ovarian: the corpus luteum secretes progesterone
endometrial (secretory phase): release of progesterone stimulates endometrial glands to secrete substances
what happens during the start of the follicular phase in the ovarian cycle and the menses in the endometrial cycle
ovarian: if there is no fertilisation to corpus luteum starts to degenerate, progesterone and oestrogen levels decrease
endometrial (menses): the decrease in progesterone and oestrogen causes the endometrium layer to be lost (menstruation)
how is the ovarian cycle regulated
the hypothalamic-pituitary-gonadal axis (HPGA) is controlled by negative and positive feedback
oestrogen (during the follicular phase) and progesterone exert negative feedback
between the two phases when oestrogen meets the critical level it exerts positive feedback to trigger ovulation
how is the endometrial cycle regulated
oestrogen and progesterone control changes in the endometrium: during the proliferative phase oestrogen causes growth of the endometrium and during the secretory phase progesterone causes proliferation to stop
FSH and LH exert feedback on the cervix and vagina: during the follicular phase cervical mucus forms channels to propel sperm and during the secretory phase cervical mucus is thicker to stop sperm reaching the uterus
how do hormonal contraceptives work
the combined pill: acts on the hypothalamus to decreases secretion of the GnHR hormone which decreases levels of FSH and LH to prevent the follicle developing and ovulation
progesterone-only pill: causes mucus to be thicker so sperm can’t reach the cervix
how does the neuroendocrine system control the ovarian and endometrial cycles
hypothalamic neurones release gonadotropin-releasing hormone (GnRH) which binds to G-coupled receptors activating them to release gonadotropins causing FSH and LH to be released
what happens during fertilisation
it occurs in the ampulla (middle section of the fallopian tube)
the sperm undergoes an acrosomal reaction to cause penetration, the acrosome (tip of the sperm) contain hydrolysing enzymes to break down granulosa cells surrounding the oocyte
the oocyte undergoes a cortical reaction which releases lots of calcium ions to stimulate the second meiotic division
what happens during pre-implantation after fertilisation
the egg moves along the fallopian tube as it undergoes meiosis and gains nourishment from secretions, this allows the endometrium to prepare for implantation
as it reaches the uterus it forms a blastocyst which is surrounded by a trophoectoderm layer that will form the placenta and amniotic sac
what happens during implantation
this happens during the secretory phase of the endometrial cycle, the blastocyst implants
the trophoblastic cells can be divided into cytotrophoblastic cells and syncytiotrophoblastic cells which secrete the hormone HCG
what are the 4 stages of endometrial invasion during implantation
hatching: the outside layer of the blastocyst is broken down by hydrolytic enzymes
apposition: trophoblastic and endometrial epithelium membranes meet, maternal glands form
adhesion: maternal and foetal trophoblast cells join together
invasion: syncytiotrophoblastic cells penetrate the endometrium and implant
what are the hormonal changes in each trimester during pregnancy
trimester 1: the corpus luteum is rescued so it can still secrete HCG, oestrogen and progesterone to support the endometrium
trimester 2+3: the placenta secretes oestrogen and progesterone for the developing embryo
what happens during quiescence (stage 0) of parturition
occurs from fertilisation until birth starts
the uterus is relaxed and insensitive to uterotonic hormones so it won’t contract
progesterone supresses myometrial contractions
what happens during activation/transformation (stage 1) of parturition
the foetal hypothalamic-pituitary-adrenal axis produces cortisol which increases the ratio of oestrogen to progesterone stimulating prostaglandin release
cervical gene expression for enzymes that hydrolyse the collagen matrix to shorten, thin and dilate the cervix
what happens during labour (stage 2) of parturition
prostaglandin and oxytocin levels increase causing myometrial contractions and cervical dilation
the baby is expelled and then the placenta
what happens during involution recovery from birth (stage 3) in parturition
spiral arteries vasoconstrict to prevent haemorrhage
placental oestrogen levels decrease to stimulate myometrial atrophy and involution so the uterus returns to normal
how do hormones control lactation
during pregnancy oestrogen and progesterone stimulate breast growth and development
after pregnancy oestrogen stimulates anterior pituitary prolactin (PRL) to initiate milk production
how does the placenta develop during pregnancy
holes in syncytiotrophoblast cells merge and fill with maternal blood, trophoblastic cells form microvilli that project into the maternal blood for exchange
what are the 4 layers in the placenta that separate maternal and foetal blood
foetal capillary endothelium, mesenchyme, cytotrophoblasts and syncytiotrophoblasts
what is exchanged across the placenta
from mother to foetus: glucose, amino acids, vitamins, hormones and antibodies
from foetus to mother: waste e.g. urea and creatinine
what happens when G protein-coupled receptors are activated
when a ligand binds the G protein-coupled receptor changes shape and GDP is exchanged for GTP
the G protein dissociates from the receptor and alpha and B subunits dissociate and can interact with effectors
the alpha subunit catalyses conversion of GTP back to GDP and the G protein reforms
how does an increase in 2.3 DPG affect the oxygen dissociation curve
shifts it to the right because it binds to haemoglobin reducing its affinity for oxygen
how does an increase in temperature affect the oxygen dissociation curve
shifts it to the right because haemoglobin has reduced affinity for oxygen
how does an increase in carbon dioxide levels affect the oxygen dissociation curve
shifts it to the right because the pH of the blood is lowered reducing haemoglobin’s affinity for oxygen
how does an increase in carbon monoxide levels affect the oxygen dissociation curve
shifts it to the left because it binds to haemoglobin preventing oxygen from binding
how does adding another gas affect Dalton’s law
total pressure stays the same because it is in a closed system
partial pressures of the other gases decreases
what are the effects of glucagon and beta adrenergic agonists on beta cells
increases cAMP levels increasing insulin secretion
how is tissue fluid produced
hydrostatic pressure decreases from arteriole to venule end but it is still higher than the hydrostatic pressure of interstitial fluid so water is forced out
the volume of the arteriole decreases and proteins stay in the capillary causes oncotic pressure to increase so water and solutes are forced out
what happens in proximal tubule cells
sodium ions move into the cell across the apical membrane either in cotransport with glucose, amino acids or phosphate ions (NaPilla)
sodium moves out across the basolateral membrane via sodium-potassium ATPase pumps
potassium ions move out of the cell across the basolateral membrane via potassium ion channels
