Physiology S1 Y1 Flashcards
What are muscle cells specialised to do?
Generate mechanical force
Are skeletal, cardiac and smooth muscles voluntary or involuntary?
Skeletal = voluntary
Cardiac and smooth = involuntary
What are neurons specialised to do?
Initiate, integrate and conduct electrical signals
- neuron to neuron = passing on electrical signals
- neuron to gland = secreting electrical signals
- neuron to muscle = contraction
What are epithelial cells specialised to do?
The selective secretion and absorption of ions and organic molecules
- different sides of cell can have different functions
What are connective cells specialised to do?
Connecting, anchoring and supporting of bodily structures
- can be loose connective tissue, dense connective tissue, bone, cartilage, adipose and blood
2 types of protein fibres?
- Collagen fibres (ropelike)
- Elastin fibres (rubberband like)
- What is extracellular fluid?
- Intertitial fluid? - What is the space containing it?
- Fluid in blood + surrounding cells
- Extracellular fluid around + between cells - interstitium
What is homeostasis?
“State of reasonably stable balance between physiological variables” they are not constant but are in a predictable range
- regulated by dynamic constancy
What is pathophysiology?
Alterations to homeostasis out of the normal range
- How are conditions in the body maintained at their set point?
- Can set points be changed and why?
- Continuous adding of energy and feedback mechanisms
- They can be reset so important conditions can be maintained if the environment changes e.g. in the presence of a pathogen body temp. increases
How does negative feedback get used in homeostasis?
Prevents compensatory responses to a loss of homeostasis and oppose a stimulus e.g. if body temp. increases, this is opposed and brought down
How does positive feedback get used in homeostasis?
Accelerates a process such as blood clotting to seal a wound
What is feedforward regulation?
Regulated variables changing are anticipated and the body is prepared for this before it occurs through use of external/internal environmental detectors and learning
What are afferent and efferent nerve pathways?
Nerves that connect receptors to the integrating center and the integrating center to effectors
What other mechanism can act as a reflex component?
Hormones
2 major effectors?
- Muscles (contract)
- Glands (secrete hormones)
4 substances that allow cells to communicate?
- Hormones - target cells in one or more places in body
- Neurotransmitters - allows neurons or effector cells to recieve/transmit signals
- Paracrine substances - target cells in close proximity of release
- Autocrine substances - act on the same cell that secreted it
What is adaptation?
Characteristic that favours the survival of an individual in a specific environment or conditions
What is acclimatization?
Adaptation due to prolonged exposure to an environmental change
Why are biological rhythms useful?
Allow homeostatic mechanisms to be used immediately as there is an anticipatory component added to the homeostatic control system (a feedforward system)
What is the pool?
The readily available quantity of a substance
What are electrolytes?
Ionic forms of mineral elements
Difference between polar and non-polar bonds?
Polar bonds have uneven distribution of electrons (creates areas of positive and negative charge) and they are hydrophilic
Non-polar bonds have equal sharing of electrons and are hydrophobic
Lipids:
- Why are they not very soluble?
- What are the four subclasses?
- Non-polar covalent bonds
- Fatty acids (saturated or unsaturated)
- Triglycerides (part of membranes)
- Phospholipids
- Steroids (4 carbon rings, not water soluble)
Amino acid structure?
R
|
NH2 - C - COOH
|
H
Primary structure is?
Sequence of amino acids
Secondary structure is?
A flexible chain that can be folded into many configurations - hydrogen bonds between polypeptide chains force chain into an alpha helix or if the chains run parallel the hydrogen bonds create a beta sheet
Tertiary structure is?
The interactions between the amino acids to alter the final structure (hydrogen bonds, ionic interactions, nonpolar interactions, disulfide bonds, Van der Waals interactions)
Quaternary structure is?
More than one polypeptide chain (each called a subunit) - held by the same interactions as the tertiary structure
Number of hydrogen bonds between guanine and cytosine?
3
Number of hydrogen bonds between adenine and thymine?
2
What are the two pyrimidine (single ring) bases?
Cytosine and thymine
What are the two purine (double ring) bases?
Adenine and guanine
What do triplets that do not code for an amino acid code for?
Stop signal
What does tRNA do?
Attaches to anticodon and reads triplets until stop codon
Why can proteins in a membrane move laterally freely?
Not chemically bound to phospholipids
2 things cholesterol does?
- Reduces how tightly phospholipids are packaged (increases fluidity)
- Involved in vesicle formation
Integral membrane proteins:
- How are they amphipathic?
- 3 functions if they are transmembrane proteins?
- Polar regions at surface, non-polar regions at centre
- Channels
- Transmission of chemical signals
- Anchoring of protein filaments
Peripheral membrane proteins:
- Why are they not amphipathic?
- How do some regulate metabolism in cell?
- How are they involved in transport?
- What do they work with the cytoskeleton to do?
- Only bound to polar part of membrane
- Some are enzymes
- Move small molecules along membrane or to the cytosol
- Regulate cell shape and contraction
What do integrins do?
Bind to proteins in extracellular matrix and link them to proteins in membranes of neighbouring cells to join cells
3 types of junctions between cells?
- Desmosomes
- Tight junctions
- Gap junctions
What are desmosomes?
Region between two cells where plasma membranes separate and proteins accumulate to act as anchoring points for cadherins which extend from the cells and bind to link the cells
What are tight junctions?
Two cells bind to block the extracellular pathway
What are gap junctions?
Linking of cytosol of cells through protein-lined channels formed via connexins
Why does diffusion occur?
Result of random thermal motion
What does flux mean?
Amount of material crossing a surface in a unit of time
5 factors the size of a flux depends on?
- Temperature (higher = increased speed)
- Mass of molecule (lower mass = higher speed)
- Surface area (larger = more diffusion)
- Medium (e.g. air allows faster movement)
- Distance (lower = higher flux)
3 types of ion channel?
- Ligand gated - specific molecule causes allosteric/covalent change so channel opens
- Voltage gated - change in membrane potential moves charge areas of protein which changes its shape
- Mechanically gated - physically deforming
What is mediated transport and what are the two types?
Transport of molecules (via conformational change of transporters) that are too large/charged to diffuse in
- Facilitated diffusion and active transport
4 factors that determine flux via mediated transport?
- Saturation of transport binding sites
- Number of transporters in the membrane
- Rate of conformational change
- Solute concentration
What is the difference between primary and secondary active transport?
Primary uses ATP and secondary uses an electrochemical gradient
2 factors that make up electrochemical gradient?
Concentration difference and electrical difference
5 steps of primary active transport (to maintain membrane potential)?
- ATP is associated to transporter which binds to 3 Na+
- ATPase dephosphorylates ATP and phosphorylates transporter
- Reduced Na+ affinity (due to conformational change) and extracellular fluid exposed
- New conformation means higher K+ affinity
- K+ binding dephosphorylates transporter = changed conformation = K+ released into intracellular fluid
4 steps of secondary active transport (use of electrochemical gradient to transport solutes against concentration gradient)?
- Low Na+/high solute in cell
- Na+ moves into cell
- Na+ binds to one site, solute to another
- Na+ and solute released into cell
What is 1 mole?
Mass in grams of a compound that is equal to its molecular weight
What is osmolarity?
Total solute concentration of a solution
Difference between permeable and selectively permeable membrane?
Permeable = equal concentration of solute and volume of water in each compartment
Semi-permeable = same concentration of solute, different volume of water in each compartment (only water moves)
What is a ligand?
Molecule/ion bound to protein by electrical attractions (not covalent) to change conformation
What is the conformation of a protein dependent on?
Location of amino acids along polypeptide chain
What is meant by the chemical specificity of a binding site?
How many types of ligands can bind (some only bind to one)
What does affinity of a binding site affect?
How tightly it binds to a ligand
2 ways binding sites are regulated?
- Changing protein shape via allosteric (one molecule binds and alters binding site) or covalent (charged groups bound) modulation
- Regulating protein synthesis and degradation
What is meant by allosteric cooperativity?
Ligand binding to first of several functional sites on a molecule which changes the affinity of other functional sites
4 determinants of reaction rate?
- Reactant concentration
- Activation energy
- Temperature
- Catalyst
What are cofactors?
Molecules that activate enzymes via allosteric regulation
What are coenzymes?
Organic molecules that act as one of the substrates (e.g. NAD+)
What are multi-enzyme reactions?
Sequence of enzyme-mediated reactions (metabolic pathway) which increase one another, which leads to formation of a product
What does affinity of a receptor mean?
Degree of binding with a substrate
What is an antagonist?
Drugs that act as competitors
What is an anagonist?
Drugs that mimic messenger
When a messenger binds to a receptor it changes its conformation which triggers? (7)
- Permeability
- Transport properties
- Electrical state
- Contraction
- Metabolism
- Secretory activity
- Rate of proliferation/differentiation
How do protein kinases activate proteins?
Transfer a phosphate
How do extracellular signals cause protein synthesis to occur?
Bind to a receptor which triggers transcription factor activation which in turn causes segment of dna to be transcribed and translated
What do lipid soluble messengers act as?
Intracellular receptor binders that act as transcription factors in the nucleus as they can diffuse through the plasma membrane
What do water soluble messengers act as?
Extracellular receptor binders that activate intracellular signalling cascades and downstream mediators
What is the difference between a first and second messenger?
First = intercellular messenger that binds to receptor
Second = substance generated/entering cytoplasm due to receptor binding
What are the 4 main types of receptor?
Type A = ligand-gated ion channel receptors
Type B = receptors that act as enzymes
Type C = receptors that interact with cytoplasmic janus kinases (JAKs)
Type D = G-protein coupled receptors
Type A - ligand gated ion channel receptors:
- What are they activated by and how does this mean they are receptors?
Activated by a ligand binding and then conformationally changing to open channel for ions which changes the membrane potential (response)
Type B - receptors acting as enzymes:
- What type of enzyme activity?
- What do they all act as? (most common type?)
- Normal sequence?
- Intrinsic
- Protein kinases (receptor tyrosine kinases as most phosphorylate tyrosine residues)
- Messenger binds, changes conformation, tyrosine groups phosphorylated, phosphotyrosines on cytoplasmic area act as sites for proteins to dock, proteins then dock and trigger signalling pathways when activated
Type C - interact with janus kinases:
- What type of kinases and how are they activated?
- Cytoplasmic kinases and receptor is conformationally changed to activate ASSOCIATED JAK
Type D - G-protein coupled:
- What are the G-proteins bound to?
- 3 subunits of G-protein + purposes?
- Normal sequence?
- Inactive receptor
- Alpha (binds to GDP (off) and GTP (on)), beta and gamma (both anchor alpha)
- Ligand binds and changes conformation of receptor, alpha subunit has higher affinity for GTP and dissociates from other subunits and binds to plasma membrane protein (e.g. ion channel or enzyme)
How is a signal usually ceased?
Enzymatic metabolism of first messenger or receptor inactivation
What are paracrine, autocrine and endocrine signalling?
Paracrine = close cells signalling eachother by releasing signalling molecules locally
Autocrine = cell releasing signalling molecules to signal itself
Endocrine = cell releasing signalling molecules to signal cell far away
What are neurotransmitters?
Chemical messengers released from neurons to respond to electrical signals
5 components of neurons?
- Processes (extensions to link neurons)
- Cell body/soma (where protein synthesis occurs)
- Dendrites (recieve inputs)
- Dendritic spines (outgrowths to increase SA and have ribosomes)
- Axon (long process to carry output to target cells)
What is axonal transport?
Organelles are moved from cell body to axon terminals
What is the major adaptation of the axon?
Wrapped in myelin to speed up transduction - myelin produced by oligodendrocytes in CNS and schwann cells in PNS
What is anterograde movement?
Kinesins (motor units) move substances from cell body to axon terminals
What is retrograde movement?
Dyneins (motor units) move substances from axon terminals to cell body
3 classes of neurons?
- Afferent neurons (info towards CNS)
- Efferent neurons (info from CNS to effector)
- Interneurons (info within CNS conveyed)
What are nerves?
Afferent+efferent neurons + connective tissue + blood vessels
What are glial cells?
Large part of CNS that surround soma, axon, dendrites for physical and metabolic support e.g. oligodendrocytes are glial cells
What is the purpose of astrocytes?
- Regulate extracellular fluid by removing K+ and neurotransmitters
- Stimulate epithelial cells to form tight junctions (blood-brain barrier)
Purpose of microglial cells?
Remove pathogens and dead/damaged neurons
Purpose of ependymal cells?
Regulate cerebrospinal fluid
What is a pathway/tract?
Group of axons travelling together in CNS
What is a commissure?
Axons link right and left halves of CNS
What are ganglia?
Cell bodies of neurons with similar functions in PNS
What are nuclei (neurons terms)?
Cell bodies of neurons with similar functions in CNS
How many cavities does the brain have and what is inside them?
4 (interconnected) filled with cerebrospinal fluid
Role of:
- Frontal lobe?
- Parietal lobe?
- Occipital lobe?
- Temporal lobe?
- Morality, project future
- Sensory, motor, language
- Sight
- Long-term memory
Forebrain (cerebrum):
- What is the central core called?
- 2 parts?
- What separates them?
- What are the ridges called?
- What are the grooves called?
- Diencephalon
- Outer grey matter (has subcortical nuclei for movement/posture) and inner white matter
- Corpus callosum
- Gyri
- Sulci
Forebrain (cerebrum):
- 2 cell types?
- Pyramidal (major output, excite)
- Nonpyramidal (major input, receive signals)
Forebrain (cerebrum):
- What is the diencephalon made up of?
- Thalamus (arousal, movement, posture, focus)
- Hypothalamus (homeostatic regulation)
- Epithalamus (controls biological rhythms)
Role of hypothalamus?
- Neural and endocrine coordination to preserve an individual (e.g. eating) and a species (reproduction) and it is connected to the pituitary
Role of cerebullum?
Coordination of movement and controls posture+balance
Brainstem:
- 3 parts?
- Role?
- Midbrain, pons, medulla oblongata
- Reticular formation by integrating info from CNS and is involved in motor functions, cardiovascular+respiratory control and swallowing
What bones protect CNS and PNS?
CNS = cranium
PNS = vertebrae
-What are the meninges?
- 4 roles?
- Membranes that line structure and add support (dura mater, arachnoid mater, pia mater)
- Cover and protect CNS
- Protect blood vessels and enclose venous sinuses
- Contain cerebrospinal fluid
- Partitions in skull
What is the blood brain barrier?
A protective and very selective barrier to keep the brain stable
What relays/transmits info between the brain and spinal cord?
Fiber tracts
What is grey matter of spinal cord made up of?
Interneurons, cell bodies+dendrites of efferent neurons, entering axons of afferent neurons, glial cells
What is white matter of spinal cord made up of?
Myelinated axons
How do afferent fibers arrive from peripheral nerves into spinal cord?
Dorsal roots
How do efferent fibers exit from the spinal cord to peripheral nerves?
Ventral roots
- How are signals carried out of the CNS?
- Divisions?
- Efferent neurons
- Somatic and autonomic
What is the somatic nervous system?
Single neuron connected to skeletal muscle (only excitatory)
- What is the autonomic nervous system?
- 2 divisions?
- 2 neurons between CNS and effector (excitatory and inhibitory)
- Sympathetic and parasympathetic
Sympathetic:
- What is it known as?
- Where do neurons leave the CNS?
- Where are ganglia?
- How does it respond?
- Fight or flight
- Thoracic and lumbar regions
- Close to spinal cord
- As a single unit
Parasympathetic:
- What is it known as?
- Where do neurons leave the CNS?
- Where are ganglia?
- What does it do?
- Rest or digest
- Brainstem and sacral regions
- Close to/within organs
- Activate specific organs
- What is the charge inside a neuron relative to the outside?
- What does the size of resting potential rely on?
- Negative (-70mV resting)
- Differences in specific ion concentrations and membrane permeability of ions
Difference between signals in graded and action potentials?
Graded = short distance
Action = long distance
What is the all or nothing response?
If a change in membrane reaches a specific threshold depolarisation will occur at full strength regardless of size of change as long as it surpasses threshold value (once threshold is reached all the Na+ channels open)
Difference between inhibitory and excitatory synapses?
Inhibitory = hyperpolarises or stabilises
Excitatory = depolarises
2 types of synapses?
Chemical (neurotransmitters)
Electrical (gap junction connections between neurons)
Steps of synaptic transmission?
- Action potential reaches pre-synaptic terminal
- Voltage gated Ca2+ channels open
- Ca2+ enters terminal
- Neurotransmitters released into synapse as Ca2+ causes SNARE docked vesicles to fuse with membrane as Ca2+ binds to synaptoagmins and conformationally changes SNARE proteins
- Neurotransmitter binds to postsynaptic receptors
- Na+ channels open in postsynaptic terminal and action potential is transmitted
What are temporal and spatial summation?
Temporal = impulses in quick succession
Spatial = many neurons activated simultaneously
Difference between between convergent and divergent synapses?
Convergent = many presynaptic impact 1 postsynaptic
Divergent = 1 presynaptic impacts many postsynaptic
2 types of postynaptic receptors?
Ionotropic (in ion channels)
Metabotropic (indirectly influence ion channels)
- Why does the amount of neurotransmitter vary between each response?
- How does the amount of neurotransmitter affect the response?
- Depends on [Ca2+] and activation of membrane receptors
- Affects the amplitude of the membrane potential changes
What are neuromodulators?
Chemical messengers that change postsynaptic cells response to neurotransmitter and the synthesis/release/reuptake/metabolism of neurotransmitter in presynaptic cell
When are neurotransmitters vs neuromodulators used?
Neurotransmitters = rapid communication
Neuromodulators = slower events like learning
7 types of neurotransmitters/neuromodulators?
- Acetylcholine
- Biogenic amines
- Amino acids
- Neuropeptides
- Gases
- Purines
- Lipids
- What is an electroencephalogram (EEG)?
- What is the difference between alpha and beta rhythm?
-Recording of brain electrical activity
- Alpha = less attention, beta = thinking hard
Difference between sensation and perception?
Sensation = aware of information from sensory receptors
Perception = aware understand the information
What are sensory receptors?
Receptors on the end of afferent neurons that convert a stimulus into a graded potential
5 types of sensory receptors?
- Mechanoreceptors (pressure/stretch)
- Thermoreceptors (cold/warmth)
- Photoreceptors (light)
- Chemoreceptors (chemicals bind)
- Nociceptors (pain)
3 forms of sensory coding?
- Type
- Intensity
- Location
Sensory coding (type):
- What is the receptive field?
- What is modality?
- Area of body stimulated
- Type of stimulus (receptors sensitive to one modality)
Sensory coding (intensity):
- What is the impact of a higher stimuli?
Summation occurs as receptors on adjacent afferent neurons are activated
Sensory coding (location):
- What indicates stimulus location?
- What does precision of locating stimulus depend on?
- When is a response the greatest?
- Stimulated receptor and unique pathway
- Convergence (greater = less activity)
- If stimulus is in the centre of the receptive field
What is lateral inhibition?
Localisation of a stimulus by the excited neuron inhibiting afferent neurons at the edge of the stimulus to increase contrast between centre and periphery of stimulated area
How is equilibrium potential achieved?
Voltage gated K+ channels open and K+ moves down concentration gradient to make the side they were on more negative - then K+ moves back the other way AS WELL AS going down the concentration gradient (the flux out is greater so there is an overall NEGATIVE charge)
What does the high membrane permeability of neurons to K+ mean?
Resting potential is close to equilibrium potential of K+
- What are graded potentials?
- 3 reasons why magnitude can vary?
- Changes in membrane potential of a small region of the plasma membrane (small region depolarised by transient application of chemical signal)
- Can depolarise or hyperpolarise
- Magnitude of stimulus
- Charge lost across membrane due to membrane permeability to ions through open membrane channels (current dies out)
Action potentials:
- What ion channels are used for initial stimulus?
- What do voltage gated ion channels allow?
- Similarity and difference between Na+ and K+ channels in membrane potential changing?
- Ligand-gated and mechanically gated
- Action potentials by allowing rapid depolarisation and repolarisation (action potential does not lose magnitude)
- Similarity = both have charged residues which allows conformational changes to respond to membrane potential
Difference = Na+ faster to respond
5 steps of the mechanism of action potentials?
- Na+ enter when stimulus opens channel
- Depolarisation opens other Na+ channels via positive feedback
- Na+ channels inactivated and then K+ channels open to stop depolarisation
- Hyperpolarisation occurs as K+ keeps fluxing out
- K+ channels then close to achieve resting potential
What is the relative refractory period?
Time between action potentials so that there is a period of no excitation to prevent damage to neurons
3 characteristics of muscle?
- High extensibility, high elasticity, produces force
How does muscle trigger movement?
Changes in shape, pressure, length and pulling on levers
Cardiac muscle:
- How are action potentials generated?
- What is electrical coupling?
- Refractory period?
- Spontaneously generated by node (pacemaker) cells - this is autorhythmicity
- If one cell has an action potential it triggers another cell to have one and so on
- 250ms
Smooth muscle:
- What changes?
- What is it controlled by?
- Length and shape of cells
- Amount of Ca2+ in cell which is controlled by autonomic nervous system - some action potentials are spontaneous though
Skeletal muscle:
- How does it move skeleton?
- How is it controlled?
- Length changes
- Motor neuron control (voluntary or reflex)
What theory underpins all the muscle types being able to change length?
Actin-myosin cross bridges and the sliding filament model
Skeletal muscle-tendon unit:
- How is force generated?
- What is aponeurosis?
- What is the role of the tendon (collagen, passive force elements)?
- What is architecture?
- Using metabolic energy
- How muscle fibres connect to tendoninous structure which is within the muscle (and the tendons are connected to bone)
- Transmits force to skeleton from muscle and from the skeleton to the muscle
- Arrangement of muscle fibres and tendons (position and function relate)
Transmission of muscle force to create movement:
- Where is force generated?
- How is force transmitted?
- What forms tendons?
- Fibres of muscle belly
- From muscle fibres to connective tissue (aponeurosis) and then through to skeleton
- Sheets of aponeurosis
Transmission of force to muscle to resist/control movement:
- How?
- Muscles resist effect force would have by generating force to absorb the impact and tendons stretch to allow joints to flex to allow impact absorption
Skeletal muscle:
- How are they adapted for high metabolic demand?
- How is action potential brought closer to cell?
- What are the 5 parts?
- Multinucleated and many mitochondria
- Tranverse (T) tubules
- Myofibrils (striated appearance), sarcolemma, sarcoplasm, sarcolemma (plasma membrane), sarcoplasmic reticulum
Myofibrils:
- What are the thick and thin filaments?
- What is the Z line?
- What is the M line?
- H zone?
- Sarcomere?
- Thick=myosin, thin=actin filaments
- Where actin meets myosin
- Centre of myosin
- Area of only myosin
- Single unit of a myosin and actin filament
Sliding filament model:
- What changes shape?
- How?
- Light band not dark band as only actin moves
- Cross bridges form and the myosin heads pull the actin filaments
What makes up an actin filament?
- Tropomyosin
- Actin
- Troponin
Actin:
- What is it?
- What does each protein have?
- A contractile protein made up of pearl-like chains (pearls=actin)
- A binding site
Tropomyosin:
- What is it?
- How does it function?
- A regulatory protein
- Overlaps myosin binding sites to inhibit interaction if it is in its relaxed state
Troponin:
- What is it?
- How does it work?
- A regulatory protein
- Reversibly binds to Ca2+ which changes it conformation to pull tropomyosin away and free the myosin binding sites on actin
Mechanism of excitation-contraction coupling? (6)
- Muscle action potential propagated into T-tubules
- Ca2+ released from lateral sac
- Ca2+ binds to troponin, tropomyosin moves = sliding filament occurs (until Ca2+ is removed)
- Cross-bridges form and generate force via power stroke to slide actin
- ATP causes release of myosin head so it can reattach
- Eventually Ca2+ is removed when there is so action potentials
What is the role of the sarcoplasmic reticulum?
Stores and releases Ca2+ upon excitation and they are connected to T-tubules so they are voltage sensitive
How skeletal activity is activated and controlled:
- How are action potentials initiated?
- What do motor neurons do?
- By nerve fibre (large diameter, myelinated) stimulation to skeletal muscle fibres (divergence)
- Innervate skeletal muscle and cell bodies in brain and spinal cord
What is a motor unit?
A motor neuron and all the skeletal muscle fibres it innervates within a muscle (there are many in a whole muscle)
- Why does a contraction form in a muscle fibre after an action potential?
- Why does the force take time to decrease?
- Tension (force) increases
- As Ca2+ takes time to be removed
3 phases of twitch contraction if one action potential occurs?
- Latent period - action potential to onset of contraction (delay due to excitation-contraction coupling)
- Contraction phase - tension developing (due to cross-bridge cycling)
- Relaxation phase - tension decreasing (due to all of the Ca2+ being sequestered)
What are tetanic contractions?
When multiple action potentials occur and there is a summation of tension (twitch contractions build up to form a higher constant force which is the tetanic contraction)
3 things the force a muscle produces in a tetanic contraction depends on?
- Number of cross bridges formed (active force generated)
- Length of muscle fibres (sarcomeres)
- Contraction velocity (speed of cross-bridge cycling)
Length of muscle fibres:
- What is the optimal length?
- When do muscles work best?
- Where does some other muscle force come from?
- The maximal overlap of actin and myosin to form the maximum number of cross bridges
- At the peak of active tension (not at really high lengths as this results in overstretching which results in muscle failure)
- Passive muscle tension (tension as it resists stretch)
Contraction velocity:
- When is active force low?
- When is active force high?
- 4 factors the force a muscle produces depends on?
- Rapid shortening (concentric) as there is less time for cross bridges to form
- Slow lengthening (eccentric) as the muscle is stretched for extra force
- Individual muscle fibres do not operate alone
- Different types of motor units and how many are activated
- Activation level of muscle
- Time since onset of activation
Activation level:
- When will all muscle fibres in a motor unit generate their maximum force?
- How are skeletal muscle fibres classified/differentiated as they are not the same mechanically or metabolically (2)?
- If threshold of motor unit is reached
- Maximal velocity of shortening
- Major pathway used to form ATP
Maximal velocity of shortening:
- 3 categories?
- How do they differ?
- Slow, fast, very fast
- The form of myosin is different which means they differ in the rate they use ATP and therefore the rate of crossbridge cycling differs
Pathways of forming ATP:
- 3 ways?
- Phosphorylation of ADP by creatine phosphate
- Oxidative phosphorylation of ADP in mitochondria
- Glycolytic phosphorylation of ADP in mitochondria
3 main types of skeletal muscle fibres and their characteristics?
- Slow-oxidative
(low myosin-ATPase activity, high oxidative capacity) - Fast-oxidative-glycolytic
(high myosin-ATPase activity, high oxidative capacity, intermediate glycolytic capacity) - Fast-glycolytic
(high myosin-ATPase activity, high glycolytic capacity)
What is activation of the 3 fibre types like?
Slow-oxidative - small force, but for long periods of time
Fast-oxidative-glycolytic - greater force, reduces over time
Fast-glycolytic - greatest force, reduces rapidly and more dramatically (faster fatigue)
How does whole muscle contraction work?
- All types of motor units are recruited but at different times
- Slower fibres activated with lower stimulus levels
- Fast fibres have a higher threshold for stimulation
How is muscle activation measured?
Electromyography (measures action potentials in muscle fibres)
What is:
- Concentric contraction?
- Isometric contraction?
- Eccentric contraction?
- Muscle shortening
- Same length
- Muscle lengthening
How is movement controlled? (4 levels/steps)
- Coordinated activation of muscles for controlled movement
1. Voluntary movement initiated by higher centres in the brain
2. Signals relayed to middle areas to coordinate movement
3. Then motor neurons activate muscles through efferent signals
4. Sensory feedback comes back from sensory receptors in muscles and joints (through afferent signals) to modulate movement
What are proprioceptors?
- Sensory receptors in the muscles and joints responsible for reflex actions
- In muscle they can be muscle spindles and golgi tendon organs
What is involuntary movement said to be?
Unconscious, automatic, protective
4 steps of the stretch reflex which protects muscle from overstretching?
- Muscle is stretched and an afferent signal is sent from muscle spindle to the spinal cord
- Synapses with motor neuron of stretched muscle cause muscle to contract and resist the stretch
- Synapses with inhibitory interneuron cause inhibition of motor neurons of flexor muscle
- Afferent signal from muscle spindle goes to brain so the movement is conscious
6 steps of the withdrawal reflex to protect from external stimuli?
- Painful stimulus
- Pain is detected by nociceptor and a signal is sent to the spinal cord
- Synapses with motor neuron of flexor muscle cause muscle to flex
- Inhibitory interneuron results in inhibition of ipsilateral (on same side) extensory muscle to facilitate movement
- Reflex crosses contralateral side to increase weight support on that side (excitatory interneuron to contralateral extensor, inhibitory interneuron to contralateral flexor)
- Afferent signal from nociceptor to higher centres (pain is now conscious)
3 issues associated with muscle dysfunction?
- Exercise associated muscle cramp (due to electrolyte depletion, dehydration or altered neuromuscular control)
- Delayed onset muscle soreness (microdamage to muscle, associated with overload, caused by eccentric exercise - as a result up-regulation of protein synthesis and adaptation occurs)
- Muscular dystrophy (muscle wasting as dystrophin is reduced - can be genetic)
What kind of disorders affect the muscle?
Neuromuscular junction or CNS disorders
Smooth muscle:
- Where is it found?
- Why can their shape change?
- Why do actin-myosin cross bridges form?
- What controls actin-myosin binding?
- Surrounding hollow structures
- Actin is attached to dense bodies in diagonal structure so it can balloon out
- Ca regulated enzyme phosphorylation of myosin
- Ca in the cell (not troponin and tropomyosin) which is controlled by the autonomic nervous system
Cardiac muscle:
- How does it contract?
- What is autorhythmicity?
- How are cells linked?
- How is tetanic contraction prevented?
- Actin-myosin cross-bridges
- Node cells producing spontaneous action potentials
- Electrical-coupling
- 250ms refractory period
What is haematocrit?
% of blood that is erythrocytes
What is bulk flow?
A rapid flow of blood throughout the body
What are reticulocytes?
Young erythrocytes in bone marrow that have a web-like structure of ribosomes
What is the breakdown product of haemoglobin?
Bilirubin (why plasma is yellow)
Role of folic acid and what does it need?
- Synthesising thymine
- Vitamin B12
- What is anaemia?
- 2 causes?
- Decrease in ability of blood to carry oxygen
- Decrease in the number of RBCs
- Low haemoglobin per RBC
Why do erythrocytes get replaced?
Erythropoietin stimulates erythropoiesis
What is haemostasis?
Stoppage of bleeding as severed blood vessels constrict and slow blood flow, glue endothelial surfaces together and clotting/formation of a platelet plug occurs
Why is exposed collagen relevant in haemostasis?
It has platelet binding via VWF which releases ADP and serotonin to change metabolism, and actin and myosin to allow contraction
- What do EDTA and heparin do?
- How does heparin stop clotting?
- What are serum tubes for?
- Prevent blood clotting in the lab
- It has plasma and clotting factors
- They have blood that clots
5 types of leukocytes?
- Lymphocytes
- Monocytes
- Neutrophils
- Eosinophils
- Basophils
- Last 3 are polymorphonuclear granlocytes
What happens if a type A person is given type B blood?
- Recipients anti-B antibodies cause transfused cells to be attacked
- Anti-A antibodies in transfused plasma cause recipients cells to be attacked
2 main primary lymphoid organs?
Thymus and bone marrow
What occurs in thymus?
T cell maturation
What are lymph nodes?
Lymphoid organs that swell in infection
What does the spleen do?
Filters blood and removes damaged erythrocytes
2 parts of the immune system and characteristics?
- Innate
- 1st line of defence
- Responds same way every time
- Fast acting, short term - Adaptive
- 2nd line of defence
- Responds differently each time
- Slower but more specific
- Distinguishes self and non-self
2 types of immune system classification?
- Soluble (IgG, IgA, cytokines, CRP, histamines)
- Cellular (different cell types)
4 barriers in the immune system?
- Structural/physical
- Skin
- Mucosal membranes - Chemical/physiological
- Stomach acid
- Fever
- pH - Phagocytic barriers
- Monocytes moved to tissue and become macrophages
- Have pattern recognition receptors that recognise pathogen associated molecular patterns (PAMPs) on bacteria - Inflammatory barrier
- Macrophages chemically attract other cells
- Neutrophils leave blood vessel
- Hot+swollen, leaky blood vessels
6 cell types in the immune system?
- Bone marrow
- Antibodies
- T cells
- NK cells
- Helper cells
- Dendritic cells
Bone marrow:
- Characteristics?
- 2 types of haematopoietic stem cells AND subdivisions?
- Pluripotent stem cells that can form any cell type (bar gametes) that turn into HSL haematopoietic stem cells that turn into blood cells
- Common lymphoid progenitor cell (CLP):
- Into lymphocytes which can be NK cells (innate) or (adaptive) B cells or T cells
- B cells linked to CD19+ (cluster of differentiation) which produces antibodies OR differentiate into plasma cells- T cells become T helper cells or cytotoxic cells
- Common myeloid progenitor cells (CMP)
- Become granulocyte macrophage progenitor cells (GMPs) or mega carycocyte erithroid progenitor cells (MEPs)
- Granulocyte macrophage progenitor cells (GMPs) become neutrophils, basophils or eosmophils
- Mega carycocyte erithroid progenitor cells (MEPs) become platelets or erythrocytes
- Common lymphoid progenitor cell (CLP):
Antibodies:
- 5 types?
- What is different about them and what do they have in common?
- IgA (surface mucosal membranes)
- IgM (ST immunity)
- IgG (LT immunity)
- IgE (allergic responses)
- IgD (unknown)
- Not all Y shaped but always have a constant and variable region
T cells:
- 2 types?
- What do they do?
- What do they recognise and how?
- Life cycle?
- Naive (never encountered pathogen)
- Memory (have)
- Kill pathogens when they recognise them (more lethal as they have more control)
- Mutation from UV as mutation changes sequences in DNA (which is placed on MHC molecules and recognised)
- Bone marrow –> T-cells –> thymus educates/matures T cells (autoimmunity can arise)
NK cells:
- Role?
- Where are MHC-class 1 found?
- What is different between everyone?
- Survey body (10% of WBC) and kill cancer cells that have lost MHC-class 1 without permission
- On endothelial cell membranes (antigen on cell surface)
- MHC
Helper cells:
- Roles?
- Produce cytokines
- Help B cells produce antibodies
Dendritic cells:
- Where?
- What do they do? (2)
- Sit in tissues and on T cell surface
- Bridge gap between innate and adaptive immunity AND engulfs pathogens
What are the 3 pillars of exercise?
- URTi and marathons (medically assessed, poor sleep/hygiene/start line/tube)
- IgA (saliva and nose) lowered (dry mouth, less saliva)
- Exercise (immune cells not adhered to blood vessels during and are secreted, but become adhered 10 hours post-exercise)
What does exercise improve for immunocompromised individuals?
Vaccine response
Exercise and cancer:
- What side-effects does it reduce?
- Why does it lower risk of cancer?
- Of chemotherapy
- Stimulates immune system to find tumour cells
3 things that impact the cardiovascular system?
- Endocrine system
- Nervous system
- Kidneys
What are the 2 loops of the cardiovascular system?
Systemic and pulmonary
Systemic loop (higher pressure):
- Where does the blood go?
- What does the aorta branch to form?
- What 2 large vessels form when venules form veins?
- From heart to major parts of body and back via the aorta from the left ventricle
- Systemic arteries which branch to for the microcirculation (arterioles, venules and capillaries)
- Inferior vena cava (blood from below heart) and superior vena cava (blood from above heart)
Pulmonary loop (lower pressure):
- Where does blood go?
- What does blood return through?
- Why do pulmonary arteries divide?
- To lungs (as blood is deoxygenated) and back via pulmonary trunk from right ventricle
- Pulmonary veins
- To take blood to each lung
What blood do arteries and arterioles carry and what is the exception?
Oxygenated blood, BUT pulmonary arteries carry deoxygenated to lungs though
What blood do veins and venules carry and what is the exception?
Deoxygenated blood, BUT pulmonary vein carries oxygenated to heart though
What is:
- Pressure?
- Flow?
- Resistance?
- Force exerted (mmHg)
- Volume moved (mL/min)
- Difficulty for blood to flow between 2 points at any pressure difference
3 factors that affect resistance?
- Blood viscosity (affected by volume and
the number of RBCs) - Blood vessel length
- Blood vessel diameter (relax to decrease
resistance)
- Main differences between veins and arteries?
- Between venules and arterioles?
- Veins have a wider lumen and fewer layers of smooth muscle, connective tissue and elastic fibres
- Arterioles are just smooth muscle, venules are just endothelium and connective tissue
Characteristics of elastic/conduit arteries?
Near the heart and have a low resistance (due to large lumen and more elastin)
Characteristics of muscular arteries?
Deliver blood to specific organs, mostly smooth muscle, involved in vasoconstriction
2 things that affect blood pressure?
- Volume
- Blood vessel elasticity
What is compliance?
How easily a structure stretches
What is systolic blood pressure?
Maximal arterial pressure reached during peak ventricular ejection
What is diastolic blood pressure?
Minimal arterial pressure reached just before ventricular ejection
Arterioles:
- 3 ways they are controlled?
- What do they control?
- What is intrinsic tone?
- How is the smooth muscle regulated?
- Neurally, hormonally, local chemically
- Flow to capillary bed via contraction and dilation
- Basal level of contraction
- Autonomically by local or extrinsic control
Arterioles:
- How do they increase resistance?
- How do they decrease resistance?
- What is local control of resistance?
- What is extrinsic control of resistance?
- Vasoconstriction to decrease flow to tissue
- Vasodilate to increase flow to tissue and pressure
- Responding to local metabolic change or blood flow change to increase blood flow to an organ OR responding to an injury via inflammation
- Hormones or sympathetic nerves causing vasodilation
Capillaries:
- 3 types?
- How do they grow?
- What does the blood flow depend on?
- Why is the forward movement of blood slow?
- What does blood velocity depend on?
- Continuous capillary (tight junctions)
- Fenestrated capillary (more permeable)
- Sinusoidal capillary (incomplete
basement membrane)
- Via angiogenesis (vascular endothelial cells release angiogenic factors)
- Other blood vessels in micro-circulation
- More time for substance exchange
- Cross-sectional area of vessel
Veins:
- What do they act as?
- What is blood pressure determined by?
- Low-pressure conduits that maintain peripheral venous pressure
- Volume and compliance
Define:
- Pericardium?
- Epicardium?
- Myocardium?
- Atrioventricular septum?
- Muscular sack enclosing heart
- Fixes inner layer of pericardium to heart
- Muscular wall of heart formed from cardiac muscle cells
-Barrier separating ventricles
What lines the inner surface of the chambers of the heart?
Endothelial cells
What is the difference between the left and right AV valve?
Left is bicuspid (2 fibrous flaps)
Right is tricuspid (3 fibrous flaps)
What is the semi-lunar valve between?
Left ventricle and aorta
Cardiac muscle:
- Why large mitochondria?
- How do the cells have electrical contact?
- What innervates?
- Produce energy and prevent fatigue
- Gap junctions
- Sympathetic nerve fibres (increase heart rate with noradrenaline binding to beta-adrenergic receptors) and parasympathetic nerve fibres (decrease heart rate with acetylcholine binding to muscarinic receptors)
Steps of heart contraction?
- Triggered by depolarisation from sino-atrial node
- Signal down atrial muscle cells to AV node
- Then down to Bundle of His
- Then it travels to the left and right Purkinje fibres by bundle branches
- The depolarisation then ends up at ventricular muscle cells and they contract
- Purkinje fibres also supply papillary muscle which tells them to contract atria before ventricles contract so backflow does not occur
What do these parts of an ECG represent:
- P wave?
- QRS complex?
- T wave?
- Atrial contraction
- Ventricular depolarisation and contraction
- Ventricular repolarisation
What is cardiac output?
Amount of blood pumped out of each ventricle in one minute (heart rate x stroke volume)
What is stroke volume?
Difference between end diastolic volume and end systolic volume (volume of blood from left ventricle per beat)
When does heart rate increase?
If blood volume drops or the heart weakens or stroke volume decreases and cardiac output stays the same
What is the Frank Starling mechanism?
- Ventricle contracts more forcefully during when systole when it has been filled to a greater degree during diastole
- Greater end diastolic volume increases muscle stretch and contraction
- It is due to the length-tension relationship (end-diastolic volume determined by how stretched the ventricular sarcomeres are pre-contraction)
What does increased contractility cause?
Greater stroke volume due to a more complete ejection of end-diastolic volume
4 factors that increase cardiac output by increasing stroke volume and/or heart rate?
- Increased end-diastolic ventricular volume
- Increased activity of sympathetic nerves to heart
- Increased plasma epinephrine (adrenaline)
- Decrease in the activity of parasympathetic nerves to the heart
How do you calculate the mean arterial pressure?
Diastolic pressure + 1/3 (systolic pressure -
diastolic pressure)
Arterial baroreceptors:
- Role?
- What is the degree of stretching directly proportional to?
- What is the integrating centre called?
- What is action potential frequency determined by?
- How are short term changes in blood pressure executed?
- Respond to changes in arterial pressure
- Blood pressure
- Medullary cardiovascular center
- Input
- Changing blood volume
What does the medullary cardiovascular centre do?
Increases arterial pressure which increases baroreceptor firing which decreases sympathetic outflow to the heart, veins and arterioles BUT increases the parasympathetic outflow to the heart
PHYSIOLOGICAL RESPONSE TO TREATING HYPERTENSION IN NOTES
4 ways of treating hypertension (high blood pressure)
- Diuretics (lower cardiac output by increasing Na and H2O excretion)
- Beta-adrenergic receptor blockers to lower cardiac output
- Ca channel blockers (reduce entry of calcium into vascular smooth muscle which results in weaker contractions and lowered peripheral pressure)
- Angiotensin-converting enzyme inhibitors (lowers peripheral pressure by causing vasodilation)
Renin-angiotensin system:
- How do the kidneys regulate blood pressure?
- Where are angiotensin-converting enzymes found?
- Role of aldosterone?
- Role of vasopressin?
- 3 things atrial natriuretic peptide does when cardiac cells produce it?
- Intra-renal baroreceptors detect changes in stretching to lower blood volume and increase renin
- On endothelial cells
- Slow-acting steroid hormone which stimulates Na+ absorption in kidneys
- Rapid-acting peptide from pituitary gland to stimulate water reabsorption
- Inhibits Na+ reabsorption
- Increases filtration rate (causing Na+ excretion)
- Inhibits action of aldosterone
Within hours of blood loss:
- What fluid is redistributed to balance?
- Symptom of that occurring?
- What mediates it?
- Interstitial fluid (moved into capillaries to increase plasma volume)
- Increased thirst, less urine
- Hormones (renin, angiotensin, aldosterone) and kidney function
What happens within days of blood loss?
Cell replacement via erythropoiesis and haemtopoiesis
MECHANICAL EVENTS OF CARDIAC CYCLE IN NOTES
What does the respiratory system allow?
Ventilation
What is most oxygen used for?
Heat loss to maintain temperature
What is VO2 max?
Maximum rate oxygen can be consumed, transported and utilised by the respiratory, cardiovascular and muscular systems
What is the main muscle in the respiratory system?
Diaphragm
What parts of the respiratory system are in the conducting zone (where minimal gas exchange occurs)?
Trachea, bronchi, bronchioles, terminal bronchioles
What parts of the respiratory system are in the respiratory zone (where gas exchange occurs)?
Respiratory bronchioles, alveolar ducts and sacs
What about the airways contributes to resistance?
Diameter (airways closest to ambient air are the widest)
What links do alveoli have?
Pulmonary artery and pulmonary vein
What gives airways such a large surface area?
Fractral branching
2 laws ventilation depends on?
- Boyle’s law (higher volume = lower pressure)
- Fich’s 1st law of diffusion (gas goes from high to low concentration)
What happens during expiration?
Diaphragm relaxes, external intercostal muscles relax, thoracic cavity reduced
What happens during inspiration?
Diaphragm contracts, external intercostal muscles contract, thoracic cavity increased
What is perfusion?
Transport of molecules to target tissues
Role:
- Pulmonary artery?
- Pulmonary veins?
- Pulmonary capillaries?
- Carries deoxygenated blood
- Carries oxygenated blood
- Carries both
What is partial pressure?
Pressure exerted by each individual gas
What is Henry’s law?
The concentration of dissolved gas is equal to the partial pressure of the gas multiplied by its solubility
What does a concentration gradient allow?
Gas exchange from high to low pressure
What is tidal volume?
Amount of air moving in and out of lungs in each respiratory cycle
What is inspiratory reserve volume?
Air taken in above tidal volume
What is expiratory volume?
Air out below tidal volume
What is the residual volume?
Volume that remains in the lungs after a forced maximal exhalation
What is inspiratory capacity?
Maximum volume of air inspired following a normal passive expiration
What is functional residual capacity?
Volume of air in lungs in lungs following a normal passive expiration
What is forced vital capacity?
Total volume of air expired following a maximal inspiration
What is total lung capacity?
Total volume of air in lungs after maximal inhalation
Flow volume loop:
- What makes it?
- What is on top and bottom?
- What is x and y axis?
- Spirometry
- Top = expiration, bottom = inspiration
- X = volume, y = flow rate
What is forced expiratory volume over 1 second (FEV)?
Amount of air expired in first second of a maximally forced expiration following a maximal inhalation
What controls expiration and inspiration at rest?
The brainstem
3 ways ventilation is changed?
- Chemoreceptors - detect O2 or CO2 changes and feed back to the respiratory centres in the brain
- Peripheral (carotid and aortic) - emergency detection for low O2 - carotid receptors rapidly respond via pH/CO2 detection system
- Central - slower by “steady state” control
What happens during exercise to increase ventilation?
pO2 is stable and pCO2 decreases (due to hyperventilation for more CO2 is removed) to increase ventilation (chemoreceptors in peripheries respond to reduced pCO2)
What else increases during exercise?
Capillary volume and ease of O2 transfer
Is ventilatory limitation usual or unusual at rest?
Unusual and would be health related
2 causes of ventilatory limitation?
- Altitude - lower barometric pressure at higher elevation and lower pCO2 in atmosphere - results in reduced ambient, alveolar and arterial pO2
- Disease - can cause ventilatory limitation e.g. cystic fibrosis causes mucous build-up due to mutant CF-transmembrane conductance regulators
5 ways heat is gained during exercise?
Convection, solar radiation, thermal radiation, conduction, metabolic heat
5 ways heat is lost during exercise?
Radiation, sweat evaporation, conduction, convection, respiratory evaporation
What does a high level of exercise over an extended period time decrease?
Plasma volume
- Can the kidneys restore body water in a deficit?
- Instead?
- No
- Help to convserve body water and electrolytes during a period of increased loss
Kidneys:
- What do they remove?
- What do they regulate?
- What do they release to regulate blood pressure?
- What process are they involved in?
- What do they produce?
- Waste products and foreign chemicals from the blood
- Total body water, salts, acid-base balance
- Hormones
- Gluconeogenesis
- An active form of vitamin D
What are the two types of nephron and their characteristics?
- Juxtamedullary - less common, loop of Henle deeper in medulla, generates osmotic gradient for water reabsorption
- Cortical - more common, loop of Henle not as deep, corpuscle in outer cortex
- What makes up the renal corpuscle?
- Role?
- A capsule and the glomerulus
- Forms filtrate from blood called the “ultra-filtrate”(no cells or proteins) which can enter tubule
Order of production of urine?
- Glomerulus
- Bowman’s capsule
- Proximal convoluted tubule
- Proximal straight tubule
- Descending limb of the loop of Henle
- Thin part of ascending limb
- Thick part of ascending limb
- Distal convoluted tubule
- Cortical collecting duct
- Medullary collecting duct
- Renal pelvis
Renal corpuscle:
- What make up the visceral layer of the Bowman’s capsule?
- What makes up the glomerulus?
- How does blood get in and out of glomerulus?
- Podocytes (surround glomerular capillaries)
- Glomerular capillaries (have small pores for filtering)
- In through wide afferent arteriole, out through thin efferent arteriole
3 barriers that separate blood in glomerulus and the fluid in the Bowman’s capsule?
- Single cell lining of capillary endothelium
- Basement membrane
- Single cell lining of the Bowman’s capsule
2 sets of capillaries in renal circulation?
- Glomerular capillaries (for filtering)
- Peritubular capillaries (supply each nephron with their own blood supply and form veins where blood leaves)
- What is the Macula densa?
- Role?
- Part of the distal convoluted tubule that runs past the Bowman’s capsule
- Detects changes in blood composition, then juxtaglomerular cells secrete renin which influences the formation of angiotensin II (used to control blood pressure - if concentration is high = vasoconstriction and increased Na+/H2O retention for higher blood pressure
3 stimuli to increase renin secretion?
- Renal sympathetic nerves
- Intrarenal baroreceptors
- Macula densa
- What are cells and intracellular/extracellular fluid compartments surrounded by?
- What does this mean the movement of water is determined by?
- A membrane permeable to water but not many substances
- The concentration of nonpenetrating solutes
What is an isotonic solution?
Same concentration of non-penetrating solutes as normal extracellular fluid
What is a hypotonic solution?
Lower concentration of non-penetrating solutes than normal extracellular fluid
What is a hypertonic solution?
Higher concentration of non-penetrating solutes than normal extracellular fluid
Steps of osmotic regulation if excess water is ingested?
- Excess water ingested
- Increased body fluid osmolarity
- Decreased firing by hypothalmic osmoreceptors
- Decreased ADH secretion
- Decreased plasma ADH
- Decreased tubular permeability to water in collecting ducts to decrease reabsorption
- Increased water secretion
Steps of volume regulation if plasma volume decreases?
- Decreased plasma volume
- Decreased venous, atrial and arterial pressures
- Increased ADH secretion
- Increased plasma ADH
- Increased tubular permeability to water in collecting ducts to increase reabsorption
- Decreased water excretion
Glomerular filtration involves forces:
- Forces favouring filtration?
- Forces opposing filtration?
- Glomerular capillary pressure and blood pressure
- Fluid pressure in Bowman’s space and osmotic force due to protein in plasma
How is glomerular filtration rate controlled?
- Physiologically (neural and hormonal input to afferent and efferent arterioles)
- Decreased by constricting afferent and dilating efferent
- Increased by dilating afferent and constricting efferent
How does reabsorption of Na+ and water differ?
Na+ is an active process using pumps, water is by osmosis (but depends on Na+ reabsorption)
How is the reabsorption of Na+ and water coupled?
- Decreased Na+ in tubular lumen decreases local osmolarity
- Increased Na+ in interstitial fluid increases local osmolarity so water moves into interstitial fluid
How does permeability of epithelium increase?
ADH (vasopressin) binds and cell signalling occurs so that aquaporins bind to the luminal membrane so that water moves into the collecting duct cells from the tubular lumen and then aquaporins bind to the basolateral membrane so water moves into the interstitial fluid
Primary active Na+ reabsorption:
- Where?
- Process?
- Proximal tubule, ascending limb of loop of Henle and collecting ducts
- Na+ actively pumped out of cells into interstitial fluid using Na+/K+-ATPase pumps so [intracellular Na+] is low and Na+ moves out of tubular lumen into tubular epithelial cells
Primary active Na+ reabsorption in proximal tubule:
- How does apical entry step of Na+ work?
- What does it drive?
- How is the SA of apical membrane of proximal tubular cells increased?
- Occurs by cotransport with organic molecules or protons
- Reabsorption of the cotransported substances and secretion of protons
- Covered in microvilli
Primary active transport of Na+ in ascending limb of loop of Henle:
- Main function?
- How is Cl- absorbed into interstitial fluid?
- To reabsorb NaCl by using Na-K-2Cl cotransporters - depend on Na+ concentration gradient made by basolateral Na+/K+-ATPase pumps
- By basolateral chloride channels
Primary active transport of Na+ in collecting ducts:
- Apical entry step?
- Diffusion into cortical collecting ducts through Na+ channels
4 steps of the coupling of water and Na+ reabsorption?
- Na+ moves from tubular lumen to interstitial fluid
- The local osmolarity decreases (increase [H2O]) in the tubular lumen and increases in the interstitial fluid (decrease [H2O])
- Net diffusion of water from lumen into interstitial fluid across tubular cells’ plasma membranes and tight junctions
- H2O, Na+ and other solutes move by bulk flow to peritubular capillaries for last step of reabsorption
What controls water permeability of cortical and medullary collecting ducts?
Physiological control
- What is the major determinant of membrane permeability (aquaporin insertion)?
- Mechanism?
- Vasopressin (ADH)
- ADH binds to receptor on basolateral membrane so cAMP is produced which activates cAMP-dependent protein kinase that phosphorylates proteins to increase rate of fusion of vesicles containing the aquaporin AQP2 - then H2O enters the collecting duct from tubular lumen and then into interstitial fluid by other aquaporin channels
What does high ADH cause?
Low urine volume due to high reabsorption
What is water diuresis?
Increased urine flow but not increased solute excretion
What is osmotic diuresis?
Increased urine flow as a result of increased solute excretion
Define:
- Hypo-osmotic?
- Hyper-osmotic?
- Iso-osmotic?
- Low osmolarity (low [solute])
- High osmolarity (high [solute])
- 2 solutions with equal osmotic pressure
What is the daily obligatory water loss?
Volume of urine per day
5 reasons why medullary interstitial fluid is hyperosmotic?
- Countercurrent anatomy of loop of Henle
- Reabsorption of NaCl in ascending limb
- Impermeability to H2O of ascending limb
- Trapping of urea in medulla
- Hairpin loops of vasa recta to minimise washout of hyperosmotic medulla
- What does it mean that the loop of Henle forms a countercurrent multiplier system?
- How does this affect the filtrate?
- Creates hyperosmotic medullary interstitial fluid and NaCl is reabsorbed into medulla via active transport in ascending limb via NKCC transporters
- Concentrated in descending loop but decreases in osmolarity in ascending limb so fluid entering distal convoluted tubule is hypo-osmotic (more dilute)
When does water stop moving out of the descending limb?
When the concentration of water is the same in the interstitial fluid and the limb
What occurs in distal convoluted tubule?
Fine tuning of Na+ and water reabsorption (influenced by ADH)
- What are vasa recta?
- What do they do?
- What happens in descending loop?
- Ascending loop?
- Hairpin loops of blood vessels that lie parallel to the loop of Henle
- Minimise excessive loss of solute and prevent interstitial gradient being washed away
- Ions in, water out
- Ions out, water in
